bluuebunny/crossref_metadata_2025_split huggingface dataset:
BWA-MEME: BWA-MEM emulated with a machine learning approach
Authors: Jung Youngmok , Han Dongsu 
Published: March 2022

AbstractMotivationThe growing use of next-generation sequencing and enlarged sequencing throughput require efficient short-read alignment, where seeding is one of the major performance bottlenecks. The key challenge in the seeding phase is searching for exact matches of substrings of short reads in the reference DNA sequence. Existing algorithms, however, present limitations in performance due to their frequent memory accesses.ResultsThis article presents BWA-MEME, the first full-fledged short read alignment software that leverages learned indices for solving the exact match search problem for efficient seeding. BWA-MEME is a practical and efficient seeding algorithm based on a suffix array search algorithm that solves the challenges in utilizing learned indices for SMEM search which is extensively used in the seeding phase. Our evaluation shows that BWA-MEME achieves up to 3.45× speedup in seeding throughput over BWA-MEM2 by reducing the number of instructions by 4.60×, memory accesses by 8.77× and LLC misses by 2.21×, while ensuring the identical SAM output to BWA-MEM2.Availability and implementationThe source code and test scripts are available for academic use at https://github.com/kaist-ina/BWA-MEME/.Supplementary informationSupplementary data are available at Bioinformatics online.
An ensemble approach to predict binding hotspots in protein–RNA interactions based on SMOTE data balancing and Random Grouping feature selection strategies
Authors: Zhou Tong , Rong Jie , Liu Yang , Gong Weikang , Li Chunhua 
Published: March 2022

AbstractMotivationThe identification of binding hotspots in protein–RNA interactions is crucial for understanding their potential recognition mechanisms and drug design. The experimental methods have many limitations, since they are usually time-consuming and labor-intensive. Thus, developing an effective and efficient theoretical method is urgently needed.ResultsHere, we present SREPRHot, a method to predict hotspots, defined as the residues whose mutation to alanine generate a binding free energy change ≥2.0 kcal/mol, while others use a cutoff of 1.0 kcal/mol to obtain balanced datasets. To deal with the dataset imbalance, Synthetic Minority Over-sampling Technique (SMOTE) is utilized to generate minority samples to achieve a dataset balance. Additionally, besides conventional features, we use two types of new features, residue interface propensity previously developed by us, and topological features obtained using node-weighted networks, and propose an effective Random Grouping feature selection strategy combined with a two-step method to determine an optimal feature set. Finally, a stacking ensemble classifier is adopted to build our model. The results show SREPRHot achieves a good performance with SEN, MCC and AUC of 0.900, 0.557 and 0.829 on the independent testing dataset. The comparison study indicates SREPRHot shows a promising performance.Availability and implementationThe source code is available at https://github.com/ChunhuaLiLab/SREPRHot.Supplementary informationSupplementary data are available at Bioinformatics online.
Age-Related Changes in the Nasopharyngeal Microbiome Are Associated With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection and Symptoms Among Children, Adolescents, and Young Adults
Authors: Hurst Jillian H , McCumber Alexander W , Aquino Jhoanna N , Rodriguez Javier , Heston Sarah M , Lugo Debra J , Rotta Alexandre T , Turner Nicholas A , Pfeiffer Trevor S , Gurley Thaddeus C , Moody M Anthony , Denny Thomas N , Rawls John F , Clark James S , Woods Christopher W , Kelly Matthew S 
Published: March 2022

Abstract

Background
Children are less susceptible to SARS-CoV-2 infection and typically have milder illness courses than adults, but the factors underlying these age-associated differences are not well understood. The upper respiratory microbiome undergoes substantial shifts during childhood and is increasingly recognized to influence host defense against respiratory pathogens. Thus, we sought to identify upper respiratory microbiome features associated with SARS-CoV-2 infection susceptibility and illness severity.

Methods
We collected clinical data and nasopharyngeal swabs from 285 children, adolescents, and young adults (&lt;21 years) with documented SARS-CoV-2 exposure. We used 16S ribosomal RNA gene sequencing to characterize the nasopharyngeal microbiome and evaluated for age-adjusted associations between microbiome characteristics and SARS-CoV-2 infection status and respiratory symptoms.

