Recently, Spencer et al. published their interesting article in Influenza and Other Respiratory Viruses providing evidence that there is no impact of diabetes status on immunogenicity of trivalent inactivated influenza vaccine in older adults. Although we agree with the conclusion, we suggest that the transportation condition of the serum samples should be added in the description of serological surveys of influenza in the future. Stability of specific influenza antibodies in sera samples stored in differing conditions should be considered.

Anthropogenic environmental changes are influencing the structure and function of many ecological communities, but their underlying mechanisms are often poorly understood. We conducted a seven-year field experiment to explore the ecological consequences of nitrogen (N) and phosphorous (P) enrichment in a high-altitude Tibetan alpine grassland. The enrichment of both N and P, but not either alone, resulted in increased plant above- and below-ground biomass. By contrast, N, but not P, enrichment reduced species richness, and altered plant phylogenetic diversity and structure. The observed decline in species richness under N addition was driven by the loss of species characterized by high leaf nitrogen content, and associated with higher soil manganese level and greater belowground competition. Our study highlights resource co-limitation of community biomass but not structure of the study grassland, while also identifying soil metal toxicity and belowground competition as important mechanisms driving community changes after nutrient amendment.

Figure legendsFigure 1. Study flow diagramFigure 2. ’Risk of bias’ summary: review authors’ judgements about each risk of bias item for each included study.

Background and Purpose: Dihydropyrimidine dehydrogenase (DPD) is a major determinant of 5-FU resistance in cancers. DPD catalyzes 5-FU into FBAL (α-fluoro-β-alanine) to lower intracellular 5-FU level. We aimed to investigate mechanism and clinical significance of FBAL-stimulated sphingosine 1-phosphate receptor 2 (S1PR2) in upregulation of DPD in colonic cancer. Experimental Approach: Cancer cells transfected or silenced S1PR2 were exposed to FBAL for analyzed S1PR2 and DPD levels. Luciferase reporter assay analyzed S1PR2-activated TWIST1 binding to DPYD promoter. Co-IP assay analyzed TWIST1 interaction with JMJD3-RNA Pol II complex binding to DPYD promoter. HT-29sh-S1PR2 or SW480TgS1PR2 cells xenografted nude mice were used to evaluate clinical significance of S1PR2-upregulated tumoral DPD. Key Results: Activation of S1PR2 upregulated DPD in colonic cancer cells and human fresh cancer specimens. FBAL was first time identified as an etiological stimulator of S1PR2 activation. The FBAL-stimulated S1PR2 increased TWIST1 binding to DPYD promoter and interacting with JMJD3-RNA Pol II complex, enhancing H3K27me3-enriched DPYD transcription elongation. Transfection of S1PR2 in SW480TgS1PR2 xenograft contributed 5-FU resistance by 45.14%, and silence of S1PR2 improved 5-FU sensitivity by 62.12% in HT-29sh-S1PR2 xenograft. S1PR2 inhibitor JTE013 prevented the FBAL-stimulated S1PR2’s effects in upregulating DPD. Cancer cells with high S1PR2 are more resistant to 5-FU, strongly suggesting clinical significance that combination use of S1PR2 inhibitors may be the appropriate 5-FU-based regimens of colonic cancers. Conclusions and Implications: The FBAL-stimulated S1PR2 increased TWIST1 binding to DPYD promoter and interacting with JMJD3-RNA Pol II, enhancing the H3K27me3-enriched DPYD transcription elongation.

Giant isopods are the most representative group of crustaceans living in the deep sea environment with a huge body size. In order to understand the genetic basis of these large animals to adapt the harsh oligotrophic environment of the deep-sea, the genome of a deep-sea (-898 m) giant isopod Bathynomus jamesi was sequenced and its genome characteristics were analyzed. The genome assembly of B. jamesi has a total length of 5.89 Gb with a contig N50 of 587.28 Kb, which is among the largest one with high continuity of the sequenced crustacean genomes. The large genome size of B. jamesi is mainly attributable to the proliferation of transposable elements, especially for DNA transposons and CR1-type LINEs, which account for more than 84% of the genome. A number of expanded gene families in the genome were enriched in thyroid and insulin hormone signaling pathways, which might have driven the evolution of its huge body size. Transcriptomic analysis showed that several expanded gene families related to glycolysis and vesicular transport were specifically expressed in its digestive organs, revealing the molecular mechanism of nutrient absorption and utilization in oligotrophic environment adaptation. Taken together, the giant isopod genome provides a valuable resource for understanding the body size evolution and adaptation mechanisms of macrobenthos to the deep-sea environment.

