bluuebunny/crossref_metadata_2025_split huggingface dataset:
Current State and Proposal of Best Practices of Standardized Patients for Spanish-Language Objective Structured Clinical Encounters in US Medical Schools
Authors: Iñiguez Reniell X. , Figueroa Narváez José A. , Diamond Lisa C. , Gregorich Steven E. , Karliner Leah , González Javier , Pérez-Cordón Cristina , Shin Tiffany M. , Izquierdo Karen , Ortega Pilar 
Published: November 2023

Introduction
Medical Spanish programs commonly engage Spanish-speaking standardized patients (SPs) for communication skills assessment, yet no studies address SP recruitment, selection, or training.

Methods
We sent questionnaires to medical Spanish faculty at 20 US medical schools to gauge their practices in recruiting and selecting Spanish-language SPs. We invited faculty to distribute a separate questionnaire to Spanish-language SPs to gather SP language abilities, training, and experience. We analyzed data using descriptive statistics and qualitative content analysis. When available, we reviewed SP video encounters to formally assess participating SPs' linguistic performance using the SP Oral Language Observation Matrix, a rating tool adapted from the Physician Oral Language Observation Matrix to assess oral medical Spanish proficiency.

Results
Eighty percent of faculty (16/20) responded. Standardized patient recruitment sources included institutional English-language SPs, Hispanic student groups and professional organizations, communities, and language professionals. Faculty-reported strategies to determine language readiness included interviewing SP candidates in Spanish and asking them to self-rate language skills using a validated scale. Fifteen SPs (54%, 15/28) from 5 schools responded to the SP questionnaire, and one third (5/15) reported that their Spanish was not assessed before being selected as an SP. In addition, one third (5/15) did not receive any initial training before performing a medical Spanish case. Raters assessed 11 different SPs using the SP Oral Language Observation Matrix, and 6 were rated as linguistically “ready” for the SP role.

Conclusions
Current approaches to recruitment, training, and language assessment of SPs vary. We propose strategies to ensure that medical Spanish encounters authentically reflect Spanish-speaking patients.
Finding needles in haystacks: identification of novel conserved PETase enzymes inStreptomyces
Authors: Verschoor Jo-Anne , Croese Martijn R. J. , Lakemeier Sven E. , Mugge Annemiek , Burgers Charlotte M. C. , Innocenti Paolo , Willemse Joost , Crooijmans Marjolein E. , van Wezel Gilles P. , Ram Arthur F. J. , de Winde Johannes H. 
Published: November 2023

AbstractThe rising use of plastic results in an appalling amount of waste which scatters into the environment affecting environmental, animal, and human health. One of these plastics is PET which is mainly used for bottles and textiles. In this research, we investigate the PET degrading ability of theIsPETase homologScLipA fromStreptomyces coelicolor.Of 96 differentStreptomycesstrains screened, 18 % were able to degrade the model substrate BHET. Three different variants of lipase A, namedScLipA, S2LipA andS92LipA were identified and analyzed in detail. ThelipAgene was deleted fromS. coelicolorM145 using CRISPR/Cas9, resulting in reduced BHET degradation.LipAoverexpression in the knock-out background significantly enhanced BHET degradation. All three enzymes were expressed inE. coliBL21 for protein purification and biochemical analysis, showing that enzymatic activity most likely resides in a dimeric form of the enzyme. The optimum pH and temperature were determined to be pH 7 and 25 °C for all three variants. Using these conditions, the activity on BHET and amorphous PET film was investigated.S2LipA efficiently degraded BHET and caused roughening and small indents on the surface of PET films, consistent with PET-degrading activity. The frequent occurrence of theS2LipA variant inStreptomycessuggests an environmental advantage towards the degradation of more hydrophobic substrates such as these polluting plastics in the environment.
Striatum supports fast learning but not memory recall
Authors: Reinhold Kimberly , Iadarola Marci , Tang Shi , Kuwamoto Whitney , Sun Senmiao , Hakim Richard , Zimmer Joshua , Wang Wengang , Sabatini Bernardo L. 
Published: November 2023

AbstractAnimals learn to carry out motor actions in specific sensory contexts to achieve goals. The striatum has been implicated in producing sensory-motor associations, yet its contribution to memory formation or recall is not clear. To investigate the contribution of striatum to these processes, mice were taught to associate a cue, consisting of optogenetic activation of striatum-projecting neurons in visual cortex, with forelimb reaches to access food pellets. As necessary to direct learning, striatal neural activity encoded both the sensory context and outcome of reaching. With training, the rate of cued reaching increased, but brief optogenetic inhibition of striatal activity arrested learning and prevented trial-to-trial improvements in performance. However, the same manipulation did not affect performance improvements already consolidated into short- (within an hour) or long-term (across days) memories. Hence, striatal activity is necessary for trial-to-trial improvements in task performance, leading to plasticity in other brain areas that mediate memory recall.
AreEscherichia colicausing recurrent cystitis just ordinary UropathogenicE. coli(UPEC) strains?
Authors: Vautrin Nicolas , Dahyot Sandrine , Leoz Marie , Caron François , Grand Maxime , Feldmann Audrey , Gravey François , Legris Stéphanie , Ribet David , Alexandre Kévin , Pestel-Caron Martine 
Published: November 2023

