Systemic sclerosis (SSc) is a connective tissue disease characterized by fibrosis in skin and internal organs, progressive vascular obliteration, and the production of autoantibodies. Diagnostic imaging is irreplaceable in both diagnosing and monitoring patients suffering from systemic sclerosis. In addition to routinely used methods, such as comparative X-ray of the hands or a contrast-enhanced examination of the upper gastrointestinal tract or chest, there is an array of less widespread examinations, with an emphasis on magnetic resonance imaging (MRI) and ultrasonography, not only in the evaluation of the musculoskeletal system. This article will review the various imaging modalities available for SSc imaging and assessment, focusing on their utility as tissue-specific diagnosis and treatment monitoring. Systemic sclerosis  belongs to a wide spectrum of connective tissue diseases—a diverse group of disorders characterised by chronic inflammation of connective tissue, usually of autoimmune origin . The mosSSc typically affects women (4:1 predilection), with the median onset at the age of 30–50 years. There is a higher morbidity within black patients than in other ethnical groups. A very high prevalence of SSc in Choctaw Native Americans suggests the possibility of a genetic factor in the pathogenesis of this disease. Reports of familial history of SSc or other autoimmune disorders in SSc patients have also shown support for the genetic grounds of SSc. The incidence rate seems stable over several decades in both Europe and the United States ,3,4,5. TThe diagnostic criteria for SSc are still not universal. The classification criteria of the American College of Rheumatology (ACR), presented in 1980 and updated by a collaboration of ACR and European League Against Rheumatism (EULAR) in 2013, are used most commonly. According to those criteria, skin thickening proximal to the metacarpophalangeal joints is sufficient proof of SSc. If it is not present, seven other signs should be evaluated: (1) skin thickening of the fingers (either sclerodactyly or puffy fingers); (2) fingertip lesions ; (3) telangiectasia; (4) abnormal nailfold capillaries; (5) pulmonary arterial hypertension (PAH) and/or interstitial lung disease; (6) Raynaud’s phenomenon; and 7) SSc-related antibodies: anticentromere and/or anti-topoisomerase I (anti-Scl-70) and/or RNA polymerase III , al, al83], The prevalence of ischaemic heart disease related to vasospasm is increased in SSc patients. The vasospasm is often triggered by low temperature, and this symptom is sometimes labeled as the Raynaud phenomenon of the heart. It might be confirmed by visualising subendocardial hypoperfusion areas during an MRI examination .MRI ‘wall tagging’ and phase contrast techniques are useful to assess fibrosis and diastolic heart failure .Native and post-contrast T1 mapping combined with T2 mapping and LGE (late gadolinium enhancement) discriminate between several myocardial diseases and notably between myocardial fibrosis and edema. The number of studies regarding T1 and T2 mapping is rapidly increasing and the available data show that native T1 mapping detects left ventricular elevated T1 in 50% of patients with SSc while a third of them had normal conventional screening (including standard CMR). This proves that T1 mapping cardiac MRI imaging frequently detects subclinical diffuse myocardial fibrosis in systemic sclerosis patients .In patients without evidence of fibrosis (in LGE), T1 mapping parameters (extracellular volume fraction (ECV), gadolinium partition coefficient (λ), pre-contrast T1, and post-contrast T1) correlated with the modified Rodnan skin score, indicating a correlation between SSc cardiac and skin fibrosis. .Moreover, T1-mapping offers incremental diagnostic value in the identification of patients with high risk of cardiovascular incidents and in addition to independently predict adverse outcomes at follow-up. Thus, CMR may be considered in cases where echocardiographic results are equivocal but the clinical picture warrants a higher index of suspicion, in order to identify high-risk patients early on and to institute prompt changes in the therapeutic management of SSc-related cardiac involvement .MRI allows to recognize one of the more common manifestations of the SSc in the GI tract—lesions of the anus and rectum. Characteristic symptoms include ventral displacement of the anterior rectal wall, decreased thickness of the anal sphincter, and its reduced contrast enhancement caused by its fibrosis . In the A recent survey implies possible applications of MRI ultrafast echo-spin sequences in diagnosing interstitial pulmonary involvement—a correlation between the results of MRI and HRCT was proven .In conclusion, SSc is associated with various radiological findings of specific organ and system manifestations of SSc, which may be apparent in its initial presentation and/or subsequent disease phases. This review may help clinicians and radiologists in the initial diagnosis and monitoring of progression of SSc.


This cohort study examines the association of participation in a summer college academic enrichment program with diversity of students in medical school and intent to practice in underserved areas. As a strategy to increase diversity, many organizations and institutions sponsor premedical summer college academic enrichment programs (SCAEPs) that may address Liaison Committee for Medical Education Standard 3.3, Diversity/Pipeline Programs and Partnerships.2 and Graduation Questionnaire.3 The AAMC Human Subjects Office exempted the study from institutional board review because it did not constitute human participant research and used deidentified data. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.This cohort study included US medical school matriculants from 2013 to 2015 who graduated through 2019 and voluntarily completed the Association of American Medical Colleges (AAMC) Matriculating Student Questionnaire5, by using program reports to the AAMC and other SCAEP participants (excluding those in SMDEP) by Matriculating Student Questionnaire self-report.2 We examined bivariate associations between SCAEP participation and sex, race/ethnicity, and first-generation college graduate (FGCG) identity and examined factors associated with sustained career intention (Matriculating Student Questionnaire and Graduation Questionnaire self-report) to practice in underserved areas by multilevel logistic regression. P values were 2-sided, and statistical significance was set at P < .05. Deidentified individual-level data linked via unique AAMC identifiers were analyzed using Stata, version 15 (StataCorp LLC).We identified SCAEP participants in the Robert Wood Johnson Foundation Summer Medical and Dental Education Program (SMDEP), which is a cost-free, 6-week national program to strengthen academic proficiency and career development of students underrepresented in health care professionsThe study sample included 29 456 graduates . A total of 15 050 (51%) were women, 4375 (15%) were graduates from racial/ethnic groups that are underrepresented in medicine, and 4255 (14%) were FGCGs . Among 25 of SCAEPs have shown an increase in the likelihood of application and matriculation to medical school associated with SCAEP attendance. We observed an association between SCAEPs and increased student diversity and that SMDEP participants were more likely to report sustained career intentions to practice in underserved areas. Because career intention to practice in underserved areas at graduation has established predictive validity,6 our findings may inform medical schools’ investments in programs to recruit diverse students whose career goals align with national needs to increase access to care.Previous studiesOur study was limited by small numbers of American Indian or Alaska Native only and Native Hawaiian or other Pacific Islander only graduates, precluding their examination as discrete groups. In addition, we could not further disaggregate the other SCAEPs , which limits generalizability of observations for this group. In the context of the current coronavirus disease 2019 (COVID-19) pandemic and recent activism in response to anti-Black racism, SCAEPs such as SMDEP  may play a particular role in medical schools’ efforts to recruit and educate a diverse physician workforce that will meet national health care needs.