Background: The vitamin D deficiency is ubiquitous among children population. Similar problem is recognized among paediatric patients with acute lymphoblastic leukaemia. The purpose of this study was to analyze the prevalence of vitamin D deficiency and investigate the connection between vitamin D status and course of induction treatment of ALL. Methods: A cross-sectional study including 59 patients with newly diagnosed ALL from May 2017 until November 2020. Results: The vitamin D insufficiency was found in 36% of patients. There were no seasonal differences in vitamin D status. Patients with optimal 25(OH)D concentration presented more profound thrombocytopenia (p=.015) and required more frequent platelet transfusions (p=0.018). The good prognosis factors as B phenotype and hyperdiploidy were also more frequent among children with higher 25(OH)D concentration (p=0.01 and p=0.014, respectively). Conclusion: The study displayed that patients with higher serum concentration of 25(OH)D presented deeper thrombocytopenia and needed more frequent transfusions. Moreover, those patients showed higher rates of B-cell leukaemia and hyperdiploid karyotype. We did not find any influence of potential sunlight exposure (defined as the season of the year at admission) on serum 25(OH)D, which supports the supplementing of vitamin D throughout the entire year. Moreover, the supplementation of vitamin D seems to be safe in the context of renal complications connected to calcium and phosphorus imbalance as no correlation between their levels and 25(OH)D concentration was found.

Background: Eosinophilic chronic rhinosinusitis is an often treatment-resistant inflammatory disease mediated by type-2 cytokines, including interleukin (IL)-5. Mepolizumab, a monoclonal antibody drug targeting IL-5, has demonstrated efficacy and safety in inflammatory airway disease, but there is negligible evidence on direct tissue response. The study aim was to determine the local effect of mepolizumab on inflammatory biomarkers in sinonasal tissue of eosinophilic chronic rhinosinusitis patients. Methods: Adult patients with eosinophilic chronic rhinosinusitis received 100mg mepolizumab subcutaneously at four-weekly intervals for 24 weeks in this prospective phase 2 clinical trial. Tissue eosinophil counts, eosinophil degranulation (assessed as submucosal eosinophil peroxidase deposition by immunohistochemistry) and cytokine levels (measured in homogenates by immunoassay) were evaluated in ethmoid sinus tissue biopsies collected at baseline and at weeks 4, 8, 16 and 24. Results: Twenty patients (47.7±11.7 years, 50% female) were included. Sinonasal tissue eosinophil counts decreased after 24 weeks of treatment with mepolizumab (101.64±93.80 vs 41.74±53.76 cells per 0.1mm 2; p=0.035), eosinophil degranulation remained unchanged (5.79±2.08 vs 6.07±1.20, p=0.662), and type-2 cytokine levels increased in sinonasal tissue for IL-5 (10.84±18.65 vs 63.98±50.66, p=0.001), IL-4 (4.48±3.77 vs 9.38±7.56, p=0.004), IL-13 (4.02±2.57 vs 6.46±3.99, p=0.024) and GM-CSF (1.51±1.74 vs 4.50±2.97, p=0.001). Conclusions: Mepolizumab reduced eosinophils in sinonasal tissue, demonstrating that antagonism of IL-5 suppresses eosinophil trafficking. With reduced tissue eosinophils, a local type-2 inflammatory feedback loop may occur. The study exposes mechanistic factors which may explain incomplete treatment response.

