Yersinia pestis. Furthermore, ancient human microbiomes from fossilized faeces, mummies and dental plaque have shown shifts in human commensals through the Neolithic demographic transition and industrial revolution, whereas environmental isolates stemming from permafrost samples have revealed signs of ancient antimicrobial resistance. Culminating in an ever-growing repertoire of ancient genomes, the quickly expanding body of bacterial aDNA studies has also enabled comparisons of ancient genomes to their extant counterparts, illuminating the evolutionary history of bacteria. In this review we summarize the present avenues of research and contextualize them in the past of the field whilst also pointing towards questions still to be answered.Groundbreaking studies conducted in the mid-1980s demonstrated the possibility of sequencing ancient DNA (aDNA), which has allowed us to answer fundamental questions about the human past. Microbiologists were thus given a powerful tool to glimpse directly into inscrutable bacterial history, hitherto inaccessible due to a poor fossil record. Initially plagued by concerns regarding contamination, the field has grown alongside technical progress, with the advent of high-throughput sequencing being a breakthrough in sequence output and authentication. Albeit burdened with challenges unique to the analysis of bacteria, a growing number of viable sources for aDNA has opened multiple avenues of microbial research. Ancient pathogens have been extracted from bones, dental pulp, mummies and historical medical specimens and have answered focal historical questions such as identifying the aetiological agent of the black death as  Despite the growing wealth of genomic data since the advent of next-generation sequencing, some domains of life remain elusive for evolutionary biologists ; in partet al. [Mycobacterium tuberculosis [Mycobacterium leprae [The first breakthrough in aDNA occurred when Higuchi et al.  were ablet al. . PCR proculosis  and Myc leprae . Müller  leprae , however leprae  . Additi leprae . Due to  leprae . Additio leprae . The deb leprae .in silico verification based on sequence patterns [The advent of high-throughput sequencing (HTS) rejuvenated the field of paleomicrobiology as sample and data output increased by orders of magnitude  and broupatterns . Signatupatterns . Generalpatterns . In depupatterns . This frpatterns , which ipatterns . In cytopatterns . Bases bpatterns . Age is patterns . Howeverpatterns . Misincopatterns .Yersinia pestis, which was recovered from the teeth of a 14th-century plague victim at 30-fold coverage [Y. pestis paleogenome verified earlier work by Drancourt et al. [et al. [The development of targeted capture sequencing enabled enrichment using modern DNA or RNA as bait, making the recovery of ancient genetic material more financially viable . Enrichmcoverage . The isot et al. . This cot et al. , which w [et al.  and open−1) in Neisseria gonorrhoeae [−1 in M. tuberculosis [Y. pestis datasets. The estimated mean ages were pushed further back the older the included sequences were and showed that the inclusion of Late Neolithic and Bronze Age samples decreased dating uncertainty immensely. Duchêne et al. [M. leprae from Schuenemann et al. [M. tuberculosis from Bos et al. [Y. pestis from Wagner et al. [Comparisons using paleogenomes facilitate a better understanding of evolutionary processes through time, enabling the inference of ancient demography and admixture, within-population evolution and calibration of the molecular clock . In clocrrhoeae  and 0.00culosis . Chronolculosis . Therefoculosis  investige et al.  analysedn et al. , M. tubs et al.  and Y. r et al. ) spanninAlongside high-profile extraction like Neandertal  and woolM. tuberculosis by Spigelman et al. [et al. [M. leprae. The realization that aDNA can be recovered from bone tissue without visual evidence of disease led to an increase in available sequences, facilitating epidemiological investigations of populations [The beginning of sequencing, and therefore also paleogenetics, was facilitated by targeted PCR amplification, making the identification of candidate targets from ancient samples vital to the success of early attempts at acquiring bacterial aDNA. Seminal research was directed at the recovery of genetic material from bone as aDNA extraction is destructive and often unsuccessful. Bones are the most common of the invaluable and finite archaeological resources suited for aDNA retrieval. The choice of study organism fell upon pathogens causing diseases that can occasionally be identified by skeletal lesions, to further increase chances of successful extraction. The choice fell upon tuberculosis (TB) and leprosy, leading to the first retrieval of bacterial aDNA of n et al. , followe [et al.  amplifyiulations  and mixeulations .M. tuberculosis soon moved from bones to mummies, where natural mummification can lead to preservation, leaving bacterial DNA sufficiently intact for amplification [et al. [et al. [Clostridium. The concern around PCR amplification producing false positives makes the validity of these early findings questionable, especially because Cano and colleagues also found clostridia in the grass sample taken from the surroundings of the iceman.The extraction of aDNA from fication . Salo et [et al.  were abl [et al. . Another [et al.  through et al. [M. tuberculosis could be amplified with PCR. Furthermore, historic medical specimens, such as organs embedded in paraffin, were proven to be viable subjects for paleomicrobiology. Jackson et al. [Bacillus anthracis DNA from anthrax victims from 1979. Devault et al. [Vibrio cholerae.Donoghue et al.  were abln et al.  amplifiet et al.  later uset al. [et al. were able to retrieve DNA from Y. pestis, and thus found the aetiological agent for the black death. They suggest that dental pulp, as a better protected niche than bones that is equally expendable, should be used to detect ancient pathogens.The inventory of aDNA sources was broadened by Drancourt et al. , who reaet al. . Teeth aet al. . Drancouet al. [et al. [et al. [et al. [Early claims of isolation of bacterial aDNA from the environment were made by Priscu et al.  and Chri [et al.  through  [et al. , however [et al. . Willers [et al.  addresse, preservation is only optimal under extremely dry or frozen conditions [et al. [Besides mummified remains, ancient human microbiomes commonly endure only in two substrates: coprolites and dental calculus . Coprolinditions . The detnditions . Despite [et al.  were abl [et al. , while d [et al. . A combi [et al. . The com [et al. .et al. [et al. [et al. [Streptococcus mutans and Porphyromonas gingivalis. Warinner et al. [et al. [et al. into question.The third possible source for human microbiomes is dental calculus. Calculus consists of dental plaque, saliva and crevicular fluid forming calcified bacterial biofilms incrementally through deposition and mineralization . Composeet al.  first pr [et al.  to use s [et al.  were ther et al.  used HTSr et al. . However [et al.  showed tLooking at all viable source of bacterial aDNA , the iniArchaeological samples used in bacterial aDNA studies show a mixture of endogenous (ante-mortem) viable ancient material and exogenous (postmortem) sequences from colonization after death of the organism . Endogenet al. [et al. looked at systematic amplification bias of the V3 regions in 16S rDNA. They showed more successful amplification for shorter V3 regions, which might have skewed earlier, untargeted aDNA studies.Other than false positives, assessing bacterial communities can be inherently problematic in paleomicrobiology. The equilibrium of the microbiome can shift quickly after death, with anaerobic bacteria persisting more successfully, which can lead to false conclusions about ancient microbiomes . Bacteriet al.  highlighDespite the inherent challenges they pose, some characteristics of bacteria favour the study of paleogenomes. The bacterial bauplan harbours unique benefits for preservation, such as increased resilience based on membrane composition. Glycosidic ether lipids and hopanoids are components of bacterial membranes not found in archaea or eukaryotes, which protect DNA from enzymatic degradation . Intraceet al. [Y. pestis, M. tuberculosis and M. leprae [The development of agriculture brought food security and a settled lifestyle to human societies, but also led to an increase in infectious disease and is considered to be the origin of many important infections . The pret al. . Molecul leprae .Y. pestis is responsible for multiple human pandemics with millions of deaths through human history and is therefore a focal species for epidemiological research [As the causal agent of plague, research . Plague research .Y. pestis have been dated to 5000 years before present (YBP) by Rasmussen et al. [Y. pestis, as the Yersinia murine toxin gene ymt is absent in all samples older than 3700 years. Valtuena et al. [Y. pestis coincided with the ‘steppe ancestry’, where human expansion from central Eurasia to Eastern and Central Europe carried plague into Europe. The steppe ancestry of plague was confirmed by Damgaard et al. [Y. pestis aDNA. Temporally, the emergence of ymt as suggested by Spyrou et al. [et al. [ymt could have caused a wide geographical spread originating in the steppe of Eurasia.The earliest infections with n et al.  through a et al.  reconstrd et al. , who anau et al.  predates [et al. , which iY. pestis, starting in the sixth century and lasting until the mid-eighth century [et al. [The first pandemic is the first recorded bubonic outbreak of  century . The res century , who rec century . Keller  [et al.  reconstret al. [Y. pestis paleogenome lying ancestral to extant strains from four 700-year-old English plague victims. Its position in the phylogenetic tree suggests that the second pandemic is the first appearance of contemporary Y. pestis. The medieval paleogenome revealed no unique derived positions when compared to modern strains. A lack of genetic divergence between Black Death and modern strains indicates that genetic factors are not causal for the catastrophic effects of the black death when compared to the less severe effects of modern plague [et al. [et al. [Y. pestis aDNA from early victims from Spain (1300–1420 CE). High similarity compared to the English paleogenome, combined with historical reports, support the theory of a single entry of the plague in the spring of 1348 near Barcelona coming from the lower Volga region of Russia through the Crimean peninsula [et al. [The second pandemic lasted from the 14th until the 18th century, with a peak mortality during the period of the Black Death from 1348 to 1351, killing an estimated 30–50 % of the European population . Bos et et al.  retrieven plague . Other i [et al.  point ou [et al.  have seqeninsula . A subseY. pestis cycling within and between rodent and human populations, or repeated introductions [et al. [Y. pestis paleogenome. A phylogeny constructed from available extant and ancient genomes groups the late second pandemic genome within a single lineage with no extant members. The most ancestral sequence in the lineage was recovered from a victim of the Black Death. Bos et al. therefore concluded that Y. pestis persisted in Europe rather than being continuously reintroduced. Spyrou et al. [Y. pestis travelled into Russia and eventually to China, the origin of the third pandemic [The subsequent 400 year duration of the second pandemic within Europe gives room for two possible explanations: long-term persistence of ductions . With th [et al.  set out pandemic .et al. [et al. [et al. [Y. pestis. Rate estimates varied 40-fold between lineages, despite recent emergence and slow mean evolutionary rates [et al. [Y. pestis, there are a high number of polytomies, which Cui et al. ascribed to bursts of fixed mutations in narrow time windows. Feldman et al. [et al. [et al. [Y. pestis [Y. pestis was estimated to be 1505–6509 YBP by Cui et al. [et al. [et al. [et al.’s estimate is likely to be less robust than Spryou et al.’s estimate. Recurring updates in date estimates highlight the difficulty of establishing a definitive timeline for bacterial evolution, especially without using aDNA. When using aDNA, however, the paleogenome used for calibration must be of sufficient coverage to avoid false-positive SNPs [The third pandemic started in the mid-19th century and disseminated worldwide through marine routes, with active foci remaining today in Africa, Asia and the Americas . Cui et et al.  collecte [et al.  and Bos  [et al. ) to lookry rates . Harbeck [et al.  also repn et al.  report t pestis . The mosi et al.  in a stu [et al.  with fou [et al.  at 5299– [et al. . Therefoive SNPs .Y. pestis is a slowly evolving and well-studied pathogen with a well-documented historical record and an abundance of paleogenomes available  [Research into archives . Soft tiarchives . Chan et [et al.  were they et al.  carried (396 CE) . The mem(396 CE) . Infecti(396 CE) .et al. [−1), which was supported by Kay et al. [−1) with their paleogenomic approach. This dating would place the recent bound of the emergence of tuberculosis after the Neolithic demographic transition, possibly emerging through zoonotic transfer from livestock. Within the paleogenetic efforts to uncover the past of TB, the Bos et al. [To date the emergence of TB, Bos et al.  used aDNy et al. , who reps et al.  study iss et al.  should bM. leprae was the causative agent for leprosy [Hansen  was the  leprosy . Leprosy leprosy . As one  leprosy .et al. [et al. [et al. [M. leprae-positive and -negative cases uncovered a significant association of the allele DRB1*15 : 01 in leprae victims, which is a known susceptibility factor in modern cases. The stigmatization and the forbidding of marriage for the infected, combined with a hormone-related decrease in fertility through leprosy, might have led to negative selection on the DRB1*15 : 01 allele [et al. [M. tuberculosis and M. leprae being widespread Europe during the first millennium CE, with only leprosy declining drastically thereafter. To test whether this is due to cross-immunity, Donoghue et al. carried out PCR amplification targeting both species in archaeological samples from the Roman period to the 13th century. Forty per cent of the samples showed co-infection, possibly indicating that an increase in mortality from TB led to a tandem decrease in leprosy.The first historical records describe symptoms of leprosy in China, India and Egypt about 600 BC . The oldet al.  extracte [et al.  reconstr [et al. , providi [et al. . Krause- [et al.  recovere1 allele . Donoghu [et al.  point atM. leprae appears to differ depending on how many aDNA