Hepatocellular carcinoma (HCC) and pancreatic cancer (PC) belong to the most lethal malignancies worldwide. Despite advances in surgical techniques and perioperative multidisciplinary management, the prognosis of both carcinoma entities remains poor mainly because of rapid tumor progression and early dissemination with diagnosis in advanced tumor stages with poor sensitivity to current therapy regimens. Both highly heterogeneous visceral carcinomas exhibit unique somatic alterations, but share common driver genes and mutations as well. Recently, circulating tumor DNA (ctDNA) could be identified as a liquid biopsy tool with huge potential as non-invasive biomarker in early diagnosis and prognosis. CtDNA released from necrotic or apoptotic cells of primary tumors, metastasis, and circulating tumor cells can reveal genetic and epigenetic alterations with tumor-specific and individual mutation and methylation profiles. In this article, we focus on clinical impact of ctDNA as potential biomarker in patients with HCC and PC. Hepatocellular carcinoma (HCC) and pancreatic cancer (PC) represent two of the most challenging visceral malignancies in oncology with rising incidence and lack of reliable biomarkers for early diagnosis, prognosis, and therapy response. PC and HCC are estimated to become the second and third respective leading causes of cancer-related death in western countries by 2030 , Topoisomerase I inhibition by irinotecan, the DNA crosslinking agents oxaliplatin and cisplatin, and the tubulin inhibitor paclitaxel  1–3, platelet-derived growth factor receptor (PDGFR) beta, c-KIT, and RAF/mitogen-activated protein/MEK was the sole drug approved for the treatment of advanced HCC between 2007 and 2016 with a response rate of less than 5% and an extended median overall survival of 2.5 months  DNA originates from normal cells exported by exosomes as well as from apoptotic and necrotic cells with highly fragmented, double-stranded DNA of approximately 150–180 base pair fragments in size being released into the bloodstream. In 1948, Mandel and Metais first reported the presence of cfDNA in human circulation followed by detection in urine, saliva, and other body fluids  DNA is becoming a research hotspot with high potential as liquid biopsy marker in cancer medicine  and digital droplet PCR (ddPCR) are the most promising methods for the detection of mutations in liquid biopsies. In general, plasma samples are used in preference over serum because of lower concentrations of wild-type DNA  in HCC patients Table . TERT pr. detected concurrent p15 and p16 methylation in 74% of ctDNA of 23 blood samples from 92% of HCC patients with tumor p15/p16 methylation , RASSF1A, and secreted frizzled-related protein 1 (SFRP1) resulted in an increased accuracy of 93% to differentiate between HCC and healthy controls    and therapy stratification in advanced non-small cell lung cancer patients (Zhang et al. Overall, ctDNA mapping of somatic driver mutations and specific epigenetic alterations has great potential in early detection and dynamic monitoring of hepatic or pancreatic carcinomas to achieve a significant decrease of mortality. However, low sensitivity of current ctDNA assays rest a major challenge.So far, ctDNA analysis in PC and HCC could reveal high frequency of common key mutations as TP53 and CDKN2A. CTNNB1 and TERT mutations and aberrant methylation of RASSF1A and CDKN2A were detected in ctDNA of HCC patients, whereas high frequency of KRAS mutations was characteristic for PC. Prospective trial data based on sufficient sample size and defined entry criteria regarding the blood draw procedure and pre-analytical variables as well as standardization of experimental techniques that demonstrate the clinical utility of ctDNA assays in PC and HCC are required.


Pterocarya stenoptera is a common fast‐growing tree species often used in the ecological restoration of riverbanks and alpine forests in central and eastern China. Until now, the characteristics of the distribution of this species' habitat are poorly known as are the environmental factors that influence its preferred habitat. In the present study, the Maximum Entropy Modeling (Maxent) algorithm and the Genetic Algorithm for Ruleset Production (GARP) were used to establish the models for the potential distribution of this species by selecting 236 sites with known occurrences and 14 environmental variables. The results indicate that both models have good predictive power. Minimum temperature of coldest month (Bio6), mean temperature of warmest quarter (Bio10), annual precipitation (Bio12), and precipitation of driest month (Bio14) were important environmental variables influencing the prediction of the Maxent model. According to the models, the temperate and subtropical regions of eastern China had high environmental suitability for this species, where the species had been recorded. Under each climate change scenario, climatic suitability of the existing range of this species increased, and its climatic niche expanded geographically to the north and higher elevation. GARP predicted a more conservative expansion. The projected spatial and temporal patterns of P. stenoptera can provide reference for the development of forest management and protection strategies.Climate change poses a serious threat to biodiversity. Predicting the effects of climate change on the distribution of a species' habitat can help humans address the potential threats which may change the scope and distribution of species.  Minimum temperature of coldest month (Bio6), mean temperature of warmest quarter (Bio10), annual precipitation (Bio12), and precipitation of driest month (Bio14) were important environmental variables influencing the prediction of the Maxent model. Under each climate change scenario, climatic suitability of the existing range of this species increased, and its climatic niche expanded geographically toward farther north and higher elevation. The GARP predicted a more conservative expansion. The results will allow researchers to identify the future suitable habitat and help in the use, management, and cultivation of P. stenoptera.To determine the potential geographical distribution and the environmental variables influencing habitat suitability for this species, we used Maxent and GARP modeling to predict the future distribution of 22.1http://www.tropicos.org/), the Global Biodiversity Information Facility (http://www.gbif.org) and the Chinese Virtual Herbarium (http://v5.cvh.org.cn/) database; the latter holds the plant distribution records of the main herbaria of China. Some results from other field survey reports and scientific research literature   for 1984–1995 data.Soil variables are important factors controlling plant distribution; they change over relatively short timescales based on direct and indirect effects caused by anthropogenic climate change  2.6 and 8.5 proposed by the Intergovernmental Panel on Climate Change were used for the years 2050 and 2070. The BCC‐CSM1.1 is recommended for use in studies of operational short‐term climate prediction and studies of climate change in China [see Wu et al.  and refer| > .90) in each set was retained for further analysis. The variables in the final environmental dataset include precipitation of warmest quarter (Bio18), precipitation of wettest quarter (Bio16), precipitation seasonality (Bio15), precipitation of driest month (Bio14), precipitation of wettest month (Bio13), annual precipitation (Bio12), mean temperature of warmest quarter (Bio10), mean temperature of wettest quarter (Bio8), minimum temperature of coldest month (Bio6), temperature seasonality (Bio4), isothermality (Bio3), and mean diurnal temperature range (Bio2).Principal component analysis and correlation analyses (Pearson's correlation coefficient) were carried out to minimize the overfitting of the model and decrease the high collinearity. Only one of the highly correlated variables  , Bio10 (14.1% of variation), Bio12 (23.2% of variation) and Bio14 (29.2% of variation)  for those four most important variables in Maxent were generated to examine the climatic preference of a Figure . Overall3.3P. stenoptera  and modeling methods (GARP and Maxent), showing that the climatic suitability of the existing distribution range increased, and the suitable habitats of the species expanded geographically to the north and to higher elevations  , mean temperature of warmest quarter (Bio10), annual precipitation (Bio12), and precipitation of driest month (Bio14) were the most important environmental variables influencing the distribution of this species. The projected spatial and temporal patterns of P. stenoptera can provide reference for the development of forest management and protection strategies.Under the climate change scenario, high‐quality distributional data play an important role in setting priorities and implementing effective protection actions. Our results indicate that the areas of suitable habitat for The authors declare no competing interest.Keliang Zhang: Formal analysis ; funding acquisition ; methodology ; writing – original draft . Huina Liu: Formal analysis ; writing – original draft ; writing – review and editing . Haolei Pan: Data curation ; investigation ; resources ; software . Yi Zhao: Data curation ; investigation ; resources ; software . Wenhao Shi: Data curation ; investigation ; resources ; software ; visualization . Silei Li: Data curation ; investigation ; resources ; visualization ; writing – original draft . Junchi Liu: Data curation ; investigation ; resources ; software ; visualization . Jun Tao: Conceptualization (lead); formal analysis ; project administration (lead); supervision (lead); writing – review and editing .