One striking change that has occurred in what fundamentally drives businesses today is the journey towards a ‘customer focused’ approach. The healthcare industry has followed the same suit. Today’s patients or beneficiaries expect the liberty of choice and the more personal or individualistic these choices become, the better. In the current digital age, patients are more informative and educated than ever. They know their rights and are voicing about their concerns at the global platforms. Healthcare Industry has no option but to meet the demands and needs of the patients. Therefore, the current healthcare landscape is undergoing essential modifications, attributed to the pressure created to meet patient centered goals. With the advent of advanced technologies and globalization, healthcare ecosystem is trying its best to meet their demand at global level, where Artificial Intelligence (AI) is playing the central role. The wave of AI has been increasing in the industry day by day. The current article articulates about how AI and data science are transforming life sciences and explains how this sector is deploying these tools to meet patient centricity.

Genomic approaches to the study of population demography rely on accurate SNP calling and by-proxy the site frequency spectrum (SFS). Two main questions for the design of such studies remain poorly investigated: do reduced genomic sequencing summary statistics reflect that of whole genome, and how do sequencing strategies and derived summary statistics impact demographic inferences? To address those questions, we applied the ddRAD sequencing approach to 254 individuals and whole genome resequencing approach to 35 mountain goat (Oreamnos americanus) individuals across the species range with a known demographic history. We identified SNPs with 5 different variant callers and used ANGSD to estimate the genotype likelihoods (GLs). We tested combinations of SNP filtering by linkage disequilibrium (LD), minor allele frequency (MAF) and the genomic region. We compared the resulting suite of summary statistics reflective of the SFS and quantified the relationship to demographic inferences by estimating the contemporary effective population size (Ne), isolation-by-distance and population structure, FST, and explicit modelling of the demographic history with δaδi. Filtering had a larger effect than sequencing strategy, with the former strongly influencing summary statistics. Estimates of contemporary Ne and isolation-by-distance patterns were largely robust to the choice of sequencing, pipeline, and filtering. Despite the high variance in summary statistics, whole genome and reduced representation approaches were overall similar in supporting a glacial induced vicariance and low Ne in mountain goats. We discuss why whole genome resequencing data is preferable, and reiterate support the use of GLs, in part because it limits user-determined filters.

Opsoclonus-myoclonus syndrome associated with neuroblastoma (OMS-NB) is a refractory paraneoplastic syndrome which often remain neurological sequelae, and detailed pathogenesis has remained elusive. We encountered a pediatric patient with OMS-NB treated by immunosuppressed therapy who showed anti-glutamate receptor δ2 antibody and increased B-cells in cerebrospinal fluid (CSF), and multiple lymphoid follicles containing abundant B-cells in tumor tissue. Unbiased B-cell receptor repertoire analysis revealed identical B-cell clone was identified as the dominant clone in both CSF and tumor tissue. These identical B-cell clone may contribute to the pathogenesis of OMS-NB. Our results could facilitate the establishment of pathogenesis-based treatment strategies for OMS-NB.

KEY POINTS: 1. COVID19 has mandated many changes to secondary care since declaration of the pandemic in 2019. Reducing the exposure of the hospital setting to patients to a minimum is therefore not only in the best interests of individual patients but also the public. 2. A steady increase in the percentage of same-day discharges of hemithyroidectomy cases has been observed over the past 3 years, with very few post-operative complications. 3. The inferences made from this communication propose that hemithyroidectomy operations can be carried out safely as day case procedures under otolaryngology departments in a district general setting. 4. Patients no longer require a drain inserted at the end of a hemithyroidectomy procedure provided adequate haemostasis has been achieved. 5. Hemithyroidectomy procedures should be prioritised as earlier on the operating list to ensure adequate time for observation in recovery and ample time for the discharge process to be completed to achieve same-day discharge.