samples are included. The most comprehensive study conducted by Schuenemann et al. [−1. This estimate is lower (rate=0.0086 Mby−1) than their previous findings incorporating fewer medieval and modern strains [et al. [−1) using five medieval strains intermediate between the two studies by Schuenemann et al. The more medieval strains that are included, the older the estimate for the most recent common ancestor, suggestive of the time-dependent rate phenomenon.The dating of the most recent common ancestor of n et al.  arrived  strains . Benjak  [et al.  report aS. enterica serovar Typhi causes typhoid fever, which is a considerable public health problem for developing countries and causes 17 million new infections and 600 000 deaths each year [S. enterica [et al. [S. enterica sv. Typhi. Shapiro and colleagues [S. enterica and S. typhimurium, conceivably still a species of Salmonella but not typhoid. Shapiro et al. suggested that the sequence corresponds to a modern, free-living soil contaminant, whose presence has been overlooked due to lack of rigorous controls.ach year . Interesnterica , which wnterica . Papagri [et al.  targetedlleagues , howeverS. enterica was generated by Vågene et al. [et al. were able to link cocoliztli to S. enterica serovar Paratyphi C. Like Typhi, Paratyphi C causes enteric fever and is transmitted via the faecal–oral route [The first aDNA e et al.  from teeal route . It has al route .et al. [S. enterica sv. Paratyphi C from 800-year-old bones and teeth from a single Norwegian skeleton. Zhou et al. called the novel strain Ragna and calculated evolutionary rates for the Paratyphi C lineage, including the paleogenome, arriving at a median rate of 0.079 Mby−1. The most recent common ancestor of all Paratyphi C genomes was estimated to have existed 1162–1526 YBP, the split of Ragna from the other lineages occurring at 456–664 YBP. Seventy-eight per cent of genes were intact core genes with uninterrupted open reading frames and only 604 SNPs (rate=0.08 Mby−1) separated Ragna and the most recent common ancestor of modern Paratyphi C. Zhou et al. note that a scarcely changed genome even after 800 years of evolution is surprising, as local ecological interaction might plausibly cause variation in gene content.Zhou et al.  providedWithin bacterial paleogenetics the work of Vågene and colleagues  is a keyT. pallidum can cause a wide range of diseases, of which syphilis and yaws cause the highest disease burden, with more than 300 000 new yaws infections being reported between 2008 and 2012 and syphilis resulting in 10.6 million cases worldwide in 2009 [T. pallidum, can cause skeletal marks like TB and leprosy, making it of great interest to paleopathologists [et al. [et al. [et al. [T. pallidum aDNA using PCR from a 200-year-old specimen from Easter Island. The study remained the only successful attempt until 2012, was based on PCR amplification alone without subsequent sequencing, and therefore lacks authentication [T. pallidum subsequently proved difficult, as several failed paleomicrobial studies illustrate [et al. [T. pallidum highly likely. Schuenemann et al. [T. pallidum retrieved from a burial site used between 1681 and 1861. Out of five excavated individuals, only three contained aDNA from T. pallidum. A phylogeny of the recovered paleogenomes together with 39 extant genomes revealed that 2 grouped with syphilis strains, while the other grouped with a yaws-causing strains. Thus Schuenemann et al. [ in 2009 . Treponeologists . As for ologists . Skeletaologists . Some soologists , leadingologists . However [et al.  found si [et al.  question [et al.  were thetication . The acqlustrate . The aDN [et al.  analysedn et al.  providedn et al.  apparentT. pallidum are from post-contact samples, and because of the difficulty of obtaining aDNA, the origin of syphilis in Europe has not yet been resolved. However, Montiel and colleagues’ work [As all paleomicrobial studies on es’ work  should bV. cholerae is the aetiological agent of cholera, with a total of seven pandemics documented since 1817 [V. cholerae infected 3–4 million people and killed nearly 100 000, showing that V. cholerae still has a high disease burden [V. cholerae strains are available for the sixth (1899–1923) and seventh pandemics. The stored strains show a replacement of the classical biotype by El Tor prior to the present pandemic [et al. [V. cholerae genome from a preserved intestine. The intestine belonged to a second pandemic 1849 cholera outbreak victim, showing sequence similarity to extant genomes of the classical biotype, indicating a common origin.nce 1817 . The firnce 1817 . In 2012e burden . The drie burden . Stored pandemic . Devault [et al.  were abl−1 was used for dating, which was estimated earlier by Mutreja et al. [V. cholera was estimated to be 430–440 YBP by Mutreja et al., who highlighted that recombination and mutational saturation biases clock rates and thus date estimates.The emergence of the El Tor strain was dated to between 1940 and 1957, with the classical strain putatively emerging between 1843 and 1860 . A strica et al. , who regH. pylori is found in the stomach of nearly half of the human population [H. pylori phylogeny [et al. [et al. [H. pylori from the faeces of Andean mummies dated to 3000 YBP. Castillo-Rojas et al. [et al. performed sequencing and alignment, lending their claims more weight. Swanston et al. [H. pylori genes from the stomach of 200–300 year-old individuals recovered from a glacier in Canada. Swanston et al. found genetic similarities to European isolates, indicating European strains were present in First Nation territory 200–300 YBP. The first paleogenome of H. pylori was retrieved from the 5300-year-old Tyrolean iceman by Maixner et al. [pulation  and whilpulation . Longstahylogeny . Linz et [et al.  showed t [et al.  amplifies et al.  were abln et al.  amplifier et al. . The palr et al. .Brucella melitensis causes brucellosis infecting livestock, from which it transmits to humans, generating 500 000 new cases annually [B. melitensis-associated skeletal marks were identified in a skeleton of Australopithecus africanus dated to 2.4 to 2.8 million YBP, suggesting a long association with hominids [et al. [B. melitensis from a 14th-century Italian skeleton through untargeted HTS. The genome groups most closely with extant Italian strains, showing a continuity of infection in Italy.annually . In humaannually . Potentihominids . Kay et  [et al.  generateet al. [Staphylococcus saprophyticus, a bacterium typically causing urinary tract infections. The bacterium Gardnerella vaginalis was also found, which commonly occurs in modern-day pregnancy-related infections.Devault et al.  conducteBorellia recurrentis is carried by the human body louse Pediculus humanus and causes louse-borne relapsing fever, which has disappeared in the Western world but formerly caused millions of deaths in Europe [et al. [n Europe . Guellil [et al.  were ablS. enterica and B. recurrentis are major achievements, as neither leave visible marks of skeletons or mummies, compounding the challenges for ancient pathogen research by making a targeted approach difficult [et al. [The recovery of the paleogenomes of ifficult . Howeverifficult , like Ka [et al. , showed Paleomicrobiology has not stopped at the recovery of individual genomes, but has also assessed ancient microbiomes. Humans carry microbes comprising thousands of different species that collectively outnumber our own cells by at least an order of magnitude . The lonet al. [et al. [Tannerella forsythia, Porphyromonas gingivalis and Treponema denticola, which supply the most important pathogens in adult periodontal disease [et al. reported the presence of genes homologous to putative antimicrobial resistance genes. Weyrich et al. [S. mutans and members of the red complex were found in the Neanderthal samples [f Campylobacter gracilis, Propionibacterium propionicum, Fretibacterium fastidiosum, Eubacterium infirmum, Peptostreptococcus stomatis and Eubacterium sphenum were retrieved from the Neanderthal extractions.The evolution of the oral human microbiome can be assessed through dental calculus and is primarily shaped by two major shifts in human diet: a shift towards carbohydrate-rich diets in the Neolithic demographic transition (~10 000 YBP) and the arrival of industrially processed flour and sugar (ca. 1850) . Adler eet al.  used HTS [et al.  analysed disease . Besidesh et al.  analysed samples . The palet al. [et al. predominantly discovered bacteria of the genus Clostridium. Cano et al. [Burkholderia picketii, an aquatic bacterium possibly originating from meltwater, entering the body. The colon harboured several Clostridium species characteristic of the contemporary human faecal flora. Rollo et al. [Clostridium. Clostridium species are likely to persist better as they are endospore-forming, low-GC, Gram-positive bacteria, which are all qualities previously described as beneficial for preservation by Willerslev et al. [Clostridium also survive due to a rapid decrease in oxygen concentration postmortem, indicating that the uncovered abundance of Clostrdium is unlikely to reflect the true state of the microbiome at the point of death [et al. [et al., found the pathogen Haemophylus parainfluenzae. Santiago-Rodriguez et al. [Clostridium, which comprised up to 96.2 % of the species in the gut. Lugli et al. [et al. [Clostridium and Pseudomonas. Lugli et al. were also able to reconstruct five paleogenomes of the species Clostridium perfringens, Clostridium algidicarnis, Pseudomonas veronii and Pseudomonas fluorescens and a genome of the genus Clostridium that could not be assigned a species. The frequent retrieval of clostridial species could be attributed to their better preservation. However, many members of the genus are also found in soil [The evolution of the gut microbiome can be assessed from both coprolites and mummified organs, which was successful early in paleomicrobiology. Ubaldi et al.  paved tho et al.  amplifieo et al.  conductev et al. . Anaerobof death . Luciani [et al. , upon anz et al.  contribui et al.  reanalys [et al.  and pred in soil . Retrievet al. [Bacteroidetes, Firmicutes, Actinobacteria and Proteobacteria typical of contemporary faecal microbiomes. The two ancient samples were more genetically alike than modern samples, possibly owing to biogeographical structuring. Tito et al. suggest that microbiomes were formerly more geographically structured, possibly due to more locally restricted diets. Cano et al. [et al. [Tito et al.  first ano et al. , througho et al. . Tito et [et al.  conducte [et al. , showed  [et al. .The study of Weyrich and colleagues  shows hoet al. [et al. [Bacillus and Actinomycetes. Willerslev et al. [Actinobacteria. Bidle and colleagues [Alphaproteobacteria, Acidobacteria, Firmicutes and Cytophaga–Flavobacterium–Bacteroides divisions. D’Costa et al. [et al. [et al. found rates of 10 Mby−1.Most environmental aDNA comes from permafrost due to the excellent conditions for preservation. Whether aDNA yielded from ice can be compared with other aDNA samples is questionable, as microbes could potentially remain metabolically active within micro-encasings of liquid water . Active et al.  from an  [et al.  amplifiev et al.  used 16Slleagues  used 16Sa et al.  investig [et al.  collecteBidle and colleagues’ work  is excepThe future of bacterial aDNA research will continue to be punctuated by spectacular findings and technological advances that are difficult to foresee, such is the nature of discovery. Yet putting aside predictable trends for improved sample sizes, chronological coverage, aDNA recovery techniques, authentication methods and sequencing technology – important though they are – it is possible to chart out more broadly the areas where bacterial aDNA research stands to make great inroads into the study of bacterial evolution.M. tuberculosis in a 1000 year old Andean mummy [The unique contribution of aDNA to the study of evolution is the ability to replace inference about the past with evidence. The repertoire of available paleogenomes , Table 1an mummy . The futBroad questions continue to elude our understanding in bacterial evolution. What drives the structuring of pathogens into distinct strains or ‘clonal complexes’? Intense sequencing of decades-old freezer collections has revealed glimpses into an evolutionary dynamism in which apparently dominant contemporary strains are revealed to be transitory . As in tet al. [Understanding the historical context of bacterial evolution, particularly the evolution of new epidemic strains, is familiar territory for population genomics, yet densely sampled paleogenomes are needed to resolve persistent problems with molecular clock rates. In common practice, clock rates estimated over timeframes of years to decades are employed to infer deeper history by extrapolation, which is a risky occupation. Yet the time-dependent rate phenomenon renders this practice potentially fatal to attempts to accurately place bacterial evolution into the correct historical context. Consequently, we remain ignorant about the dates of deep splits in the phylogenies we routinely publish, and unable to draw safe inferences based on such dates. Establishing robust timeframes is crucial to determine, for example, whether AMR spreads due to rapid mobility, as described by Sheppard et al. , or whetet al.  suggest.What are the genes and genetic variants that predispose bacteria to cause disease? Ancient genomes offer unique opportunities to understand the substitutions, and the sequence of evolutionary events that preceded major outbreaks. This is particularly valuable for mutations that were so successful that they subsequently became ubiquitous. Yet it is unlikely that bacterial paleogenomes will be incorporated systematically into genome-wide association studies because of concerns over (i) confounding factors between ancient and modern genomes, hosts and environments, and (ii) obtaining high-quality phenotypes. Instead, identification of potential virulence-conferring mutations is most likely to provide candidate loci directly for experimental studies.More generally, how have human–microbe interactions influenced the evolution of each species? Understanding the landscape of the human microbiome prior to major transitions such as the Neolithic revolution and antibiotic revolution will be fundamental to progress. Recent discoveries in human and bacterial aDNA have highlighted this as particularly promising ground. aDNA studies have precipitated a major revision to our understanding of recent human and bacterial evolution, for example the spread of steppe ancestry across Eurasia, and the plagues carried with it . The ind


