Dear Editor, I agree that accurate representation of research is of great importance, and Iapologize for these mistakes.I am grateful to Dr Anne Witt and Dr Sheila Kredit for drawing attention to errors I havemade in Appendix 1 of ‘Re-thinking Benign Inflammation of the Lactating Breast:Classification, Prevention, and Management’.Dr Witt and Dr Kredit are correct to state that I have falsely represented: study andThe rates of follow-up in the Witt et al. systematic review.Analysis of Witt et al. in Anderson et al.’sThe Witt et al. study is not a randomized controlled study (RCT), but a nested case-controlstudy. It is referred to as ‘quasi-experimental’ in the Anderson et al. systematic review, notas an RCT. In Appendix 1 of my article, I wrongly represent the numbers who responded tofollow-up emails in the Witt et al. study, wrongly attributing these inaccurate numbers toAnderson et al. The Witt et al. study demonstrated excellent follow-up in the cohort whoreceived Therapeutic Breast Massage in Lactation (TBML) and also in the control group.Although debate is welcomed, and accurate representation of research essential, Inevertheless contend that TBML should not be recommended to breastfeeding women asevidence-based management of breast inflammation on the basis of Witt et al.’s study, for fourreasons:1. TBML was delivered as one element in a complex breastfeeding intervention. Itsefficacy was evaluated in small numbers for mastitis and plugged ducts, in the absenceof a control group.TBML was delivered in the context of full breastfeeding support provided by an InternationalBoard Certified Lactation Consultant/registered nurse and/or breastfeeding medicine physician,which included latch correction, feeding patterns, antibiotic prescription, milk removal oranalgesia as clinically indicated. The component of the study which investigates efficacy ofTBML for mastitis and plugged ducts is a small, pre- and post-TBML assessment , which lacks a comparison group. That is,pre- and post-intervention comparisons do not take into account the neurobiological effects ofpatient expectation (placebo effect), as Witt et al. acknowledge in their article.2. TBML did not show improvements in pain at 2-day and 12-week follow-up when theengorgement group was compared to the control group.Of the 15 participants with engorgement [in the TBML intervention group], measurementswere taken from each breast, giving a total of 30 separate pain scores . . . These scoreswere treated independently (n = 30) in the pre-post analysis and combined (n = 15) for thecomparison between the intervention and control groups, making interpretation quitedifficult.Anderson et al. state in their analysis of Witt et al.,In the component of Witt et al. which investigates efficacy of TBML for engorgement, theintervention group (n = 15) was compared to a control group (n = 73); 47% of the interventiongroup had severe engorgement compared to 7% of the control group. Comparison of theengorgement intervention and control groups showed no meaningful difference in pain at day 2nor in pain, exclusive breastfeeding or breastfeeding complications at week 12 in emailfollow-up.3. Pre- and post-TBML improvements can be explained by the ductal dilations (milkejection) and milk removal components of TBML alone.TBML in the Witt et al. study achieves milk removal by alternating hand expression of milkwith the massage technique, and by allowing direct breastfeeding of the infant during TBML(see Supplement Appendix A). The reduction in breast pain and also in size of plugged ductsobserved immediately after TBML can be explained by the milk removal components of TBML alone,which are associated with milk ejections and ductal dilations.4. There is no pathophysiological model which explains the proposed efficacy of thegentle areola-to-axilla massage component of TBML.Is increased lymphatic drainage the proposed pathophysiological mechanism of light massagefrom the areola to the axillae? If so, this proposed mechanism isn’t supported by the latestresearch concerning the function of lymphatic vasculature. Interstitial fluid diffuses intothe initial lymphatic capillaries in response to rising pressure gradients between breaststroma and lymphatic capillaries, which mechanically opens these capillaries. Lymphaticcollection vessels contain valves, have smooth muscle in their walls, and are intrinsicallycontractile, actively pumping lymph towards the nodes. Although there is no convincingphysiological rationale to support the belief that application of external pressurefacilitates lymphatic removal of breast stroma interstitial fluid, there is reason to beconcerned that an external pressure application which moves towards the axilla risks increasedintra-alveolar milk pressures.Various breast massage techniques are offered to breastfeeding women around the world, as DrWitt and Dr Kredit note. Anderson et al. analyse the efficacy of a range of massage techniquesin three RCTs and three quasi-experimental studies, including Witt et al.’s study of TBML.Although Anderson et al. conclude ‘Overall, different types of breast massage were reported aseffective in reducing immediate pain for the participants’, I contend that neither Witt etal.’s data or Anderson et al.’s data support Therapeutic Breast Massage as an evidence-basedintervention for presentations of lactation-related breast inflammation, despite its inclusionin Academy of Breastfeeding Medicine Clinical Protocol #36: The mastitis spectrum.Using the GRADE Working Group grades of evidence in their Summary of Findings, Anderson etal. report low certainty of outcomes for reduction in pain, increase in breast milk supply,and reduction or resolution of symptoms of breast inflammation, noting that ‘the true effectmay be substantially different from the estimate of the effect’. Anderson et al. observe thatthe ability to replicate or generalize results of the six studies are limited by:Significant heterogeneity of study methods, interventions and outcome measuresLack of detailed explanation of breast massage techniquesUse of invalidated toolsSmall sample sizes and Oketani massage techniques, or requirement for seven consecutive days of massage combined with preparation of freshtopical cactus and aloe leaf lotion and pre- and post-massage application of aloe and cactusflesh, may not be practical in many settings.Anderson et al. also note that requirement for extensive training for traditional Gua Sha breastfeeding women are commonly referred to multiple providers for unproveninterventions when problems emerge. Many popular treatments such as TBML lack both aconvincing evidence-base and a robust underlying pathophysiological model. Such treatments mayincrease the financial burden for families and health systems, and raise the spectre ofdiscriminatory breastfeeding support globally, with ease of access limited to affluentfamilies in advanced economies.Because clinical breastfeeding support remains a research frontier,Thank you for the opportunity to correct my mistaken representation of the Witt et al. andAnderson et al. studies in Appendix 1 of my article, for which I apologize. I welcomerespectful discussion and debate concerning interpretation of existing studies and also theopportunity to amend errors, knowing that as clinicians and researchers we share the samecommitment to improved outcomes for breastfeeding women and their babies.Pamela DouglasKind regards,


Thermal manipulation has garnered considerable attention for its potential applications in diverse areas, including microelectronics, thermal logic devices, and thermoelectrics. Manipulating heat transfer in nanostructured materials is particularly desirable, especially for structures with high thermal conductivity used in thermal dissipation. However, the demand for high-power micro/nano chips exceeds the capabilities of even cutting-edge thermal management technologies, which currently represent a bottleneck in further development. Conversely, structures with low thermal conductivity are of interest in various areas such as thermal barriers and thermoelectrics. Understanding heat transfer is thus a fundamental problem that requires comprehensive study. However, studying heat transfer in nanostructures presents significant challenges due to the dominance of interfaces, boundaries, and imperfections in its behavior, and the underlying physical mechanisms remain unclear .This Special Issue, entitled “Heat Transfer in Nanostructured Materials”, provides a platform for presenting original and review articles that showcase recent advances in heat transfer within low-dimensional materials and nanofluids. The issue will systematically introduce and discuss the design, construction, characterization, and potential applications of these structures.−1 K−1. Li et al. [2 nanowires that showed an increase in jump during metal-insulator transition temperature with increasing sample thickness. Phonons were identified as major carriers that dominate thermal transport in the nanowires. Jiang et al. [Low-dimensional structures have demonstrated significant potential for nanoscale dissipation as thermal interface materials (TIMs). Lv et al.  developei et al.  revealedg et al.  investigg et al.  examinedg et al.  presente3O4 nanoparticles as nanofluids. The connector enhanced the heat transfer coefficient within the second microchannel by increasing the randomness of molecules and particles, refreshing the fluid’s memory before entering the second channel. The effects of Reynolds number and nanoparticles on the connector were also studied, revealing that introducing Fe3O4 nanoparticles increased overall thermal conductivity and the heat transfer coefficient. The connector effectively promoted the random motion of molecules and nanoparticles, with the enhancement being significant at low Reynolds numbers but becoming negligible with increasing Reynolds number. This paper also presented a brief review of current advancements in studying the effects of nanoparticles on fluid thermal conductivity, viscosity, and heat transfer coefficient. Arshad et al. [Heat transfer via nanofluids has emerged as an effective approach for thermal management in complex systems. Optimization of nano additives and microchannel designs can significantly improve heat transfer efficiency. Apmann et al.  investigd et al.  reportedThis Special Issue is expected to be of interest to readerships in both fields of science and engineering. Understanding heat transfer mechanisms in nanostructured materials is fundamental for further developments of nanoscale devices, yet it remains an extreme challenge. We anticipate more emerging works focusing on depicting the underlying physical pictures of heat transfer and developing strategies for thermal manipulation in nanostructures.