IGF2BP2 is known to affect both life span and energy expenditure. The positively selected mutations detected in IGF2BP2 likely affected the functionality of the encoded protein. IGF2BP2, which has been reported to simultaneously prolong life span and increase energy expenditure, could be responsible for the evolution of shortened MLS associated with the loss of flying ability.Acquisition or loss of flying ability is evolutionarily linked with maximum life span (MLS) in mammals and birds. Although ecological factors, such as extrinsic mortality, may lead to either shortened or extended life spans through natural selection, MLS is influenced by complex molecular and metabolic processes, and the genetic changes associated with flying ability that have led to either a longer or shorter MLS are unknown. Here, we examine the parallel evolution of flight in mammals and birds and investigate positively selected genes at branches where either the acquisition (in little brown bats and large flying foxes) or loss  of flight abilities occurred. Although we found no shared genes under selection among all the branches of interest, 7 genes were found to be positively selected in 2 of the branches. Among the 7 genes, only  Positively selected genes at the branches of interest. It has been proposed that species with lower extrinsic mortalities have longer life spans because they can invest in long‐term survival  receptors may have contributed to the evolution of their long life spans  and the little brown bat (Myotis lucifugus), as volant species with a longer MLS in mammals; and two penguins, the Adélie penguin (Pygoscelis adeliae) and the emperor penguin (Aptenodytes forsteri), and eight ratites, the common ostrich (Struthio camelus), the emu (Dromaius novaehollandiae), the great spotted kiwi (Apteryx haastii), the little spotted kiwi (Apteryx owenii), the okarito brown kiwi (Apteryx rowi), the greater rhea (Rhea americana), the lesser rhea (Rhea pennata), and the cassowary (Casuarius casuarius), as nonvolant birds with a shorter MLS. We then searched for positively selected genes among the different lineages to identify genes that evolved in parallel and are related to both flying and life span. Genes detected among multiple branches where changes in flying ability had occurred are discussed for their possible roles in energy expenditure and alteration in life spans.To shed light on the parallel evolution of either longer or shorter MLSs with that of either acquisition or loss of flight ability, it is necessary to examine candidate genes that have been subject to positive selection in multiple lineages of birds that have lost their flying ability in addition to those of mammals that have evolved the ability to fly. The purpose of our research was to detect positively selected genes at the branches where the acquisition or loss of flying ability occurred, using whole‐genome‐sequenced mammals and birds, and to explore the genes responsible for shorter or longer MLSs associated with the evolution of the loss or acquisition of flying ability. We chose two bats, the large flying fox (22.1Felis catus), cow (Bos taurus), dog (Canis lupus familiaris), elephant (Loxodonta africana), horse , human being (Homo sapiens), marmoset , mouse (Mus musculus), opossum (Monodelphis domestica), pig (Sus scrofa), platypus (Ornithorhynchus anatinus), rabbit (Oryctolagus cuniculus), rat (Rattus norvegicus), and sheep (Ovis aries) were selected as nonvolant species, and the large flying fox (Pteropus vampyrus) and little brown bat (Myotis lucifugus) were selected as volant species. All genome sequences were obtained from Ensembl 98 , emperor penguin (Aptenodytes forsteri), common ostrich (Struthio camelus), emu (Dromaius novaehollandiae), great spotted kiwi (Apteryx haastii), little spotted kiwi (Apteryx owenii), okarito brown kiwi (Apteryx rowi), greater rhea (Rhea americana), lesser rhea (Rhea pennata), and cassowary (Casuarius casuarius) were selected as nonvolant species, and the American crow (Corvus brachyrhynchos), Anna's hummingbird , bald eagle , mallard (Anas platyrhynchos), budgerigar (Melopsittacus undulatus), chimney swift (Chaetura pelagica), common cuckoo (Cuculus canorus), crested ibis (Nipponia nippon), downy woodpecker (Picoides pubescens), golden‐collared manakin (Manacus vitellinus), killdeer (Charadrius vociferus), little egret (Egretta garzetta), medium ground finch (Geospiza fortis), peregrine falcon , pigeon (Columba livia), and zebra finch (Taeniopygia guttata) were selected as volant species. Genomes of the zebra finch, emu, and the three kiwis were obtained from Ensembl 98 , reportedly the longest‐living bat, and the flightless brown kiwi  were not included in our analysis as their assembled genome sequences included many gaps and a sufficient number of orthologous genes was not available. Analyses for mammals and birds were conducted separately. We performed reciprocal basic local alignment search tool (BLAST) searches and obtained the highest score pairs of one‐to‐one orthologs using the BLASTp algorithm in National Center for Biotechnology Information (NCBI) BLAST v.2.6.0+  or those that rarely fly (such as the tinamou or hoatzin). For mammals, the genome sequences of the cat . We focused on genes detected via both calculations with a gene tree and species tree, and the genes detected by both PAML and aBSREL analyses were considered candidates under positive selection. To evaluate parallel and/or convergent evolution between avian and mammalian species, we used one‐to‐one ortholog information between humans  and zebra finches (the reference species in birds) inferred by BLASTp  terms and pathways using the over‐representation test with Fisher's exact test and the Benjamini–Hochberg procedure in PANTHER version 14.1  ; Visualization ; Writing‐original draft ; Writing‐review & editing . Daiki X. Sato: Formal analysis (supporting); Writing‐original draft (supporting); Writing‐review & editing (supporting). Takashi Makino: Formal analysis (supporting); Writing‐review & editing (supporting). Masakado Kawata: Conceptualization ; Supervision (lead); Writing‐original draft ; Writing‐review & editing (lead). Fig S1‐S19Click here for additional data file.Table S1‐S52Click here for additional data file.


Oreolalax major was determined using polymerase chain reaction (PCR). It includes 13 protein-coding genes (PCGs), 2 ribosomal RNA (rRNA) genes and 19 transfer RNA (tRNA) genes (GenBank accession number KU310894). The features of O. major have one more tRNA gene (MettRNA) behind the original one before ND2 which is similar to Leptobrachium boringii. Phylogenetic analyses were based on the concatenated sequences of the 13 protein-encoding genes of O. major and other related species.In this study, the near complete mitogenome sequence  of  Oreolalax major (Liu & Hu 1960) belongs to family Megophryidae, genus Oreolalax. It is an endemic species of China, which is distributed in Hengduan Mountains of western Sichuan and southern Gansu Provinces  was collected from Wawushan Nature Reserve, Hongya , Sichuan, China in June, 2015. It was fixed in 75% ethanol and deposited in the Museum of Sichuan Agricultural University. The total DNA was extracted and purified from muscle tissue using the Ezup pillar genomic DNA extraction kit . We used twenty-three pairs of polymerase chain reaction (PCR) primers published by Zhang et al. , 2 ribosomal RNA (rRNA) genes and 19 transfer RNA (tRNA) genes (GenBank accession number KU310894). The features of O. major have one more tRNA gene (MettRNA) behind the original one before ND2 which is similar to Leptobrachium boringii tRNA and GlutRNA genes. We regrettably did not sequence the region between 12S rRNA and Cyt b genes which contains 4 rRNA genes and 1 D-loop region because of difficult to amplify. There are two types of initiation codons used for 13 PCGs and most PCGs initiate from ATG, while others  start with GTG. In addition, 5 PCGs  terminate in incomplete stop codon T, the same number of PCGs  use complete stop codon TAA, and the rest of PCGs end with AGG. The 12S rRNA and 16S rRNA are determined to be 936 bp and 1598 bp long respectively and all the tRNA genes can constitute typical cloverleaf secondary structure exclude Ser(AGY)tRNA.The near complete mitochondrial genome of The NJ analysis of the combined data set indicates that all samples of Megophryidae form a strong supported  monophyletic group  and all


