bluuebunny/crossref_metadata_2025_split huggingface dataset:
Covariant Fitness Clusters Reveal Structural Evolution of SARS-CoV-2 Polymerase Across the Human Population
Authors: Wang Chao , Elghobashi-Meinhardt Nadia , Balch William E. 
Published: January 2022

AbstractUnderstanding the fitness landscape of viral mutations is crucial for uncovering the evolutionary mechanisms contributing to pandemic behavior. Here, we apply a Gaussian process regression (GPR) based machine learning approach that generates spatial covariance (SCV) relationships to construct stability fitness landscapes for the RNA-dependent RNA polymerase (RdRp) of SARS- CoV-2. GPR generated fitness scores capture on a residue-by-residue basis a covariant fitness cluster centered at the C487-H642-C645-C646 Zn2+binding motif that iteratively evolves since the early phase pandemic. In the Alpha and Delta variant of concern (VOC), multi-residue SCV interactions in the NiRAN domain form a second fitness cluster contributing to spread. Strikingly, a novel third fitness cluster harboring a Delta VOC basal mutation G671S augments RdRp structural plasticity to potentially promote rapid spread through viral load. GPR principled SCV provides a generalizable tool to mechanistically understand evolution of viral genomes at atomic resolution contributing to fitness at the pathogen-host interface.
Common neural functions during children’s naturalistic and controlled laboratory mathematics learning
Authors: Amalric Marie , Cantlon Jessica F 
Published: January 2022

AbstractA major goal of human neuroscience is to understand how the brain functions in the real world, and to measure neural processes under conditions that are ecologically valid. A critical step toward this goal is understanding how brain activity during naturalistic tasks that mimic the real world, relates to brain activity in more traditional laboratory tasks. In the present study, we used intersubject correlations to locate reliable stimulus-driven cerebral processes among children and adults in a naturalistic video lesson and a laboratory forced-choice task that shared the same arithmetic concept. We show that relative to a control condition with grammatical content, naturalistic and laboratory arithmetic tasks evoked overlapping activation within brain regions previously associated with math semantics. The regions of specific functional overlap between the naturalistic mathematics lesson and laboratory mathematics task included bilateral intraparietal cortex, which confirms that this region processes mathematical content independently of differences in task mode. These findings suggest that regions of the intraparietal cortex process mathematical content when children are learning about mathematics in the real world.
Assessing and assuring interoperability of a genomics file format
Authors: Niu Yi Nian , Roberts Eric G. , Denisko Danielle , Hoffman Michael M. 
Published: January 2022

AbstractBackgroundBioinformatics software tools operate largely through the use of specialized genomics file formats. Often these formats lack formal specification, and only rarely do the creators of these tools robustly test them for correct handling of input and output. This causes problems in interoperability between different tools that, at best, wastes time and frustrates users. At worst, interoperability issues could lead to undetected errors in scientific results.MethodsWe sought (1) to assess the interoperability of a wide range of bioinformatics software using a shared genomics file format and (2) to provide a simple, reproducible method for enhancing inter-operability. As a focus, we selected the popular Browser Extensible Data (BED) file format for genomic interval data. Based on the file format’s original documentation, we created a formal specification. We developed a new verification system, Acidbio (https://github.com/hoffmangroup/acidbio), which tests for correct behavior in bioinformatics software packages. We crafted tests to unify correct behavior when tools encounter various edge cases—potentially unexpected inputs that exemplify the limits of the format. To analyze the performance of existing software, we tested the input validation of 80 Bioconda packages that parsed the BED format. We also used a fuzzing approach to automatically perform additional testing.ResultsOf 80 software packages examined, 75 achieved less than 70% correctness on our test suite. We categorized multiple root causes for the poor performance of different types of software. Fuzzing detected other errors that the manually designed test suite could not. We also created a badge system that developers can use to indicate more precisely which BED variants their software accepts and to advertise the software’s performance on the test suite.DiscussionAcidbio makes it easy to assess interoperability of software using the BED format, and therefore to identify areas for improvement in individual software packages. Applying our approach to other file formats would increase the reliability of bioinformatics software and data.
Digenic genotypes: the interface of inbreeding, linkage, and linkage disequilibrium
Authors: Smith Reginald D. 
Published: January 2022

