bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigation of latent representation of toxicopathological images extracted by CNN model for understanding compound propertiesin vivo
Authors: Maedera Shotaro , Mizuno Tadahaya , Kusuhara Hiroyuki 
Published: July 2023

AbstractToxicopathological images acquired during safety assessment elucidate an individual’s biological responses to a given compound, and their numerization can yield valuable insights contributing to the assessment of compound properties. Currently, toxicopathological images are mainly encoded as pathological findings, evaluated by pathologists, which introduces challenges when used as input for modeling, specifically in terms of representation capability and comparability. In this study, we assessed the usefulness of latent representations extracted from toxicopathological images using Convolutional Neural Network (CNN) in estimating compound propertiesin vivo. Special emphasis was placed on examining the impact of learning pathological findings, the depth of frozen layers during learning, and the selection of the layer for latent representation. Our findings demonstrate that a machine learning model fed with the latent representation as input surpassed the performance of a model directly employing pathological findings as input, particularly in the classification of a compound’s Mechanism of Action and in predicting late-phase findings from early-phase images in repeated-dose tests. While learning pathological findings did improve accuracy, the magnitude of improvement was relatively modest. Similarly, the effect of freezing layers during learning was also limited. Notably, the selection of the layer for latent representation had a substantial impact on the accurate estimation of compound propertiesin vivo.
Whole-brain dynamics and hormonal fluctuations across the menstrual cycle: The role of progesterone and age in healthy women
Authors: Avila-Varela Daniela S. , Hidalgo-Lopez Esmeralda , Dagnino Paulina Clara , Acero-Pousa Irene , Agua Elvira del , Deco Gustavo , Pletzer Belinda , Escrichs Anira 
Published: July 2023

AbstractRecent neuroimaging research suggests that female sex hormone fluctuations modulate brain activity. Nevertheless, how brain network dynamics change across the female menstrual cycle remains largely unknown. Here, we investigated the dynamical complexity u nderlying three menstrual cycle phases (i.e., early follicular, pre-ovulatory, and mid-luteal) in 60 healthy naturally-cycling women scanned using resting-state fMRI. Our results revealed that the preovulatory phase exhibited the highest variability over time (node-metastability) across the whole-brain functional network compared to the early follicular and mid-luteal phases, while the early follicular showed the lowest. Additionally, we found that large-scale resting-state networks reconfigure along the menstrual cycle phases. Finally, we used multilevel mixed-effects models to examine the impact of hormonal fluctuations and age on whole-brain and resting-state networks. We found significant age-related changes across the whole brain, control, and dorsolateral attention networks. Additionally, we observed progesterone-related changes, specifically within limbic and somatomotor networks. Overall, these findings evidence that both age and progesterone modulate brain network dynamics along the menstrual cycle.
Differentiable Search of Evolutionary Trees
Authors: Hettiarachchi Ramith , Swartz Avi , Ovchinnikov Sergey 
Published: July 2023

AbstractInferring the most probable evolutionary tree given leaf nodes is an important problem in computational biology that reveals the evolutionary relationships between species. Due to the exponential growth of possible tree topologies, finding the best tree in polynomial time becomes computationally infeasible. In this work, we propose a novel differentiable approach as an alternative to traditional heuristic-based combinatorial tree search methods in phylogeny. The optimization objective of interest in this work is to find the most parsimonious tree (i.e., to minimize the total number of evolutionary changes in the tree). We empirically evaluate our method using randomly generated trees of up to 128 leaves, with each node represented by a 256-length protein sequence. Our method exhibits promising convergence (< 1% error for trees up to 32 leaves, < 8% error up to 128 leaves, given only leaf node information), illustrating its potential in much broader phylogenetic inference problems and possible integration with end-to-end differentiable models. The code to reproduce the experiments in this paper can be found athttps://github.ramith.io/diff-evol-tree-search.
Hospital length of stay and discharge type prediction using deep learning
Authors: Ramachandra Vikas , Sanghi Prateek 
Published: July 2023

