bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutational landscape and in silico structure models of SARS-CoV-2 spike receptor binding domain reveal key molecular determinants for virus-host interaction
Authors: Nelson-Sathi Shijulal , Umasankar P. K. , Sreekumar E. , Nair R. Radhakrishnan , Joseph Iype , Nori Sai Ravi Chandra , Philip Jamiema Sara , Prasad Roshny , Navyasree K. V. , Ramesh Shikha , Pillai Heera , Ghosh Sanu , Santosh Kumar T. R. , Pillai M. Radhakrishna 
Published: January 2022

Abstract
Background
SARS-CoV-2, the causative agent of COVID-19 pandemic is a RNA virus prone to mutations. Formation of a stable binding interface between the Receptor Binding Domain (RBD) of SARS-CoV-2 Spike (S) protein and Angiotensin-Converting Enzyme 2 (ACE2) of host is pivotal for viral entry. RBD has been shown to mutate frequently during pandemic. Although, a few mutations in RBD exhibit enhanced transmission rates leading to rise of new variants of concern, most RBD mutations show sustained ACE2 binding and virus infectivity. Yet, how all these mutations make the binding interface constantly favourable for virus remain enigmatic. This study aims to delineate molecular rearrangements in the binding interface of SARS-CoV-2 RBD mutants.

Results
Here, we have generated a mutational and structural landscape of SARS-CoV-2 RBD in first six months of the pandemic. We analyzed 31,403 SARS-CoV-2 genomes randomly across the globe, and identified 444 non-synonymous mutations in RBD that cause 49 distinct amino acid substitutions in contact and non-contact amino acid residues. Molecular phylogenetic analysis suggested independent emergence of RBD mutants. Structural mapping of these mutations on the SARS-CoV-2 Wuhan reference strain RBD and structural comparison with RBDs from bat-CoV, SARS-CoV, and pangolin-CoV, all bound to human or mouse ACE2, revealed several changes in the interfacial interactions in all three binding clusters. Interestingly, interactions mediated via N487 residue in cluster-I and Y449, G496, T500, G502 residues in cluster-III remained largely unchanged in all RBD mutants. Further analysis showed that these interactions are evolutionarily conserved in sarbecoviruses which use ACE2 for entry. Importantly, despite extensive changes in the interface, RBD-ACE2 stability and binding affinities were maintained in all the analyzed mutants. Taken together, these findings reveal how SARS-CoV-2 uses its RBD residues to constantly remodel the binding interface.

Conclusion
Our study broadly signifies understanding virus-host binding interfaces and their alterations during pandemic. Our findings propose a possible interface remodelling mechanism used by SARS-CoV-2 to escape deleterious mutations. Future investigations will focus on functional validation of in-silico findings and on investigating interface remodelling mechanisms across sarbecoviruses. Thus, in long run, this study may provide novel clues to therapeutically target RBD-ACE2 interface for pan-sarbecovirus infections.
Cardiac physiology and metabolic gene expression during late organogenesis among F. heteroclitus embryo families from crosses between pollution-sensitive and -resistant parents
Authors: Bozinovic Goran , Feng Zuying , Shea Damian , Oleksiak Marjorie F. 
Published: January 2022

Abstract
Background
The teleost fish Fundulus heteroclitus inhabit estuaries heavily polluted with persistent and bioaccumulative chemicals. While embryos of parents from polluted sites are remarkably resistant to toxic sediment and develop normally, embryos of parents from relatively clean estuaries, when treated with polluted sediment extracts, are developmentally delayed, displaying deformities characteristic of pollution-induced embryotoxicity. To gain insight into parental effects on sensitive and resistant phenotypes during late organogenesis, we established sensitive, resistant, and crossed embryo families using five female and five male parents from relatively clean and predominantly PAH-polluted estuaries each, measured heart rates, and quantified individual embryo expression of 179 metabolic genes.