Results
Nasopharyngeal microbiome composition varied with age (PERMANOVA, P &lt; .001; R2 = 0.06) and between SARS-CoV-2–infected individuals with and without respiratory symptoms (PERMANOVA, P  = .002; R2 = 0.009). SARS-CoV-2–infected participants with Corynebacterium/Dolosigranulum-dominant microbiome profiles were less likely to have respiratory symptoms than infected participants with other nasopharyngeal microbiome profiles (OR: .38; 95% CI: .18–.81). Using generalized joint attributed modeling, we identified 9 bacterial taxa associated with SARS-CoV-2 infection and 6 taxa differentially abundant among SARS-CoV-2–infected participants with respiratory symptoms; the magnitude of these associations was strongly influenced by age.

Conclusions
We identified interactive relationships between age and specific nasopharyngeal microbiome features that are associated with SARS-CoV-2 infection susceptibility and symptoms in children, adolescents, and young adults. Our data suggest that the upper respiratory microbiome may be a mechanism by which age influences SARS-CoV-2 susceptibility and illness severity.
IL-23 Monoclonal Antibodies for IBD: So Many, So Different?
Authors: McDonald Benjamin D , Dyer Emma C , Rubin David T 
Published: March 2022

Abstract
Interleukin [IL]-23 is a member of the IL-12 family of cytokines and has been implicated in multiple inflammatory disorders including psoriasis, psoriatic arthritis, and the inflammatory bowel diseases [IBDs]. Blockade of both IL-12 and IL-23 using an antibody that targets a shared subunit is highly effective in treating psoriasis, and recent data suggest similar efficacy in IBD with minimal adverse events. In this review, we summarise published data on the efficacy of anti-IL-12/23 therapies in IBD as well as emerging data on more selective anti-IL-23 specific therapies. Last, we discuss novel therapeutics under development which target the IL-23 pathway in unique ways and suggest that a biomarker-driven approach will soon guide clinicians to prescribe anti-IL-23 therapies to the patients most likely to respond to them.
Cardiac sympathetic denervation in the prevention of genetically mediated life-threatening ventricular arrhythmias
Authors: Schwartz Peter J. , Ackerman Michael J. 
Published: March 2022

Abstract
Proper management of patients affected by genetic disorders causing life-threatening arrhythmias is important for several reasons, including even societal ones, given the predominantly young age of those affected. Incorrect management often has dire consequences, ranging from unnecessary psychologic damage for the patients whose life becomes too limited by the fear of sudden death to equally avoidable tragedies when the entire armamentarium of effective therapies is not fully utilized. In this review, we focus primarily on long QT syndrome (LQTS) and catecholaminergic polymorphic ventricular tachycardia (CPVT) and deal specifically with the clinical impact of the most commonly used cardiac sympathetic denervation (CSD), namely left cardiac sympathetic denervation (LCSD). The two of us have used LCSD in the management of our patients with either LQTS or CPVT for a very long time and have been involved in ∼500 such interventions. It is on the basis of this personal and direct experience that we wish to share our views with clinical cardiologists and electrophysiologists, adult and paediatric, and with genetic cardiologists. We will begin by reviewing the history and rationale underlying sympathetic denervation therapy and will continue with a disease-specific intensification of therapy, and then with a discussion on how the impressive efficacy of LCSD should translate into guideline-directed therapy in both current and future guidelines, in order to upgrade the quality of care in the era of precision medicine.
Electromechanical reciprocity and arrhythmogenesis in long-QT syndrome and beyond
Authors: Odening Katja E , van der Linde Henk J , Ackerman Michael J , Volders Paul G A , ter Bekke Rachel M A 
Published: March 2022