AbstractThe length of hospital stay (LOS) and the type of discharge are important indicators of how well care is provided at a hospital. The purpose of this study is to leverage in-patient data collected at the hospital to help determine the factors that influence the length of hospital stay and type of discharge. Our research focuses on estimating if the person survived or not after they were admitted to the hospital, as well as the type of discharge. The study uses a retrospective design and examines information from hospital discharged patients’ medical records. Demographic information, diagnosis, treatment, and discharge status were included in the data. We have used the PEDALFAST dataset which stands for PEDiatric Validation of Variables in Trauma. A survey of patients to find out how they feel about the quality of care they received while they were in the hospital was also a part of the study dataset. The findings of this study will shed light on the ways in which various factors influence the LOS in the hospital and the type of discharge, assisting in the formulation of strategies to enhance the quality and effectiveness of health care delivery.
Publication bias in otorhinolaryngology meta-analyses in 2021
Authors: Mohammadian Fatemeh , Bastaninejad Shahin , Irani Shirin 
Published: July 2023

AbstractIntroductionOne concern in meta-analyses is the presence of publication bias (PB) which leads to the dissemination of inflated results. In this study, we assessed how much the meta-analyses in the field of otorhinolaryngology in 2021 evaluated the presence of PB.MethodsSix of the most influential journals in the field were selected. A search was conducted, and data were extracted from the included studies. In cases where PB was not assessed by the authors, we evaluated the risk of its presence by designing funnel plots and performing statistical tests.Results75 systematic reviews were included. 51% of them used at least one method for assessing the risk of PB, with the visual inspection of a funnel plot being the most frequent method used. 29% of the studies reported a high risk of PB presence. We replicated the results of 11 meta-analyses that did not assess the risk of PB and found that 63.6% were at high risk.DiscussionOur results indicate that systematic reviews published in some of the most influential journals in the field do not implement enough measures in their search strategies to reduce the risk of PB, nor do they assess the risk of its presence.
Meta-analysis on Plasmodium falciparum sulfadoxine-pyrimethamine resistance-conferring mutations in India identifies hot spots for genetic surveillance
Authors: Sinha Abhinav , Kar Sonalika , Chauhan Charu , Yadav CP , Kori Lokesh 
Published: July 2023

BackgroundIndia is on track to eliminate malaria by 2030 but emerging resistance to the first-line antimalarials is a recognized threat. As Artesunate+Sulfadoxine-Pyrimethamine (AS+SP) is the drug-of-choice for uncomplicated P. falciparum malaria in most of India, it becomes evident to systematically monitor the validated mutations in Pfdhfr and Pfdhps genes across India. No systematic and robust countrywide surveillance has been reported for these parameters in India.MethodsWe included studies that reported data on SP-resistance markers in P. falciparum across India from 2008. Five major databases were exhaustively searched. Individual and pooled prevalence estimates of mutations were obtained through random- and fixed-effect models. The study is registered with PROSPERO (CRD42021236012).ResultsA total of 37 publications with data from 80 districts, 21 states and 3 UTs were included. The two PfDHFR mutations, C59R and S108N were the most prevalent mutations and appear to be stabilized/fixed. Although rarest overall, the prevalence of I164L was observed to be as high as 32%. The PfDHFR double mutants were the most prevalent overall. The prevalence of triple and quadruple mutations was 6% and 5%, respectively which is an area of immediate concern. For PfDHPS, the most prevalent mutation was A437G. For PfDHFR/PfDHPS quintuple and sextuple mutations, it was observed that despite a low overall prevalence of these mutations, some areas are critical for surveillance.ConclusionThe analysis brings forward the SP-resistance hot spots and emphasizes critical gaps, and challenges, and suggests focal and local malaria genetic surveillance (including drug resistance markers) till malaria is eliminated.Key pointsThis manuscript concludes that currently used first-line drugs for P. falciparum malaria, particularly sulfadoxine-pyrimethamine, have a high likelihood of failing in near future. Although currently effective, the evidence is backed by molecular meta-analyses data on drug resistance markers in India. The policy makers and program managers may use this robust data to decide whether it is time to change these currently used anti-malarials in India before it is too late. It also identifies certain hot spots for continuous genetic monitoring of the molecular markers for timely actions.
Extraordinary preservation of gene collinearity over three hundred million years revealed in homosporous lycophytes
Authors: Li Cheng , Wickell David , Kuo Li-Yaung , Chen Xueqing , Nie Bao , Liao Xuezhu , Peng Dan , Ji Jiaojiao , Jenkins Jerry , Williams Mellissa , Shu Shengqiang , Plott Chris , Barry Kerrie , Rajasekar Shanmugam , Grimwood Jane , Han Xiaoxu , Sun Shichao , Hou Zhuangwei , He Weijun , Dai Guanhua , Sun Cheng , Schmutz Jeremy , Leebens-Mack James H. , Li Fay-Wei , Wang Li 
Published: July 2023