AbstractMany traits in populations are well understood as being Mendelian effects at single loci or additive polygenic effects across numerous loci. However, there are important phenomena and traits that are intermediate between these two extremes and are known as oligogenic traits. Here we investigate digenic, or two-locus, traits and how their frequencies in populations are affected by non-random mating, specifically inbreeding, linkage disequilibrium, and selection. These effects are examined both separately and in combination to demonstrate how many digenic traits, especially double homozygous ones, can show significant, sometimes unexpected, changes in population frequency with inbreeding, linkage, and linkage disequilibrium. The effects of selection on deleterious digenic traits are also detailed. These results are applied to both digenic traits of medical significance as well as measuring inbreeding in natural populations.
Time-resolved proximity labeling of protein networks associated with ligand-activated EGFR
Authors: Perez Verdaguer Mireia , Zhang Tian , Paulo Joao A. , Wallace Callen , Watkins Simon C. , Gygi Steven P. , Sorkin Alexander 
Published: January 2022

ABSTRACTLigand binding to the EGF receptor (EGFR) triggers multiple signal transduction processes and promotes endocytosis of the receptor. The mechanisms of EGFR endocytosis and its crosstalk with signaling are poorly understood. Here, we combined peroxidase-catalyzed proximity labeling, isobaric peptide tagging and quantitative mass-spectrometry to define the dynamics of the proximity proteome of ligand-activated EGFR. Using this approach, we identified a network of signaling proteins, which remain associated with the receptor during its internalization and trafficking through the endosomal system. We showed that Trk-fused gene (TFG), a protein known to function at the endoplasmic reticulum exit sites, was enriched in the proximity proteome of EGFR in early/sorting endosomes and localized in these endosomes, and demonstrated that TFG regulates endosomal sorting of EGFR. This study provides a comprehensive resource of time-dependent nanoscale environment of EGFR, thus opening avenues to discovering new regulatory mechanisms of signaling and intracellular trafficking of receptor tyrosine kinases.
Comprehensive analysis of disease pathology in immunocompetent and immunocompromised hamster models of SARS-CoV-2 infection
Authors: Ramasamy Santhamani , Kolloli Afsal , Kumar Ranjeet , Husain Seema , Soteropoulos Patricia , Chang Theresa L. , Subbian Selvakumar 
Published: January 2022

ABSTRACTThe pathogenesis of SARS-CoV-2 in the context of a specific immunological niche is not fully understood. Here, we used a golden Syrian hamster model to systematically evaluate the kinetics of host response to SARS-CoV-2 infection, following disease pathology, viral loads, antibody responses, and inflammatory cytokine expression in multiple organs. The kinetics of SARS-CoV-2 pathogenesis and genomewide lung transcriptome was also compared between immunocompetent and immunocompromised hamsters. We observed that the body weight loss was proportional to the SARS-CoV-2 infectious dose and lasted for a short time only in immunocompetent hamsters. Body weight loss was more prominent and prolonged in infected immunocompromised hamsters. While the kinetics of viral replication and peak live viral loads were not significantly different at low and high infectious doses (LD and HD), the HD-infected immunocompetent animals developed severe lung disease pathology. The immunocompetent animals cleared the live virus in all tested tissues by 12 days post-infection and generated a robust serum antibody response. In contrast, immunocompromised hamsters mounted an inadequate SARS-CoV-2 neutralizing antibody response, and the virus was detected in the pulmonary and multiple extrapulmonary organs until 16 days post-infection. These hamsters also had prolonged moderate inflammation with severe bronchiolar-alveolar hyperplasia/metaplasia. Consistent with the difference in disease presentation, distinct changes in the expression of inflammation and immune cell response pathways and network genes were seen in the lungs of infected immunocompetent and immunocompromised animals. This study highlights the interplay between the kinetics of viral replication and the dynamics of SARS-CoV-2 pathogenesis at organ-level niches and maps how COVID-19 symptoms vary in different immune contexts. Together, our data suggest that the histopathological manifestations caused by progressive SARS-CoV-2 infection may be a better predictor of COVID-19 severity than individual measures of viral load, antibody response, and cytokine storm at the systemic or local (lungs) levels in the immunocompetent and immunocompromised hosts.
Now I can see: how brand interactions influence channel loyalty and purchase intention in optical physical stores
Authors: Bilro Ricardo Godinho , Dias Fernando 
Published: January 2022