Objectives: To analyze the incidence of pharyngeal reflux in laryngopharyngeal reflux patients over a 24-hour period and find out the key timing of pharyngeal reflux. Design: Retrospective descriptive analysis Setting: Single institution. Participants: Sixty-nine patients with LPR and twenty-six normal controls Methods: We reviewed 69 patients who visited our clinic with LPR-related symptoms and were proven to have pharyngeal reflux via 24‐hour multichannel intraluminal impedance‐pH (24hr MII‐pH) monitoring. Quantitative analysis was conducted for the LPR profiles, such as the acidity of reflux, nighttime reflux, and positional reflux. The time series of pharyngeal reflux episodes and mealtimes were analyzed over a 24-hour period. Also, we recruited 26 normal controls. We compared the timing of pharyngeal reflux between LPR patients and asymptomatic controls. Results: The quantitative analysis revealed that pharyngeal reflux occurred 4.88 ± 4.59 times over 24 hours. Weakly acidic pharyngeal reflux was more abundant than acidic or weakly alkaline reflux. Pharyngeal reflux occurred mainly during daytime in the upright position. The most frequent timing of pharyngeal reflux episodes was within 2 hours after meals. Additionally, there was no significant difference of the timing of post-prandial reflux between LPR patients and asymptomatic controls. Conclusion: The key timing of pharyngeal reflux in patients with LPR was post-prandial 2 hours.

The herbaceous legume Mimosa pudica is an invasive weed in many tropical and subtropical regions, as a serious problem for farmers since it is difficult to clear by hand. Moreover, it has water impermeable seeds, i.e. physical dormancy (PY), which could persist longer in the soil seed bank than non-dormant seeds, making big challenge in weed control. The aim of this study were to test the effect of various methods known to break PY in seeds of M. pudica, to identify the site(s) of water entry into seeds of M. pudica and also compare results of dormancy-breaking methods for seeds of M. pudica with those of 36 other species of Mimosa reported in the literature. Mechanical scarification, wet heat and cycles of wet heat and ice water effectively broke PY. Following wet heat at 80 ˚C for 10 min, water uptake was via the hilar region but not the pleurogram. Since PY has been reported in 36 species of Mimosa tested that includes invasive, rare and endemic species, it seems obvious that this kind of dormancy is not the cause of weediness in M. pudica. Further, the 36 species represent four of the five taxonomic sections of Mimosa, and thus it is likely that seeds of most of all of the about 500 species in the genus have PY.

Atrial Fibrillation (AF) poses a significant burden to patients as well as the healthcare system. It can be a complex diagnosis and requires a holistic approach to treatment. Every patient with AF should be evaluated for the need for anticoagulation therapy to prevent systemic embolization. In those that require long-term anticoagulation, a novel oral anticoagulation agent (NOAC) has become the drug of choice. In recent years there have been huge developments in the field of anticoagulation in AF with the presence of the various NOACs on the market. However, there remains uncertainty around prescribing in obese patients.

A density functional theory (DFT) approach was used to investigate the interaction of cystine with Cu9 cluster at B3LYP/LANL2DZ/6-311++G(d,p) level of theory. It was observed that cystine interacts with copper cluster majorly through its disulfide and –COOH groups. The simulated Raman spectrum confirmed the cleavage of disulfide linkage by the disappearance of the –S-S- stretching mode, in good agreement with the earlier reported experimental study. As noted by the peaks observed due to Cu-S and Cu-O stretching mode in the simulated Raman spectrum, cystine is inferred to have chemisorbed on Cu9. Using NBO analysis, it was revealed that oxygen and sulfur donate electron pairs to copper in the Cu9-cystine system. Additionally, the MK[ESP] charge and FMO analysis supported the above mentioned results significantly.

Introduction Sarcoidosis is a systemic inflammatory disorder associated with ventricular arrhythmias (VAs) and sudden death in the context of cardiac involvement. Established guidelines advocate implantable cardioverter-defibrillator (ICD) implantation in specific subcohorts, but there is a paucity of data on outcomes. Methods and Results We conducted a systematic review of published literature to assess outcomes in patients with cardiac sarcoidosis (CS) treated with ICD. Observational studies of patients with definite or probable CS and ICD implantation were identified from multiple databases from inception to 21 st May 2021. Outcomes of interest included appropriate and inappropriate ICD therapies in addition to all-cause mortality. Study quality was assessed individually using the Newcastle Ottawa Scale (NOS). Eight studies were identified comprising 530 patients, with follow-up period of 24 to 66 months (weighted average 40 months). Mean age was 53.9 years with ejection fraction of 41.3%. Overall incidence of appropriate therapy, reported in all studies, was 39% during follow-up. Left ventricular systolic dysfunction (LVSD) with ejection fraction < 40% was a predictor of appropriate therapy in the majority of studies, as were sustained VAs during electrophysiological testing (EP) in one study. Inappropriate therapy was documented in six studies and primarily driven by atrial arrhythmias. All-cause mortality was reported in six studies, with incidence of 6.0% over a median follow-up period of 42 months. Only three studies achieved good quality in the comparability domain of NOS. Conclusions Appropriate ICD therapy in patients with CS is commonly associated with LVSD, which may act as a surrogate for scar burden. The utility of EP testing in this setting remains unclear.