AbstractHomosporous lycophytes (Lycopodiaceae) are a deeply diverged lineage in the plant tree of life, having split from heterosporous lycophytes (SelaginellaandIsoetes) ∼400 million years ago (MYA). Compared to the heterosporous lineage, Lycopodiaceae has markedly larger genome sizes and remains the last major plant clade for which no genomic data has been available. Here, we present chromosomal genome assemblies for two homosporous lycophyte species, the allotetraploidHuperzia asiaticaand the diploidDiphasiastrum complanatum. Remarkably, despite that the two species diverged ∼350 MYA, around 30% of the genes are still in syntenic blocks. Furthermore, both genomes had undergone independent whole genome duplications and the resulting intra-genomic syntenies have likewise been preserved relatively well. Such slow genome evolution over deep time is in stark contrast to heterosporous lycophytes and is correlated with a decelerated rate of nucleotide substitution. Together, the genomes ofH. asiaticaandD. complanatumnot only fill a crucial gap in the plant genomic landscape, but also uncover a possibly unique genomic contrast between homosporous and heterosporous species.
Antimicrobial activity of diverse chemotypes ofLippia graveolensagainstAeromonas hydrophilaisolated from tilapia
Authors: García-Pérez Josué , Pérez-Sabino Juan , Mendoza-Elvira Susana , da Silva Antonio Jorge Ribeiro , Ulloa-Rojas Juan 
Published: July 2023

AbstractObjetiveThis study aimed to evaluate the antimicrobial efficacy of essential oil (EO) from diverse chemotypes ofLippia graveolensagainst oxytetracycline-resistantAeromonas hydrophila, which primarily affects the tilapia aquaculture (Oreochromissp) in Guatemala.MethodologyL. graveolenswere collected in three departments in Guatemala, the EO was obtained by hydrodistillation and characterized by gas chromatography and mass spectrometry (GC/MS). Subsequently, an antimicrobial assay was conducted by screening the disk and dilution susceptibility tests, and evaluation of synergistic interactions among the chemotypes, each test being carried out in triplicate.ResultsThe analysis revealed the presence of twenty-seven compounds in the EO obtained from the chemotypes, the main class being monoterpene. The major constituents identified were cis-Dihydro-β-terpineol (8.84%) in chemotype I, carvacrol (51.82%) in chemotype II, and thymol (79.62%) in chemotype III. All EO chemotypes ofL. graveolensdemonstrated the ability to inhibit theA. hydrophilagrowth. Thymol chemotype exhibited the strongest inhibitory effect against bacterial growth, with a minimum inhibitory concentration (MIC) of 92.4 µg/mL and a minimum bactericidal concentration (MBC) of 184.8 µg/mL. Furthermore, the results suggest that there is no synergistic or additive effect when combining different chemotypes ofL. graveolens.ConclusionsThis the first report ofL. graveolenschemotypes exhibiting antimicrobial activity against oxytetracycline-resistantA. hydrophila. The findings suggest the chemotype thymol could be a potential treatment for infections in the tilapia aquaculture in Guatemala.
A structural and functional analysis of opal stop codon translational readthrough during Chikungunya Virus replication
Authors: Li Raymond , Sun Kaiwen , Tuplin Andrew , Harris Mark 
Published: July 2023