Cancer is still one of the leading causes of death worldwide, despite that tremendous resources are being invested in drug discovery . Recent The majority of cancer medications consist of small molecule inhibitors. These inhibitors are engineered to enhance their efficacy by binding to specific cellular protein targets, which in turn initiate a series of downstream changes in cancer signaling and metabolic pathways . High-thin vivo patient-derived xenograft (PDX) samples  proliferation-associated phenotypes, or 2) intermediate phenotypes, such as transcriptomic alterations. Numerous well-established data portals, including The Cancer Genome Atlas (TCGA), DepMap Portal , and The samples . These i samples . These t samples . The selFunctional screening for cancer drug discovery: from experimental approaches to data integration” is to highlight the recent advances in high-throughput functional genetic approaches, especially how results from such new technologies can be applied for future studies in cancer drug mechanisms of action. To achieve this goal, we carefully reviewed every submitted manuscript and screened for highly qualified reviewers. Eventually, we accepted and published nine articles including eight “Original Research” articles, and one systematical “Review” article on the mechanism and clinical trials of hepatocellular carcinoma immunotherapy  in the onset and progression of gastric cancer (GC). Ren et al. developed a necroptosis-related prognostic signature to reveal immune infiltration, which could predict drug sensitivity and inform personalized drug therapy for hepatocellular carcinoma (HCC) patients. Wang et al. reported a novel hub gene signature closely associated with ferroptosis, serving as a potentially effective biomarker for predicting the prognosis of HCC patients.The research articles presented in this Research Topic encompass efforts in cancer drug discovery from both experimental and computational perspectives. Liu et al. conducted a comprehensive analysis to elucidate the roles of cuproptosis-associated genes in tumor biology and cancer drug sensitivity across various cancers. Chen et al. discovered a novel diagnostic four-gene signature for hepatocellular carcinoma based on an artificial neural network, with applications in drug screening. Li et al. explored the functional effects of FDX1 in tumors, and further validated the inhibitory effect of FDX1 in copper-induced cell death, confirming FDX1’s role as a cuproptosis biomarker. Ruan et al. leveraged pan-cancer analysis to identify DDX56 as a prognostic biomarker associated with immune infiltration and drug sensitivity. Zhang et al. uncovered an LncRNA signature related to cuproptosis, serving as a novel biomarker of prognosis in immunotherapy and drug screening for clear cell renal cell carcinoma.We believe that the articles featured in this Research Topic can offer valuable insights into the application of functional screening methods for cancer drug discovery. The findings presented in these studies are anticipated to enhance our understanding of the molecular mechanisms governing cancer progression and, ultimately, we hope they will positively impact drug and target discovery in the near future.


This method has broad-range applicability to understanding microbial communities and their associations with biosignatures and soil carbon and mineralogic characteristics relevant to climate science and astrobiology.Permafrost is important from an exobiology and climate change perspective. It serves as an analog for extraplanetary exploration, and it threatens to emit globally significant amounts of greenhouse gases as it thaws due to climate change. Viable microbes survive in Earth's permafrost, slowly metabolizing and transforming organic matter through geologic time. Ancient permafrost microbial communities represent a crucial resource for gaining novel insights into survival strategies adopted by extremotolerant organisms in extraplanetary analogs. We present a proof-of-concept study on ∼22 Kya permafrost to determine the potential for coupling Raman and fluorescence biosignature detection technology from the NASA Mars Perseverance rover with microbial community characterization in frozen soils, which could be expanded to other Earth and off-Earth locations. Besides the well-known utility for biosignature detection and identification, our results indicate that spectral mapping of permafrost could be used to rapidly characterize organic carbon characteristics. Coupled with microbial community analyses, this method has the potential to enhance our understanding of carbon degradation and emissions in thawing permafrost. Further, spectroscopy can be accomplished  It is located along the valley floor of Goldstream Creek in a region of discontinuous permafrost. Permafrost in this area is syngenetic ice-rich silt (loess) formed through sediment deposition, causing the permafrost layer to expand upward , a custom-built deep ultraviolet (DUV) Raman and fluorescence spectrometer designed by the NASA Jet Propulsion Laboratory. This same technology is employed on the Mars Perseverance rover. MOBIUS uses a 248.56 nm NeCu pulsed laser  . The laser spot is annular in shape with an outer diameter of ∼44 mm and an effective illuminated area of 3540 μm2  at a spectral resolution of 3.8 cm−1/pixel. For fluorescence measurements, a grating of 300 lines/mm was used with a spectral range of 250–410 nm and a resolution of 0.16 nm/pixel. Spectral positions were calibrated before sample measurements by validating the position of the zero-order reflection, the secondary laser line at 252.93 nm . Local Raman maps covered 0.5 × 0.5 mm at 100 um spacing, resulting in 25 individual point spectra at 1200 laser pulses per point (30-second acquisitions).et al.,Raman scan locations were selected based on the fluorescence intensity distribution obtained during the initial survey to prioritize areas of intense fluorescence that may indicate the presence of concentrated organic/biological material. A Canon camera provided context imaging of the mapped sample with a ∼20 mm/pixel resolution. Data processing was performed using custom Python programs and visualization tools based on a Loupe software package to process and visualize hyperspectral Raman and fluorescence data sets Uckert, . Spectra2.3.We performed triplicate DNA extractions from each core section  directly from 0.5 g of soil using the FastDNA Spin Kit for Soil . An additional cleanup to remove humic material and other inhibitors was performed using the Qiagen DNeasy PowerClean Pro Cleanup Kit . The 16S rRNA gene was amplified with the 515F/926R barcoded primer sets and conditions recommended by the Earth Microbiome Project. Libraries were sequenced on the Illumina MiSeq platform, generating 2 × 250 bp paired-end reads.et al.,et al.,et al.,et al.,et al.,et al.,et al.,16S rRNA amplicon sequences were processed using the exact sequence variants (ESVs) pipeline in QIIME2, version 2022.2  16S ribosomal RNA sequences database (updated 2022/10/30) Madden,  and extr3.3.1.−1). The appearance of this Raman peak in a fluorescence spectrum is consistent with the prevalence of water ice in permafrost . The relative intensity of the water band to organic fluorescence varied significantly between and throughout each sample and provides a measure of relative changes in the organic/ice concentration ratio.The three permafrost samples exhibited consistent fluorescence signatures indicative of a similar continuum of organic matter present throughout each sample. This signature comprised broad fluorescence peaks at ∼320 and ∼410 nm, typical of biological macromolecules such as nucleic acids and proteins, which are consistent with expectations based on the prevalence of biomass in permafrost , 2B Fri. The twormafrost , 2B. How2O stretching mode. However, when measured with higher spectral resolution and longer exposures, this was better resolved as an asymmetric peak with a narrow component at 3155 cm−1 and a broader, weaker component at 3350 cm−1   . Proteobacteria and Firmicutes were the most abundant phyla , followed by Acidobacteria (1.1%) and Chloroflexi (0.62%) . We did Clostridium sensu stricto 13, Bacillus, Pseudomonas, Massilia, and Ralstonia), which together account for 78% of all sequences, to known 16S rRNA gene sequences. Close relatives (>97% sequence identity) have been isolated from an assortment of environments and conditions and employ a diversity of life and metabolic strategies, indicating that multiple divergent mechanisms can be employed to survive in ancient cryoenvironments.To better understand the microbial inhabitants of late Pleistocene permafrost, we compared ESV sequences of the five most abundant genera . In contrast to Clostridium, close relatives of Bacillus ESVs are primarily mesophilic (plus a few psychrophiles) and are derived from various environments and conditions. Previous data suggest that Clostridium may persist as vegetative cells in permafrost, while Bacillus form endospores , which can then be subsampled for DNA sequencing. Since there is fine-scale variation in permafrost soils, sequencing the same imaged regions will likely reveal relationships between spectral signatures and community structure.Permafrost cross-sections showed a widespread distribution of partially degraded organic carbon, pockets of water ice, and known microbial constituents. While we found no definitive spectral signatures corresponding to microbial community structure, this may be due to subsectioning methods. Given the high prevalence of organic material in permafrost, signatures from individual microbes may be lost in the background continuum of signals from all other organic matter present when analyzed with spectroscopy alone. To ameliorate this in our first-order analysis, core sections were divided into two pieces: one for spectroscopy and the other for microbial analysis. In the future, fluorescence and Raman spectroscopy can be applied to the core samples et al.,Previous analyses from the tunnel demonstrated that replicate samples from directly adjacent cores had small variations in microbial community structure but highly significant differences when comparing permafrost of different radiocarbon ages located tens of meters apart  , and the action of microbial communities as they slowly metabolize and transform organic matter through geologic time  and slow  thaw. Together with carbon dating of sampled strata, microbial analyses, and greenhouse gas measurements, this has the potential to identify and predict the relationships among many complex factors  and reveal how these ultimately drive the contribution of permafrost thaw to the climate change equation.These methods provide a unique means of studying permafrost in a changing climate. The 1700 billion tons of ancient carbon stored in permafrost exists in varying forms, from labile to recalcitrant (Jorgenson 4.3.et al.,et al.,et al.,et al.,Characterizing Earth's ancient permafrost microbial diversity and survival strategies provides a baseline to guide the search for microbial life on other frozen desert worlds. Permafrost is found in the subsurface of Mars and is expected in the mixed crustal and ice silicates of icy planets and moons across the Solar System, including Ceres, Callisto, and possibly Ganymede and Titan Johnson, . Microbiet al.,The ability to rapidly and successfully characterize microbiologic and chemical conditions of ice and carbon-rich environments has important implications for extraplanetary exploration and studying permafrost on Earth. Recent breakthroughs in rapid DNA sequencing (Castro-Wallace et al.,et al.,et al.,et al.,et al.,et al.,et al.,in situ sampling methodologies with established microbial community interrogation techniques will save time in site exploration, retrieval methodology, and post-retrieval analysis while building a library to be used as a proxy for exoplanet biosignatures.Permafrost on Earth is dynamic in structure and formation, providing additional proxies for hypersaline environments such as brine lenses, legacy frozen substrate, and ice-rich sediment or ice wedges (Niederberger 5.et al.,in situ could greatly reduce transport and laboratory cost, shortening the timeline from sampling to results. Creating an index of microbial community characteristics and survival mechanisms for extraplanetary exploration will inform the search for extraterrestrial life. As the search for life continues, any information to constrain search locations saves money and shortens the time to discovery. Proxies for exobiology detection currently exist on Earth, and every effort should be made to systematically characterize their diversity before they are lost to climate change.Up to 40% of northern latitude permafrost may thaw by the end of the century (Chadburn


Drug reaction with eosinophilia and systemic symptoms (DRESS).Five articles are published in this Frontiers' Research Topic on Chen et al., offering an elegant review of DRESS. This comprehensive review delves into the pathogenesis of DRESS, potential biomarkers, and the relevant therapeutic rationales. With our current understanding of the genetic susceptibility, models of antigen presentation, and T-cell activation by drugs, DRESS along with other severe cutaneous adverse drug reactions can no longer be dismissed as unpredictable, at least for specific drugs. Prevention of DRESS associated with some medications is possible; the most successful example is that of HLA B1502 screening prior to carbamazepine use in the Han Chinese population . PLHIV experience a higher frequency of drug eruptions when compared with the non-HIV population . Immune Kuchinskaya et al.. This report underscores the challenges in recognizing and differentiating DRESS from other systemic inflammatory syndromes with similar presentations and laboratory findings. Lastly, Manieri et al. provided us a review of DRESS in childhood and highlighted that rapid-onset DRESS affects children more often than adults and is usually triggered by antibiotics or iodinated contrast media rather than by anticonvulsants.Furthermore, DRESS do occur in children, as highlighted in the case report by In conclusion, this Frontiers Research Topic provides valuable insights into the complex realm of DRESS, offering a deeper understanding of its mechanisms, treatment options, and challenges in various populations.Enjoy the wealth of knowledge shared in this Research Topic on DRESS!BJ: Writing — original draft, Writing — review & editing. YL: Writing — original draft, Writing — review & editing. SN: Writing — original draft, Writing — review & editing.