Results
Pollution-induced embryotoxicity manifested as morphological deformities, significant developmental delays, and altered cardiac physiology was evident among sensitive embryos resulting from crosses between females and males from relatively clean estuaries. Significantly different heart rates among several geographically unrelated populations of sensitive, resistant, and crossed embryo families during late organogenesis and pre-hatching suggest site-specific adaptive cardiac physiology phenotypes relative to pollution exposure. Metabolic gene expression patterns (32 genes, 17.9%, at p < 0.05; 11 genes, 6.1%, at p < 0.01) among the embryo families indicate maternal pollutant deposition in the eggs and parental effects on gene expression and metabolic alterations.

Conclusion
Heart rate differences among sensitive, resistant, and crossed embryos is a reliable phenotype for further explorations of adaptive mechanisms. While metabolic gene expression patterns among embryo families are suggestive of parental effects on several differentially expressed genes, a definitive adaptive signature and metabolic cost of resistant phenotypes is unclear and shows unexpected sensitive-resistant crossed embryo expression profiles. Our study highlights physiological and metabolic gene expression differences during a critical embryonic stage among pollution sensitive, resistant, and crossed embryo families, which may contribute to underlying resistance mechanisms observed in natural F. heteroclitus populations living in heavily contaminated estuaries.
The evolution of insect visual opsin genes with specific consideration of the influence of ocelli and life history traits
Authors: Guignard Quentin , Allison Jeremy D. , Slippers Bernard 
Published: January 2022

Abstract
Background
Visual opsins are expressed in the compound eyes and ocelli of insects and enable light detection. Three distinct phylogenetic groups of visual opsins are found in insects, named long (LW), short (SW) and ultraviolet (UV) wavelength sensitive opsins. Recently, the LW group was found to be duplicated into the LW2b and the LW2a opsins. The expression of LW2b opsins is ocelli specific in some insects (e.g., bees, cricket, scorpion flies), but the gene was not found in other orders possessing three or less ocelli (e.g., dragonflies, beetles, moths, bugs). In flies, two LW2b homologs have been characterised, with one expressed in the ocelli and the other in the compound eyes. To date, it remains unclear which evolutionary forces have driven gains and losses of LW opsins in insects. Here we take advantage of the recent rapid increase in available sequence data (i.e., from insect genomes, targeted PCR amplification, RNAseq) to characterize the phylogenetic relationships of 1000 opsin sequences in 18 orders of Insects. The resulting phylogeny discriminates between four main groups of opsins, and onto this phylogeny we mapped relevant morphological and life history traits.

Results
Our results demonstrate a conserved LW2b opsin only present in insects with three ocelli. Only two groups (Brachycera and Odonata) possess more than one LW2b opsin, likely linked to their life history. In flies, we hypothesize that the duplication of the LW2b opsin occurred after the transition from aquatic to terrestrial larvae. During this transition, higher flies (Brachycera) lost a copy of the LW2a opsin, still expressed and duplicated in the compound eyes of lower flies (Nematocera). In higher flies, the LW2b opsin has been duplicated and expressed in the compound eyes while the ocelli and the LW2b opsin were lost in lower flies. In dragonflies, specialisation of flight capabilities likely drove the diversification of the LW2b visual opsins.

Conclusion
The presence of the LW2b opsin in insects possessing three ocelli suggests a role in specific flight capabilities (e.g., stationary flight). This study provides the most complete view of the evolution of visual opsin genes in insects yet, and provides new insight into the influence of ocelli and life history traits on opsin evolution in insects.
Development and evaluation of a meat mitochondrial metagenomic (3MG) method for composition determination of meat from fifteen mammalian and avian species
Authors: Jiang Mei , Xu Shu-Fei , Tang Tai-Shan , Miao Li , Luo Bao-Zheng , Ni Yang , Kong Fan-De , Liu Chang 
Published: January 2022

Abstract
Background
Bioassessment and biomonitoring of meat products are aimed at identifying and quantifying adulterants and contaminants, such as meat from unexpected sources and microbes. Several methods for determining the biological composition of mixed samples have been used, including metabarcoding, metagenomics and mitochondrial metagenomics. In this study, we aimed to develop a method based on next-generation DNA sequencing to estimate samples that might contain meat from 15 mammalian and avian species that are commonly related to meat bioassessment and biomonitoring.