AbstractChikungunya virus (CHIKV) is an alphavirus, transmitted byAedesspecies mosquitoes. The CHIKV positive-sense RNA genome contains two open reading frames, coding for the non-structural (nsP) and structural proteins of the virus. The non-structural polyprotein precursor is proteolytically cleaved to generate nsP1-4. Intriguingly most isolates of CHIKV (and other alphaviruses) possess an opal stop codon close to the 3’ end of the nsP3 coding sequence and translational readthrough is necessary to produce full-length nsP3 and the nsP4 RNA polymerase. Here we investigate the role of this stop codon by replacing the arginine codon with all three stop codons in the context of both a subgenomic replicon and infectious CHIKV. Both opal and amber stop codons were tolerated in mammalian cells, but the ochre was not. In mosquito cells all three stop codons were tolerated. Using SHAPE analysis we interrogated the structure of a putative stem loop 3’ of the stop codon and used mutagenesis to probe the importance of a short base-paired region at the base of this structure. Our data reveal that this stem is not required for stop codon translational readthrough, and we conclude that other factors must facilitate this process to permit productive CHIKV replication.
Integrated genetic code expansion and structural bioinformatics reveal disrupted supramolecular assembly in a genetic disorder
Authors: Marino Valerio , Phromkrasae Wanchana , Bertacchi Michele , Cassini Paul , Chakrabandhu Krittalak , Dell’Orco Daniele , Studer Michèle 
Published: July 2023

ABSTRACTDeciphering the structural effects of variants is essential for understanding the pathophysiological mechanisms of genetic diseases. Using a neurodevelopmental disorder called Bosch-Boonstra-Schaaf Optic Atrophy Syndrome (BBSOAS) as a genetic disease model, we applied a combined Genetic Code Expansion (GCE) and structural bioinformatics strategy to assess the pathogenic impact of several human NR2F1 variants. Nonsense mutations in the ligand binding domain (LBD) resulted in truncated proteins, while missense variants significantly affected the folding of NR2F1 monomers as well as its supramolecular complexes. The GCE-enabled covalent and site-specific capture of transient supramolecular interactions in living cells revealed the variable quaternary conformations of NR2F1 variants and pinpointed the disrupted interplay with dimeric partners and the newly identified cofactor, CRABP2, while the computational analyses of the NR2F1 structure delineated the molecular basis of the impact of the variants on the isolated and complexed structures. The revealed consequence of the pathogenic mutations on the conformation, supramolecular interplay, and alterations in the cell cycle, viability, and subcellular localization of the different variants reflect the heterogeneous disease spectrum and establish the foundation for further understanding the complexity of BBSOAS.
Development of a Whole-Cell Biosensor for β-Lactamase Inhibitor Discovery
Authors: Jeffs Mitchell A. , Gray Rachel A.V. , Sheth Prameet M. , Lohans Christopher T. 
Published: July 2023

ABSTRACTThe clinical utility of the β-lactam antibiotics has been endangered by the production of β-lactamases by β-lactam-resistant pathogenic bacteria such asEscherichia coli, Pseudomonas aeruginosaandAcinetobacter baumannii. Collectively, these enzymes can degrade every clinically available β-lactam, jeopardizing antimicrobial therapy. Although extensive efforts have been made to develop β-lactamase inhibitors, inhibitor-resistant β-lactamases emerge rapidly. In addition, there are currently no clinically available inhibitors against the metallo-β-lactamases, a group of β-lactamases of great global concern. To further inhibitor discovery efforts, new assays are required to assess inhibitor efficacy, particularly in a cellular context. We report the development of a whole-cellE. colibiosensor which can quantify β-lactamase inhibition in a cellular context. Upon administration of an effective inhibitor, a β-lactam is rescued from β- lactamase-catalyzed degradation, resulting in the emission of a luminescent signal by the biosensor. This platform was validated using a panel of clinically relevant β-lactamases and was applied to quantitatively study the potency of a selection of currently used and reported β-lactamase inhibitors. This rapid method can account for factors like membrane permeability and can be employed to identify new β-lactamase inhibitors.
A novel inducible von Willebrand Factor Cre Recombinase mouse strain to study microvascular endothelial cell-specific biological processesin vivo
Authors: Yadav Dinesh , Conner Jeremy A. , Wang Yimin , Saunders Thomas L. , Ubogu Eroboghene E. 
Published: July 2023