Streptococcus pyogenes (Sp) Cas9 revealed through these techniques.Cas9 is an RNA-guided endonuclease from the type II CRISPR-Cas system that employs RNA–DNA base pairing to target and cleave foreign DNA in bacteria. Due to its robust and programmable activity, Cas9 has been repurposed as a revolutionary technology for wide-ranging biological and medical applications. A comprehensive understanding of Cas9 mechanisms at the molecular level would aid in its better usage as a genome tool. Over the past few years, single-molecule techniques, such as fluorescence resonance energy transfer, DNA curtains, magnetic tweezers, and optical tweezers, have been extensively applied to characterize the detailed molecular mechanisms of Cas9 proteins. These techniques allow researchers to monitor molecular dynamics and conformational changes, probe essential DNA–protein interactions, detect intermediate states, and distinguish heterogeneity along the reaction pathway, thus providing enriched functional and mechanistic perspectives. This review outlines the single-molecule techniques that have been utilized for the investigation of Cas9 proteins and discusses insights into the mechanisms of the widely used By measuring the resonance energy transfer efficiency   studies the surface structure and properties of samples by detecting the extremely weak interatomic interaction between the sample surface and a miniature force-sensitive sensor , whereas PAM-distal mismatches still allow for the stable binding of the complex to DNA targets. Specifically, 9–10 PAM-proximal matches are sufficient for ultrastable SpCas9–gRNA binding. Moreover, as the dwell-time analysis shows two characteristic binding times, a two-step mechanism of Cas9–RNA binding involving PAM surveillance and RNA-DNA heteroduplex formation (see the next section) was proposed . Fully unwound protospacer DNA coupled with full R-loop formation possibly drives the docking of the HNH domain, thus licensing cleavage-competent SpCas9 (see the following section “DNA dissociation after cleavage”). Modifications of gRNA or the engineering of SpCas9 could rebalance the unwinding-rewinding equilibrium and make it stricter to reach the cleavage-competent state, thus minimizing off-target effects. et al. et al. et al. et al. et al. et al. et al. et al. et al. et al. et al.SpCas9 is a multidomain DNA endonuclease. Structures of SpCas9 showed two distinct lobes, the alpha-helical recognition (REC) lobe and the nuclease lobe (NUS), as well as the more variable C-terminal domain (CTD) , the 3’ flap generated by the cleaved NTS is possibly exposed and can be digested by exonucleases ( et al.One distinguished characteristic of SpCas9 is its stable binding to the on-target site after cleavage. Both ucleases  (Wang et  et al.. Therefo et al.in vitro, could facilitate the dissociation of DNA-cleaved SpCas9 from DNA. Zhang et al. used optical tweezers to examine the consequence of encountering a BLM helicase with a DNA-bound dSpCas9 from both sides ( et al. et al. et al. et al.The long lifetime of the SpCas9–gRNA–DNA complex limits the efficient usage of each SpCas9 protein and impairs the repair of DSBs (Clarketh sides . They prAs evident from this review, single-molecule studies provide not only a fundamental understanding of Cas9 mechanisms but also a framework for rational design aiming at improving Cas9 efficiency and minimizing off-target effects. Based on these studies, a detailed dynamic picture of DNA interrogation and cleavage of SpCas9 has been generated . Upon coQian Zhang, Ziting Chen and Bo Sun declare that they have no conflict of interest.


IARC). Hepatocellular carcinoma is the most common type of liver cancer representing about 90% of all the cases of hepatic malignancy  mainly: METTL6, GSTZ1, ADH4, ADH1A, and LCMT1 can be utilized as a predictor of HCC patient’s prognosis. Yang et al., have demonstrated the role of HIF2-alpha, a key metabolic regulator, along with VEGF in cellular proliferation and migration of HCC cells in response to insufficient radiofrequency ablation. Angiogenesis plays a very important role in the pathogenesis of several types of cancer including HCC. Tang et al., have shown that expression of angiogenesis-related genes (ARGs) exhibits predictive value in the prognosis of HCC patients. They identified about differential expression of 97 ARGs and further constructed 9 genes-based models to predict the prognosis of HCC. Tang et al., have demonstrated the importance of senescence-related genes in the prognosis of HCC patients. Their study demonstrates that cellular senescence-related genes can be utilized as a prognostic marker as well as a biomarker of therapeutic response. These studies altogether establish the importance of metabolic alterations related to gene expression and angiogenesis in the prognosis of HCC patients.Metabolic alterations are considered a hallmark of cancer . Tian etWang et al., have identified that genes related to N6-methyladenosine (m6A): B2M and SMOX can serve as prognostic signature and their expression may guide to design of novel therapeutic strategies for HCC patients. In a similar study, Huang et al., have demonstrated a 12 genes-based risk signature model in the prognosis of HCC patients. They have shown that SDC3, NCF2, BTN3A3, and WARS genes can serve as novel prognostic factors for HCC.Epigenetic modifications regulate several aspects of cellular physiology and different disease progression by regulating the gene expression machinery. The role of epigenetic alterations in the pathogenesis of different types of cancers including HCC is well-established but not completely understood. By utilizing the publicly available databases, Wang et al., have established a correlation between mitophagy-related genes and immune infiltration in a subset of HCC patients. They have shown that a subset of patients exhibiting higher mitophagy-related gene expression show poor prognosis and suppressed immune function. In another study, Qu et al., have shown that M2-like macrophage markers like PAM and LGALS3 expression positively correlate with the sensitivity of simvastatin and ARRY-162. Further, they have predicted ten anticancer drugs with higher sensitivity towards the high-mitophagy gene expression group. Further, Cao et al., have shown that March ligases expression regulates immune cell infiltration in HCC tumors. By utilizing the TCGA data set of liver cancer patients, Wang et al., have shown that genes related to copper metabolism correlate with immune infiltration in HCC. Their finding may be very useful in establishing the immunotherapy response biomarker. Liang et al., have shown that ferroptosis regulator membrane protein SLC7A11 exhibits the highest expression correlation with the immune checkpoint gene PD-L1. They have also established that SLC7A11 can serve as an independent prognostic signature itself for HCC patients. Furthermore, another study by Zhang et al., has shown that ferroptosis-related genes were significantly correlated with tumor immune infiltration and immune checkpoint genes expression. Long et al., have also explored the correlation of immune regulatory genes with HCC patients’ survival. Their study has demonstrated that 5 immune regulatory genes expression has significant predictive importance in HCC patients’ survival. In a review article Si et al., have discussed the importance of IL32 and IL34 expression in HCC pathogenesis and therapeutic targeting.Immune therapeutics are revolutionizing cancer treatment, so it’s high time to identify the novel immune modulators of HCC pathogenesis and potential immune therapy targets. in silico analysis of publicly available databases, and very limited validation has been done in laboratory conditions. Most of the studies are correlative, so it will be premature to conclude their direct role of a predicted gene signature in HCC pathogenesis. More preclinical and clinical studies are needed to validate these findings.In general authors of these articles have done molecular characterization of HCC patient samples gene expression, and immune infiltration and studied their impact on the prognosis of HCC patients. Some studies have explored the correlation between gene signatures and therapeutic response along with their prognostic values. The role of metabolic alteration-related genes, angiogenesis-related genes, and genes involved in different types of cell death such as cuproptosis and ferroptosis have been shown to possess prognostic value and correlate well with the different immune phenotypes of HCC tumors. A key limitation of most of the studies is that results are based on purely