Results
In this project, we found the meat composition from 15 species could not be identified with the metabarcoding approach because of the lack of universal primers or insufficient discrimination power. Consequently, we developed and evaluated a meat mitochondrial metagenomics (3MG) method. The 3MG method has four steps: (1) extraction of sequencing reads from mitochondrial genomes (mitogenomes); (2) assembly of mitogenomes; (3) mapping of mitochondrial reads to the assembled mitogenomes; and (4) biomass estimation based on the number of uniquely mapped reads. The method was implemented in a python script called 3MG. The analysis of simulated datasets showed that the method can determine contaminant composition at a proportion of 2% and the relative error was < 5%. To evaluate the performance of 3MG, we constructed and analysed mixed samples derived from 15 animal species in equal mass. Then, we constructed and analysed mixed samples derived from two animal species (pork and chicken) in different ratios. DNAs were extracted and used in constructing 21 libraries for next-generation sequencing. The analysis of the 15 species mix with the method showed the successful identification of 12 of the 15 (80%) animal species tested. The analysis of the mixed samples of the two species revealed correlation coefficients of 0.98 for pork and 0.98 for chicken between the number of uniquely mapped reads and the mass proportion.

Conclusion
To the best of our knowledge, this study is the first to demonstrate the potential of the non-targeted 3MG method as a tool for accurately estimating biomass in meat mix samples. The method has potential broad applications in meat product safety.
Association of hyperchloremia with all-cause mortality in patients admitted to the surgical intensive care unit: a retrospective cohort study
Authors: Song Keke , Yang Tingting , Gao Wei 
Published: January 2022

Abstract
Background
Serum chloride (Cl−) is one of the most essential extracellular anions. Based on emerging evidence obtained from patients with kidney or heart disease, hypochloremia has been recognized as an independent predictor of mortality. Nevertheless, excessive Cl− can also cause death in severely ill patients. This study aimed to investigate the relationship between hyperchloremia and high mortality rate in patients admitted to the surgical intensive care unit (SICU).

Methods
We enrolled 2131 patients from the Multiparameter Intelligent Monitoring in Intensive Care III database version 1.4 (MIMIC-III v1.4) from 2001 to 2012. Selected SICU patients were more than 18 years old and survived more than 72 h. A serum Cl− level ≥ 108 mEq/L was defined as hyperchloremia. Clinical and laboratory variables were compared between hyperchloremia (n = 664) at 72 h post-ICU admission and no hyperchloremia (n = 1467). The Locally Weighted Scatterplot Smoothing (Lowess) approach was utilized to investigate the correlation between serum Cl- and the thirty-day mortality rate. The Cox proportional-hazards model was employed to investigate whether serum chlorine at 72 h post-ICU admission was independently related to in-hospital, thirty-day and ninety-day mortality from all causes. Kaplan-Meier curve of thirty-day and ninety-day mortality and serum Cl− at 72 h post-ICU admission was further constructed. Furthermore, we performed subgroup analyses to investigate the relationship between serum Cl− at 72 h post-ICU admission and the thirty-day mortality from all causes.

Results
A J-shaped correlation was observed, indicating that hyperchloremia was linked to an elevated risk of thirty-day mortality from all causes. In the multivariate analyses, it was established that hyperchloremia remained a valuable predictor of in-hospital, thirty-day and ninety-day mortality from all causes; with adjusted hazard ratios (95% CIs) for hyperchloremia of 1.35 (1.02 ~ 1.77), 1.67 (1.28 ~ 2.19), and 1.39 (1.12 ~ 1.73), respectively. In subgroup analysis, we observed hyperchloremia had a significant interaction with AKI (P for interaction: 0.017), but there were no interactions with coronary heart disease, hypertension, and diabetes mellitus (P for interaction: 0.418, 0.157, 0.103, respectively).

Conclusion
Hyperchloremia at 72 h post-ICU admission and increasing serum Cl− were associated with elevated mortality risk from all causes in severely ill SICU patients.
Comparison of GRACE and TIMI risk scores in the prediction of in-hospital and long-term outcomes among East Asian non-ST-elevation myocardial infarction patients
Authors: Yanqiao Lu , Shen Lan , Yutong Miao , Linghong Shen , Ben He 
Published: January 2022

Abstract
Background
Risk stratification in non-ST segment elevation myocardial infarction (NSTEMI) determines the intervention time. Limited study compared two risk scores, the Thrombolysis in Myocardial Infarction (TIMI) and Global Registry of Acute Coronary Events (GRACE) risk scores in the current East Asian NSTEMI patients.