Acta Cryst. (2012), E68, m381–m382.Corrigendum to  et al. , there was an error in the name of the first author.In the paper by Mouas


Polymers. They are mainly regular research articles, but two reviews are also present in this analysis. The main topics appear related to (nano)composites, entangled polymers, ring polymers, nanotubes, polyelectrolytes, brushes and polymers at interfaces. The most used simulation methods are molecular dynamics, Brownian dynamics, and Monte Carlo, with the only exception being a paper dealing with metamaterials. The evolution of the fraction of publications falling into one of these fields over the past 50 years is visualized in This editorial deals with the most cited papers published in the years 2018–2019 in the section “Polymer Theory and Simulation” of the journal In the most cited contribution, Zhang et al.  studied Issa and Luyt  reviewedFei et al.  investigSefiddashti et al.  studied Karatrantos et al.  reviewedSingh et al.  optimizeZhang et al.  studied Rathee et al.  focused Wang et al.  studied Pan et al.  investigHou  determinZheng et al.  studied Chremos and Douglas  characteLee and Jung  conducteShchetnikava et al.  performeJehser et al.  investigZhou et al.  focused Tsamopoulos et al.  studied Last but not least, Zhang et al.  focused


Acta Cryst. (2008), E64, o1702.Erratum to  et al. .This article reports the correction of a paper by Mo


To the Editor: Lu et al.  (


In the above article by Bonilha et al. , online-The publisher apologizes for this omission.


Sir,et al.et al.,We thank Gould None to declare.


A series of predictive scoring systems is available for stratifying the severity of conditions and assessing the prognosis in patients with HBV-related liver diseases. We show nine of the most popular serum biomarkers and their models  that have gained great interest from clinicians. Compared with traditional scoring systems, these serum biomarkers and their models are easily acquired, simple, and relatively inexpensive. In the present review, we summarize the latest studies focused on these serum biomarkers and their models as diagnostic and prognostic indexes in HBV-related liver diseases. Hepatitis B virus (HBV) infection is a worldwide epidemic. According to WHO, ~2 billion people worldwide have been infected with HBV, of whom 240 million have chronic HBV infection (CHB) . In totaSeveral scoring systems are available to assess liver function and the severity of liver injury, such as the Child-Pugh (CP) score or the model for end-stage liver disease (MELD) score. However, some limitations of these two scores have been described , 6. ReceThis review summarizes the results of the latest research on these serum biomarkers and their models as diagnostic and prognostic indices in HBV-related liver diseases. Furthermore, we examine the future directions in this field of research.Serum CysC is a cysteine proteinase inhibitor produced at a constant rate and freely filtered by the glomerular membrane. Several studies suggest that CysC is an accurate indicator of mild renal dysfunction in contrast to classic biomarkers such as the serum creatinine (Cr) or Cr-based formulae , 8. PrevWan et al.  developeRecently, Wu et al.  reportedSerum Hcy is a sulfur-containing amino acid that is formed as an intermediary during hepatic methionine metabolism. It may either be remethylated to methionine or catabolized in the transsulfuration pathway to cysteine. Serum Hcy is well-documented as a predictor for cardiovascular diseases –18. The Zhu and Ma  showed tSerum CRP is an acute phase protein found in the blood stream, the levels of which increase in response to inflammation. It has also been extensively studied in coronary artery diseases, malignant tumors, tissue necrosis, and bacterial translocation –27. SeveZhu et al.  showed tCAR, which is calculated as CRP level divided by the albumin level, was initially used to assess the outcome of patients with acute medical admissions and sepsis , 34. TheHuang et al.  found thIn a following investigation, Wang et al.  showed t10TBil × 0.66) +  [The ALBI score was initially reported by Johnson et al. to estimate liver function status in HCC patients . The ALB×−0.085) . The ALB×−0.085) , 43. FurChen et al.  reportedDuring the same year, Chen and Lin  showed tNext, Lei et al.  also demQi  reportedOne year thereafter, Wang et al.  revealedFujita et al.  reportedIn a prospective study including 229 HCC patients who underwent hepatectomy, Zou et al.  reportedMore recently, Mai et al.  reportedLemoine et al.  first prLi et al.  reportedNext, Ren et al.  demonstrMoreover, Liu et al.  showed tIn agreement with these findings, Lee et al.  also shoA meta-analysis by Lian et al.  reportedWang et al.  demonstrNext, Zhang et al.  indicateNevertheless, Li et al. , Huang eNext, Hu et al.  demonstrDuring the same year, Desalegn et al.  found thNext, Hamidi et al.  showed tWang et al.  demonstrWang et al.  found thIn a following investigation, Pang et al.  also demPark et al.  showed tLiu et al.  demonstrFinally, Wang et al.  and Yu eAPRI was suggested by Wai et al.  to prediWai et al.  reportedShin et al.  found thDuring the same year, Lin et al.  indicateFurthermore, Zhang et al.  suggesteIn a subsequent investigation, Hung et al.  demonstrNext, Liu et al.  proposedAdditionally, Lesmana et al.  showed tWang et al.  indicateGumusay et al.  also sugDuring the same year, Ucar et al.  reportedShrivastava et al.  concludeXiao et al.  showed tIn contrast, Houot et al.  indicateMoreover, Huang et al.  also fouJin et al.  performeA systemic review and meta-analysis were performed on data from 39 studies including 16 articles focused on APRI alone, 21 articles on APRI and FIB-4, and two articles on FIB-4 for detecting different levels of liver fibrosis in patients with CHB. Xiao et al.  demonstrFinally, Mao et al.  showed t1/2 [The FIB-4 index was initially developed by Sterling et al. to predict significant fibrosis in patients with HCV/HIV coinfection . The for1/2 . The FIBMallet et al.  stated tIn a subsequent investigation, Kim et al.  pointed Additionally, Erdogan et al.  suggesteMa et al.  demonstrKoksal et al.  showed tKim et al.  confirmeMore recently, Lee et al.  denoted Li et al.  reportedHowever, Zhu et al.  showed tFurthermore, Kim et al.  indicateA meta-analysis by Li et al.  indicateAnother meta-analysis by Yin et al.  showed tGAR is calculated as GGT level divided by albumin level. It is an accurate and low-priced index to identify patients with obvious fibrosis or cirrhosis.Li et al.  reportedThis review assessed the value of serum biomarkers and their models in HBV-related liver diseases. The significance of serum CysC, serum Hcy, serum CRP, CAR, ALBI score, FIB-4 index, APRI, GPR, and GAR in the diagnosis and prognosis of HBV-related liver diseases has been indicated in many studies, as shown above. The most crucial studies regarding these serum biomarkers and their models are summarized in The last decade has seen significant progress in the development of noninvasive liver disease assessments in CHB patients. These assessments are not only used to identify patients with a high risk of adverse outcomes but also to monitor disease progression and therapeutic responses after interventions. Additionally, several studies also pointed out that these models should be used in combination with other noninvasive indices to achieve more efficient diagnostic and prognostic efficiency. Of course, the clinical utility of these serum biomarkers and their models as diagnostic and prognostic indices in HBV-related liver diseases requires further verification, and concrete steps should be undertaken to define standards that can serve as guidelines for effectively using serum biomarkers and their models as tools for diagnostic and prognostic assessments.