The purpose of this study was to describe the ocular findings, structural ocular complications, and vision impairment in a cohort of Lassa fever survivors in Kenema, Sierra Leone. A retrospective, uncontrolled, cross-sectional study of 31 Lassa fever survivors (62 eyes) who underwent an ophthalmic evaluation in January 2018 at the Kenema Government Hospital in Kenema, Sierra Leone was performed. Data collection included demographic information, ocular/systemic symptoms, visual acuity (VA), and ophthalmic examination findings. Main outcome measures included anterior and posterior segment ophthalmic manifestations and level of VA impairment in Lassa fever survivors. Anterior segment findings included cataract (18%) and pterygium (2%), while posterior segment manifestations consisted of glaucoma (6%), preretinal hemorrhage (2%), and lattice degeneration (2%). Findings suggestive of prior sequelae of uveitis included chorioretinal scarring (5%), retinal fibrosis (3%), and vitreous opacity (2%). Visual acuity was normal/mildly impaired in 53 eyes (85%), moderately impaired in 6 eyes (10%), and 3 eyes (5%) were considered blind by the World Health Organization (WHO) criteria. Median VA was worse in Lassa fever survivors with ophthalmic disease findings (p<0.0001) for both anterior segment (p<0.0001) and posterior segment disease (p<0.013). Untreated cataract was a significant cause of visual acuity impairment (p<0.0001). Lassa fever survivors in this cohort were found to have cataract and posterior segment findings that potentially represent sequelae of uveitis associated with visual impairment. Future studies are warranted to improve our understanding of the spectrum of ocular disease in this emerging infectious disease of public health consequence. Arenaviridae family. Lassa fever is endemic to the West Africa countries of Benin, Ghana, Liberia, Guinea, Mali, Sierra Leone and Nigeria, affecting 100,000 to 300,000 people annually, and causing approximately 5,000 deaths per year  19–50). The median time from the date of Lassa fever diagnosis to the date of ophthalmic examination was 10.03 years (IQR 6.0–12.0). Five patients (16.1%) reported eye symptoms including pain, redness, and blurry vision during the acute phase of Lassa fever. At the time of ophthalmic examination, Lassa fever survivors reported ocular symptoms including blurry vision (42%), itching (13%), pain (6%), redness (6%), tearing (6%), loss of near vision (3%), and floaters (3%) . Review Anterior segment findings included cataract (18%) and pterygium (2%). One patient had a traumatic cataract from penetrating corneal injury, which had self-sealed without surgical repair and showed evidence of uveitis with focal posterior synechiae . This siOphthalmic manifestations in the posterior segment included the presence of glaucomatous optic neuropathy (6%), chorioretinal scarring (5%), retinal fibrosis (3%), peripheral drusen (3%), preretinal hemorrhage (2%), lattice degeneration (2%), and vitreous opacity (2%) . There wVisual acuity was normal or mildly impaired in 53 eyes (85%), moderately impaired in 6 eyes (10%), and 3 eyes (5%) were considered blind according to the World Health Organization classification of visual impairment . The thrWe analyzed the impact of ocular structural complications on visual acuity, which are summarized in any ophthalmic abnormality by exam (p > 0.05). Individuals with any ocular abnormalities were likely to be older  compared to patients evaluated without ocular findings . Patients who were older tended to report blurred vision symptoms  than younger patients . Gender was not associated with the presence of ocular complications or blurred vision symptoms .A significant minority of Lassa fever survivors (42%) reported blurred vision and we thus assessed the relationship of this patient-reported symptom to visual acuity impairment and ophthalmic findings. No association was observed between individuals with reported blurred vision and at least moderate visual acuity impairment . In addition, no association was observed between blurred vision and evidence of Audiovestibular symptoms and joint pain have been reported in Lassa fever survivors and their relationship to ophthalmic disease was analyzed. Seven patients were found to have audiovestibular symptoms (23%) including 6 with hearing loss and 1 patient with tinnitus, which developed after acute Lassa fever. Hearing loss included bilateral disease (1), right ear (2), left ear (1) and unspecified (2). Hearing loss was not associated with patient-reported blurred vision or the presence of posterior segment or anterior segment disease findings . Joint pain was similarly unassociated with ocular findings (p > 0.05) in our series of patients, although like hearing loss, was observed in a modest proportion (26%) of patients evaluated.The ophthalmic sequelae of Lassa fever have not been well-characterized, and the aim of this study was to provide a preliminary investigation of the ophthalmic manifestations in Lassa fever survivors. Ocular involvement during the acute phase of Lassa fever has been reported to manifest as conjunctivitis, typically starting on day 7 of illness and lasting for a duration of 5 days . SubconjBlurry vision was a common visual complaint with over 40% of patients describing this symptom at the time of ophthalmic evaluation. The majority of patients (85%) had normal or mild vision impairment according to the WHO classification of visual impairment. While McCormick et al identified cases of uveitis with transient vision loss, we did not observe signs of active uveitis in our cohort of Lassa fever survivors who were evaluated . MoreoveThere are few reports in the literature documenting the prevalence and causes of visual impairment in the general population in West Africa. The Tema Eye Survey, a population-based cross-sectional study of 5,603 participants residing in an urban West African location, reported a 17.1% prevalence of visual impairment and 1.2% rate of blindness in Tema, Ghana, West Africa . RefractOther untreated ophthalmic conditions that were observed in our study of Lassa fever survivors included open globe trauma, cataract and advanced glaucoma. Specifically, cataract and end-stage glaucoma were identifiable causes of blindness (vision loss worse than 20/400) in three patients (9.7%). A dense mature cataract precluded view to the fundus in one of these patients, and thus it is unknown whether there were other posterior segment findings suggestive of cataract formation related to intraocular inflammation or if the cataract was merely age-related. The mechanism of glaucoma is unknown in the two patients with end-stage glaucoma and hand motions visual acuity; however, they did not have visible sequelae of prior ocular inflammation. In comparison, a retrospective study of a hospital population in Sierra Leone, West Africa conducted in 1989 and 1992 revealed that senile cataract was the major cause of blindness  followed by uveitis despite a significant decrease in blindness from onchocerciasis . BlindneLong-term systemic symptoms were also present at the time of ophthalmologic examination, including joint pain (26%), hearing loss (16%), and headache (16%). Hearing loss is a well-documented and potentially profound sequelae of Lassa fever, and a literature review of five hospital-based and population-based studies of Lassa fever survivors revealed that approximately one-third (4%-75%) of Lassa virus-infected patients developed sudden sensorineural hearing loss . Our limAnimal studies have been utilized to better understand the pathogenesis of LASV in the eye and to investigate the possibility of LASV persistence in this immune-privileged site , 21. WalArenaviridae family include accounts of similar descriptions of chorioretinal scarring in lymphocytic choriomeningitis virus (LCMV) [The few reports of ocular involvement in other members of the s (LCMV) –24. Thiss (LCMV) . In parts (LCMV) . In a res (LCMV) . Mets ets (LCMV) . LCMV ins (LCMV) .Ocular manifestations in viral hemorrhagic fever disease is not limited to Lassa fever and has been described previously with other hemorrhagic fevers including Ebola virus disease (EVD) and Marburg virus disease . A singlToxoplasma gondii. Selection bias was also a potential limitation, as patients may have presented for an ophthalmic examination primarily if they reported ocular symptoms. Future controlled, longitudinal studies with larger sample sizes are planned to characterize the prevalence of ocular disease and the spectrum of ophthalmic complications associated with Lassa fever.Limitations of our study include the cross-sectional, retrospective nature of the study. Because ophthalmic examination occurred at a single time point, the patient’s baseline eye disease was unknown, and we were unable to ascertain whether the patients’ cataract or chorioretinal scarring occurred as an immediate consequence of Lassa virus infection. Understanding the timing of the ocular findings following acute Lassa virus infection will allow clinicians and investigators to understand the potential relationship between the ocular findings identified and Lassa fever. It is currently unknown whether the etiology of chorioretinal scarring was from prior trauma or other infectious agents such as In summary, this cross-sectional, retrospective study highlights the first detailed characterization of ophthalmic manifestations in Lassa fever survivors. Evidence of cataract and prior sequelae of intermediate and posterior uveitis were present in this cohort of Lassa fever survivors. Moderate vision impairment was present in 10% of the patients in our study, highlighting the need for further investigation into ophthalmic complications of LASV infection during the acute phase of disease and convalescence. Future studies are warranted to improve our understanding of long-term ophthalmic sequelae and the spectrum of ocular disease in Lassa fever survivors, particularly given its high annual incidence in West Africa and our ophthalmology field’s mandate to understand emerging infectious diseases of public and global health consequence.S1 Dataset(XLSX)Click here for additional data file.