Methods
This retrospective observational study consecutively collected patients in a large academic hospital between 01/01 and 11/01/2017 and followed for 4 years. Patients were scored by TIMI and GRACE scores on hospital admission. In-hospital endpoints were defined as the in-hospital composite event, including mortality, re-infarction, heart failure, stroke, cardiac shock, or resuscitation. Long-term outcomes were all-cause mortality and cardiac mortality in 4-year follow-up.

Results
A total of 232 patients were included (female 29.7%, median age 67 years), with a median follow-up of 3.7 years. GRACE score grouped most patients (45.7%) into high risk, while TIMI grouped the majority (61.2%) into medium risk. Further subgrouping the TIMI medium group showed that half (53.5%) of the TIMI medium risk population was GRACE high risk (≥ 140). Compared to TIMI medium group + GRACE < 140 subgroup, the TIMI medium + GRACE high-risk (≥ 140) subgroup had a significantly higher in-hospital events (39.5% vs. 9.1%, p < 0.05), long-term all-cause mortality (22.2% vs. 0% p < 0.001) and cardiac death (11.1% vs. 0% p = 0.045) in 4-year follow-up. GRACE risk scores showed a better predictive ability than TIMI risk scores both for in-hospital and long-term outcomes. (AUC of GRACE vs. TIMI, In-hospital: 0.82 vs. 0.62; long-term mortality: 0.89 vs. 0.68; long-term cardiac mortality: 0.91 vs. 0.67, all p < 0.05). Combined use of the two risk scores reserved both the convenience of scoring and the predictive accuracy.

Conclusion
GRACE showed better predictive accuracy than TIMI in East Asian NSTEMI patients in both in-hospital and long-term outcomes. The sequential use of TIMI and GRACE scores provide an easy and promising discriminative tool in predicting outcomes in NSTEMI East Asian patients.
Reporting of abstracts in studies that used routinely collected data for exploring drug treatment effects: a cross-sectional survey
Authors: Liu Mei , Wang Wen , Wang Mingqi , He Qiao , Li Ling , Li Guowei , He Lin , Zou Kang , Sun Xin 
Published: January 2022

Abstract
Background
In recent years, studies that used routinely collected data (RCD), such as electronic medical records and administrative claims, for exploring drug treatment effects, including effectiveness and safety, have been increasingly published. Abstracts of such studies represent a highly attended source for busy clinicians or policy-makers, and are important for indexing by literature database. If less clearly presented, they may mislead decisions or indexing. We thus conducted a cross-sectional survey to systematically examine how the abstracts of such studies were reported.

Methods
We searched PubMed to identify all observational studies published in 2018 that used RCD for assessing drug treatment effects. Teams of methods-trained collected data from eligible studies using pilot-tested, standardized forms that were developed and expanded from “The reporting of studies conducted using observational routinely collected health data statement for pharmacoepidemiology” (RECORD-PE) statement. We used descriptive analyses to examine how authors reported data source, study design, data analysis, and interpretation of findings.

Results
A total of 222 studies were included, of which 118 (53.2%) reported type of database used, 17 (7.7%) clearly reported database linkage, and 140 (63.1%) reported coverage of data source. Only 44 (19.8%) studies stated a predefined hypothesis, 127 (57.2%) reported study design, 140 (63.1%) reported statistical models used, 142 (77.6%) reported adjusted estimates, 33 (14.9%) mentioned sensitivity analyses, and 39 (17.6%) made a strong claim about treatment effect. Studies published in top 5 general medicine journals were more likely to report the name of data source (94.7% vs. 67.0%) and study design (100% vs. 53.2%) than those in other journals.