AbstractAn abundance of literature describes physiological and pathological determinants of cardiac performance, building on the principles of excitation–contraction coupling. However, the mutual influencing of excitation–contraction and mechano-electrical feedback in the beating heart, here designated ‘electromechanical reciprocity’, remains poorly recognized clinically, despite the awareness that external and cardiac-internal mechanical stimuli can trigger electrical responses and arrhythmia. This review focuses on electromechanical reciprocity in the long-QT syndrome (LQTS), historically considered a purely electrical disease, but now appreciated as paradigmatic for the understanding of mechano-electrical contributions to arrhythmogenesis in this and other cardiac conditions. Electromechanical dispersion in LQTS is characterized by heterogeneously prolonged ventricular repolarization, besides altered contraction duration and relaxation. Mechanical alterations may deviate from what would be expected from global and regional repolarization abnormalities. Pathological repolarization prolongation outlasts mechanical systole in patients with LQTS, yielding a negative electromechanical window (EMW), which is most pronounced in symptomatic patients. The electromechanical window is a superior and independent arrhythmia-risk predictor compared with the heart rate-corrected QT. A negative EMW implies that the ventricle is deformed—by volume loading during the rapid filling phase—when repolarization is still ongoing. This creates a ‘sensitized’ electromechanical substrate, in which inadvertent electrical or mechanical stimuli such as local after-depolarizations, after-contractions, or dyssynchrony can trigger abnormal impulses. Increased sympathetic-nerve activity and pause-dependent potentiation further exaggerate electromechanical heterogeneities, promoting arrhythmogenesis. Unraveling electromechanical reciprocity advances the understanding of arrhythmia formation in various conditions. Real-time image integration of cardiac electrophysiology and mechanics offers new opportunities to address challenges in arrhythmia management.
The HOG pathway and the regulation of osmoadaptive responses in yeast
Authors: de Nadal Eulàlia , Posas Francesc 
Published: March 2022

Abstract
Cells coordinate intracellular activities in response to changes in the extracellular environment to maximize their probability of survival and proliferation. Eukaryotic cells need to adapt to constant changes in the osmolarity of their environment. In yeast, the high-osmolarity glycerol (HOG) pathway is responsible for the response to high osmolarity. Activation of the Hog1 stress-activated protein kinase (SAPK) induces a complex program required for cellular adaptation that includes temporary arrest of cell cycle progression, adjustment of transcription and translation patterns, and the regulation of metabolism, including the synthesis and retention of the compatible osmolyte glycerol. Hog1 is a member of the family of p38 SAPKs, which are present across eukaryotes. Many of the properties of the HOG pathway and downstream-regulated proteins are conserved from yeast to mammals. This review addresses the global view of this signaling pathway in yeast, as well as the contribution of Dr Hohmann's group to its understanding.
The Constructionist Approach to Emotional Aging: Theoretical Insights and Predictions
Authors: Mikkelsen Mai Bjørnskov , O’Toole Mia Skytte 
Published: March 2022

Abstract
In this article, we introduce a constructionist approach to understanding emotional aging in adulthood. The purpose of the paper is to show how constructionism offers a promising avenue for gaining new insights into age-related changes in emotional experiences. We begin by introducing the constructionist theoretical framework and illustrating how constructionism may shape conceptualizations of emotional aging in adulthood. We compare the constructionist conceptualization of emotional aging with existing conceptualizations of emotional aging derived from prominent theories of emotional aging, focusing on how such conceptualizations highlight different aspects of emotional aging (e.g., different mechanisms) and overlook or downplay other aspects. We conclude by explicating what constructionism may offer research on emotional aging, including considerations of research agendas, study designs, and method of measurement.
A Panel Study of Attitudes toward Ethnic Minorities and the Role of Changes in Individuals’ Economic Situations
Authors: Hendriks Inge , Lubbers Marcel , Scheepers Peer 
Published: March 2022