PurposeThis study aims to analyse the effect of brand interactions such as personal interaction, problem-solving, reliability and store physical appearance on channel loyalty and purchase intention in optical physical stores.Design/methodology/approachThe hypotheses are tested through quantitative research based on a questionnaire with a sample of 414 respondents. Researchers conduct multiple regressions to analyse the data.FindingsThe findings reveal that channel loyalty and purchase intention are positively influenced differently. Person-to-person interactions play a vital role in both constructs (dependent variables). This study also offers relevant managerial implications and future research avenues.Originality/valueDespite the relevance of purchase intention in the literature, almost no studies have been published about the intention to buy glasses in the optical physical stores, a relevant contribution this paper offers to the literature. The finding that the store’s physical aspect did not prove to be influential for channel loyalty is also an innovative and relevant contribution of this research.
Examining our own relationships to racism as the foundation of decolonising systemic practices. ‘No time like the present’
Authors: Chin Jasmine , Hughes Gillian , Miller Ashley 
Published: January 2022

AbstractRacist discourses embedded in our social structures can have a profoundly negative impact on people's emotional well‐being. This paper calls for a re‐focusing within systemic therapy on anti‐colonial and social justice approaches specifically on addressing racism. We propose that if we are to make this shift in our practice, we need to first engage in processes of self‐reflexivity about the impact of racism on ourselves and our personal relationships. We draw on Paolo Freire's idea of ‘conscientisation’, or consciousness raising – a form of self‐reflexivity through the lens of power, and on the work of McKenzie‐Mavinga, who highlights the importance of therapists developing their awareness and understanding of how racism operates in their lives. We illustrate these ideas through an exploration of how we have approached this work within a long‐standing peer supervision group.
Clinical feasibility of transfer to combined therapy with peritoneal dialysis and hemodialysis for patients on peritoneal dialysis: A prospective multicenter study in Japan
Authors: Maruyama Yukio , Yokoyama Keitaro , Higuchi Chieko , Sanaka Tsutomu , Tanaka Yoshihide , Sakai Ken , Kanno Yoshihiko , Ryuzaki Munekazu , Sakurada Tsutomu , Hosoya Tatsuo , Nakayama Masaaki ,   for the EARTH (Evaluation of the Adequacy of Renal replacement THerapy) study group
Published: January 2022

AbstractIntroductionAlthough combined therapy with peritoneal dialysis (PD) and hemodialysis (HD) is widespread in Japan, its clinical utility has been reported only in retrospective or before‐and‐after test lacking a control group.MethodsWe conducted a prospective, multicenter, observational cohort study of 176 incident PD patients and compared patient survival and changes in clinical parameters between patients on different dialysis modalities.ResultsDuring a median follow‐up of 41 months, 47 patients transferred to combined therapy and 35 patients transferred directly to HD. Patients transferred to combined therapy had a significantly better survival than those transferred directly to HD. However, we could not establish this difference in a multivariate analysis because only six patients died among these groups. The decreases in urea nitrogen and serum creatinine were more prominent among patients directly transferred to HD.ConclusionThis is the first report revealing clinical feasibility of transfer to combined therapy for PD patients.
Performance Targets and Ex Post Incentive Plan Adjustments†
Authors: Hyun Jeong‐Hoon , MatĚjka Michal , (Seung Hwan) Oh Peter , Ahn Tae Sik 
Published: January 2022