Predicting how seeds persist in the soil seed bank based on easy-to-measure traits is of prime importance to improve management strategies in grazing, farming, and species invasion. We found that seeds that are smaller and rounder are more likely to form persistent seed banks at a global scale, using the 1303 species. The relationship between seed bank persistence and seed mass and shape was not affected by phylogeny or mean annual precipitation. However, the relationships is not significant in woody perennials. Species with smaller seeds are more likely to form persistent seed banks at sites with low soil sand content, in grassland systems or at low mean annual temperatures. Species with rounder seeds are more likely to form a persistent seed bank at higher latitudes. Our results suggest that seed burial mechanics exert environmental filtering on seed traits, and help improve to assess vegetation restoration capacity.

Bovine Rotavirus A (boRVA) strains are a major causative agent of diarrhea in calves. It inflicts important economic losses to the beef and dairy industry. Importantly, this virus has a zoonotic relevance due to its ability to reassort with human rotaviruses. In this study, we describe a novel boRVA associated with diarrhea in calves and closely related with human rotavirus strains based on whole genome characterization.

Lignocellulose, as the key structural component of plant biomass, is of recalcitrant structure and is difficult to degrade. Meanwhile, the improper handling of plant residues is accelerating the process of global warming. Interestingly, we noticed that the xylophagous beetle, Trypoxylus dichotomus has a significant ability to decompose lignocellulosic biomass. However, no study has been conducted to elucidate the digestion mechanism from a genome-wide aspect for this beetle. Based on sequencing and assembling, the draft genome size of T. dichotomus is 636.27 Mb, with 95.37% scaffolds anchored onto 10 chromosomes. The phylogenetic results indicated that T. dichotomus and its closely related scarabaeid species Onthophagus taurus split from each other in the early Cretaceous. Furthermore, two digestive gene families (Trypsin and Enoyl-(Acyl carrier protein) reductase) have experienced significant expansion, accounting for the high degradation efficiency of lignocellulose. Additionally, the collinearity analysis revealed that chromosome breakages and rearrangements occur in the evolution of T. dichotomus due to chromosomes 6 and 8 of T. dichotomus being intersected with chromosomes 2 and 10 of Tribolium castaneum respectively. As suggested by the larval intestinal transcriptome comparative analyses, the digestive ability of midgut is much stronger than that of hindgut, even though susceptible to different food habits. This study reported the well-assembled and annotated genome of this rhinoceros beetle, providing genomic and transcriptomic bases for further understanding the functional mechanism and evolutionary history of lignocellulolytic digestion of the beetle.

Purpose：the 5-year survival rate of children with acute lymphoblastic leukemia (ALL) is 85–90%, with a 10–15% rate of treatment failure. Thus, an in-depth understanding of the biological characteristics of these patients is essential. Approximately 30% of pediatric B cell precursor (BCP)-ALL patients remain uncharacterized by the genetic analyses at the time of diagnosis. The present study aimed to characterize the spectrum and clinical relevance of recurrent driver gene mutations in a large single-center cohort of pediatric ALL. Methods：we identified the spectrum of somatic mutations in 219 pediatric ALL by next-generation sequencing and analyzed the correlation with the clinical data. Results: a total of 381 gene mutations, including SNVS and InDels, were identified in 66 different genes in 152/219 patients. Conclusion: this study depicted the specific genomic landscape of Chinese pediatric ALL and revealed the relevance between mutational characteristics and clinical features of Chinese pediatric ALL.