Dear Editors,Milesi et al. , 2019 arConsider first the model that lies behind Table 1 and using algebra rather than the confusing R syntax employed by the authors:The null hypothesis is that i et al.  do. Nevei et al. , p. 2635There are a number of points to note about this model and the data used by Milesi et al.  to estimi et al.  do not pTurning to Table 2, we find that the authors do not fit the three-level models (F2 nested within F1 nested within F0) that are required, i.e.,Even though Milesi et al.  wrongly The authors are of course correct to state that no one experiment can be definitive. Arguably, more attention to experimental design is warranted to have appropriately powered multi-generational rodent experiments such as this one and others (e.g. Kubsad et al.


The steady increase in the price of protein feed ingredients and the retraction of antibiotics from diets has encouraged nutritionists to search the alternatives for protein source and functional feedstuffs that can substitute the role of antibiotic growth promoters in poultry production. With crude protein of 24-30%, in vitro protein digestibility of 80% and proportion of essential amino acids of 47%, seed from ripe papaya may be exploited as the alternative protein feed ingredient for poultry. Moreover, the growth promoting effect, antimicrobial and antiparasitic activities, and immunomodulatory and antioxidative activities may confirm the potential of papaya seed as a functional feedstuff that could replace the role of antibiotic growth promoters for poultry. The in-depth study is needed to further elucidate the functionalities of papaya seed onpoultry. This review provides the updates on the nutritional contents of papaya seed, the potential of papaya seed as an alternative to conventional protein-rich ingredient, the growth-promoting effect of feeding papaya seed, the antimicrobial and antiparasitic activities of papaya seed, antioxidative activities of papaya seed, and the immunomodulatory activity of papaya seed on poultry. Carica papaya L.) seed is one of the agro-industrial by-products that have been included in poultry rations, due to its substantial amounts of crude protein, fat, and ash [Agro-industrial by-products have recently attracted a growing interest from the nutritionists as feed ingredients for poultry. Dealing with environmental pollution and high cost of poultry feed, the utilization of agro-industrial by-products as feed ingredients is beneficial for the environmental health and sustainable poultry production . Papaya  and ash . Papaya  and ash , antimic and ash -6, and i and ash ,8 for poPapaya is a tropical fruit that is available throughout the year . Papaya The updates regarding the nutritional contents of papaya seed, the potential of papaya seed as an alternative to conventional protein-rich ingredient, the growth promoting effect of feeding papaya seed, the antimicrobial and antiparasitic activities of papaya seed, antioxidative activities of papaya seed, and the immunomodulatory activity of papaya seed on poultry are presented in the present review.The use of agro-industrial by-products in poultry rations has been encouraged due to the steady increase in price of conventional feedstuffs. Among the agro-industrial by-products, papaya seed has been explored extensively as the potential of feed ingredients for poultry. The latter by-product contains substantial amounts of crude protein, fat, and ash that may be utilized by the chickens. et al. [et al. [Papaya seed meal also contains a substantial amount of minerals that may, therefore, essential for the metabolism, body functions, and health of poultry . Maisaraet al.  reportedet al.  documentet al.  demonstret al. ,10,17. Aet al. . El-Safy [et al.  documentet al. [et al. [In general, plant-derived products are rich in vitamins, including papaya seed. In the study of Maisarah et al. , it was  [et al.  revealed [et al. . On thiset al. [in vitro protein digestibility of papaya seed meal was 80.7%. It seems that the presence of anti-nutrient factors, particularly trypsin inhibitors and tannins, did not substantially inhibit the digestion and absorption of protein, as their quantities are relatively low in papaya seed [Protein is one of the most important constituents in poultry rations as it serves vital metabolic functions, building and constructing of body tissues, repairing of body cells, and maintaining of good health . Beyond et al.  reportedaya seed .et al. [et al. [Amino acids are essential components that are used to build body tissues of poultry . Besideset al.  formerlyet al. . The latet al. . Indeed,et al. . In the  [et al.  suggeste [et al. ,23,24, iRaja ducks. Likewise, Nideou et al. [et al. [Kabir chicks.In the post-antibiotic era, the presence of natural growth promoters for poultry is highly essential. Indeed, the retraction of antibiotics growth promoters from diets has been attributed to the retarded growth rate and thus poor economic performance of poultry farming. Although the studies are still limited, it was shown that papaya seed meal was able to improve the production performances of poultry, including increasing growth rate, egg production, and feed efficiency of poultry. In broiler chickens, Muazu and Aliyu-Paiko  showed tu et al.  documentu et al. . Moreove [et al.  reportedet al. [The definite mechanism by which papaya seed improved the growth performance of poultry remains unclear, but Muazu and Aliyu-Paiko  suggesteet al.  further et al. . The latet al. [Salmonella enteritidis, Vibrio vulnificus, Proteus mirabilis, and Bacillus cereus. Likewise, Peter et al. [Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Salmonella typhi. Similar to the previous study, Hidayati et al. [E. coli and S. typhi, while Masfufatun et al. [Vibrio cholerae and opportunistic pathogenic yeast Candida albicans. In accordance with this, the earlier study also showed the antifungal activity of papaya seed toward Aspergillus flavus, C. albicans, and Penicillium citrinum as reported by Singh and Ali [It is generally known that seeds of tropical fruits are rich in phytochemicals that may be essential to control and modulate the population of pathogens in the gastrointestinal tract of humans and animals. With regard particularly to papaya, the seeds from such fruit have been reported to contain alkaloids, flavonoids, steroids, saponins, papain, and terpenoids possessing antimicrobial as well as antiparasitic activities -6. Indeeet al.  reportedr et al.  showed ti et al.  demonstr and Ali .in vitro studies assessing the antimicrobial activities of papaya seed have been published, the in vivo study confirming such antimicrobial properties in poultry is, however, still lacking. The majority of in vivo studies more focus on the antiparasitic activities of papaya seed (in the forms of powder or extract), as presented in et al. [et al. [et al. [Although a number of n et al.  suggesten et al.  revealed [et al.  pointed  [et al.  reported [et al.  revealed [et al. . However [et al. .et al. [et al. [in vitro, in which Salla et al. [et al. [2O2 oxidative stress. In accordance, an earlier study by Nakamura et al. [In general, plants are known as good natural antioxidant sources that may be useful for poultry. Papaya seed has long been explored for its potential as natural source of antioxidants. The study by Kadiri et al.  clearly  [et al.  reported [et al.  revealed [et al. ,13. The a et al.  found th [et al.  documenta et al.  documentet al. [et al. [Recently, there is a growing interest among the poultry nutritionists to find the natural antioxidants as the alternative to chemical-based antioxidants. The use of chemical-based antioxidants is actually worried to induce a carcinogenic effect on humans as the consumers of poultry products . In the et al.  showed t [et al.  noticed  [et al. .in vitro study, Mojica-Henshaw et al. [et al. [et al. [et al. [The immune defense toward infections is crucial for maintaining the health of poultry. In the traditional human medicine, papaya seed has traditionally been used to improve the immune system of people . In the w et al.  showed t [et al.  reported [et al.  revealed [et al.  reported [et al. . To dateet al. [et al. [et al. [Several bioactive components have been suggested to play a pivotal role in immunomodulatory and anti-inflammatory activities of papaya seed. Kadiri et al.  suggeste [et al.  reported [et al.  revealed [et al. . It seem [et al.  pointingPapaya seed is agro-industrial by-product that is rich in protein and exhibits the growth-promoting effect, antimicrobial and antiparasitic activities, and immunomodulatory and antioxidative activities that are worthwhile as a functional feedstuff for substituting the role of antibiotic growth promoters for poultry. The in-depth study is needed to further elucidate the functionalities of papaya seed on poultry.SS prepared and revised the manuscript. SS read and approved the final manuscript.The author declares that he has no competing interests.Veterinary World remains neutral with regard to jurisdictional claims in published institutional affiliation.


It influences academic achievement, future personal health, social well-being and therefore, is of public health significance. The objective of the study was to determine the intelligence quotient (IQ) and academic performance of primary school children in Enugu-East LGA.children who met the inclusion criteria were recruited from both public and private primary schools in the Local Government Area (LGA) using a proportionate multistage sampling technique. Academic performance was classified into high, average and low academic using past records of class assessment. Intelligence quotient was assessed using the Raven´s Standard Progressive Matrices (RSPM) and was grouped into optimal and suboptimal. A semi-structured questionnaire was used to obtain data such as-age, gender, socio-economic indices and family size of the study participants. Analysis was done with Statistical Package for Social Sciences (IBM-SPSS).a total of 1,122 pupils aged 6 to 12 years were recruited. Optimal IQ and high academic performance were found in 54.0% and 58.8% of the study participants. Being from upper social class, in private school, and family size less than 4 were the significant determinants of high IQ and good academic performance (p<0.001).low socio-economic status, large family size and public school attendance impact negatively on IQ and academic performance. Hence, measures to curb large family sizes (i.e.>4 children) and improve the socio-economic status of families are needed environmental measures to improve intelligence and academic performance. Intelligence is the aggregate or global capacity of an individual to act purposefully, to think rationally and to deal effectively with the environment . GeneralIntellectual capacity (measured as intelligence quotient or IQ) is said to be one of the determinants of poor school performance of children . AcademiThis was a cross-sectional descriptive study involving school-aged children (6 to 12 years) in Enugu-East local government area of Enugu State. The study was carried out over a 3-month period from November 2017 to February 2018. Children who had attended same school for the three preceding terms, whose parents gave consent and the child assented to participate in the study if seven years and above were recruited into the study. Children who met the inclusion criteria were recruited from both public and private primary schools using a proportionate multistage sampling technique. In the first stage, simple random sampling by balloting was used to select one public and one private school from each political ward. In stage two, based on the total number of estimated pupils in each school, samples were allocated accordingly using the proportionate allocation method. With proportionate allocation method, the sample size of each school was proportionate to the population of the school. In stage three, the allocated sample size for each school was re-allocated proportionately across pupils in the different classes. In stage four, within each class, the pupils to be studied were selected randomly using a computer generated table of random numbers.et al. , respectively (ectively . YoungerRelationship between socio-demographic variables and academic performance: the association between socio-demographic characteristics and academic performance are shown in et al. [et al. [et al. [et al. [et al. [et al. [et al. [The proportion of children with optimal IQ in this study were more than those with suboptimal IQ. This differed from the observations of similar studies which assessed intelligence using the same tool. Ejekwu et al. . in Enug [et al.  in Jos a [et al.  in Akure [et al. . studied [et al.  and Ijar [et al.  like the [et al.  in Osun  [et al.  in Ethioet al. [et al. [et al. [et al. [et al. [et al. [et al. [et al. [This study showed a significant association between age and intelligence quotient. Those who had optimal intelligence were significantly younger than those with suboptimal IQ. Ejekwu et al.  also not [et al.  noted a  [et al. . Convers [et al.  in Ugand [et al.  in Ethio [et al.  and Ejek [et al.  observed [et al.  and Ampo [et al.  documentet al. [et al. [The relationship between socio-economic class, intelligence quotient and academic performance may be mediated by a third factor. The lower IQ in lower socio-economic class is largely attributable to the unfavourable environmental factors that usually accompany poverty. Indices of social disadvantage such as the risk of diseases/illnesses for example iron deficiency anaemia, under-nutrition and low level of parental education are common among persons in the lower socio-economic and could lead to impaired cognitive function , 30. Foret al. , 30. Ano [et al.  reportedet al. [et al. [et al. [et al. [et al. [The result of this study showed that children in public schools were more likely to perform sub-optimally in the test of intelligence and to have a low academic performance. This trend was also documented by Adedeji et al. , Ijaroti [et al.  and Mill [et al. . This co [et al.  and Abeb [et al. . Females [et al. . Boys ar [et al. . GeneralAge, low socio-economic status, large family size and public school attendance impact negatively on IQ and academic performance. Hence, measures to curb large family sizes and improve the socio-economic status of families should be put in place.There has been differing reports in the proportion of school-aged children with optimal intelligent quotient, and most of the studies studied intelligence quotient only and concentrated only in the government owned schools;There has been no consensus on the relationship between intelligence quotient and academic performance. Some authors noted a positive correlation where high IQ was associated with high academic performance, while some found no correlation between the two.This study has gone a step further to look at both intelligent quotient and academic performance in both government owned schools and private owned schools;Low socio-economic status, large family size and public school attendance impact negatively on IQ and academic performance;IQ and academic performance were positively correlated with each other.