Abstract
This study applies the dynamic perspective of realistic conflict theory to assess whether and the extent that individuals’ negative attitudes toward ethnic minorities changed and were linked to changes in individuals’ economic situations. Employing Dutch panel data, we found that negative attitudes toward ethnic minorities were remarkably stable. Differences in attitudes toward ethnic minorities were more pronounced between individuals than within individuals. The small changes that did occur over the 10-year study period were hardly explained by economic characteristics. Only increased individual dissatisfaction with the national financial situation was associated with more negative attitudes. These results cast doubt on whether attitudes toward ethnic minorities are susceptible to change and raise questions about realistic conflict theory’s relevance in explaining attitudinal change.
Transcriptome Analysis of Plasmodium falciparum Isolates From Benin Reveals Specific Gene Expression Associated With Cerebral Malaria
Authors: Guillochon E , Fraering J , Joste V , Kamaliddin C , Vianou B , Houzé L , Baudrin L G , Faucher J F , Aubouy A , Houzé S , Cot M , Argy N , Taboureau O , Bertin G I ,   NeuroCM group, Alao Jules , Affolabi Dissou , Biokou Bibiane , Degbelo Jean-Eudes , Deloron Philippe , Dramane Latifou , Jafari-Guemouri Sayeh , Labrunie Anaïs , Ladipo Yélé , Lathiere Thomas , Massougbodji Achille , Mowendabeka Audrey , Papin Jade , Pipy Bernard , Preux Pierre-Marie , Raymondeau Marie , Royo Jade , Sossou Darius , Techer Brigitte 
Published: March 2022

Abstract
Cerebral malaria (CM) is the severest form of Plasmodium falciparum infection. Children under 5 years old are those most vulnerable to CM, and they consequently have the highest risk of malaria-related death. Parasite-associated factors leading to CM are not yet fully elucidated. We therefore sought to characterize the gene expression profile associated with CM, using RNA sequencing data from 15 CM and 15 uncomplicated malaria isolates from Benin. Cerebral malaria parasites displayed reduced circulation times, possibly related to higher cytoadherence capacity. Consistent with the latter, we detected increased var genes abundance in CM isolates. Differential expression analyses showed that distinct transcriptome profiles are signatures of malaria severity. Genes involved in adhesion, excluding variant surface antigens, were dysregulated, supporting the idea of increased cytoadhesion capacity of CM parasites. Finally, we found dysregulated expression of genes in the entry into host pathway that may reflect greater erythrocyte invasion capacity of CM parasites.
Structural insight into replicative helicase loading in Escherichia coli
Authors: Horikoshi Naoki , Kurumizaka Hitoshi 
Published: March 2022

Abstract
DNA replication is an essential, precisely regulated process that occurs once in a cell cycle. In the Gram-negative bacterium Escherichia coli, the replicative helicase EcDnaB and the helicase loader EcDnaC play key roles in the initiation step at the replication origin, oriC. EcDnaB and EcDnaC form a heterododecamer, in which hexameric EcDnaB is bound to hexameric EcDnaC. Using genetic, biochemical and structural biology approaches, many groups have probed the mechanism of replicative helicase loading, using helicases and helicase loaders from various species. Recent X-ray crystallography and cryogenic electron microscopy (cryo-EM) structural studies of the EcDnaB–EcDnaC complex revealed that the interaction of DnaC with DnaB triggers distortion accumulation on the closed ring of hexameric DnaB, inducing DnaB subunits to adopt the open helical form for replication progression. The high-resolution crystal structure of the DnaB–DnaC complex solved by Nagata et al. contributed to a better understanding of the conformational rearrangement of the DnaB ring. In addition to the structural alterations in DnaB subunits by DnaC, the binding of single-stranded DNA (ssDNA) substrates alters the ATP- and ADP-bound forms of DnaB and DnaC. These studies have proposed mechanisms by which DnaC regulates helicase loading onto ssDNA.
Modeling Realized Covariance Matrices: A Class of Hadamard Exponential Models
Authors: Bauwens Luc , Otranto Edoardo 
Published: March 2022

Abstract
Time series of realized covariance matrices can be modeled in the conditional autoregressive Wishart model family via dynamic correlations or via dynamic covariances. Extended parameterizations of these models are proposed, which imply a specific and time-varying impact parameter of the lagged realized covariance (or correlation) on the next conditional covariance (or correlation) of each asset pair. The proposed extensions guarantee the positive definiteness of the conditional covariance or correlation matrix with simple parametric restrictions, while keeping the number of parameters fixed or linear with respect to the number of assets. Two empirical studies reveal that the extended models have superior forecasting performances than their simpler versions and benchmark models.
Discretionary Responses in Frontline Encounters: Balancing Standardization with the Ethics of Office
Authors: Pedersen Kirstine Zinck , Pors Anja Svejgaard 
Published: March 2022