The potential benefits of Reporting and Data Systems (RADS) are well known: improve the communication between the radiologists and physicians; reduce the omission of relevant information in reports; reduce the variability and errors in image interpretation; facilitate the monitoring of results and provide a tool to ensure quality and research. Furthermore, the slightest error in the interpretation of the legend describing the results of an imaging study can modify both the medical decision to start or not a treatment, and to do it with a more or less invasive technique.In this sense, for example, the American College of Radiology (ACR) started the development of the Breast Imaging Reporting and Data System (BI-RADS) in 1993. In recent years, several systems have been developed to diagnose other malignancies based on BI-RADS. However, its utility has yet to be demonstrated which is why scoring systems are continually being revised to apply them to daily clinical practice. The RADS systems developed so far are specially designed for breast, colorectal, gynecological, liver, lung, prostate and thyroid cancers.Incorporation of Reporting and Data Systems into Cancer Radiology” Research Topic. These manuscripts demonstrate how RADS benefit cancer patients, and how improvements to these systems can further benefit patients and optimize disease outcomes. For instance, in Wang et al., the authors investigated the value of contrast-enhanced ultrasound in the differential diagnosis and risk stratification of ACR TI-RADS category 4 and 5 thyroid nodules with non-hypovascular, establishing a risk score with ability to improve both aspects.These aspects are clearly reflected in the research papers accepted in the “Sun et al., it was evaluated the value of multiparametric magnetic resonance imaging (MIR) including synthetic MRI, diffusion-weighted imaging, dynamic contrast enhanced MRI, and clinical features in breast imaging–reporting and data system (BI-RADS) 4 lesions, and develop an efficient method to help patients avoid unnecessary biopsy.In Zhou et al., the authors established a predictive model incorporating clinical features and contrast enhanced ultrasound liver imaging- reporting and data system (CEUS LI-RADS) to improve the prediction of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) patients.In Singh et al., to minimize inter-radiologist variability, the diagnostic performance of an in-house developed semi-automated model using machine learning methods for prostate imaging-reporting and data system version 2.1 (PI-RADS v2.1) scoring was evaluated in prostate cancer patients. The authors in Meng et al., assessed the value of using quantitative parameters from synthetic magnetic resonance imaging (SyMRI) and the Kaiser score (KS) to differentiate benign and malignant breast lesions in patients, identifying that the incorporation of T1 values improves the sensitivity and specificity of the KS protocol alone.In Yang et al., a retrospective study was performed to create a predictive machine learning model based on liver imaging and reporting and data system (LI-RADS) features to identify microvascular invasion in hepatocellular carcinoma (HCC) patients, concluding that LI-RADS may help optimize the management of these patients.In Wu et al., the authors conducted a retrospective Chinese population-based study of patients screened for lung cancer by computed tomography to assess the correlation between the probability of lung cancer and the number of lung nodules, concluding that this probability does not change with the number but does change with the size of the nodules.Finally, in All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.


Thus, migratory behaviour neither weakens nor strengthens bird–haemosporidian cophylogenetic congruence, suggesting that other avian host traits are more influential in generating phylogenetic congruence in this host–parasite system.Parasites display various degrees of host specificity, reflecting different coevolutionary histories with their hosts. Avian hosts follow multiple migration patterns representing short but also long distances. As parasites infecting migratory birds are subjected to multiple environmental and biotic changes through their flyways, migration may disrupt or strengthen cophylogenetic congruence between hosts and parasites. On the one hand, parasites might adapt to a single migratory host, evolving to cope with the specific challenges associated with the multiple habitats occupied by the host. On the other, as migrants can introduce parasites into new habitats, higher rates of host switching could also disrupt cophylogenetic patterns. We analysed whether migratory behaviour shapes avian haemosporidian parasite–host cophylogenetic congruence by testing if contributions of host–parasite links to overall congruence differ among resident and short-, variable- and long-distance migrants globally and within South America only. On both scales, we found significant overall cophylogenetic congruence by testing whether overall congruence differed between haemosporidian lineages and bird species. However, we found no difference in contribution towards congruence among links involving resident  Using a worldwide avian haemosporidian database  collected from 347 different host species and representing 430 localities around the globe , 101 host species and 113 localities.We extracted the dataset on haemosporidian lineages from the MalAvi database  each represented ~25% of our global dataset with most tropical species (~67%) sampled in South America. Haemosporidian parasites and their avian hosts showed phylogenetic congruence greater than expected by chance on both global and regional scales .In the Bayesian models evaluating the effect of host migratory distance category on the squared residual values of each individual link , we found that hosts contribute equally to parasite–host cospeciation independently of whether or not they migrate, or their migration distance  and 2. Wet al., Parasite–host cospeciation occurs when both clades speciate in tandem, creating congruent phylogenies, which can occur due to neutral processes such as host dispersal and isolation or due to host-driven selection such as host defence (Clayton et al., et al., et al., et al., et al., et al., et al., et al., et al. (Plasmodium juxtanucleare, a haemosporidian parasite previously observed only in Galliformes, infected wild passerines in Brazil. Such events can disrupt cophylogenetic congruence, leading to apparent incongruence between haemosporidians and their hosts (Ricklefs et al., Host defences may favour parasite cospeciation and lead to congruent phylogenies between parasites and their hosts, if they select for specific counter-adaptations that limit parasite success to the original host species (Clayton , et al.  recentlyet al., et al., et al., et al., et al., et al., et al., Furthermore, we demonstrated that host migratory behaviour does not affect haemosporidian cophylogenetic congruence, suggesting that other host features can be more important in determining haemosporidian infection of novel hosts, such as cell invasion ability or immunological defence. Similarly, even though migrants can disperse haemosporidians (de Angeli Dutra et al., et al., Culex quinquefasciatus in Hawaii and New Zealand enabled the infection of local endemic and naïve fauna by Plasmodium species, especially the highly generalist Plasmodium relictum (Warner RE, et al., Vectors can also play a fundamental role in determining haemosporidian parasite transmission in nature (Yan et al. (Leucocytozoon, another related genus of avian haemosporidian parasites. As we also observed, host phylogeny influenced parasite–host cophylogeny in all models, indicating that other phylogenetically conserved host traits may contribute towards parasite–host cophylogeny. However, the narrower climatic niche and higher host specificity of Leucocytozoon spp. (Valkiūnas, et al., et al., et al., Leucocytozoon parasites, whereas migrants may be exposed to parasites from multiple regions and continents. This pattern could also lead to links involving associations between Leucocytozoon lineages and resident hosts contributing more towards cophylogenetic congruence compared to those involving migrant hosts. It is worth mentioning, however, that our relatively small number of migrants, especially for the South American analyses, might have hidden an association between migratory status and haemosporidian–bird cospeciation.It is important to note, however, that Jenkins et al.  identifiPlasmodium and Haemoproteus separately. Nonetheless, we detected an effect of host phylogeny on host–parasite cophylogenetic congruence, suggesting that congruence among parasites and their hosts may be linked to other host traits, and possibly also to vector specificity. It must be noted that, despite the fact haemosporidians and their avian hosts appear to have coevolved, these parasites are still capable of switching to phylogenetically distant hosts (Ferreira-Junior et al., Here, we demonstrate that haemosporidian parasites and their avian hosts generally share a common evolutionary history and show significantly congruent phylogenies. Furthermore, we also found that bird migration is not weakening or strengthening the congruence observed between parasites and their hosts, even when considering different spatial scales or the genera


Coxiella, Francisella, Rickettsia or Candidatus Midichloria mitochondrii endosymbionts, indicative of their importance to tick physiology. Genomic and experimental data suggest that endosymbionts promote tick development and reproductive success. Here, we review the limited information currently available on the potential roles endosymbionts play in enhancing tick metabolism and fitness. Future studies that expand on these findings are needed to better understand endosymbionts’ contributions to tick biology. This knowledge could potentially be applied to design novel strategies that target endosymbiont function to control the spread of ticks and pathogens they vector.Ticks transmit pathogens and harbour non-pathogenic, vertically transmitted intracellular bacteria termed endosymbionts. Almost all ticks studied to date contain 1 or more of  There are 2 main tick families Ixodidae (hard ticks), which possesses a sclerotized hard shield called scutum, and Argasidae (soft ticks), which lacks scutum , Francisella endosymbionts (FEs), Rickettsia endosymbionts (REs) and Candidatus Midichloria mitochondrii (CMM)  and hard ticks   and the argasid tick O. amblus (CLEOA) revealed that they have complete pathways to produce thiamine (vitamin B1), riboflavin (vitamin B2), niacin (vitamin B3), biotin (vitamin B7) and folate (vitamin B9)  and pyridoxine (vitamin B6)  and A. sculptum (CeAS-UFV) have complete pathways to synthesize riboflavin, biotin and folate and partial pathways for niacin, pantothenic acid and pyridoxine  has complete pathways for the synthesis of riboflavin, pyridoxine, biotin and folate and a partial pathway for the synthesis of thiamine , A. maculatum (FLE-Am) and F. persica, the endosymbiont of the soft tick Argas arboreus, showed that they possess complete pathways for the synthesis of riboflavin, biotin and folate  but F. persica seems to only possess a partial pathway for this process  and CLEAA, CLEOA and CERM possess complete pathways to produce lipoic acid , NADP+, pyridoxal 5′-phosphate, S-adenosyl-L-methionine and thiamine diphosphate .Many cofactors and coenzymes that are critical to the functioning of essential enzymes are derived from B vitamins Douglas, . Severalin silico flux balance analyses of CRt and CE of R. sanguineus (CRs) identified excessive production of the amino acid proline, which is thought to play a significant role in arthropods due to its involvement in energy production and nitrogen metabolism  to O. moubata restored its reproductive fitness, indicating a role for FLE-Om in provisioning B vitamins required for normal tick development and reproduction , which in turn reduced the blood intake of the tick (Zhong et al., et al., H. longicornis, administration of antibiotics to R. sanguineus and R. microplus also reduced the density of CEs and tick blood intake, and transcriptomic analysis of CERM-free R. microplus metanymphs revealed that genes associated with tick blood-feeding capacity such as DAP-36, lipocalin, trypsin inhibitor-like family, Kunitz-type inhibitors, cystatin and evasins were significantly under-expressed (Guizzo et al., et al., et al., et al., Experiments also suggest that endosymbionts may contribute to the blood-feeding capacity of ticks . TreatmeI. ricinus and feeding females with tetracycline-containing bovine blood produced CMM-free ticks within 2 generations. Larvae that hatched from eggs laid by CMM-free females consistently performed poorly during blood feeding, suggesting that CMM is required for the emergence of larvae with intact blood-feeding ability (Guizzo et al., I. ricinus nymphs fed with gentamicin-treated blood had significantly lower engorgement weights, lower moulting proportions and lower weights of moulted unfed adult females in comparison to nymphs fed on antibiotic-free blood (Militzer et al., Francisella symbionts in H. doenitzi significantly increased in number during blood feeding, and Rickettsia sp. phylotype G021 and CMM multiplied massively in I. pacificus and I. ricinus, respectively, following blood meals (Sassera et al., et al., et al., CMM is the most common endosymbiont associated with D. variabilis and A. americanum larvae infected with Rickettsia symbionts displayed increased motility than uninfected larvae [42]. The locomotive ability of newly hatched larvae was determined on flat and inclined surfaces and Rickettsia-containing larvae displayed increased locomotive speed relative to uninfected larvae. Tick motility plays a role in host-questing success; thus, infection with Rickettsia symbionts may impact the disease risk posed by tick-borne pathogens.Finally, et al., et al., et al., et al., Coxiella, Francisella and Candidatus Midichloria branches (Epis et al., et al., et al., et al., In summary, a major function of tick endosymbionts seems to be the provisioning of B vitamins, especially riboflavin, biotin and folate . B vitamet al., et al., C. burnetii and F. tularensis are not vertically transmitted (Genchi et al., et al., Relatedly, another aspect of tick biology that we do not fully understand is how CEs and FEs evolved from pathogenic ancestors (Gerhart C. burnetii and F. tularensis (Zogaj and Klose, et al., In addition to vertical transmission, an essential factor that sustains endosymbiosis is the presumed dependence of ticks on nutrients provided by endosymbionts. Going forward, functional studies to identify specific metabolites that sustain tick–endosymbiont relationships should be prioritized. Developing genetically tractable tick–endosymbiont model systems would accelerate this area of research by facilitating the disruption of endosymbiont genes to assess their impact on tick physiology and fitness. Although methodologies to culture and genetically manipulate CEs or FEs have not yet been developed, genetic tools and culture media are available for related pathogens et al., et al., et al., Future functional studies should also device alternatives to the current practice of using antibiotics to generate endosymbiont-free ticks. This is because antibiotics may eliminate other members of the tick microbiota, thus making it difficult to determine whether any observed effect is solely due to the loss of the endosymbiont. Another key aspect to consider while investigating endosymbiont function is the potential contributions made by the rest of the tick microbiota towards tick physiology. For instance, gut microbiota may modify metabolites present in blood meal to make them amenable for use by tick or endosymbiont. Similarly, antibacterial peptides produced by the tick innate immune system in response to gut bacteria could impact the location and functions of tick endosymbionts (Narasimhan et al., Lastly, targeting keystone taxa among tick microbiota is an innovative approach to inhibit the spread of ticks. Recent studies showed that microbiota were disrupted in ticks fed on blood from mice vaccinated against keystone taxa (Mateos-Hernández