Electronic nicotine delivery systems , consisting of a battery, heating element and e-liquid, have evolved significantly with wide variation in design, components, operating powers, and chemical constituents. Generated aerosols have been reported to contain potentially toxic substances. We conducted a systematic review to assess what is known about the presence of toxicants in ENDS aerosols in order to inform how system design could mitigate risk.Articles reporting on or evaluating design characteristics of ENDS and aerosol constituents were included and summarized.The search identified 2,305 articles, of which 92 were included after full-text review. Findings were grouped into 6 major categories of potentially harmful chemicals: carbonyls, volatile organic chemicals, trace elements, reactive oxygen species and free radicals, polycyclic aromatic hydrocarbons, and tobacco-specific nitrosamines. In general, higher concentrations of aerosol toxicants are associated with increased power or voltage. Aerosol toxicants are also associated with e-liquid flavoring agents existing as primary ingredients or as products of thermal degradation.Improved ENDS design can reduce toxicant levels. Additional research is needed to develop a framework for optimizing system characteristics to minimize exposure, especially with respect to heating power and e-liquids. Both manufacturers and regulatory agencies have roles in reducing toxicants and potential health risks from ENDS. Electronic nicotine delivery systems (ENDS) consist of a battery, a heating element , and liquid (“e-liquid”). The heated coil aerosolizes the e-liquid which consists of propylene glycol (PG), vegetable glycerin (VG), nicotine, and flavoring agents. ENDS were introduced commercially in China in 2003 and to the United States and Europe between 2006 and 2007 . The ENDThe aerosols produced by ENDS have been reported to contain potentially toxic substances, which the user inhales . PreviouWe conducted a systematic review of the literature in order to collate and integrate the literature assessing the design characteristics of ENDS associated with the production or release of potentially harmful substances in inhaled aerosols. We approached our review from the perspective of advancing understanding of how ENDS design could inform scientific and policy discussion around how to modify potential risks associated with their use.A registered protocol does not exist for this systematic review. A PRISMA checklist is available in supporting information .The review included articles reporting on  or evaluating  ENDS design characteristics and aerosol constituents, with a specific focus on the measurement of chemical species in aerosols produced by heated-coil ENDS.exclusively analyzing the known major and expected aerosol constituents nicotine, PG, and VG) were also excluded as these are expected aerosol constituents when liquids containing them are aerosolized.We excluded articles first by duplicates (n = 287), then a title and abstract screening, and finally by a full-text screening. Irrelevant studies included , but were not limited to, articles not assessing ENDS aerosol, letters, commentaries, or other reviews, second-hand or third-hand aerosol/residue assessments from ENDS, and environmental exposure studies. Additionally, studies retrieved that were not available in English or were published anonymously were also eliminated at this stage. At the full-text screening, studies were eliminated upon the basis of 4 criteria: wrong study design , no primary data , no full text (n = 17), and assessed major aerosol constituents only , internally (Group B), or non-replicated (Group C) for a specific major chemical category. Because we did not quantitatively combine study results, no articles were excluded based on risk of bias.We defined risk of bias We searched Ovid MEDLINE, Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Daily and Versions electronic databases, selecting articles published from 1946 until May 07, 2020. We employed the following keywords: "electronic nicotine device," “vape,” “vaping,” "electronic nicotine delivery system," "electronic cigarette," "e-cigarette," “ecig,” and "e-cigs." These terms were combined with the following terms: “acetaldehyde,” “acrolein,” “aerosol,” “air pollutant,” “aldehyde,” "aromatic amine," “atomizer,” “carbonyl,” “coil wire,” “e-liquid,” “exp flavoring agents,” “exp metals, heavy,” “exp temperature,” “formaldehyde,” "free radical," “glycerol,” "heavy metal," “nitrosamine,” “phenol,” "polycyclic aromatic hydrocarbon," “propylene glycol,” “thermal degradation,” “toxic,” “toxicity,” “vocs,” “volatile,” and "volatile organic compounds".Our search strategy identified 2,305 articles, and full-text review resulted in inclusion of 92 studies . We grouBecause there is overlap in the physical properties of categories, chemicals were sorted on the basis of general consensus in the literature as well as physical characteristics. The carbonyl category consisted of chemicals containing a carbonyl moiety; examples include formaldehyde and acetaldehyde. VOCs were defined as organic compounds with a boiling point between 50 and 250 °C , such asOur search identified publications reporting ENDS characteristics and major toxicant chemical groups in aerosols . We idenWe further categorized articles based on their reporting of ENDS attributes and how differences in devices and operating conditions influence the presence of aerosol toxicants ; the abset al. [et al. [et al. [et al. [et al. [et al. [et al. [et al. [et al. [et al. [et al. [et al. [et al. [et al. [Numerous studies have evaluated the relationship between power supplied to the atomizer heating element and aerosol carbonyl concentrations. Salamanca et al.  reported [et al.  observed [et al.  marked p [et al.  conclude [et al.  detected [et al.  identifi [et al.  observed [et al.  observed [et al.  conclude [et al.  observed [et al.  found th [et al.  observed [et al.  observed [et al.  observedet al. [et al. [et al. [et al. [et al. [The available literature suggests a similar relationship between voltage and the amount of carbonyls in ENDS aerosol. Uchiyama et al.  observed [et al.  observed [et al.  observed [et al.  observed [et al.  observedet al. [Suboptimal ENDS operating conditions result in what is commonly referred to as a “dry puff”, during which coil heating occurs in the absence of sufficient e-liquid to produce aerosol. Suboptimal ENDS operation can result in higher concentrations of carbonyls in aerosol. Farsalinos et al.  observedet al. [et al. [et al. [et al. [et al. [et al. [Coil location, orientation, and resistance may also affect carbonyl production. Farsalinos et al.  observed [et al.  also obs [et al.  reported [et al.  observed [et al.  similarl [et al.  identifiet al. [et al. [et al. [et al. [et al. [et al. [et al. [et al. [et al. [et al. [Several studies, but not all, have observed that carbonyl and VOC production varies by device type. Uchiyama et al.  reported [et al.  observed [et al.  examined [et al.  observed [et al.  observed [et al.  did not  [et al.  observed [et al.  conclude [et al.  reported [et al.  reportedet al. [et al. [et al. [et al. [3 in aerosol produced with 24 e-liquid flavors. Beauval et al. [et al. [et al. [et al. [et al. [et al. [et al. [et al. [et al. [et al. [et al. [Numerous articles have reported that e-liquid constituents impact carbonyl aerosol concentrations. Kim et al.  observed [et al.  observed [et al.  demonstr [et al.  observedl et al.  observed [et al.  observed [et al.  observed [et al.  observed [et al.  detected [et al.  detected [et al.  observed [et al.  observed [et al.  observed [et al. , 38. Rei [et al.  observed [et al.  observedet al. [E-liquid composition also impacts the transfer of chemicals to the aerosol. Erythropel et al.  observedA common technique for carbonyl analysis is to bubble aerosol through 2,4-dinitrophenylhydrazine (DNPH). This allows carbonyls to form carbonyl-DNPH adducts that can be detected with high performance liquid chromatography. Hemiacetals are formed through the reaction of a carbonyl with a hydroxyl, such as one on PG or VG, and become unreactive to DNPH. The stability of hemiacetal adducts formed when reactive carbonyls, such as formaldehyde, interact with VG or PG is controversial, as are the implications of the results. Though not directly observed, some investigators suggest that the stability of the carbonyl-DNPH adduct drives equilibria of hemiacetals, acetals, and free carbonyls towards that of the carbonyl-DNPH adduct and the formation of hemiacetals is reversed in DNPH solution ; others et al. [et al. [et al. [et al. [et al. [et al. [Various ENDS operating parameters increase the concentrations of hemiacetals in aerosol. Jensen et al.  reported [et al.  observed [et al.  increase [et al.  reported [et al.  observed [et al.  reportedet al. [et al. [et al. [et al. [et al. [et al. [et al. [et al. [et al. [et al. [Important relationships have been observed between trace elements in ENDS aerosols and variations in power, device, air-flow, coil material, and e-liquid. Zhao et al.  observed [et al.  observed [et al.  identifi [et al.  detected [et al.  identifi [et al.  analyzed [et al.  evaluate [et al.  observed [et al.  observed [et al.  did not et al. [et al. [et al. [The concentration of free radicals in aerosol has been reported to vary by power and associated coil temperature. Bitzer et al.  observed [et al.  observed [et al.  observedet al. [et al. [et al. [The effects of device type on free radicals have been examined. Bitzer et al.  observed [et al.  observed [et al.  found fret al. [et al. [et al. [et al. [13 radicals per puff of menthol, citrus, and tobacco flavors, respectively. Bitzer et al. [The composition of e-liquid affects the concentrations of free radicals in aerosol. Bitzer et al.  observed [et al.  observed [et al.  analyzed [et al.  generater et al.  analyzedet al. [et al. [et al. [et al. [PAH concentrations in aerosol vary with device and e-liquid but are generally low if detected. Flora et al.  analyzed [et al.  did not  [et al.  systemat [et al.  analyzed [et al.  and ENDSet al. [et al. [et al. [Studies of different ENDS products have observed low or undetectable levels of TSNAs. Flora et al.  did not  [et al.  analyzed [et al.  observed [et al. , they aret al. [et al. [et al. [Garcia-Gomez et al.  analyzed [et al.  found ci [et al.  reportedet al. [et al. [et al. [et al. [et al. [Lee et al.  detected [et al. , 70 obse [et al.  observed [et al.  reported [et al.  identifiet al. [et al. [et al. [et al. [El-Hellani et al.  focused  [et al.  reported [et al.  explored [et al. , 113 repet al. [Belushkin et al.  completeWe identified 92 articles reporting ENDS characteristics and aerosol toxicants, the majority of which used analytic techniques replicated by other researchers and many of which attempted to define relationships between changes in ENDS characteristics and aerosol constituents. Device characteristics relevant to the current review of ENDS are power, voltage, resistance, temperature, coil material, device, and e-liquid. The major chemical constituents were differentiated into carbonyls, VOCs, trace elements, ROS and free radicals, PAHs, and TSNAs.et al. [The ENDS industry evolves rapidly, and contemporary scientific observations may not maintain relevancy over time. Williams et al.  characteFirst, improving the safety profile of e-liquids would be a critical first step in manufacturing and regulation to reduce the likelihood of adverse health consequences from ENDS use. The risk associated with inhaling ENDS aerosol is associated with “unintentional” contaminants , “intentional” constituents , and the conversion of unintentional and intentional constituents into new chemical species during aerosolization. The literature suggests that numerous new chemicals are created during aerosolization that are not present in the native e-liquid , 59, 94.power = voltage2/resistance) affects the potential risk associated with the use of ENDS. Aerosol toxicants generally increase with increased power and voltage applied to the metal coil for heating. Power per surface area of coil may be a stronger predictor of toxicant production in aerosol than power alone [Second, the relationship between power, resistance, and voltage . This appears to be more common among top-coil designs due to inadequate wicking and could be mitigated with improved wicking to the top coil or the use of bottom, vertically oriented coils. In addition to coil location, wicking material has also evolved. In earlier generations of ENDS, the wick was primarily silica-based. With newer generations, the ENDS industry has begun to explore other wicking materials such as cotton, stainless steel, bamboo, and ceramic. Various wicking materials will deliver e-liquid to the coil at different rates; to avoid the dry puff phenomenon, these rates should be taken into consideration to ensure that the coil is properly saturated with e-liquid at all operating temperatures. The viscosity and density of the e-liquid will also determine its mobility, capillary action, and delivery to the coil, influencing the likelihood of a dry puff. Some ENDS manufacturers have included microprocessors that will deactivate heating once a certain temperature threshold is reached (e.g. >350 °C), which may minimize toxicant production from a dry puff without compromising user experience by suppressing aerosol production.Fourth, atomizer heating elements are an identified source of aerosol metals, and metals used for construction of coils and other components  should be selected to minimize metal breakdown and leaching. Commonly identified metals were Cu, Pb, Ni, Sn, and Zn. Coils are traditionally Ni, Ti, kanthal , stainless steel, and nichrome (Ni and Cr), whereas solder joints are Sn or Pb and wires are Cu . The resOur review has several limitations. First, due to the variability in reporting we were unable to quantitatively estimate and provide confidence intervals around the relationships between device operative parameters  and resulting toxicant levels in the aerosol. Second, we did not specifically assess the influence of human puffing topography variability on toxicity. The ability to quantitate “estimates of effect” would become increasingly possible if the market were to contract, products were regulated, devices were standardized for clinical therapeutic interventions, and researchers were to rigorously report operating parameters to allow comparison across studies.Toxicants with potential risk to health exist in aerosol produced by ENDS. Available literature suggests that ENDS can be designed to minimize exposure to potentially harmful aerosol toxicants. Minimizing toxicants in aerosol through consideration and optimization of design could serve to reduce health risks associated with the use of ENDS as part of a comprehensive approach to reducing tobacco harm on the population level.S1 Checklist(DOC)Click here for additional data file.S1 Table(DOCX)Click here for additional data file.