AbstractMouse models are invaluable to understanding fundamental mechanisms in vascular biology during development, in health and different disease states. Several constitutive or inducible models that selectively knockout or knock in genes in vascular endothelial cells exist; however, functional and phenotypic differences exist between microvascular and macrovascular endothelial cells in different organs. In order to study microvascular endothelial cell-specific biological processes, we developed a Tamoxifen-inducible von Willebrand Factor (vWF) Cre recombinase mouse in the SJL background. The transgene consists of the human vWF promoter with the microvascular endothelial cell-selective 734 base pair sequence to drive Cre recombinase fused to a mutant estrogen ligand-binding domain [ERT2] that requires Tamoxifen for activity (CreERT2) followed by a polyadenylation (polyA) signal. We initially observed Tamoxifen-inducible restricted bone marrow megakaryocyte and sciatic nerve microvascular endothelial cell Cre recombinase expression in offspring of a mixed strain hemizygous C57BL/6- SJL founder mouse bred with mT/mG mice, with >90% bone marrow megakaryocyte expression efficiency. Founder mouse offspring were backcrossed to the SJL background by speed congenics, and intercrossed for >10 generations to develop hemizygous Tamoxifen-inducible vWF Cre recombinase (vWF-iCre/+) SJL mice with stable transgene insertion in chromosome 1. Microvascular endothelial cell-specific Cre recombinase expression occurred in the sciatic nerves, brains, spleens, kidneys and gastrocnemius muscles of adult vWF-iCre/+ SJL mice bred with Ai14 mice, with retained low level bone marrow and splenic megakaryocyte expression. This novel mouse strain would support hypothesis-driven mechanistic studies to decipher the role(s) of specific genes transcribed by microvascular endothelial cells during development, as well as in physiologic and pathophysiologic states in an organ- and time-dependent manner.
#SuperLibrarian – the evolving role of librarians in technology spaces
Authors: Pierre – Robertson Petronetta 
Published: July 2023

Purpose
The purpose of this paper is to discuss changes in the roles of librarians against the backdrop of emerging technologies.

Design/methodology/approach
Through reflection on practice drawn from the author’s 30 years in librarianship, this paper explores the evolving role of librarians in the constantly developing technological environment and demonstrates how librarians can combine information resources, technology and research assistance in these constantly changing spaces. It also explores how technology enhances the role of the librarian, with specific reference to ChatGPT.

Findings
The author stressed the need for library courses for credit to allow for feedback, assessment and critical thinking. The need for continuing professional development for librarians was highlighted. Additionally, areas such as Scholarly Publishing, Metrics and Analytics, Academic Integrity and Intellectual Property were identified as areas of focus for the 21st century Librarian.

Research limitations/implications
This study is limited to changes in roles as a result of emerging technologies which impact librarians. It is set in the Caribbean.

Practical implications
This paper is relevant for librarians, regardless of their geographical location, who are also required to be fluid, keep on the cutting edge, adapt and adopt to deliver service in the face of constantly advancing technology.

Originality/value
This paper is a reflection on an original experience from a Caribbean territory. it also explores recent developments in technology, more specifically ChatGPT, and its impact on the roles of librarians. It provides contributions to the ongoing discourse on the evolving role of the librarian from a different perspective.
Defining and establishing a restaurant wine culture
Authors: Taylor D. Christopher , Russen Michelle , Dawson Mary , Reynolds Dennis 
Published: July 2023

Purpose
Applying signaling theory to Schein’s organizational culture framework, this study aims to explain how restaurants communicate that their establishments value wine through multiple cultural attributes.

Design/methodology/approach
A phenomenological research design was adopted to conduct three focus groups with 14 restaurateurs about wine culture. Conversational analysis with Straussian coding was used.

Findings
A comprehensive definition of wine culture was provided, and five factors emerged that signal the presence of a wine culture. A wine presence includes a wine list, marketing efforts, community involvement and restaurant aesthetics. Employee traits are defined by individual attributes, communications skills and overall knowledge (training). Restaurant identity reflects the cultural alignment and customer relationship expectations set forth by ownership. Organizational structure reflects a restaurant’s hierarchy within which an individual or department is afforded the freedom to invest in wine. Future alignment reflects generational differences and trends in wine preferences and consumption.

Research limitations/implications
Researchers are provided a wine-culture definition and framework for wine research. Restaurants can use the study’s findings to formulate strategies for establishing a wine culture.

Originality/value
This study provided a framework for restaurateurs who wish to be known for wine to implement. Researchers and restaurateurs may facilitate communication between guests, staff and an organization regarding wine as a means of creating a competitive advantage.