Conclusions
The under-reporting of key methodological features in abstracts of RCD studies was common, which would substantially compromise the indexing of this type of literature and prevent the effective use of study findings. Substantial efforts to improve the reporting of abstracts in these studies are highly warranted.
Development of a data classification system for preterm birth cohort studies: the RECAP Preterm project
Authors: Bamber Deborah , Collins Helen E. , Powell Charlotte , Gonçalves Gonçalo Campos , Johnson Samantha , Manktelow Bradley , Ornelas José Pedro , Lopes João Correia , Rocha Artur , Draper Elizabeth S. 
Published: January 2022

Abstract
Background
The small sample sizes available within many very preterm (VPT) longitudinal birth cohort studies mean that it is often necessary to combine and harmonise data from individual studies to increase statistical power, especially for studying rare outcomes. Curating and mapping data is a vital first step in the process of data harmonisation. To facilitate data mapping and harmonisation across VPT birth cohort studies, we developed a custom classification system as part of the Research on European Children and Adults born Preterm (RECAP Preterm) project in order to increase the scope and generalisability of research and the evaluation of outcomes across the lifespan for individuals born VPT.

Methods
The multidisciplinary consortium of expert clinicians and researchers who made up the RECAP Preterm project participated in a four-phase consultation process via email questionnaire to develop a topic-specific classification system. Descriptive analyses were calculated after each questionnaire round to provide pre- and post- ratings to assess levels of agreement with the classification system as it developed. Amendments and refinements were made to the classification system after each round.

Results
Expert input from 23 clinicians and researchers from the RECAP Preterm project aided development of the classification system’s topic content, refining it from 10 modules, 48 themes and 197 domains to 14 modules, 93 themes and 345 domains. Supplementary classifications for target, source, mode and instrument were also developed to capture additional variable-level information. Over 22,000 individual data variables relating to VPT birth outcomes have been mapped to the classification system to date to facilitate data harmonisation. This will continue to increase as retrospective data items are mapped and harmonised variables are created.

Conclusions
This bespoke preterm birth classification system is a fundamental component of the RECAP Preterm project’s web-based interactive platform. It is freely available for use worldwide by those interested in research into the long term impact of VPT birth. It can also be used to inform the development of future cohort studies.
The effect of BKV reactivation on cytokines behavior in kidney transplanted patients
Authors: Rahimi Zahra , Yaghobi Ramin , Afshari Afsoon , Roozbeh Jamshid , Mokhtari Mohammad Javad , Hosseini Ali Malek 
Published: January 2022

Abstract
Background
BK virus associated nephropathy (BKVAN) is one of the common causes of graft loss among kidney transplanted recipients (KTRs). The current treatment for BKV nephropathy is decreasing the immunosuppressive regimen in KTRs. Interleukin-27 (IL-27) is a multifunctional cytokine that might be the front-runner of an important pathway in this regard. Therefore, in current study it is tried to evaluate the changes in the expression level of IL-27 and some related molecules, resulting from BKV reactivation in KTR patients.

Methods
EDTA-treated blood samples were collected from all participants. Patients were divided into two groups, 31 kidney transplant recipients with active and 32 inactive BKV infection, after being monitored by Real time PCR (Taq-Man) in plasma. Total of 30 normal individuals were considered as healthy control group. Real time PCR (SYBR Green) technique is used to determine the expression level of studied genes.

Results
The results of gene expression comparisons showed that the expression level of IL-27, IFN-γ, TNF-α, TNFR2 and IRF7 genes was significantly higher in inactive group in comparison to active group. The expression level of TLR4 was lower in both active and inactive groups in comparison to control group. ROC curve analysis showed that IL-27 and IRF7 are significantly different amongst other studied genes. Finally, the analyses revealed that the expression level of most of the studied genes (except for TNF-α and TLR4) have significant correlation with viral load.

Conclusions
Our findings revealed that IL-27, IFN-γ, TNF-α, TNFR2 and IRF7 expression level is higher in inactive group and TLR4 expression level is lower in patients’ groups in comparison to control group. Also, ROC curve analysis showed IL-27 and IRF7 can significantly differentiate studied groups (BKV active vs. inactive). Therefore, these results might help elucidating the pattern in charge of BKV reactivation in kidney transplanted patients.