Nature has always been, and still is, a source of foods and ingredients that are beneficial to human health. Nowadays, plant extracts are increasingly becoming important additives in the food industry due to their content in bioactive compounds such as polyphenols  and caroAndrographis paniculata medicinal herb as possible inhibitors of NFκB (nuclear factor kappa-light-chain-enhancer of activated B cells) transcriptional activity of pure analogues. Yeon et al. [Sideritis raeseri subps. raeseri essential oil against common food spoilage and pathogenic microorganisms and evaluated its antioxidant and antiproliferative activity. Salehi et al. [In this context, Concha-Meyer et al.  studied n et al.  evaluaten et al. . They con et al.  examinedn et al.  reportedn et al.  where len et al.  investigi et al.  reviewedi et al.  reviewedStill more research is needed to explore more and in depth the health beneficial effects of plant extracts, since nature certainly has more to give to humans.


Saccharomyces cerevisiae, Candida albicans and Schizosaccharomyces pombe and a few others, are a huge and untapped resource of organisms. These microorganisms have entered the scientific mainstage but still require the development of technologies and technical resources to speed up their further development.Non-conventional yeasts, i.e., the vast biodiversity beyond already well-established model systems such as This Special Issue on non-conventional yeasts adds to the effort to popularize novel yeasts and contains 10 papers covering a range of organisms and fields of application.Kluyveromyces in the conversion of a waste stream to bioethanol is described by Leandro et al. [Yarrowia lipolytica, is reviewed by Do et al. [The use of o et al. . Dairy io et al. .Brettanomyces nowadays gains interest for beverage innovations—particularly in the reduction of alcohol content—as described by Tiukova et al. [Aspergillus flavus growth is described by Gonda et al. [Pichia kluyveri, Torulaspora delbrueckii or Lachancea thermotolerans, were studied for their flavor contributions in sequential wine fermentations by Oliveira and Ferreira [Lachancea thermotolerans, Wickerhamomyces anomalus, and Zygotorulaspora florentina, was used in beer co-fermentations by Canonico et al. [Beverage production using non-conventional yeasts is on the rise and also a key topic in this Special Issue. Previously regarded as spoilage yeasts, a et al. . This paa et al. . The rola et al. . Other nFerreira . Here ito et al. . An inteMeyerozyma, Spathaspora and Wickerhamomyces was studied by Carneiro et al. [Yarrowia lipolytica strain was developed by Tramontin et al. [Production of specific compounds by microorganisms is a strongly growing field in biotechnology. Xylitol production by o et al. . The pron et al. . The taxn et al. . This geIn summary, these papers describe a suite of applications of nonconventional yeasts in diverse biotechnological applications. They will further advance the field and stimulate growth in these areas.


By contrast, facial-expression recognition was not significantly correlated with measures of depression, positive or negative affect, empathy, or autistic-like traits. Because the range of affective factors considered in this study and its use of multiple expression-recognition tasks mean that it is a relatively comprehensive investigation of the role of affective factors in facial expression recognition, we carried out a direct replication. In common with Palermo et al. , scores on the DASS anxiety subscale negatively predicted performance on the emotion recognition tasks across multiple analyses, although these correlations were only consistently significant for performance on the emotion-labelling task. However, and by contrast with Palermo et al. , other affective factors (e.g. those related to empathy) often also significantly predicted emotion-recognition performance. Collectively, these results support the proposal that affective factors predict individual differences in emotion recognition, but that these correlations are not necessarily specific to measures of general anxiety, such as the DASS anxiety subscale.Evidence that affective factors  are significantly related to individual differences in emotion recognition is mixed. Palermo  Although it is widely acknowledged that substantial individual differences in facial expression recognition exist, the factors that underpin these individual differences are poorly understood . Many stEvidence from studies investigating the relationship between affective factors and facial expression recognition has been mixed. For example, while studies of clinical samples have found that anxious or depressed people show impaired facial expression recognition e.g. ,3), some, some3])Interpreting the mixed results for affective factors and facial expression recognition described above is complicated because different studies have investigated different affective factors and/or used different methods to assess facial expression recognition. Direct replications  are one way to address this difficulty because they allow for more direct comparison of results across studies .et al. [In the light of the above, we directly replicated one recent study of the possible link between affective factors and facial expression recognition . We choset al.  for our et al. [N = 63) scores on the anxiety scale of the depression anxiety and stress scales (DASS) were negatively correlated with their performance on Palermo et al.'s [r = −0.287, p = 0.023) and emotion-labelling  tasks. By contrast with their results for anxiety, participants' performance on neither of these emotion-recognition tasks was significantly correlated with their scores on questionnaires measuring a range of other affective factors . Performance on a third emotion recognition test , the negative affect scale of the PANAS, scores on the autism quotient (AQ), scores on the empathy quotient (EQ), scores on the affective component of the basic empathy scale (BES), or scores on the cognitive component of the BES.Hypothesis 4. Performance on Bänziger et al.'s [et al.'s  multimodhttps://psyarxiv.com/fg8yz/. This preregistration was performed prior to data collection and analysis.This article received in-principle acceptance (IPA) on 26 April 2019. Following IPA, the accepted Stage 1 version of the manuscript was preregistered on the OSF at 2.2.1.et al. [et al.'s [Palermo et al.  tested 6et al.  recommenet al.'s  original2.2.et al. [et al. [et al. [et al. [We used the same emotion-matching task as Palermo et al. . This is [et al. . Images  [et al. . Partici [et al.  and desc [et al. , allowin [et al. , and wer2.3.et al. [et al. [et al. [et al. [et al. [et al. [et al. [We used the same emotion-matching task as Palermo et al. . This is [et al. , but wit [et al.  were als [et al. . Each fa [et al.  and desc [et al.  paper. P [et al. , allowin [et al.  were sho2.4.et al. [This test, described in full in Bänziger et al. , is an o2.5.et al. [et al.'s [et al.'s [Each participant completed the same affective factor questionnaires used by Palemro et al. . These aet al.  DASS, Waet al.'s  PANAS, Bet al.'s  AQ, Baroet al.'s  EQ and Jet al.'s  BES.3.et al. [et al. [As in Palermo et al. , the DAS [et al. , we ran et al. [et al. [All subscale and component scores tested by Palermo et al.  were cal [et al. . Cronbac3.1.et al. [Outliers (scores on a measure that were more than three standard deviations from the mean score for that measure) were adjusted to score one point higher than the closest non-outlier score (following ). As a pet al.  .Scores on the emotion matching task and the DASS anxiety subscale were not significantly correlated .Scores on the emotion labelling task and the DASS anxiety subscale were significantly negatively correlated  who scored within the maximum and minimum values for each measure as reported in et al. [We also conducted additional robustness checks restricting the sample to only those participants N = 06 who scr = −0.245, p = 0.011). Scores on the DASS anxiety subscale were negatively correlated with performance on the emotion-matching task  and the MERT , but these correlations were not significant.In this smaller dataset, scores on the DASS anxiety subscale were negatively and significantly correlated with performance on the emotion-labelling task . Conet al. ) and theet al. . So as tet al.'s  study, thttps://osf.io/kexhr/ and in our supplemental materials. These analyses showed little evidence that the BFNE, SIAS or SPS consistently predicted emotion recognition.Analysis code for these exploratory analyses and full results are publicly available at 4.3.https://osf.io/kexhr/).All data and analysis code are publicly available on the Open Science Framework . Nonetheless, we suggest that, collectively, our results show clear support for Palermo et al.'s claim that the DASS anxiety subscale predicts individual differences in general emotion recognition.Replicating Palermo et al. , particiet al. [et al. [et al's results suggested that individual differences in emotion recognition were predicted specifically (i.e. uniquely) by scores on the DASS anxiety subscale, our results (and our results for EQ in particular) do not support this claim. However, our results for EQ and emotion recognition are consistent with those of some previous studies that also found that people who scored higher on measures of empathy or lower on measures of autistic-like traits performed better on emotion-recognition tasks . Inde. Indeet et al. By contrast with our results for the DASS anxiety subscale, we saw little evidence that any of these measures significantly predicted emotion recognition. We tentatively propose that these null results for social anxiety suggest that the power of DASS anxiety in predicting emotion recognition is unlikely to reflect individual differences in social anxiety specifically, despite some researchers having previously suggested social anxiety may be particularly important for emotion recognition . How. Howet aet al.'s [et al.'s results, we found that other affective factors, most notably those related to empathy (e.g. the EQ) also appeared to predict general emotion recognition. Collectively, these results support the proposal that affective factors predict individual differences in emotion recognition, but that these correlations are not necessarily specific to measures of general anxiety, such as the DASS anxiety subscale, and may also extend to measures of empathy.In conclusion, we found that general emotion recognition was negatively correlated with scores on the DASS anxiety subscale, replicating Palermo et al.'s  results.