Integrative neuroscience involves investigations into the sensory, motor, and cognitive systems. In contrast, translational neuroscience moves fundamental knowledge and interdisciplinary discoveries into clinical practice or applications to benefit human health. Bridging the gap between both fields could profoundly impact our comprehension of brain function and clinical applications . SpecifiFujiki et al., introduced the “quadripulse theta burst transcranial magnetic stimulation” (QTS), a new way to overcome failure rates in producing motor evoked potentials by transcranial magnetic stimulation. These authors employed a similar stimulation pattern as in previous studies (Szelényi et al., Chandrasekaran et al. introduced a novel, highly flexible spinal electrode array for cervical dorsal root stimulation employed in people with motor complete spinal cord injury. This targeted stimulation increased volitionally generated force and tactile sensations within a 6–8-week period, but only in particular muscles showing discernable force production during the pre-intervention assessment. These results are comparable to those found by other authors (Freyvert et al., The first two papers in this Research Topic have reported new methods to push the limits of precision in brain and spinal cord neurostimulation. They are relevant because non-invasive neurostimulation of the brain, peripheral nerves, and the spinal cord has unprecedented clinical interest. In this context, Soto et al. is a review covering the development of new active vestibular implantable devices to regain or modulate specific systemic functions. Like cochlear implants, pacemakers, or deep brain stimulators, the vestibular neuroprostheses are a strong example of how bridges between integrative and translational neuroscience are needed to achieve beneficial breakthroughs that will impact the lives of individuals. Vestibular dysfunction affects over 1.8 million people worldwide (Chow et al., The third paper by Ilic et al. deals with visual imagery in dreams of congenitally blind people. This theme is controversial (Andrade, Ilic et al. in this Research Topic analyses studies on the presence and nature of visuospatial imagery in dreams of blind people to elucidate how blind people “see”, whether they may recreate visuospatial imagery via sensory substitution, and whether they can dream in images. At the neurophysiological level, neuroimaging and sensory substitution studies suggest that the “blind” occipital cortex may be able to integrate non-visual sensory inputs, generating visuospatial impressions and enabling the development of a typical spatiotemporal organization of early visual areas even in the life-long absence of vision. This could explain the ability of some congenitally blind individuals to draw symbolic representations of various visual images in striking likeness to those drawn by normally sighted. Therefore, elucidating the mechanistic nature of visual impressions could open new translational possibilities for treating these neuro-disabilities.The fourth article by Andrade, . It has Mesmoudi et al. presented another interesting research covering the gap between integrative neuroscience and translational neuroscience in the context of the recent global health crisis of COVID-19, in which the discovery of ACE2 receptor mechanisms played a fundamental role in understanding this sickness. They employed data on mRNA expression levels of genes provided by the Allen Institute for Brain Science. Moreover, the localization of brain functions was provided by the LinkRbrain platform. These authors investigated which cognitive and sensorimotor functions are associated with the brain regions where ACE2/TMPRSS2 is overexpressed, hypothesizing that the infection might particularly affect them. The results show that central regions specific to ACE2 and MPRSS2 were localized in the brain stem, the subcortical, the orbitofrontal, and some occipital areas (see also Chen et al., Finally, In conclusion, these five papers, taken together, emphasize that we must bridge the gap between knowledge and practice, between theory and therapy. Thus, the synergy between integrative and translational neuroscience involving new neurotechnological developments could serve as the bridge that will lead us to a future where neurological conditions are better comprehended and more effectively treated. As we persist in exploring the frontiers of the brain, let us bear in mind that we could discover the key to unlocking the full potential of neuroscience for the benefit of humanity through the fusion of these two established disciplines.EM: Writing—review and editing. GC: Writing—review and editing. KS: Writing—review and editing. AL: Writing—review and editing.


Wnt signaling in endocrine and metabolic disorders” aims to emphasize the functional role of the Wnt signaling pathway in human endocrinology, focusing on metabolic disease. Endocrine and metabolic disorders encompass a wide range of conditions affecting various organ systems and physiological processes. The Wnt signaling pathway, originally recognized for its role in embryonic development and tissue homeostasis , used for more than 1,300 years in China as a treatment for lumbodynia, may exert its therapeutic effect on steroid-induced ischemic necrosis of the femoral head, is through targeting exosomal microRNAs (miRNAs) to regulate multiple signaling pathways, including Wnt, PI3K-Akt, and MAPK . In another original report investigating miRNAs and Wnt signaling, Tripathi et al. demonstrate that miR-539-3p overexpression in osteoblasts downregulates several components of the Wnt signaling pathway and deteriorates trabecular microarchitecture, leading to decreased bone formation in ovariectomized mice. In the third original article in our Research Topic, a group of investigators led by Xiaolin Tu found that the small molecule C91 (CHIR99021) promotes osteogenic differentiation of bone marrow stromal cells via the activation of Wnt signaling .The first study in this Research Topic clarified that one of the mechanisms by which the “Vilaseca et al. provide an interesting overview of the functional roles of estrogen deficiency in the processes involved in the development of Alzheimer’s disease, including Wnt signaling and glucose transport in the brain, amyloid precursor protein processing to form senile plaques, and Tau phosphorylation forming neurofibrillary tangles.Franco et al. elegantly explain the main differences between the physiological roles of canonical Wnt signaling  and its pathological involvement in the development of several human diseases, including cancer. Correctly interpreting the molecular bases of Wnt signaling and metabolism, ideally in a cell-type and tissue-specific manner (Franco et al.; A very comprehensive review concludes our Research Topic: In conclusion, understanding the intricate interplay between Wnt signaling and endocrine/metabolic disorders holds great promise for the development of targeted therapies and improved patient outcomes.FC: Writing – review & editing. GS: Writing – original draft