Venoms are ecological innovations that have evolved numerous times, on each occasion accompanied by the co-evolution of specialised morphological and behavioural characters for venom production and delivery. The close evolutionary interdependence between these characters is exemplified by animals that control the composition of their secreted venom—an ability that in part depends on the production of different toxins in different locations of the venom gland. This spatial heterogeneity was recently documented in venomous snakes, raising the question of whether snakes can control the composition of secreted venom, which has implications for our understanding of human snakebites. Here, we examine the potential adaptive role of toxin spatial heterogeneity in snakes. We show that the main defensive and predatory peptide toxins are produced in distinct regions of the venom glands of the black-necked spitting cobra (Naja nigricollis), but that these distributions likely reflect developmental effects. Indeed, we detected no significant differences in venom collected via defensive ‘spitting’ or predatory ‘biting’ events from the same specimens representing multiple lineages of spitting cobra. We also found the same spatial distribution of toxins in a non-spitting cobra, and show that heterogeneous toxin distribution is a feature shared with a viper with primarily predatory venom. These findings suggest that heterogeneous distributions of toxins is not an adaptation to controlling venom composition in snakes. Instead, it likely reflects physiological constraints on toxin production by the venom glands, opening avenues for future research on mechanisms of functional differentiation of populations of protein-secreting cells within adaptive contexts.

This study presents a 57-year-old male patient with COVID-19 who had had no lung disease before COVID-19 pneumonia. However, after COVID-19 pneumonia with sequels and treatments that include corticosteroids and IL-6 receptor antagonists, an invasive pulmonary aspergillus (IPA) cavity occurred immediately.

Objective: To evaluate gestational weight gain (according to the Institute of Medicine recommendation) and pregnancy outcomes by comparing the Western and Asia-Pacific Pre-pregnancy Body Mass Index. Design: A retrospective study. Setting: Maternal and Child Health Clinics in Brunei. Population or Sample: Health medical records of mothers. Methods: Demographic factors, pre-pregnancy Body Mass Index, gestational weight gain, and maternal and neonatal outcomes were retrieved. Univariate analyses were applied. Main outcome measures: Maternal and neonatal outcomes. Results: 170 records were extracted. Adverse neonatal outcomes (p=0.036) were detected when gestational weight gain was evaluated using the Asia-Pacific pre-pregnancy Body Mass Index as compared to that of the Western (p=0.440). The prevalence of obese women was significantly higher (95%CI: 36.0, 51.3) compared to (95%CI: 11.4, 23.1)(p<0.001). The gestational weight gain above the recommended guideline was also significantly higher (95%CI: 71.1, 84.0) compared to (95%CI: 60.6, 75.0) (p<0.001). Conclusions: Evaluating gestational weight gain using the Asia-Pacific pre-pregnancy Body Mass Index and the Institute of Medicine guidelines was significant in detecting adverse neonatal outcomes and prevalence of obesity in the Asian pregnant women population in Brunei. This retrospective study served as a platform for more rigorous study on larger population.

The Balearic shearwater (Puffinus mauretanicus) is the most threatened seabird in Europe. The fossil record suggests that human colonisation of the Balearic Islands resulted in a sharp decrease of the population size. Currently, populations continue to be decimated mainly due to predation by introduced mammals and bycatch in longline fisheries, and some studies predict their extinction by 2070. We present the first high-quality reference genome for the species which was obtained by a combination of short and long-read sequencing. Our hybrid assembly includes 4,169 scaffolds, with a scaffold N50 of 2.1 Mbp, a genome length of 1.2 Gbp, and BUSCO completeness of 96%, which is amongst the highest across sequenced avian species. This reference genome allowed us to study critical aspects relevant to the conservation status of the species, such as an evaluation of overall heterozygosity levels and the reconstruction of its historical demography. Our phylogenetic analysis using whole-genome information resolves current uncertainties in the order Procellariiformes systematics. Comparative genomics analyses uncover a set of candidate genes that may have played an important role into the adaptation to a pelagic lifestyle of Procellariiformes, including those for the enhancement of fishing capabilities, night vision and the development of natriuresis. This reference genome will be the keystone for future developments of genetic tools in conservation efforts for this Critically Endangered species.