Sehnal  is corrected.The article by  et al. Sehnal  are corrected.Two citations in the article by


In the issue entitled “Role of Medical Imaging in Cancers”, 33 papers have been collected . All the papers focus on different topics, mainly on the role of positron emission tomography (PET) imaging in the management of oncological patients. Cancers, in order to apply this in diverse settings of disease. Castaldo et al. [o et al.  and Schio et al.  evaluateo et al. . The seco et al.  showed to et al.  found a n = 16) affected by high-risk soft tissue sarcoma, the authors of [Indeed, radiomics can be used as a tool for the prediction of outcomes in terms of response to therapy or prognosis in patients undergoing immune check point inhibitors, as stated by Polverari et al. . The usethors of  found thThe residual papers focused on different topics by analyzing diverse imaging modalities from preclinical , to gold


References on tables are misplaced.In the original article, there was a mistake in In In In the original article some references are misplaced.Inflammatory Response Under Impaired Lung Mechanics – Where Sterols Come into Play,” paragraph 5, the cited reference Ertunc and Hotamisligil, 2016 was incorrectly placed. It should be Jin et al., 2018. In paragraph 6, the cited reference Veldhuizen et al., 1996, 1997; Vazquez De Anda et al., 2000; Maitra et al., 2002 should be Ertunc and Hotamisligil, 2016. The cited reference Fessler and Summer, 2016 should be Veldhuizen et al., 1996, 1997; Vazquez De Anda et al., 2000; Maitra et al., 2002. The cited reference Glasser et al., 2003; Hamvas et al., 2004; Lawson et al., 2004; Stevens et al., 2005; Henderson et al., 2013; Liptzin et al., 2015; Salerno et al., 2016 should be Fessler and Summer, 2016. The cited reference Cassel et al., 2008 should be Glasser et al., 2003; Hamvas et al., 2004; Lawson et al., 2004; Stevens et al., 2005; Henderson et al., 2013; Liptzin et al., 2015; Salerno et al., 2016. In paragraph 7, the cited reference Vilaysane et al., 2010; Wree et al., 2014; Lv et al., 2018 should be Cassel et al., 2008. The cited reference Zhou et al., 2013 should be Gasse et al., 2007. The cited reference So et al., 2007; Ertunc and Hotamisligil, 2016 should be Vilaysane et al., 2010; Wree et al., 2014; Lv et al., 2018. The cited reference; Gasse et al., 2007; Robert et al., 2016 should be So et al., 2007; Ertunc and Hotamisligil, 2016.In section “SP-C Modifications in Animal Models,” paragraph 1, the cited reference Lawson et al., 2005; Glasser et al., 2008, 2013a,b; Glasser and Senft, 2009; Ruwisch et al., 2020 should be Glasser et al., 2003; Ruwisch et al., 2020. The cited reference Jolley et al., 1999 should be Glasser et al., 2001; Glasser et al., 2003. The cited reference Lawson et al., 2005; Glasser et al., 2008, 2013a,b; Glasser and Senft, 2009 should be Jolley et al., 1999. In paragraph 2, the cited reference Lawson et al., 2005 should be Lawson et al., 2005; Glasser et al., 2008; Glasser et al., 2009; Glasser et al., 2013a,b. The cited reference Madala et al., 2011 should be Lawson et al., 2005. The cited reference Glasser et al., 2008 should be Madala et al., 2011. The cited reference Glasser et al., 2009 should be Glasser et al., 2008. The cited reference Glasser and Senft, 2009 should be Glasser et al., 2009. The cited reference Glasser et al., 2013b should be Glasser et al., 2008; Glasser et al., 2009. The cited reference Glasser et al., 2008 should be Glasser et al., 2013b. In paragraph 3, the cited reference Glasser et al. (2001), Bridges et al. (2003), should be Glasser et al., 2001, 2008. The cited reference Lawson et al., 2011, should be Bridges et al., 2003; in line 17, first Nureki et al., 2018 should be Lawson et al., 2011; in line 35, Venosa et al., 2019 should be Nureki et al., 2018. The cited reference Katzen et al., 2019 should be Venosa et al., 2019. The cited reference Nogee et al., 2001 should be Katzen et al., 2019.In section “SP-C Mutations in Human Patients,” paragraph 1, the cited reference Ono et al. (2011), Litao et al. (2017) should be Nogee et al., 2001; in line 3 Thomas et al., 2002; Ono et al., 2011; Kuse et al., 2013; Avital et al., 2014; Hevroni et al., 2015 should be Nogee et al., 2001; in line 9 Thomas et al., 2002; Ono et al., 2011; Kuse et al., 2013; Avital et al., 2014; Hevroni et al., 2015 should be Ono et al., 2011; Litao et al., 2017. The cited reference Cottin et al., 2011; Ono et al., 2011 should be Ono et al., 2011; Kuse et al., 2013; Avital et al., 2014; Hevroni et al., 2015. The cited reference Cottin et al., 2011, Hevroni et al., 2015 should be Cottin et al., 2011; Ono et al., 2011. The cited reference Thomas et al., 2002; Abou Taam et al., 2009; Cottin et al., 2011; Ono et al., 2011; Avital et al., 2014 should be Cottin et al., 2011; Hevroni et al., 2015. The cited reference Thouvenin et al., 2010; Hevroni et al., 2015 should be Thomas et al., 2002; Abou Taam et al., 2009; Cottin et al., 2011; Ono et al., 2011; Avital et al., 2014, and Abou Taam et al., 2009 should be Thouvenin et al., 2010; Hevroni et al., 2015. The cited reference Avital et al., 2014 should be Abou Taam et al., 2009. The cited reference Lawson et al. (2004) should be Avital et al., 2014. The cited reference Cottin et al., 2011 should be Lawson et al., 2004 and Nogee et al. (2001), Chibbar et al. (2004), Hamvas et al. (2004), Lawson et al. (2004), Cameron et al. (2005), Stevens et al. (2005), Soraisham et al. (2006), Mechri et al. (2010), Thouvenin et al. (2010), Citti et al. (2013), Park et al. (2018) should be Cottin et al., 2011.In section “paragraph 2, the cited reference Korfei et al., 2008 should be Nogee et al., 2001; Chibbar et al., 2004; Hamvas et al., 2004; Cameron et al., 2005; Stevens et al., 2005; Soraisham et al., 2006; Mechri et al., 2010; Thouvenin et al., 2010; Citti et al., 2013; Litao et al., 2017; Park et al., 2018. The cited reference Wambach et al., 2010 should be Korfei et al., 2008. The cited reference Amin et al., 2001 should be Wambach et al., 2010. The cited reference Chibbar et al., 2004; Hamvas et al., 2004; Tredano et al., 2004; Rosen and Waltz, 2005; Stevens et al., 2005; Bullard and Nogee, 2007; Guillot et al., 2009; Mechri et al., 2010; Cottin et al., 2011; Citti et al., 2013; Henderson et al., 2013; Hepping et al., 2013; Turcu et al., 2013; Akimoto et al., 2014; Avital et al., 2014; van Hoorn et al., 2014; Kroner et al., 2015; Liptzin et al., 2015; Peca et al., 2015; Griese et al., 2016; Liu et al., 2016; Hayasaka et al., 2018 should be Amin et al., 2001. The cited reference Lawson et al., 2004; Setoguchi et al., 2006; Markart et al., 2007; van Moorsel et al., 2010; Cottin et al., 2011; Ono et al., 2011; Kuse et al., 2013 should be Chibbar et al., 2004; Hamvas et al., 2004; Tredano et al., 2004; Rosen and Waltz, 2005; Stevens et al., 2005; Bullard and Nogee, 2007; Guillot et al., 2009; Mechri et al., 2010; Cottin et al., 2011; Citti et al., 2013; Henderson et al., 2013; Hepping et al., 2013; Turcu et al.,2013; Akimoto et al., 2014; Avital et al., 2014; van Hoorn et al., 2014; Kroner et al., 2015; Liptzin et al., 2015; Peca et al., 2015; Griese et al., 2016; Liu et al., 2016; Hayasaka et al., 2018 and Hamvas et al., 2004; Abou Taam et al., 2009; Mechri et al., 2010; Cottin et al., 2011; Litao et al., 2017 should be Lawson et al., 2004; Setoguchiet al., 2006; Markart et al., 2007; van Moorsel et al., 2010; Cottin et al., 2011; Ono et al., 2011; Kuse et al., 2013. In paragraph 3, the cited reference Amin et al., 2001 should be Hamvas et al., 2004; Abou Taam et al., 2009; Mechri et al., 2010; Cottin et al., 2011; Litao et al., 2017. The cited reference Lawson et al., 2004; Stevens et al., 2005; Hamvas, 2010; Henderson et al., 2013 should be Amin et al., 2001. The cited reference Liptzin et al., 2015; Salerno et al., 2016 should be Lawson et al., 2004; Stevens et al., 2005; Henderson et al., 2013. The cited reference Tredano et al., 2004; Abou Taam et al., 2009; Thouvenin et al., 2010; Ono et al., 2011 should be Liptzin et al., 2015; Salerno et al., 2016. The cited reference Thouvenin et al., 2010; Cottin et al., 2011 should be Abou Taam et al., 2009; Thouvenin et al., 2010; Ono et al., 2011. The cited reference Tredano et al., 2004; Ono et al., 2011 should be Thouvenin et al., 2010; Cottin et al., 2011 and Ruwisch et al., 2020 should be Ono et al., 2011.In Lung Fibrosis and Cholesterol” the cited reference Xu et al., 2012 should be Kreuter et al., 2018. The cited reference Baritussio et al., 1980 should be Kreuter et al., 2018. The cited reference Turley et al., 1981 should be Baritussio et al., 1980. The cited reference Milos et al., 2016 should be Turley et al., 1981. The cited reference Liao and Laufs, 2004; Jain and Ridker, 2005 should be Kreuter et al., 2018 and Thomas et al., 2002 should be Liao and Laufs, 2004; Jain and Ridker, 2005.In section “The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.