AbstractSpecific determinants associated with UropathogenicEscherichia coli(UPEC) causing recurrent cystitis are still poorly characterized. The aims of this study were (i) to describe genomic and phenotypic traits associated with recurrence using a large collection of recurrent and paired sporadic UPEC isolates, and (ii) to explore within-host genomic adaptation associated with recurrence using series of 2 to 5 sequential UPEC isolates. Whole genome comparative analyses between 24 recurrent cystitis isolates (RCIs) and 24 phylogenetically paired sporadic cystitis isolates (SCIs) suggested a lower prevalence of putative mobile genetic elements (MGE) in RCIs, such as plasmids and prophages. The intra-patient evolution of the 24 RCI series over time was characterized by SNP occurrence in genes involved in metabolism or membrane transport, and by plasmid loss in 5 out of the 24 RCI series. Genomic evolution occurred early in the course of recurrence, suggesting rapid adaptation to strong selection pressure in the urinary tract.However, RCIs did not exhibit specific virulence factor determinants and could not be distinguished from SCIs by their fitness, biofilm formation, or ability to invade HTB-9 bladder epithelial cells. Taken together, these results suggest a rapid but not convergent adaptation of RCIs that involves both strain- and host-specific characteristics.Author summaryThe recurrence of cystitis is a frequent but poorly understood phenomenon. There are currently many hypotheses trying to explain recurrence, but data on large collections of well-characterized clinical isolates are lacking. In order to identify specific recurrence-associated markers, we conducted a large genomic and phenotypic study involving 48 well-characterized cystitis isolates: 24 recurrent cystitis isolates (RCIs) and 24 pairs of isolates causing sporadic cystitis (SCIs). Moreover, we were able to explore intra-host overtime RCI evolution, by analyzing up to 5 sequential UPEC isolates per RCI series. Our results suggest that RCI rapidly adapt to their host through mobile genetic elements loss and SNP accumulation in genes involved in metabolism and membrane transport. However, no convergent genomic nor phenotypic evolution was observed between isolates collected from distinct patients. Taken together, these results suggest a host-shaped evolution of RCIs, highlighting a need for future studies focused on the host-pathogen relationships.
Distinct Roles of Kif6 and Kif9 in Mammalian Ciliary Trafficking and Motility
Authors: Fang Chuyu , Pan Xinwen , Li Di , Chen Yawen , Li Luan , Gao Qi , Li Dong , Zhu Xueliang , Yan Xiumin 
Published: November 2023

AbstractCiliary beat and intraflagellar transport (IFT) depend on dynein and kinesin motors. Kinesin-9 family members Kif6 and Kif9 are implicated in ciliary motilities across protists and mammals. How they function and whether they act redundantly, however, remain unclear. Here, we show that they play distinct roles in mammals. Kif6 forms puncta that move bidirectionally without or with IFT-B particles along axonemes, whereas Kif9 is immobilized on ciliary central apparatus. Only Kif6 binds to and glides microtubules, and the activities are self-inhibited.Kif6deficiency in mice impairs directional ciliary beat across ependymal tissues and cerebrospinal fluid flow, resulting in severe hydrocephalus and high mortality, whereasKif9deficiency induces mild hydrocephalus without obviously defective ciliary beat and life span. BothKif6-/-andKif9-/-males are infertile but show respectively oligozoospermia with poor sperm motility and defective forward motion of sperms. These results suggest Kif6 as a motile cilia-specific IFT motor and Kif9 as a central apparatus regulator.
Hippocampal networks support reinforcement learning in partially observable environments
Authors: Pedamonti Dabal , Mohinta Samia , Dimitrov Martin V. , Malagon-Vina Hugo , Ciocchi Stephane , Costa Rui Ponte 
Published: November 2023

AbstractMastering navigation in environments with limited visibility is crucial for survival. While the hippocampus has been associated with goal-oriented navigation, its specific role in real-world behaviour, particularly in scenarios with partial observability, remains elusive. To investigate this, we combined deep reinforcement learning (RL) modelling with behavioural and neural data analysis. First, we trained RL agents to perform reward-based navigational tasks in partially observable environments. We show that agents equipped with recurrent hippocampal circuitry, as opposed to purely feedforward networks, successfully learned the tasks, resembling animal behaviour. By employing neural dimensionality reduction, our models predicted reward, strategy and temporal representations, which we validated using large-scale hippocampal neuronal recordings. Moreover, hippocampal RL agents predicted state-specific trajectories and action certainty, which mirror empirical findings. In contrast, agents trained in fully observable environments failed to capture experimental data, suggesting that partial observability is often implicit in goal-driven tasks. Finally, we show that hippocampal-like RL agents demonstrated improved generalisation across novel task conditions. In summary, our findings suggest a key role of hippocampal networks in facilitating learning in naturalistic environments.
Fold-and-fuse neurulation in zebrafish requires Vangl2
Authors: MacGowan Jacalyn , Cardenas Mara , Williams Margot Kossmann 
Published: November 2023