However, in vivo validation is currently lacking. A previous metatranscriptomics study into the cause of idiopathic chronic diarrhoea in macaques reported the presence of an unidentified protozoan parasite related to Trichomonas vaginalis. In this work, we performed a reanalysis of the published data in order to identify the parasite species present in the macaque gut. We also leveraged the information-rich metatranscriptomics data to investigate the parasite behaviour in vivo. Our results indicated the presence of at least 3 genera of Trichomonad parasite; Tetratrichomonas, Pentatrichomonas and Trichomitus, 2 of which had not been previously reported in the macaque gut. In addition, we identified common in vivo expression profiles shared amongst the Trichomonads. In agreement with previous findings for other Trichomonads, our results highlighted a relationship between Trichomonads and mucosal bacterial diversity which could be influential in health and disease.Trichomonads, anaerobic microbial eukaryotes members of the phylum Parabasalia, are common obligate extracellular symbionts that can lead to pathological or asymptomatic colonization of various mucosal surfaces in a wide range of animal hosts. Results from previous  The vast majority of this work has focused on the human sexually transmitted parasite Trichomonas vaginalis. However, the importance of the proposed mechanisms during colonization of the complex mucosal environment in vivo is unclear. Validation of hypotheses in the natural setting is essential to avoid misinterpretation of results  microbiota  were used to examine Parabasalia gene expression. For transcript annotation, assembled parasite contigs were aligned to the T. vaginalis G3 annotated proteins  and Table S3 .A et al., de novo assembled contigs homologous to Parabasalia genes of interest, with E value, percentage identity and query coverage cut-off values of 1 × 10−10, 88% and 90%, respectively. To broaden the taxonomic sampling for genes of interest, additional homologues were identified by consulting the literature and through the use of online BLAST . Summary statistics for the dataset and assembly are presented in Table S1. The de novo assembly is available in Data file S2.We aimed to investigate the identity of Trichomonad parasites reportedly present in this dataset (Westreich α) loci to identify the Parabasalia colonizing the macaque gut. Amongst all the samples, we assembled 58, 10 and 11 18S rRNA, actin and EF-1α sequences, respectively, which shared greater than 88% sequence identity with reference Parabasalia sequences for at least 90% of their length (Table S2). We assessed the diversity of sequences present by maximum likelihood analysis and identified 10 well-supported clades for the 18S rRNA locus , 4 for the actin locus , and 1 for the EF-1α locus . We generated phylogenies using representative sequences from each clade alongside a range of Parabasalia reference sequences in order to refine the identity of the parasite sequences. Analysis of a single representative sequence from each of the 18S rRNA sequence groups revealed at least 3 major lineages, related to Tetratrichomonas, Pentatrichomonas and Trichomitus spp., with strong bootstrap support only present for the latter  parabasalid genera which were identified , followed by Pentatrichomonas (mean abundance 0.025%) and Tetratrichomonas (mean abundance 0.020%). A substantial number of sequences (mean abundance 0.093%) were identified as parabasalid in origin but could not be assigned to a particular genus. Unidentified parabasalid reads appeared more abundant among animals in which Tetratrichomonas, Pentatrichomonas or Trichomitus classified reads were abundant, likely suggesting that they originated from 1 or more of these genera.To taxonomically assign the metatranscriptome reads, we included entified . AccordiTrichomonas (mean abundance 0.019%). This most likely reflects the greater representation of Trichomonas whole genome sequences available in the reference database, including T. vaginalis and T. gallinae, whereas the genera of interest were only represented by in vitro RNA-Seq data, which is likely to have an incomplete gene content. However, while it cannot be ruled out that Trichomonas spp. were present amongst the samples, we have focused our analysis on the most likely genera based on the phylogenetic results. Only 2 control macaques showed a total abundance of Parabasalia greater than 0.125%, limiting the statistical power for tests correlating variables with Parabasalia abundance amongst the control animals.In addition, a notable fraction of reads were classified as et al., We focused on the most abundant putative Parabasalia-derived contigs to explore the most biologically important functions, which are summarized in Trichomitus with strong support, and an additional contig NODE_1833 may have originated from Pentatrichomonas or Tetratrichomonas, although this was poorly supported. In addition, we identified a contig with high similarity to T. vaginalis coronin, an actin-binding protein implicated in phagocytosis . Results suggested that the lysozyme-like contig NODE_2008 originated from T. vaginalis genes previously implicated in pathobiology. Of particular interest for parasite adhesion to host or microbial cells . Cysteine peptidases are also implicated in Trichomonas pathobiology , a secreted cysteine peptidase demonstrated to induce host cell apoptosis  based on the microbial profile showed clear separation between the healthy and ICD groups. The macaques with ICD appeared to resolve into 3 subgroups, potentially indicating distinct microbial communities . An obvibundance . Of partP values derived from linear regression ranged from 0.21 to 0.27), although this is likely to have been influenced by the Parabasalia scarcity amongst the control animals , whereas Parabasalia abundance did not . Intriguingly, ICD macaques with greater Parabasalia abundance appeared to more closely resemble control macaques in terms of alpha diversity.Our results suggested a possible relationship between parasite abundance and microbiota diversity. Amongst the macaques with ICD, there was a significant positive relationship between Parabasalia abundance and microbial alpha diversity measures . There was also a significant negative relationship between Parabasalia abundance and Simpson evenness, indicating a more non-uniform distribution of abundance amongst microbial taxa in animals with greater abundance of Parabasalia . However animals . In addivs all correlation analysis at the genus level. We focused on the macaques with ICD and included only the most abundant taxa (greater than 0.005% in at least 1 sample). Amongst 358 taxa, with a total of 64 261 possible interactions, our results indicated 11 606 significant abundance correlations between genera. Of the 3 parabasalid genera of interest, Tetratrichomonas showed the greatest number of significant correlations with bacteria (110) followed by Pentatrichomonas (53), and Trichomitus, which showed far fewer significant correlations (17). Tetratrichomonas and Pentatrichomonas substantially overlapped in terms of bacterial genera showing significant positive and negative correlations, possibly indicating shared relationships with bacteria. In contrast, Trichomitus did not share common negative or positive relationships with any bacterial genera with either of the other parabasalid genera , with a moderate network clustering coefficient of 0.431, indicating a greatest potential interdependence with bacteria. Within network 3, the closeness centrality of Tetratrichomonas was 0.465, the 10th highest in the 41-node network, suggesting a relatively central hub-like position in comparison to most bacterial nodes. In contrast, Pentatrichomonas (network 7) and Trichomitus (network 23) inhabited smaller and more sparsely interconnected components, with 7 and 2 genera, respectively.To investigate specific interactions between Parabasalia and bacterial members of the microbiota, we performed an all d genera . Amongstmponents . Of the Tetratrichomonas and Pentatrichomonas were Gram negative, but this pattern did not extend to Trichomitus , 5 out of 53 for Pentatrichomonas  and 2 out of 17 for Trichomitus . This may indicate that the microbial community structure and interdependence was dramatically different between the ICD and control conditions.The majority of relationships identified amongst the macaques with ICD were not consistent amongst the control group. Only 1188 out of 11 606 total significant relationships for the macaques with ICD were homodirectionally concordant amongst the control animals, including 2 out of 110 relationships for Tetratrichomonas and Pentatrichomonas , but not Trichomitus, amongst the macaques with ICD compared with the healthy controls. The original authors ruled out several known common GI pathogens  as the cause of ICD by culture and microscopy-based methods. To complement this, we searched the dataset for potentially pathogenic viral lineage amongst the taxonomic profile. We focused on a selection of 29 potential primate-infecting eukaryotic viruses which we identified by the literature search .We performed a differential abundance analysis between the ICD and control groups in order to investigate any potential impact of the parabasalids on disease aetiology. Interestingly, differential abundance analysis suggested a moderate significantly higher abundance of Tetratrichomonas abundance . We identified a significant negative relationship between the abundances of 12 MetaCyc pathways and that of Tetratrichomonas amongst the macaques with ICD  and glycogen storage and processing (Müller, et al., T. vaginalis BspAs have been implicated in host adhesion in vitro (Handrich et al., T. vaginalis BspAs are differentially expressed in response to Mycoplasma symbionts, suggesting a potential role in parasite–bacteria interactions in modulating parasite binding to host cells (Margarita et al., Our results suggested commonality in the expressed functional genes across the Trichomonads. We observed similar energy generation mechanisms for the macaque-infecting parabasalids as have been previously reported for et al., et al., et al., et al., et al., Trichomitus, our results suggested Tetratrichomonas had the greatest abundance correlation with differences in the microbiota. Tetratrichomonas participated in the greatest number of significant abundance correlations, and was a central node within a densely interconnected microbial positive correlation network. Correlation networks have been effectively utilized to identify keystone species within microbial communities with biological significance (Duran-Pinedo et al., Pentatrichomonas and Tetratrichomonas. In addition, of particular interest, a positive abundance correlation with Prevotella, which we observed for Tetratrichomonas in the macaque gut, has been described for T. vaginalis in the human UGT (Martin et al., et al., Tetratrichomonas and Pentatrichomonas were Gram negative. This is notable because other Trichomonads such as Dientamoeba fragilis (Chan et al., in vitro growth. Microbial interactions identified in this study varied hugely between the diseased and healthy conditions, similarly to previous results from the healthy and diseased human oral microbiota (Duran-Pinedo et al., et al., et al., Our results also indicated a potential influential interaction between Trichomonads and microbial diversity in the macaque gut, as has been reported for other hosts and mucosa (El Sayed Zaki et al., et al., et al., T. vaginalis (Pinheiro et al., Trichomitus, whereas Tetratrichomonas was the only Trichomonad genus correlated with bacterial functional expression. Negative correlation of Tetratrichomonas abundance with bacterial degradation pathways for monosaccharides such as GlcNAc and Sia5NAc, potentially derived from mucin glycoproteins (Yurewicz et al., et al., Previous studies have suggested the interaction between Trichomonads and the vaginal microbiota is bidirectional. The microbial profile can influence the ability of Trichomonads to colonize the mucosa (Rathod Campylobacter genus amongst the animals with ICD was originally reported (Westreich et al., Pentatrichomonas and Tetratrichomonas could indicate a causal role in disease. High P. hominis abundance in macaques with ICD was previously reported, but not causally liked to disease (Laing et al., et al., T. gallinae and Tritrichomonas musculis decreases GI microbial diversity (Ji et al., et al., et al., The absence of several known GI bacteria pathogens and microbial parasites was confirmed by culture and microscopy-based methods, and thus may be excluded as causative agents of ICD in the macaques. We performed an additional search for potentially pathogenic viruses amongst the datasets. However, we did not identify any clear differences for any putative host-infecting virus when comparing between diseased and control animals, suggesting viral infection may not be the primary cause of ICD. A greater abundance of reads classified as originating from the in vivo. Reference sequences from closely related parasite strains would also have greatly facilitated analysis (Breitwieser et al., in vivo metatranscriptome (Li et al., Our results revealed a relatively low parasite abundance in the macaque fecal samples, highlighting the need for greater sequencing depth or selective target enrichment (Gaudin and Desnues, in vivo insight into Trichomonad mucosal colonization, which validates numerous in vitro studies (Müller, et al., et al., et al., et al., et al., In summary, these metatranscriptomics analyses of Trichomonads in the macaque gut have provided the first