ABSTRACTPerformance evaluations are typically based on a formula that specifies in advance all performance measures, their relative incentive weights, and targets to be met. However, beginning‐of‐year performance targets can become outdated due to unforeseen events that call for ex post adjustments to formula‐based incentive plans to restore incentives. We discuss three types of ex post incentive plan adjustments—end‐of‐year subjective performance evaluation, changes in next‐year relative incentive weights, and changes in next‐year performance targets—and empirically examine the extent to which they are used to discourage failure to meet a target by a wide margin. Specifically, we use 2004–2015 data on formula‐based bonus plans, subjective performance evaluations, and performance in Korean state‐owned enterprises. Consistent with our predictions, we find that very low performance relative to target is associated with (i) low subjective evaluations and (ii) an increase in next‐year incentive weights, conditions that render areas with poor performance more important in future evaluations. These findings are more pronounced on performance dimensions of high importance and less pronounced when very low performance is due to an adverse uncontrollable shock. Finally, we find evidence that ex post incentive plan adjustments are associated with future performance improvements. Combined, our findings suggest that ex post incentive plan adjustments can be used to strengthen incentives when performance targets get outdated.
Anatomical position of the palmar/plantar nerves at the metacarpal/metatarsal distal level in horses: An in vivo study by means of ultrasonography
Authors: Maia Beatriz Tofani , Vendruscolo Cynthia do Prado , de Souza Anderson Fernando , Zoppa André Luis do Valle De 
Published: January 2022

AbstractThe neurovascular bundle of the equine distal cannon can dynamically vary with limb position, and this can affect the performance of low 4‐ or 6‐point block. This study aims to identify and describe the anatomical position and variations of the lateral and medial palmar/plantar nerve at the metacarpal/metatarsal distal level in horses by ultrasonography. Eight mares underwent ultrasound examination on the lateral and medial palmar/plantar sides of the metacarpus/metatarsus. Images were obtained for measurements of the cross‐sectional area of the nerve, distances between the nerve and the skin surface, branch of the suspensory ligament (SL), deep digital flexor tendon (DDFT) and superficial digital flexor tendon (SDFT) with limbs supported and elevated. The distance to the skin for forelimbs was higher on the lateral side when the limb was elevated (p < 0.001). The comparisons between supported and elevated limbs on the same side showed longer distances to the skin with the limb supported on the medial side (p < 0.001). Hindlimbs showed longer distances to the skin with the limb supported on the medial face (p = 0.027). The anatomical position of palmar/plantar nerves was similar between the lateral and medial sides of the limb, generally being in contact with the dorsal edge of DDFT. The strategy of elevating the limb during the injection of the low 4‐ or 6‐point block can lead to a higher risk of puncture of the digital sheath.
Comparison of Indian and Nepalese media on “Nepal's New Political Map”
Authors: Aryal Saroj K. , Bharti Simant S. 
Published: January 2022

AbstractA newly revised political map was published by the Nepalese government on May 20, 2020, which includes, as part of Nepali territory, the disputed areas of Lipulekh, Kalapani, and Limpiyadhura. The long‐existing border dispute between India and Nepal gets heated up again. Nepal considered the updated political map as a retaliation toward India and India considered it as a breach of the friendship line between the two countries. During this period, the media from both sides were engaged and the narrative that we find contradicts each other in many ways. This review article conducts a media analysis and present the different narratives that we found during these period.
Rabbit antithymocyte globulin dose and early subclinical and clinical rejections in kidney transplantation
Authors: Mehta Rajil B. , Shimko Kristen , Zhang Xingyu , Puttarajappa Chethan , Wu Christine , Sharma Akhil , Molinari Michele , Tevar Amit D. , Hariharan Sundaram , Sood Puneet 
Published: January 2022