In contrast, in Li+-containing buffer, SERT showed only low force interactions. Conversely, the vestibular mutant SERT-G402H merely displayed the high force population. These observations provide physical evidence for the existence of two binding sites in SERT. The dissociation rate constant of both binding sites was extracted by varying the dynamics of the force-probing experiments. Competition experiments revealed that the two sites are allosterically coupled and exert reciprocal modulation.Crystal structures and experiments relying on the tools of molecular pharmacology reported conflicting results on ligand binding sites in neurotransmitter/sodium symporters (NSS). We explored the number and functionality of ligand binding sites of NSS in a physiological setting by designing novel tools for atomic force microscopy (AFM). These allow for directly measuring the interaction forces between the serotonin transporter (SERT) and the antidepressant S-citalopram (S-CIT) on the single molecule level: the AFM cantilever tips were functionalized with S-CIT via a flexible polyethylene glycol (PEG) linker. The tip chemistry was validated by specific force measurements and recognition imaging on CHO cells. Two distinct populations of characteristic binding strengths of S-CIT binding to SERT were revealed in Na Aa (Drosophila melanogaster dopamine transporter) (The serotonin transporter (SERT) is a member of the monoamine neurotransmitter sodium symporter (NSS) family . Its epoAa  and dDATsporter) , indicatsporter)  of NSS tsporter) .To date, a series of crosslinkers have been developed for covalent conjugation of functional molecules to atomic force microscopy (AFM) cantilever tips. Some conventional linkers are NHS-PEG-aldehyde , NHS-PEGForce measurements were conducted on living CHOK1 cells  stably eThe validity of the tip chemistry was also shown by topography and recognition imaging (TREC) . TREC isFrom a large amount of repeated force measurements using the same conditions, two populations with distinct unbinding forces  were obs3H]HT uptake was not detectable  and the width (xB) of prominent energy barriers of the interaction for the individual force populations by plotting the unbinding forces as a function of the force loading rate  for both S1 and S2  were in agreement with those determined for the S1 site by force spectroscopy (0.032 ± 0.005 s–1) (We extracted the dissociation rate constant (k1 and S2 . We reli1 and S2  was empl005 s–1) .Dissociation of S-CIT at the central S1 site is delayed, if the vestibular S2 site is occupied by either S- or R-CIT . This obThe flexible PEG linker between the AFM tip and the CIT molecule provides the unique opportunity to explore the binding sites of different depths in transmembrane transporter. Force sensing in physiological conditions allowed for the extraction of dynamic information, thus unequivocally documenting the existence of two binding sites in SERT. Furthermore, our force experiments revealed a positive allosteric effect on the S2 site induced by the binding of S-CIT at S1 site. Given the importance of allosteric regulation in biology and pharmacology, SMFS provides a unique approach to explore transient binding sites in clinically relevant membrane transporters for addressing the modulation of interaction forces between ligands and allosterically coupled binding sites.Indeed, such an allosterically enhanced binding strength of S-CIT at the S2 site could be a critical contribution for the capture of the S2 site by X-ray crystallography. The X-ray structure of SERT bound with S-CIT  verifiedWe notice that the only common amino acid residue of S2 site revealed by the crystal structure and previous studies is the arginine R104. The involvement of R104 in S2 site is partially supported by the experiment of recognition imaging . The bloFurther developed AFM techniques have provided the possibility to measure the depth of ATP binding site in mitochondrial uncoupling protein 1 (UCP1)  or to reAll authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Globally, wetlands are in decline due to anthropogenic modification and climate change. Knowledge about the spatial distribution of biodiversity and biological processes within wetlands provides essential baseline data for predicting and mitigating the effects of present and future environmental change on these critical ecosystems. To explore the potential for environmental DNA (eDNA) to provide such insights, we used 16S rRNA metabarcoding to characterise prokaryote communities and predict the distribution of prokaryote metabolic pathways in peats and sediments up to 4m below the surface across seven New Zealand wetlands. Our results reveal distinct vertical structuring of prokaryote communities and metabolic pathways in these wetlands. We also find evidence for differences in the relative abundance of certain metabolic pathways that may correspond to the degree of anthropogenic modification the wetlands have experienced. These patterns, specifically those for pathways related to aerobic respiration and the carbon cycle, can be explained predominantly by the expected effects of wetland drainage. Our study demonstrates that eDNA has the potential to be an important new tool for the assessment and monitoring of wetland health. These aspects include: 1) identification of sensitive indicators  for discriminating different types of anthropogenic disturbance ; 2) demonstrating consistency of indicator responses across different wetlands and wetland types; and 3) using temporal sampling to show whether reverse trends in indicators of anthropogenic disturbance are detectable in wetlands undergoing restoration.S1 FigFilled circles represent sample depths.(TIF)Click here for additional data file.S2 Fig(TIF)Click here for additional data file.S3 Fig(TIF)Click here for additional data file.S1 Table(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.


Dear Editor,JAK2 V617F mutation, insertion and/or deletion (indel) mutations of CALR exon 9 are the second most common driver mutations in the myeloproliferative neoplasms (MPN) of essential thrombocythemia and primary myelofibrosis and their detection is considered a major diagnostic criterion for these malignancies. It is becoming increasingly apparent that MPNs harboring CALR mutations  may occur in patients with BCR-ABL1-positive chronic myeloid leukemia (CML) as evidenced by a wave of recently reported cases. The CALR-positive MPN and CML may appear concurrently with composite morphology or sequentially with either malignancy revealed as a consequence of specific treatment for one of the malignancies (Table 1CALR-mutated MPN in the remaining 12/24 (50 %) cases. Evidence exists for molecular abnormalities occurring within a single clone and in distinct clonal populations.After the JAK2 V617F mutation in all newly presenting CML cases (McCarron et al., 2012[CALR and MPL mutations in all likelihood would show a similar redundancy. Given the low incidence but increasing awareness of co-existing CML and MPN, testing for the relevant rearrangement should therefore be implemented when there is clinical, hematological or morphological evidence.While co-existence of CML and another MPN has clinical relevance with respect to selection and timing of tyrosine kinase inhibitor therapy, there is currently insufficient follow-up data to ascertain overall survival of such cases. There is limited value in assessing the The author declares no conflicts of interest.


Older adults’ behavioral stage of change for adopting fall prevention interventions, and their use of evidence-based interventions are not well understood. A survey was administered to older adults (65 years+) (n=1063) to understand their stage of change and fall prevention behaviors. Descriptive statistics were calculated and logistic regression conducted to determine factors most related to stage. The distribution of subjects by stage was precontemplation (17%), contemplation (2%), preparation (5%), action (15%), and maintenance (61%). The strongest variable related to being in an action stage  was screening positively for fall risk . The most common preventive actions for those in an action stage were taking Vitamin D (37%), and having vision tested (30%). Older adults at risk for a fall are ready to take action to prevent falls; health promotion should focus on increasing knowledge and use of different evidence-based interventions.


Alternative splicing generates multiple protein isoforms from one primary transcript and represents one of the major drivers of proteomic diversity in human cells . AlternaAlthough significant progress has been made in recent years, important questions still remain to be addressed. In particular, we need to determine (i) the role(s) of the majority of the splicing isoforms during physiological  processes, (ii) the factors involved in their production, and (iii) how splicing is integrated with other gene expression regulatory programs.RAD6B gene and their association with melanoma pathogenesis [SMN2 gene [moso bamboo (an important forest species) by supporting the translation of a fraction of transcript isoforms targeted by nonsense-mediated mRNA decay (NMD) pathway [Trichophyton rubrum (a dermatophytic fungus) suggesting strategies employed by dermatophytes in response to antifungal therapy [This special issue collects recent insights addressing the above interrogatives. More specifically, Palombo and colleagues illustrate the function of two splicing factors (hnRNPM and SRSF3) in regulating DHX9 poison exon, with potential implications in Ewing sarcoma proliferation and sensitivity to chemotherapy , whereasogenesis , while Mogenesis , which mMN2 gene . In thei pathway . Taking  therapy .This special issue also includes four reviews. In particular, Biamonti and colleagues discuss the key role played by alternative splicing in cancer cell plasticity and tumor heterogeneity . The posWe hope that the articles and reviews included in this special issue will illuminate new progresses in the field of alternative splicing and its function(s) in physiological and pathological conditions.


Needs during and following end-of-life (EOL) experiences are distinctive for sexual and gender minority (SGM) people and, in particular, older lesbian, gay, and bisexual women (LGB) women; however, access to supportive services is limited. This poster presents findings from a qualitative study of older (60+) LGB women who have lost a spouse or partner. This work draws on queer gerontological theory, addressing issues of individual agency, systemic silence, and marginalization by invisibility of older SGM women in order to illuminate specific areas in which policy may be changed and improved. The study analyzed participants’ (n = 16) reflections on their experiences of losing a loved one, including how they sought out and received essential grief support and the type of support they would have preferred and from whom, particularly immediately following their spouse or partner’s death. Thematic analysis revealed three main findings: 1) having a women-identifying support presence at the time of death for both themselves and their spouse or partner; 2) needing LGB women  during EOL for support; and 3) preferring grief groups comprised of other LGB women  based on their feelings of difference from gay men and heterosexual/non-SGM women and men. Findings reveal the need for a better understanding among healthcare and social work support professionals regarding LGB women’s grief needs and preferences; grief options  grief groups); and how to implement policy changes reflecting these needs and preferences.


The Saint Louis University GWEP partners with a rural Missouri critical access hospital and an urban Federally Qualified Health Center to support their transformations into an Age-Friendly Health System in their community. With an emphasis on the 4Ms, programmatic innovations include development and training of: 1) electronic health records integration of the Rapid Geriatric Assessment (RGA) for patients 65+ years old; 2) RGA-based protocol for Medicare Annual Wellness Visits (MAWV); 3) Interprofessional health care team approach; 4) Evidence-based or Evidence-Informed treatment interventions, including Cognitive Stimulation Therapy (CST), exercise and strengthening program, caregiver support, and Circle of Friends, an intervention for loneliness and social isolation. Outcomes will be presented which suggest increased assessment practices and improvement in functional and cognitive status. Successes and lessons learned regarding strategies to develop an Age-Friendly Health System in two different primary care settings will be discussed.