Streptococcus agalactiae, Staphylococcus aureus, and others. It is necessary to identify mechanisms of infection, define clinical and subclinical states of disease, determine exposure time, and identify pathogen-specific characteristics. Evolvement of management strategies that incorporated hygienic procedures , post milking standing period of animal and strategic use of antibiotic or herbal therapy at dry-off, nutritional supplementation, fly control, body condition score optimization, etc., resulted in widespread control of mastitis. The udder, teat of animal, scientific management of milking, automatic milking procedure, genetic selection are considered as important factors to control mastitis. As farm management changed, scientists were directed to redefine control of mastitis caused by opportunistic pathogens of environmental sources and have sought to explore management strategies which will maintain animal well-being in a judicial way. Although significant advances in mastitis management have been made changing herd structure, changing climatic scenario and more rigorous milk processing standards ensure that mastitis will remain important issue for future research.Mastitis in dairy cattle is the most common management disorder that causes higher economic losses by lowering production and quality of milk leads to substantial economical loss. The aim of this article was to review worldwide important advances in strategies to control mastitis for production augmentation in dairy cattle. Many scientists worked to identify effective strategies to control mastitis caused by  Mastitis is defined as inflammation of parenchyma of mammary glands and is characterized by physical, chemical, and usually bacteriological changes in milk and pathological changes in glandular tissues .The significance of study focus on that the global problem of mastitis which is multifactorial disease but lacked research that allowed prioritizing effect of different strategies to control it. The treatment of mastitis would not be the only solution and called for research to define the value of various unproven management practices. In India (tropics), annual economic loss due to mastitis was reported INR 60532.1 million, where the majority was found due to sub-clinical mastitis (70-80%) which accounted around INR 43653.2 million , -10, 6-10et al. [et al. [et al. [Streptococcus uberis. Bhakat et al. [et al. [et al. [S. agalactiae which was responsible for occurrence of clinical mastitis [Bharti et al.  reported [et al.  conclude [et al.  reportedt et al.  reported [et al.  recommen [et al.  had studmastitis .et al. [et al. [Bharti et al.  reported [et al.  found thet al. [et al. [S. agalactiae and S. aureus and prevalence of IMI had declined. Advances in milking machines had greatly improved vacuum stability and installation standards for milking systems had been developed. Scientists reported that milking machine could influence new IMI by serving as a fomite, allowing cross-infections within cows, and damaging teat sphincters. They demonstrated that only 6.6% of new IMI were accounted by milking machine and concluded that there was no convincing evidence linking the machine milking to overall prevalence of herd infection. Bhakat et al. [Bhakat et al.  reported [et al.  reported [et al. . By thist et al.  reportedet al. [et al. [et al. [Paul and Bhakat  found thet al.  standard [et al.  reported [et al.  found co [et al. . Somatic [et al.  and futuet al. [et al. [et al. [et al. [Paul et al.  had been [et al.  found th [et al. . It is a [et al. . It was  [et al.  found th [et al.  found in [et al.  tested tet al. [Bharti and Bhakat  reportedet al.  reportedThis review highlights the worldwide important advances in strategies to control mastitis for production augmentation in dairy cattle. Role of udder, teat of animal, scientific management of milking procedure, automatic milking procedure, BCS, genetic selection procedure, hygiene, nutritional aspects, animal behavior, etc., is considered to control mastitis. There is a need to provide infrastructure, necessary facilities and training to help farmers to efficiently adopt proven strategies that minimize occurrences of mastitis which result in production of higher quantity and quality of milk and continued advances in management and control of mastitis are very much necessary to ensure sustainability of dairy farming.CB conceptualized and drafted the review, prepared, and edited the manuscript. AM, DKM, AMa, SR, and AC collected literatures. MKG and TKD edited and finalized the manuscript. All authors read and approved the final manuscript.


Dear Editor,et al. [I read with interest the rapid review by Gupta et al.  concerniet al. . During et al. . There iet al.  If modelet al. .This consideration extends to the handling of faecal wastes discharged from hospitals and others sources. Sewage discharged from two hospitals in Beijing during the SARS outbreak was identified as positive for SARS‐CoV‐1 . Using qNone.I declare no competing interests.


Pu et al.  report tPu et al.  induced Pu et al.  support 2In the study by Pu et al. , pregnanIn addition to glyphosate and water, Roundup Maxload contains a quaternary amine surfactant with the warning, “harmful if swallowed” . This quThe sEH inhibitors mitigate pain and digestive tract ulcers . If Roun


A similar criticism can be made of the Stewart and Chambless  meta‐anaet al.  used as et al.  study ciet al.  effectivet al.  populati (et al.  also cit (et al.  as a ref (et al.  study waet al. (et al. (et al. (Whilst Wakefield et al.  acknowleet al. . This paet al. . Given t (et al.  are of d (et al.  seek to  (et al.  meta‐ana (et al. .et al. (The Wakefield et al.  study seet al.  is not wAll authors declare no conflict of interest.


International Journal of Molecular Sciences in which they evaluated atherosclerosis and other pathophysiological mechanisms involved in cardiovascular disease (CVD) in patients with human papillomavirus (HPV). The paper explored new biomarkers that could be used for affected individuals. They mentioned the cardio-ankle vascular index (CAVI), proposed by Shirai et al. [Tonhajzerova et al.  publishei et al.  in 2006,0 (Equation (2)) is the mathematically corrected formula that has been derived from the CAVI formula. Spronck et al. [0 values [0 has been doubted by the developer of CAVI because it has some flaws and cannot provide accurate measurements of arterial stiffness.s: systolic blood pressure; Pd: diastolic blood pressure; ρ: blood density; Δ P: Ps – Pd; a, b: coefficients; P0: reference pressure (100 mmHg).CAVIk et al.  claimed 0 values . It is w0 was proposed by Spronck et al. [0. Unlike CAVI, which uses Pd and Ps in its formula, in calculating CAVI0, only Pd, not Ps, is used. Another difference between CAVI and CAVI0 is the use of P0 in the formula of CAVI0. Although Spronck et al. [0 is independent of blood pressure, in a large study on 5293 individuals, Shirai et al. [0 is not accurate because of its strong dependency on Pd. Another reason that CAVI0 provides equivocal results is that Spronck et al. [The use of CAVIk et al.  in 2017.k et al.  claimed k et al. ,7.It is also interesting to know that the information about CAVI has been recently updated. Takahashi et al.  showed t0, we can say that PWV and parameter β can be considered as more reliable indices. As Tonhajzerova et al. [As there are many concerns about using CAVI and CAVIa et al.  mentionea et al. . The useBlood pressure is dependent on arterial stiffness  and arterial stiffness can be accelerated in the presence of hypertension . Conside


Host behaviour is a critical determinant of infectious disease dynamics: how individual animals interact with, or ‘contact’, each other dictates whether and which diseases transmit between them. For an example using pathogens of current concern among human populations, sharing an elevator with someone might lead to you contracting SARS-CoV-2 (which transmits through respiratory droplets), but it will not lead to you contracting monkeypox (which transmits through extended skin–skin contact) or HIV . Animals should therefore evolve to be discriminatory about whom they contact, and those decisions may depend on the nature of that contact: indeed, you likely have different criteria for deciding with whom to share an elevator versus fluids. Similarly, pathogens should evolve traits that increase their transmission success, and these traits may differ depending on the type of contact required for transmission. These two ideas—that pathogens affect the evolution of host behaviour and host behaviour affects pathogen evolution—have long been assumed, but are notoriously difficult to test ,2.et al. [et al. [In a recent paper, Collier et al.  take an  [et al.  categoriet al. [Poor connectivity, as appears to characterize fluid exchange networks, should intuitively offer pathogens fewer transmission opportunities than the typically highly connected physical and non-physical contact networks, and thus select for different pathogen traits. Collier et al.  use an eet al. [et al. [Through this neat and logical series of steps, Collier et al.  show tha [et al.  were conet al. [can transmit through non-physical contact, it is likely that physical contact or contact involving fluid exchange will dramatically increase the chance of that transmission. Importantly, this point has recently been illustrated by monkeypox: while the virus does not require sexual contact to transmit, the extended skin–skin contact it does require is likely to happen during sex, and as a result the virus has, to date, mostly been infecting men who have sex with men [The paper strongly suggests that the false dichotomy between diseases that transmit through sexual and non-sexual contact reduces our ability to understand transmission dynamics. Collier et al.  point ouet al. , that thwith men . Insightet al. [More broadly, sex is underrepresented in studies of wildlife disease ecology. For example, across taxa, tests of parasite-mediated sexual selection hypotheses have revealed that choosers can detect and avoid potential mates infected with parasites . Of couret al.  point ouet al. .et al. [et al. [That individuals can detect and avoid infected conspecifics is an observation that Collier et al.  raise aset al. . Howeveret al. . Overall [et al.  draw fro [et al. . For exa [et al. –14 and t [et al. . The eff [et al. , and the [et al. , both of [et al. ,18).et al. [To further complicate this picture, how the presence of a disease affects network structure likely depends on which of the four contact types identified by Collier et al.  the pathet al. , though et al. ,21. For et al. .et al. [Further, while the costs of missing out on each of the contact types in et al.  are corret al. [Overall, Collier et al.  link thret al. ,18, it r


Acoustic sensors have been in commercial use for more than 60 years. Acoustic sensing technologies have been studied extensively, and the information, transmission, reception, transformation, processing and application of acoustic signals have been developed, with acoustic sensors as a central focus. An acoustic sensor is a device that converts a sound wave signal into an electrical signal. The design and development of acoustic sensors are very important technological and scientific issues. Acoustic sensors are widely used in industrial, medical and numerous other applications including environmental and health monitoring, chemical and biochemical detection, and signal processing devices. The papers that form this Special Issue cover a variety of approaches and models related to acoustic sensors and their applications.Liu et al.  aimed toRong et al.  proposedDeng et al.  designedBente et al.  proposedLiang et al.  presenteYao et al.  investigVetrab and Gosztolya  used hybLiu and Abdulla  introducScheuer and DeCorby  applied In the tenth study, Han et al.  developeFinally, in the last paper, Jang et al.  introduc