AbstractAntithymocyte globulin (ATG) is a commonly used induction agent in kidney transplant recipients. However, the optimal dosing has not been well defined. Our protocol aims for a 5–6 mg/kg cumulative dose. It is unclear if a dose lower than 5 mg/kg is associated with more rejection.We performed a retrospective cohort study of patients who received a kidney transplant at our center between January 1, 2013 and December 31, 2016. Primary outcome was biopsy proven acute rejection (clinical and subclinical) in the first 6 months after kidney transplant. CMV viremia in high risk (D+/R−) recipients and BK viremia was compared as a secondary endpoint.Of the 543 patients, the Low Dose (LD) group (n = 56) received <5 mg/kg ATG and Regular Dose (RD) group (n = 487) received ≧5 mg/kg. Patients in RD were more sensitized (higher PRA and CPRA). LD received a dose of 4 ± 1.1 mg/kg ATG whereas RD received 5.6 ± .3 mg/kg ATG (P < .001). TCMR (Banff 1A or greater) was present in 34% of patients in LD versus 22% in RD (P = .04) (OR 2.1; 95%CI 1.12–3.81; P = .019). There was no difference in the incidence of CMV or BK viremia.ATG doses lower than 5 mg/kg may be associated with a heightened risk of rejection despite a low degree of sensitization.
An observational study of the Covid‐19 situation following the first pan‐European mass sports event
Authors: Cuschieri Sarah , Grech Stephan , Cuschieri Andrea 
Published: January 2022

AbstractBackgroundAll events in Europe, including EURO2020 football championship, were postponed due to Covid‐19 in 2020. Instead, Euro2020 took place in 2021, as mitigation measures were relaxed, cross‐country mobility increased and the Delta variant was spreading across Europe. This study explored the possibility of an increased Covid‐19 spread across Europe following EURO2020 matches.MethodsCovid‐19 data on cases, vaccination and delta variant for participating countries, host cities/regions and neighbouring countries, for May till July 2021, were obtained from European Centre for Disease Prevention and Control, Our World in Data, Johns Hopkins COVID‐19 Dashboard and the UK Government website. EURO2020 data were obtained from the Union of European Football Associations official website.ResultsA general increase in Covid‐19 positivity trend in Europe was observed following a week of EURO2020 matches across most countries and host cities. A similar trend was observed for the Delta variant sample positivity rate. The increased incidence was mostly among the young generation (<49 years). A decline in positive cases was observed on a national level for most countries following the Finals match.ConclusionThe EURO2020 was an anticipated mass sports event, and it was the first‐time spectators were allowed to enter stadiums in Europe. Stadiums instituted several mitigations to safeguard the spectators although reports of transmission were still present. The major challenges were the gatherings outside the stadiums that might have contributed to these observations. Targeted restrictions might be required during mass sport events especially in the presence of highly transmissible variant(s) and low vaccination rates among the young generation.
Property and inequality: Housing dynamics in a nineteenth‐century city
Authors: Rodger Richard 
Published: January 2022

AbstractThe internal structure of the city is analysed through the ownership, tenancy, and management of residential property using assessed rents to reflect current market value. The analysis reveals the interactions of agents, institutions, and trusts, and explores ownership in terms of gender, absenteeism, occupational categories, portfolio sizes, and values. Rents are used to develop both an index of housing affordability according to occupations, and an index of dissimilarity in rental variations within and between streets to provide a nuanced and more realistic understanding of the internal dynamics of an entire city—Edinburgh. While empirical material underpinning the analysis is place‐specific, the underlying urban processes and relationships are generalizable, and provide a comprehensive overview of residential property relationships.
Investing for retirement: Terminal wealth constraints or a desired wealth target?
Authors: Donnelly Catherine , Khemka Gaurav , Lim William 
Published: January 2022

AbstractWe investigate how well different investment strategies can give pre‐retirees more certainty about their income in retirement, whilst allowing them to benefit from taking investment risk. Under an expected utility‐maximizing framework, we find that a loss aversion utility function gives a high degree of certainty about its desired wealth target and is robust to different market models. Imposing terminal wealth constraints does not improve the certainty of achieving the desired target enough to counterbalance the increased chance of obtaining a lower income. The power utility function is not robust to different market models and becomes too risk‐averse with wealth constraints.