This article has been corrected: The authors requested replacement of Figure 4h (upper panel). Originally, to represent the morphology of brown adipose tissue (BAT) in the Middle-Aged group, the authors used the same image in Figure 3c (lower panel) and Figure 4h (upper panel). To avoid misinterpretation, they have replaced the Middle-Aged, Rest panel  with a representative image from the original set of experiments. This alteration does not affect the results or conclusions drawn in this work.


Recombinant human insulin plays an important role in the gut maturation of preterm infants. This meta-analysis was carried out to assess the efficacy and safety of enteral recombinant human insulin in decreasing the time to full enteral feeding in preterm infants. The pooling of data from four clinical trials yielded a significant decrease in the time to full enteral feeding in preterm infants under both low  and high doses of insulin . These findings require confirmation by further large trials that evaluate the efficacy and safety of enteral insulin, especially at supraphysiological doses. A preterm birth is categorized as the birth of a baby before 37 weeks of gestation . Around Studies on animal models suggest that maternal milk contains factors that stimulate the development of the gastrointestinal tract . These iSome clinical trials have been conducted on this topic, but they have not been systematically evaluated. In this study, we aim to evaluate the efficacy and safety of enteral human recombinant insulin in reducing the time to full enteral feeding in preterm infants. Our meta-analysis will help to determine if this intervention can prevent feeding intolerance and associated complications in this vulnerable population.This meta-analysis was conducted according to the guidelines of the Preferred Reporting Items for Systematic Review (PRISMA) . The PRIWe initially screened articles based on titles and abstracts and then screened them by reading the full text of the research articles. Two separate authors (FQ and MA) conducted the screening, and any conflicts and discrepancies were resolved through discussion with the third author (MA). We included controlled clinical trials that enrolled preterm infants and compared the efficacy of recombinant human insulin concentration with placebo or no treatment. Our outcomes of interest were the reduction in the time to full enteral feeding and the incidence of serious adverse events.2 statistic. We evaluated the efficacy of enteral insulin in two doses: (a) the physiological dose (400 µIU/mL milk) present in human colostrum (low dose) and (b) a supraphysiological dose (2000 µIU/mL milk) (high dose) [We pooled the data using RevMan 5.4 software under a random-effects model using mean differences (MDs) and risk ratios (RRs) with their 95% confidence intervals (CIs). Heterogeneity was assessed by the Igh dose) .The screening process identified four trials meeting the inclusion criteria that contributed five comparisons to the meta-analysis with a total of 388 participants  ,14,15,16The quality assessment of RCTs was carried out using the revised Cochrane Risk of Bias (RoB 2.0) tool . One tri2 = 48%; 2 = 0%; The results of our meta-analysis show that the use of enteral recombinant human insulin significantly decreased the time to full enteral feeding in preterm infants at both low  should be evaluated.


Anemia in patients with chronic kidney disease (CKD) is associated with increased morbidity and mortality, decreased quality of life, and substantial health care costs. Iron therapy is recommended, usually in combination with an erythropoiesis-stimulating agent (ESA), in many CKD patients with anemia and low iron levels to raise hemoglobin levels to a range of 10 to 12 grams per deciliter; iron deficiency is defined by a ferritin score less than 100 micrograms (mcg) per liter and transferrin saturation (TSAT) less than 20%.To examine the use of intravenous (IV) iron and it's associated economic and clinical outcomes in Medicare beneficiaries with stage 3 or stage 4 CKD and anemia.This was a retrospective cohort analysis using 2006 and 2007 Medicare 5% Standard Analytic Files (SAF). Use of therapy with IV iron and/or ESAs was identified among patients diagnosed with CKD and anemia. The study index quarter was the first quarter in 2006 during which the patient had primary or secondary diagnoses of both CKD and anemia. Based on the receipt of IV iron or ESA treatment in the index quarter, patients were classified into 1 of 4 treatment groups: IV iron and ESA; IV iron without ESA; ESA without IV iron; neither IV iron nor ESA. Therapy with oral iron was not measurable with this database. Clinical and economic outcomes, including the progression to advanced CKD stages, development of anemia, mortality, hospitalization, and net Medicare reimbursement  for all-cause health care services, were examined for 1 year following the index quarter. Between-group differences were tested using Pearson chi-square for categorical variables and the Kruskal-Wallis nonparametric test for reimbursement. Multivariate logistic regression models were estimated to assess the associations of mortality, inpatient hospitalization, skilled nursing facility (SNF) admission, and hospice care with treatment regimen, controlling for patient demographic and clinical characteristics.Of the 4,310 study patients with both CKD and anemia, 2,913 (67.6%) received neither IV iron nor ESA; 984 (22.8%) received ESA without IV iron; 277 (6.4%) received IV iron and ESA; and 136 (3.2%) received IV iron without ESA in the index quarter. Logistic regression analyses showed that patients receiving neither IV iron nor ESA (reference group) were at increased risk of death compared with patients receiving both IV iron and ESA . Additionally, patients receiving neither IV iron nor ESA were more likely to be hospitalized compared with patients receiving both IV iron and ESA , IV iron without ESA , and ESA without IV iron . Further, patients not receiving IV iron or ESA were more likely to be admitted to an SNF than patients receiving both IV iron and ESA , IV iron without ESA , and ESA without IV iron . Patients receiving neither IV iron nor ESA in the index quarter had the highest mean [SD] total Medicare reimbursement per patient in the subsequent year  compared with patients receiving IV iron without ESA , IV iron and ESA , or ESA without IV iron .Use rates of IV iron and ESA in a sample of Medicare enrollees with CKD and anemia in 2006 suggest that anemia management therapies may be underutilized; however, oral iron therapy use was not measurable with the study database, and therapies initiated after the index quarter were not measured. Patients not treated with IV iron or ESA had significantly higher rates of hospitalization and SNF admission than patients treated with either IV iron or ESA. Further, mortality was significantly higher in patients receiving neither IV iron nor ESA than in patients who received IV iron and ESA. Additionally, total all-cause health care costs were higher among patients receiving neither IV iron nor ESA treatment compared with patients treated with IV iron and/or ESA.


Due to a production error, the funder University of Bern was erroneously omitted. Statement to be added, “Open access funding by University of Bern.” The corrected Funding statement appears below:“Data collection and publication was supported financially by the canton of Aargau. Internal funding of research time. JJ work in tobacco prevention is funded by a career development award (CDA) funded by Swiss Academy of Medical Sciences (SAMS) (YTCR-34/19). Open access funding by University of Bern.”The publisher apologizes for this mistake. The original article has been updated.