The unprecedented global climate change has severely impacted our environment and engendered severe threats to agricultural productivity . This haThe advancements in genomics and gene editing technologies have offered immense opportunities and potential solutions for the genetic improvement of crops . A plethThe deployment of these technologies has laid down the foundation of modern breeding for effectively channelizing the underutilized diversity hidden in the crop wild relatives into elite gene pools . The advDhakate et al., “Advances in crop breeding through precision genome editing” by Nerkar et al. and “Integrating CRISPR-Cas and next-generation sequencing in plant virology” by Mushtaq et al. that have very well built up the narrative of the Research Topic. The other crop-specific comprehensive reviews entitled “CRISPR for accelerating genetic gains in under-utilized crops of the drylands: progress and prospects” by Sharma et al., “Recent advances in date palm genomics-a comprehensive review” by Rahman et al., “Unclasping potentials of genomics and gene editing in chickpea to fight climate change and global hunger threat” by Singh et al., “A CRISPR way for accelerated improvement of cereal crops” by Basu et al., “CRISPR/Cas genome editing system and its application in potato” by Zhang et al., “Physiological and molecular basis of drought and heat stress tolerance to enhance productivity and nutritional quality of peanuts in harsh environments” by Puppala et al., “A perspective on selectable marker-free genome engineered rice: past, present and future scientific realm” by Singh et al. and “CRISPR/Cas genome editing in potato: current status and future” by Tiwari et al. provide an up-to-date detailed compilation of the published research in date palm, dry-land crops, peanuts, chickpea, potato, and rice.In this Research Topic, we have collated a total of 19 articles, including original research and review articles, to get an essence of the spectrum of current efforts undertaken by applying modern tools for crop trait improvement. To develop a background on the theme, we have included three review articles entitled “Comprehending the evolution of gene-editing platforms for crop trait improvement” by Dhakate et al., Tiwari et al. and Basu et al. have comprehensively reviewed the evolution of CRISPR/Cas systems into new-age methods of genome engineering across various plant species and the impact that they have had on tweaking plant genomes and associated outcomes on crop improvement initiatives. Hou et al. reviewed the four types of CRISPR/Cas structures and mechanisms available today and the application of CRISPR/Cas9 systems in overcoming the challenges of self-incompatibility and improving the quality and resistance of potato. The review describes how precise knocking or targeted mutagenesis of S-RNase and Sli genes using CRISPR/Cas9 has helped to create self-compatible and self-incompatible potatoes, respectively. Additionally, the suitability of CRISPR/Cas9 and CRISPR/Cas13a systems in knocking out more than 22 genes has been detailed. Kor et al. have described the role of RNA Pol III promoters in precisely targeting genetic variants in genome editing. Nerkar et al. has focused on the advancements in crop breeding through precision genome editing. This review has included an overview of different breeding approaches for agronomic traits such as disease resistance, abiotic stress tolerance, herbicide tolerance, yield, and quality improvement, reduction of anti-nutrients, improved shelf life; genome editing tools and approaches used for crop improvement and an update on the regulatory approval of the genome-edited crops. Sharma et al. has described the opportunities of implementing genome editing technologies in under-utilized crops to increase genetic gains.There has been continuous evolution in the development of gene editing-based technologies involving CRISPR/Cas platforms. Traditionally used CRISPR/Cas nucleases followed Sequence-Specific Nucleases (SSNs) such as Zinc-Finger Nucleases (ZFNs) and Transcription Activator-Like Effector Nucleases (TALENs), and led to domains such as epigenome editing, base editing, and prime editing. Zang et al. generated Nud mutants in wheat (TaNud) and barley (HvNud) using CRISPR/Cas9-based gene editing and investigated the heritability of the mutations in wheat. Nud gene is a transcription factor controlling the formation of the caryopsis, and loss-of-function mutation in the gene leads to the naked hull phenotype in barley. With the latest CRISPR/Cas9-based gene editing, combined with PCR-RE (polymerase chain reaction-restriction enzyme) approach, Zang et al. achieved a high editing efficiency (51.7%) of the three Nud alleles/homologs in wheat. This study has proven that with the improved vector system and CRISPR/Cas technology, it is not difficult to achieve precise genetic modification even in complex polyploid crops such as wheat which remained calcitrant to genetic modification technologies for a long time.Ravikiran et al. comprehensively investigated genetic variation in RSHT tolerance with the GWAS approach using the cutting-edge genotyping arrays available in rice. They utilized three GWAS models to identify significant marker-trait associations (MTAs) for spikelet fertility and grain yield. Most significantly, the authors reported a set of stable MTAs for both traits, showing an advantage of 6–10 g for yield and up to 28% for spikelet fertility. Additionally, they identified promising tolerant genotypes that carried favorable alleles of 29, 28, 25, or 24 putative MTAs, which could serve as new donors in nurseries.Heat and drought stresses cause substantial yield losses to crop production. According to the latest estimates, the heatwave episodes will particularly intensify in the Indo-Gangetic plains of India, which supports rice–wheat cropping system . SimulatPuppala et al. focuses on the significant progress that has been made towards the characterization of germplasm for drought and heat stresses tolerance and identifying MTAs and QTLs associated with drought tolerance. Advances in phenomics and artificial intelligence to accelerate the timely and cost-effective collection of phenotyping data in large germplasm/breeding populations are also reviewed and discussed. A holistic breeding approach that considers drought and heat-tolerant traits to simultaneously address both stresses is introduced as a successful strategy to produce climate-resilient peanut genotypes with improved nutritional quality.Peanuts exposed to drought stress at the reproductive stage are prone to aflatoxin contamination, which imposes a restriction on the use of peanuts as health food and also adversely impacts the peanut trade . The revKumar et al. reported development of bread wheat variety HD3411 following marker-assisted backcross breeding for drought tolerance. They reportedly transferred four drought tolerance quantitative trait loci (QTLs) controlling traits, viz. canopy temperature, normalized difference vegetative index, chlorophyll content, and grain yield from the drought-tolerant donor line, C306 into a popular high-yielding, drought-sensitive variety HD2733. Marker-assisted selection coupled with stringent phenotypic screening was used to develop a promising genotype, HD3411. The line HD3411 has shown higher yield over selected cultivars and has been identified for varietal release and testing in the northeastern plain zone of the wheat-growing region in India.Mushtaq et al. have shown that the NGS coupled with CRISPR-based genome editing have enabled rapid engineering of resistance by directly targeting specific genomic sites of plant viruses and viroids. They also discussed the emerging developments in NGS technologies and CRISPR/Cas-based DNA or RNA tests for the characterization of plant viruses along with their potential advantages and limitations. Kaur et al. employed BSA-seq approach in a wild species of rice Oryza glaberrima and identified a novel locus on chromosome 6 for resistance to root-knot nematode (Meloidogyne graminicola). They reported 3 potential candidate genes within QTLs qNR6.1, qNR6.2 and qNR2.1. This research has expanded the breadth of genes available for resistance to root-knot nematode and the possibilities of deploying new genes in rice breeding.Besides abiotic stresses, plant disease outbreaks threaten global food security significantly. The crop pathogens are responsible for a substantial reduction in global crop yield and productivity. The global burden of viral, bacterial and fungal pathogens in farmers’ fields ranges between 20% and 30% . It poseMontesinos-López et al. in the article “A general-purpose machine learning R library for sparse kernels methods (SKM) with an application for genome-based prediction” demonstrated the usefulness of six machine learning models based on sparse kernel algorithm in two major crops, wheat and maize. Most importantly, this new package with six models allows user to use different formats of data, i.e., binary, categorical, count and continuous response variables. Recently, ML models are also being explored to resolve the off-target problems associated with CRISPR-Cas9. An article on ‘Machine learning in the estimation of CRISPR-Cas9 cleavage sites for plant system’ by Das et al. developed models on three ML-based techniques to estimate the cleavage sites of a given sgRNA. Out of the 11 trained models, the models based on the random forest technique, Artificial Neural Networks (ANN1-ReLU) and Support Vector Machine (SVM-Linear), performed better in the estimation of CRISPR-Cas9 cleavage sites showing an accuracy of 96.27%.Machine learning (ML) and artificial intelligence (AI) algorithms have been increasingly used nowadays to improvise genomic prediction models to predict the phenotypes of newly developed breeding lines. Punica granatum L.) breeding programs. The genetic architecture of seed-type trait has not been investigated much using modern approaches, and this has hampered the development of farmer-preferred and commercially viable pomegranate varieties. The recent advances in whole genome sequencing and transcriptome profiling in pomegranate have opened vistas for large-scale discovery of markers for trait discovery and improvement. A previous study in pomegranate had identified novel pre-miRNAs for seed-type trait in pomegranate . We believe that the articles compiled in this Research Topic will expand the existing knowledge on the strategies of crop improvement to mitigate climate change and ensure future food security.To summarize, a diverse collection of research and review articles included in this Research Topic has generated valuable information on the development of genetic and genomic resources in a variety of cereals , legumes (chickpea and peanut), fruit  and underutilized dryland crops. While, the review articles presented information on the evolution and refinement of new-age genomics, genome editing, and genome prediction models based on ML and AI algorithms for crop improvement, the research articles involved their application culminating into disease resistant, drought and heat resistant, high yielding crop varieties for instance line HD3411 in wheat (


Trianthema portulacastrum Linn. on dermal wounds via removal of oxidative stress and inflammation’ by Ekta Yadav et al., RSC Adv., 2018, 8, 21621–21635, https://doi.org/10.1039/C8RA03500H.Correction and removal of expression of concern for ‘Ameliorative effect of biofabricated ZnO nanoparticles of  The authors regret that there was an error in This correction supersedes the information provided in the Expression of Concern related to this article.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.