AbstractPolicy reforms of public service encounters often seek to control, delegate, or eliminate discretion at the frontline. In this article, we show that rather than eclipsing discretion, the technologies meant to standardize and optimize decision making in public service delivery introduce rough categorizations and scripts for action that make new types of discretionary responses and workarounds necessary. Here, accounts of street-level discretion as grounded in self-serving coping strategies are inadequate to capture discretion-as-used in the frontline encounter. The article proposes a Weberian ethics of office approach to frontline discretion that contributes to current more appreciative perspectives on street-level discretion. Through a comparative ethnography of first encounters in three Danish public service bureaucracies, we develop a typology of office-based discretionary responses to standardization. We label the three types as adaptive handling, attentive compensation, and affective encouragement. Our study of doctors, midwives, and citizen-service bureaucrats suggests that discretionary possibilities differ in relation to organizational context and level of professional training. However, across cases the discretionary responses are indicative of the frontline practitioners’ casuistic practices of balancing professional virtues, client-orientation, and managerial demands in the quest to deliver fair and responsive services. Accordingly, securing the conditions for the exercise of discretion in frontline encounters is essential to the responsible provision of public services.
The effects ofEpichloëendophytes on the growth and competitiveness ofAchnatherum sibiricumare mediated by soil microbe diversity
Authors: Qu Yaobing , Qin Tianzi , Shi Xinjian , Chen Jing , Liu Hui , Zhao Nianxi , Gao Yubao , Ren Anzhi 
Published: March 2022

AbstractMany grasses are infected by systemic fungal endophytes that occur in aboveground plant tissues. Both aboveground endophytic fungi and belowground soil microbes can influence plant growth, but studies on their simultaneous effects on plant growth and competitiveness are limited. This study aims to investigate whether the role of aboveground endophytic fungi in the growth and competitive ability of the host grasses was influenced by soil microbes. In this study, we used Epichloë endophyte-infected and endophyte-free Achnatherum sibiricum as plant materials. A wet sieving method was adopted to obtain microbial inocula with different diversities (com, combined microbe fraction, high diversity; sm, small microbe fraction, low diversity). A three-factor randomized block design was used. The first factor was the endophyte infection status of A. sibiricum. The second factor was the microbial composition of the soil inocula. The third factor was the planting type. Growth and competitive characters were measured after 16 weeks. The results showed that a soil microbe inoculation was detrimental to the growth of A. sibiricum. Epichloë endophytes significantly mitigated the inhibitory effect of soil microbes on A. sibiricum planted alone. When A. sibiricum was planted with Stipa grandis, there was a significant interaction between Epichloë endophytes and soil microbes on the interspecific competition of A. sibiricum. When inoculated with small microbial community fraction, Epichloë endophytes significantly improved the interspecific competitive ability of host plants. When inoculated with combined microbial community fraction, however, Epichloë endophytes had no significant effect on host competition. The results showed that the interaction between Epichloë endophytes and soil microbes contributed more to the interspecific competitive ability than either Epichloë endophytes or soil microbes alone.
Tension offloading improves cutaneous scar formation in Achilles tendon repair
Authors: Abbas Darren B , Lintel Hendrik , Griffin Michelle , Guardino Nicholas J , Guo Jason L , Spielman Amanda F , Cotterell Asha C , Parker Jennifer B L , Januszyk Michael , Wan Derrick C 
Published: March 2022

Abstract
Hypertrophic scar formation and non-healing wounds following Achilles tendon repair arise from poor vascularity to the incisional site or from excess mechanical stress/strain to the incision during the healing process. The embrace® scar therapy dressing is a tension offloading device for incisional scars. This study explored the effects of tension offloading during Achilles scar formation. A healthy 30-year-old male without any medical co-morbidities developed an acute rupture of his left Achilles tendon. The patient underwent open repair 1 week after injury. At post-operative day (POD) 14, the patient started daily tension offloading treatment on the inferior portion of the incision through POD 120. By POD 120, the untreated portion of the Achilles incision appeared hypertrophic and hyperpigmented, while the treated portion of the scar appeared flat with minimal pigmentation changes. The 12-week treatment of tension offloading on an Achilles tendon repair incision significantly improved cosmesis compared to untreated incision.