Arabidopsis thaliana), neighbor cues reduce the activity of the photosensory receptors phytochrome B (phyB) and cryptochrome 1, releasing photoreceptor repression imposed on PHYTOCHROME INTERACTING FACTORs (PIFs) and leading to transcriptional reprogramming. The phyB-PIF hub is at the core of all shade-avoidance responses, whilst other photosensory receptors and transcription factors contribute in a context-specific manner. CONSTITUTIVELY PHOTOMORPHOGENIC1 is a master regulator of this hub, indirectly stabilizing PIFs and targeting negative regulators of shade avoidance for degradation. Warm temperatures reduce the activity of phyB, which operates as a temperature sensor and further increases the activities of PIF4 and PIF7 by independent temperature sensing mechanisms. The signaling network controlling shade avoidance is not buffered against climate change; rather, it integrates information about shade, temperature, salinity, drought, and likely flooding. We, therefore, predict that climate change will exacerbate shade-induced growth responses in some regions of the planet while limiting the growth potential in others.When exposed to changes in the light environment caused by neighboring vegetation, shade-avoiding plants modify their growth and/or developmental patterns to access more sunlight. In Arabidopsis ( The signaling network involved in shade avoidance responses integrates information from environmental variables such as temperature, water availability, and salinity. Shade avoidance responses are changes in plant growth and/or developmental patterns elicited by modifications of the light environment caused by neighboring vegetation. Their function is to increase access to sunlight and reduce the risk of future shade .There are four strategies  to achieve these goals: (a) To overtop neighbors, elevating the foliage above vegetation shade; (b) to move the position of the foliage on the horizontal plane away from the shade of neighbors; (c) to reduce the proportion of the foliage placed at the shaded base of the canopy; and (d) to modify the phenology to elude the time when deep shade is present.The growth and developmental responses inherent to each one of these strategies, respectively, include (a) enhanced elongation of the stem or petioles and the shift of leaves to a more erect position (enhanced leaf hyponasty); (b) asymmetric growth of the stem or the leaves (the phototropic response of light-grown seedlings can be included within this class of shade avoidance responses) and asymmetric branching; (c) the inhibition of branching at the base of the plant, the reduction of expansion of shaded leaves and the advanced senescence of basal leaves; and (d) the accelerated transition to reproduction (flowering) to complete the life cycle before shade becomes too deep and the delayed seed germination until shade disappears.Glycine max) (Helianthus annuus) (Triticum aestivum) (Hordeum vulgare) (Sorghum bicolor) (Zea mays)  and sunflower   and sunf annuus) , reduce estivum) , barley vulgare) , and sorbicolor) , and enhbicolor)  and orieea mays)  and sunfea mays) . Enhanceunflower . The widArabidopsis thaliana) for which the molecular events are best understood. We propose that the output of this network integrates different light, temperature, salinity, drought, and likely flooding cues and is, therefore, affected by climate change.Different species may show selected components of the shade-avoidance syndrome and shade avoidance is actually weak in shade-tolerant plants adapted to the understory of tree canopies . This reThe presence of neighbors modifies diverse features of the physical and chemical environment, including mechanical cues , which cCompared with isolated plants, the intensity of neighbor cues shows three phases of progressive strength with closer proximity to these neighbors and increased size particularly of their green organs . First, A. thaliana, sunlight activates phyB and cry1 to repress shade avoidance responses. The loss-of-function mutants of these photosensory receptors show shade avoidance responses under full sunlight  shows enhanced expression of the PHYA gene and phyA accumulation, which combined with a higher specific intrinsic activity of phyA and enhanced activation of inhibitors of shade avoidance prevents hypocotyl elongation in far-red rich environments  (BES1 to reduce cotyledon expansion under shade (Some of the downstream targets of PIFs are transcription factors themselves . A consp (ATHB2) , which m (ATHB2)  and ARFs (ATHB2) . Also, Per shade .PIF gene expression levels. For instance, prolonged exposure to low blue light enhances the expression of PIF4  targets IAAs to degradation in the proteasome  and shadHFR1  to SPA4 form a complex that acts as an E3 ubiquitin ligase substrate recognition module . In the Cardamine hirsuta, which is, therefore, more stable and helps reduce shade avoidance in this shade-tolerant species , YUC5, YUC8, and YUC9 are shade induced within 15 min in cotyledons  mutant deficient in auxin synthesis  gene subfamily occurs 15–45 min after the beginning of neighbor cues, even in the pin3 pin4 pin7 and yuc2 yuc5 yuc8 yuc9 mutants  shows that both conditions elicit similar hypocotyl elongation but very different reprogramming of gene expression  of leaves (9-CIS-EPOXICAROTENOID DIOXIGENASE 3 and 5 (NCED3/5) expression (a rate-limiting enzyme) and higher abscisic acid (ABA) levels  levels . Gene ex) levels . Whether) levels . Intrigu) levels .Medicago sp.) or sunflower which perform heliotropism to continuously reposition their leaves according to the solar position  and hence of the AN3 targets GROWTH REGULATING FACTOR1 (GRF1), GRF3, and GRF5 involved in cell proliferation (CYTOKININ OXIDASE 6 (CKX6) gene involved in the breakdown of cytokinin, a response proposed to be mediated by enhanced auxin levels in leaf primordia  (HOMEOBOX PROTEIN 21 (HB21), HB40, and HB53 genes and these transcription factors, together with BRC1, increase the expression of NCED3   a known 1 (BRC1) . In turnof NCED3   (FLOWERING LOCUS T (FT) and its paralog TWEEN SISTERS OF FT (TSF)  . The AraFT (TSF) . As FT eed ratio . In rapied ratio   by direct binding to its promoter (ORE1 expression indirectly by binding to and enhancing the expression of ABA INSENSITIVE 5 (ABI5), ENHANCED EM LEVEL (EEL) and ETHYLENE INSENSITIVE 3 (EIN3) followed by direct activation of ORE1 by these transcription factors  and REPRESSOR OF ga1-3 (RGA) (ABI5 (SOM)  , ABI5 (OA) (ABI5  and the I5 (SOM) , all of I5 (SOM) . Active I5 (SOM) . In addiromoters .In many areas of the planet, plants are experiencing a temperature increase that is so fast that it jeopardizes their ability to adapt. Moreover, global temperatures will continue to rise to an extent that will depend on the adoption of strong climate actions . In paraPIF4 gene (PIF4 (PIF4 promoter (PIF7 transcript (a third temperature sensor), increasing its rate of translation and hence PIF7 protein abundance , whereas warmth has little effect on expression and increases protein stability , necessary for BES1 activity , transcriptional regulators (ARFs and BES1/BZR1), and post-transcriptional regulators  fulfill crucial organ- and/or environment-specific functions.The importance of shade avoidance of liquid–liquid phase separation, chromatin remodeling, and carbon allocation is beginning to emerge.The activity of key components of the shade avoidance network responds not only to neighbor cues but also to temperature, water availability, salinity, and/or oxygen availability, acting as cellular integrators of above- and belowground information.To what extent is the signaling network involved in shade avoidance responses in Arabidopsis conserved in other species?What is the specific function of the negative regulators of shade-avoidance responses that increase their expression in response to neighbor cues?Which genes provide organ specificity to core shade-avoidance proteins such as PIFs or COP1?What are the patterns and mechanisms of integration of the auxin and sugar signals moving from the cotyledons to the growing hypocotyl? Is a similar convergence observed for other interorgan communication processes such as control of bud outgrowth?Is there deep signaling integration between soil resources-sensing mechanisms affected by climate change  and the perception of neighbor cues by aerial organs?Can shade avoidance responses modify the impact of climate change on plants?


Central line-associated bloodstream infections (CLABSI) are associated with increased morbidity, mortality, and healthcare costs. Many CLABSIs can be prevented using evidence-based care. To make this information more accessible and actionable, we developed interactive dashboards that translate data on CLABSI-related metrics and prevention efforts into visual formats that can be easily understood by healthcare professionals.A multidisciplinary work group of data analysts, infectious diseases physicians, and infection preventionists determined the content and layout of the dashboards. A query was written to extract necessary data elements from the Electronic Medical Record and NHSN. Data was then exported and used to build the dashboards using Tableau® software. The dashboard can be filtered at the facility level or at the unit level., one intensive care unit (ICU) , and one cardiovascular ICU (CVICU) . The central line standard utilization ratio (SUR) was higher for the CVICU ( >1.5), followed by the ICU (≈1), and the general ward (< 1). Blood culture intensity (number of blood cultures collected/patient-days) was less for the general ward (< 5%), variable for the ICU (8-14%), and persistently higher for the CVICU (11%). Compliance with daily chlorhexidine bathing was higher for both the CVICU (80%) and the ICU (75%) compared to the general ward (40-60%). The CLABSI rate per 1,000 central line-days has been downtrending for the CVICU and uptrending for the ICU. Besides lower compliance with daily chlorhexidine bathing, the examined ICU has also recently shown a higher proportion of long-term devices (40%), calculated as proportion of central lines ≥ 7 days/all central lines, compared to the CVICU (25%).We present the dashboard of one general ward Dashboards should contain meaningful outcomes and standardized process metrics that are mapped to strategic goals and be timely to support prompt identification of deviations. Our CLABSI dashboards are effective tools for communicating and tracking performance data. Filtering at the unit level allows us to identify unique unit characteristics, or “fingerprints,” and recognize specific areas for improvement. This enables us to develop targeted interventions for each unit.All Authors: No reported disclosures


Despite evidence suggesting a decline in the physical activity of middle-aged adults, 40–64-year-olds participation in group exercise is actually increasing. One potential reason for this increase in activity is the increase in a range of different online group exercise formats and contexts. Recent research suggests that people join, participate, and stay involved in, exercise groups that reflect who they are - a process of social identification. The purpose of this research is to qualitatively explore participants’ experiences and facilitators of social identification related to the online group exercise platform known as Zwift.Zwift participants (n = 17) aged between 40-64 (midlife)  were recruited into the study for three stages of data collection: (stage 1) an initial semi-structured interview exploring participant exercise history and use of Zwift, (stage 2) completing a two-week post exercise diary to capture their experiences of social identification after participation, (stage 3) a follow up final interview to explore topics raised over the first two data collection steps. This generated 23 hours of interviews, that were then transcribed and combined with the participant diaries resulting in 468 pages of data.Reflexive thematic analysis was used to identify themes from the data. The results from this analysis indicate the following themes from the data: (1) Online exercise as an enabling facilitator of exercise identity; (2). Online exercise provides exercise identity continuity or exercise identity creation depending on the exercisers, exercise history; (3) Online exercise identification via communities goes through phases of identification; (4) Two-way communication contributes to perceptions of identification phases of identification; and (5) Social identity leadership is demonstrated by online exercisers norms, behaviours and beliefsOverall, this research highlights three key suggestions for mid-life physical activity promotion: (1) That facilitators and processes of social identification may be context specific; (2) That social identification processes should be considered in the design of online exercise; and (3) That online exercise that enables social identification should be considered as a vehicle of maintaining/ increasing exercise participationThe study was funded by the researcher.