Objective of the present analysis is to represent the phenomenon of Heat–mass transfer on MHD micro polar fluids caused by permeable and continuously stretching sheet along with slip impacts fostered in a porous medium. Consequently, the equation of energy includes the term of non-uniform heat source/sink. The equation regarding species concentration in cooperates the terms indicating order of chemical reaction to characterize the chemically reactive species. The application software MATLAB with governing syntax of bvp4c technique are employed to reduce equations of momentum, micro-rations, heat, and concentration into suitable required simplifications to derive necessary arithmetic manipulations of available non-linear equations. Various dimensionless parameters are portrayed in the available graphs with essential consequences. Analysis discovered that micro-polar fluid improves velocity and temperature profile while it suppresses micro-rations profile also magnetic parameter ( Investigations of micro polar fluids are of significant recognition because of numerous applications in various industries particularly suspension solutions, solidification of liquid crystals, animal bloods, and exotic lubricants. Bhargava and Takhar2 explored heat transfer of the micro-polar boundary layer (BL) near a stagnation point on a moving wall. Anika et al.3 analyzed consequences of thermal diffusion on the unsteady viscous MHD micro-polar fluid flow past an infinite plate together with hall and ion-slip current. Bhargava et al.4 performed numerical investigations for micro-polar transfer phenomena prompted by non-linear stretching sheet availing two distinct techniques of finite element and finite difference. Takhar et al.5 exercised mixed convection in MHD flow of micro-polar fluids across the stretchy sheet. Bhargava and Rana et al.6 examined nonlinear convective heat and mass transfer in a micro-polar fluid with continuously variable conductivity by employing the objectives of finite element technique.In recent past academic attainment of micro-polar fluid has drawn attracted attention among several engineering community and scientist community as a reason of its limited circumference associated with Newtonian fluids. These fluids are influentially determined by spin inertia and reinforces stress moments and body moments. The theory of microfluids is identified as complex theory against the case of constitutively linear theory and the corresponding underlying mathematical manipulations are not easily amenable to the solution of non-trivial problems in this field. A subclass of these fluids is defined as the micropolar fluids that exhibits micro-rotational effects and micro-rotational inertia. The classical framework of Navier–Stokes model founds certain degree of limitation particularly listing as it cannot describes and elaborates the category of fluids pertaining microstructure characteristics, fluids possessing effective and influential applications. Therefore, analysis of micro polar fluids suggested by Eringen7 has fascinated many researchers to investigate alike problems on the boundary layer (B.L.) flow due to a stretching sheet, as it has numerous applications in industry like the extrusion of polymer sheet by a dye, crystal growing, continuous casting and drawing of plastic films. The pace of cooling and the stretching process are the only factors that directly affect the desired properties of the finished product. The stretching sheet may not be necessarily linear, as we can take in nonlinear fashion also, even though problem may not have noticeable technological relevance. In view of this, Vajravelu8 proposed the flow across a nonlinearly stretching sheet, while Cortell10 studied the flow and heat-transport caused by a stretching sheet for two unalike types of thermal boundary (TB) conditions on the sheet, viz., constant surface temperature (CST) and prescribed surface temperature (PST). Ganji et al.11 reported analytical solution for magneto hydrodynamic flow due to a stretching sheet in nonlinearly manner. Similar work has been studied by Ishak et al.12, Prasad et al.13, Van Gorder et al.14, Raftari et al.15, Abbas and Hayat16, Dadheech et al.17, Olkha et al.18 and Abel et al.19, among others.The flow of fluid across continuously stretching sheet under the influence of available magnetic field has significant emphasis on several domains of engineering particularly plasma investigations, geothermal energy extraction etc. Investigations pertaining to MHD effects on flow of fluid under consideration past a stretching sheet are indexed in an open literature. The first study by Crane20 examined chemically reactive species diffusion due to a plane elastic surface. Abo-Eldahab and Salem21 studied flow and heat transfer of non-Newtonian power law fluid flow with mass diffusion and chemical reaction on a moving cylinder under consideration of magnetic field effect. Chauhan and Jakhar22 reported 2D non-Newtonian flow and heat transport in a channel with suction at the top and a naturally permeable medium at the bottom. Chauhan and Ghiya23 suggested heat-transfer in second order fluid flow in between two stable permeable disks together with the consequences of magnetic field. Kumar24 investigated analysis of finite element combined with heat-mass transfer in hydromagnetic micro-polar flow past a stretching sheet. Emad et al.25 explored the investigations of flowing/suction impacts on the hydromagnetic heat-transfer by the application of mixed convection from continuously stretching surface together with internal heat generation/absorption. Tripathy et al.26 examined the numerical evaluations of hydromagnetic micropolar fluids past the stretching sheet embedded in a porous channel together with non-uniform heat sources and permissible chemical reactions. Chen and Taiwan27 inspected the theory of heat-mass transfer in MHD flow prompted by natural convection from permeable and suitably inclined stretching surface embedded with variable temperature of wall and concentration. Alam et al.28 examined numerical proposals of combined free-forced convection and mass transfer flow past the available vertical, porous plate in the porous channel together with heat generation and thermal diffusions. Aydin and Kaya29 investigated the MHD mixed convective heat transfer flow about the suitably inclined plate. Reddy and Reddy30 suggested investigations of mass transfer and heat generation consequences on MHD free convection flow across the inclined vertical surface in porous medium. Patil et al.31 proposed the influential consequences of Eyring–Powell fluid across the stretching surface in the existence of magnetic field and chemical reactions.The consolidated impacts of heat mass diffusion together with chemical reaction has their dominant significance on several processes emerging in cooling of nuclear reactors, thermal insulation, geothermal reservoirs etc. Andersson et al.32 established melting impacts on the mechanism of heat transfer. Yacob et al.33 examined melting heat transfer in boundary layer stagnation point flow towards a stretching/shrinking sheet in a micropolar fluid. Hayat et al.34 examined Powell-Eyring stagnation point flow towards a surface stretching linearly with melting heat transfer. Melting heat and mass transport effects in non-Newtonian flow over a stretching surface with non-linear radiation and magnetic field effect was discussed by Khan et al.35. Gireesha et al.36 investigated melting heat transfer in MHD flow of dusty Casson fluid over a stretching surface.Fundamental phenomenon of melting heat transfer finds dominant significance in various technological and industrial exercises like comprehending melting of permafrost, magma solidification, metal purification, welding etc. Epstein and cho et al.37 investigated slip effects in viscoelastic fluid flow through porous medium due to a porous oscillatory stretched sheet. Govindarajan et al.38 discussed slip and mass transfer effects in a vertical channel under consideration of heat source and radiation. Olkha and Dadheech40 discussed entropy analysis for MHD flow for different non-Newtonian fluid caused by a stretching sheet with slip effect and heat source. Dadheech et al.41 investigated MHD flow for Casson fluid caused by a stretching sheet with slip effect. Dadheech et al.42 discussed entropy analysis for Williamson fluid caused by a vertical plate with Cattaneo-Christov heat flux and slip effect. The boundary layer flow for different fluids and geometrical configurations has been considered by59 in the presence of magnetic field.A fluid sometimes gets adhered to the solid boundary but in some circumstances, it does not get a hold like as in suspensions, melting of polymers, emulsion processes and several other non-Newtonian fluids often exhibits macroscopic wall slip. Fluids which manifest boundary slip finds applications in various domains such as polishing of heart valves, internal cavities and various other technological procedures. Ali et al.In perspective of given literature review we have observed that there are relatively few studies are performed on MHD Micro-Polar fluid prompted by melting stretching sheet. The main objective of current study is to determine flow behavior and heat transfer of Micro-Polar over a melting stretching sheet. The novelty of the presented work is increased by substantial validating slip effects with chemical reaction and non-uniform heat source/sink. The examinations furnished in the given article can be further utilized to make investigations in fuel industries, flow of crushed water problems, and in the extrusion of polymer sheets. The consequences of the investigations made are employed in various engineering designs, metallurgy industries also for improving the working efficiency of systems for flow of thermos fluids.26 with relevant boundary conditions are given as:In the momentum equation we take micropolar fluid, magnetic field and porous medium term. The magnetic field Bo is applied perpendicular to the stretching sheet and the effect of induced magnetic field is neglected since the magnetic Reynolds number is assumed to be small. We further assume that the impressed electric field is zero and Hall effect is neglected.The thermal contribution of non-uniform heat source and sink is introduced effectively in the energy equation.The mass transfer phenomenon due to diffusion of chemically reactive foreign species has been accounts for by considering the chemical reaction term of first order.Steady two-dimensional incompressible micro-polar fluid flows caused by a stretching sheet are examined. Corresponding velocity components mentclass2pt{minimContinuity equationMomentum equationAngular momentum equationEnergy equationSpecies equationhere 39) for flow, concentration and temperature is21)The appropriate boundary condition –52–5) reThe local “skin friction coefficient” The “couple stress” at the surfaceThe “local surface heat flux 19. Later it has been determined that computed consequences had essential significant influences.The essential objective of given investigation is to demonstrate the influence of several physical parameters on velocity mentclasspt{minimaquations  are evalmentclass2pt{minim, in micropolar fluids, the material parameter that can affect the velocity profile is known as the micropolar fluidity parameter (K). When the micropolar fluidity parameter (K) increases, it implies that the microstructure or internal degrees of freedom have a stronger effect on the fluid flow. This can lead to an increase in the complexity of the flow patterns and the velocity profile.Figure Figure Figure Figure Figure Figure Figure Figure Contours showing the impact of micro-rotation parameter, Moreover, the micro-rotation parameter affecting the velocity and temperature of a micropolar fluid more intensely near the surface slightly varies according to the boundary conditions (i.e. when The velocity The influence of The concentration profile Reduction in velocity In the present analysis, a numerical investigation of micro polar fluid flow due to melting stretchy surface in a porous medium has been carried out. The influence of abundant quantities on velocity, microrotation, temperature and concentration distribution are outlined as follows:


Similarly to the previous Special Issue entitled “Molecular Mechanisms of Allergy and Asthma” , this SpConsidering their pivotal role in allergies, T cell-related molecular and cellular mechanisms were the focus of four independent investigational works. Perveen et al.  showed tSeveral other papers focused on the molecular mechanisms related to mast cells (MCs), the pivotal effector cells behind allergic responses. Ashikari and coworkers  identifiFurthermore, while Nguyen and colleagues  focused Finally, Zhernov et al. exhaustively described the molecular mechanisms behind eosinophilic esophagitis  and scomIt is with great pleasure that I am presenting the articles included in this Special Issue to the asthma and allergy research community.