Coccinella undecimpunctata Linnaeus (1758) (Coleoptera: Coccinellidae). Tens of individuals of both sexes were discovered at a single location, indicating that the species may already be established on South Georgia. Transport connectivity with this site suggests that the species most likely arrived recently from the Falkland Islands as a stowaway on a ship. We discuss the implications of our discovery for the continued development of South Atlantic biosecurity.Biological invasions represent a growing threat to islands and their biodiversity across the world. The isolated sub‐Antarctic island of South Georgia in the South Atlantic Ocean is a highly protected area that relies on effective biosecurity including prevention, surveillance and eradication to limit the risk of biological invasions. Based on an opportunistic field discovery, we provide the first report of an introduced ladybird beetle on South Georgia. All specimens discovered belong to the Eurasian species  Coccinella undecimpunctata. The species may already be established and reproducing on the island and likely arrived from the Falkland Islands as a stowaway on a ship. This discovery has implications for the continued optimisation of South Atlantic biosecurity and global island conservation.During a scientific expedition in South Georgia, we incidentally discovered the presence of the introduced ladybird beetle  The entCoccinella undecimpunctata is established in North America  (Coleoptera: Coccinellidae) on South Georgia.Among the approximately 6000 described species , sex determination relied on the sexual dimorphism of the 8th abdominal segment: males have a “notch” on the posterior margin of the sternite . Cutting through the posterior tip of the abdomen to expose the reproductive system enabled determination of the sex of most individuals. For a few specimens that were kept intact (2.3t‐tests were used to investigate if the widths of the pronotum and of the head differed between sexes. Maps of South Georgia were based on topographic data from thematicmapping.org and South Georgia GIS (2023). Figures were assembled in Inkscape . Antarctic fur seals  move between the sea and their resting areas via the sampling location and a group of moulting king penguins (Aptenodytes patagonicus) was present in the vicinity. Consequently, organic debris and feathers were abundant below and between rocks in the sampled area.In January 2023, we recorded the presence of ladybirds on the southern side of Stromness Bay, South Georgia Figure . DespiteC. undecimpunctata Linnaeus (1758). Specimens had small and elongate bodies  and of the head (1.1 ± 0.05 mm) – and these were not significantly related to sex (two‐sided Welch 4C. undecimpunctata Linnaeus (1758) on the sub‐Antarctic island of South Georgia. There is little doubt that the presence of this Eurasian species is due to human activity. C. undecimpunctata may be reproducing on South Georgia given the presence of both sexes and the number of individuals found relative to search effort. However, the species was detected only in a small area and not at any other sampling site on the northern peninsulas nor in King Haakon Bay and may therefore be at an early stage of biological invasion ; data curation (lead); formal analysis (lead); investigation (lead); methodology (lead); project administration (supporting); software (lead); supervision (supporting); validation (lead); visualization (lead); writing – original draft (lead); writing – review and editing (lead). Helen E. Roy: Formal analysis (supporting); validation (supporting); writing – review and editing (supporting). Peter Convey: Conceptualization (supporting); funding acquisition (supporting); investigation (supporting); methodology (supporting); project administration (supporting); writing – review and editing (supporting). Paul Brickle: Conceptualization (supporting); funding acquisition (supporting); methodology (supporting); project administration (supporting); resources (supporting); writing – review and editing (supporting). Rosemary J. Newton: Conceptualization (supporting); funding acquisition (supporting); methodology (supporting); project administration (supporting); writing – review and editing (supporting). Wayne Dawson: Conceptualization (supporting); data curation (supporting); formal analysis (supporting); funding acquisition (lead); methodology (supporting); project administration (lead); resources (lead); supervision (lead); validation (supporting); writing – original draft (supporting); writing – review and editing (supporting).The authors declare no competing interests.


Diabetes mellitus is defined as a group of metabolic diseases characterized by hyperglycemia, which when untreated can lead to long-term complications, including micro- and macrovascular complications. Tight glycemic control with intensive insulin therapy has been suggested to reduce the risk of such complications in several diabetes populations; however, such an approach can also be associated with risks and challenges. There are currently several modalities available to deliver insulin and monitor glucose levels to achieve glycemic goals in diabetic patients. In July 2012, the Agency for Healthcare Research and Quality (AHRQ) published a systematic review on the comparative effectiveness of insulin delivery systems and glucose-monitoring modalities in diabetic patients receiving intensive insulin therapy. Studies from 44 publications included in the review compared the effects of continuous subcutaneous insulin infusion (CSII) with multiple daily injections (MDI) and/or real time-continuous glucose monitoring (rt-CGM) with self-monitoring of blood glucose (SMBG) among children, adolescents, or adults with either type 1 (T1DM) or type 2 diabetes (T2DM), or pregnant women with pre-existing diabetes (either T1DM or T2DM). This comparative effectiveness review evaluated which modality results in improved glycemic control, less hypoglycemia, better quality of life, and/or improved clinical outcomes. The numerous technologies and the challenges that clinicians face when determining which patient population may benefit from different insulin delivery systems and glucose-monitoring approaches motivated AHRQ to synthesize the available information to assist health professionals in making evidence-based practice decisions for their patients. The review also delineates advances in insulin delivery and glucose-monitoring systems, practical methods to achieve tight glycemic control and strategies to minimize associated risks, as well as highlights gaps in research and areas that need to be addressed in the future.To (a) educate health care professionals on the findings from AHRQ’s 2012 comparative effectiveness review on insulin delivery and glucose-monitoring modalities in patients with diabetes; (b) apply review findings to make treatment decisions in clinical practice; and (c) identify shortcomings in the current research and future directions relating to the comparative effectiveness of insulin delivery and glucose-monitoring modalities for patients with diabetes.The AHRQ systematic review of randomized clinical trials reveals that both insulin delivery modalities (CSII and MDI) demonstrate similar effectiveness on glycemic control and severe hypoglycemia in children and adolescents with T1DM and in adults with T2DM. In adults with T1DM, hemoglobin A1c decreased more with CSII than with MDI with low strength of evidence, but one study heavily influenced these results. In children and adults with T1DM, the use of CSII was associated with improved quality of life compared with MDI, with low strength of evidence, while there was insufficient strength of evidence to make conclusions regarding the quality of life for adults with T2DM. The study investigators suggest that the modality to deliver intensive insulin therapy can be individualized to patient preference in order to maximize quality of life. On all measured outcomes, there was insufficient or low strength of evidence regarding pregnant women with pre-existing diabetes.The AHRQ investigators found studies comparing the effectiveness of glucose-monitoring modalities in individuals with T1DM only. The systematic review demonstrates that rt-CGM is associated with greater lowering of A1c compared with SMBG (high strength of evidence) without affecting the risk of severe hypoglycemia (low strength of evidence) or quality of life (low strength of evidence) in nonpregnant individuals with T1DM, particularly when compliance with device use is high. Additional findings suggest that the use of sensor-augmented insulin pumps (rt-CGM + CSII) is superior to the use of MDI/SMBG use in lowering A1c in nonpregnant individuals with T1DM (moderate strength of evidence). Comparison of other outcome measures did not yield firm conclusions due to low or insufficient evidence.