AbstractShaping of the future brain and spinal cord during neurulation is an essential component of early vertebrate development. In amniote embryos, primary neurulation occurs through a “fold-and-fuse” mechanism by which the edges of the neural plate fuse into the hollow neural tube. Failure of neural fold fusion results in neural tube defects (NTDs), which are among the most devastating and common congenital anomalies worldwide. Unlike amniotes, the zebrafish neural tube develops largely via formation of a solid neural keel that later cavitates to form a midline lumen. Although many aspects of primary neurulation are conserved in zebrafish, including neural fold zippering, it was not clear how well these events resemble analogous processes in amniote embryos. Here, we demonstrate that despite outward differences, zebrafish anterior neurulation closely resembles that of mammals. For the first time in zebrafish embryos, we directly observe enclosure of a lumen by the bilateral neural folds, which fuse by zippering between at least two distinct closure sites. Both the apical constriction that elevates the neural folds and the zippering that fuses them coincide with apical Myosin enrichment. We further show that embryos lackingvangl2, a core planar cell polarity and NTD risk gene, exhibit delayed and abnormal neural fold fusion that fails to enclose a lumen. These defects can also be observed in fixed embryos, enabling their detection without live imaging. Together, our data provide direct evidence for fold-and-fuse neurulation in zebrafish and its disruption upon loss of an NTD risk gene, highlighting the deep conservation of primary neurulation across vertebrates.HighlightsThe anterior neural tube of zebrafish undergoes “fold-and-fuse” neurulation to enclose a lumen, highlighting conservation of primary neurulation mechanisms across vertebrates.Anterior neural tube closure is delayed and abnormal in zebrafish embryos lacking the planar cell polarity genevangl2, occurring by excessive “buttoning” rather than smooth “zippering” and failing to enclose a lumen.Neural tube defects (NTDs) are visible in fixedvangl2deficient embryos, enabling simple assessment of neural tube phenotypes with potential utility in screening NTD risk genes.
Inflammation primes the kidney for recovery by activating AZIN1 A-to-I editing
Authors: Heruye Segewkal , Myslinski Jered , Zeng Chao , Zollman Amy , Makino Shinichi , Nanamatsu Azuma , Mir Quoseena , Janga Sarath Chandra , Doud Emma H , Eadon Michael T , Maier Bernhard , Hamada Michiaki , Tran Tuan M , Dagher Pierre C , Hato Takashi 
Published: November 2023

AbstractThe progression of kidney disease varies among individuals, but a general methodology to quantify disease timelines is lacking. Particularly challenging is the task of determining the potential for recovery from acute kidney injury following various insults. Here, we report that quantitation of post-transcriptional adenosine-to-inosine (A-to-I) RNA editing offers a distinct genome-wide signature, enabling the delineation of disease trajectories in the kidney. A well-defined murine model of endotoxemia permitted the identification of the origin and extent of A-to-I editing, along with temporally discrete signatures of double-stranded RNA stress and Adenosine Deaminase isoform switching. We found that A-to-I editing of Antizyme Inhibitor 1 (AZIN1), a positive regulator of polyamine biosynthesis, serves as a particularly useful temporal landmark during endotoxemia. Our data indicate that AZIN1 A-to-I editing, triggered by preceding inflammation, primes the kidney and activates endogenous recovery mechanisms. By comparing genetically modified human cell lines and mice locked in either A-to-I edited or uneditable states, we uncovered that AZIN1 A-to-I editing not only enhances polyamine biosynthesis but also engages glycolysis and nicotinamide biosynthesis to drive the recovery phenotype. Our findings implicate that quantifying AZIN1 A-to-I editing could potentially identify individuals who have transitioned to an endogenous recovery phase. This phase would reflect their past inflammation and indicate their potential for future recovery.
Universal Digital High Resolution Melt for the detection of pulmonary mold infections
Authors: Goshia Tyler , Aralar April , Wiederhold Nathan , Jenks Jeffrey D. , Mehta Sanjay R. , Sinha Mridu , Karmakar Aprajita , Sharma Ankit , Shrivastava Rachit , Sun Haoxiang , White P. Lewis , Hoenigl Martin , Fraley Stephanie I. 
Published: November 2023

AbstractBackgroundInvasive mold infections (IMIs) such as aspergillosis, mucormycosis, fusariosis, and lomentosporiosis are associated with high morbidity and mortality, particularly in immunocompromised patients, with mortality rates as high as 40% to 80%. Outcomes could be substantially improved with early initiation of appropriate antifungal therapy, yet early diagnosis remains difficult to establish and often requires multidisciplinary teams evaluating clinical and radiological findings plus supportive mycological findings. Universal digital high resolution melting analysis (U-dHRM) may enable rapid and robust diagnosis of IMI. This technology aims to accomplish timely pathogen detection at the single genome level by conducting broad-based amplification of microbial barcoding genes in a digital polymerase chain reaction (dPCR) format, followed by high-resolution melting of the DNA amplicons in each digital reaction to generate organism-specific melt curve signatures that are identified by machine learning.MethodsA universal fungal assay was developed for U-dHRM and used to generate a database of melt curve signatures for 19 clinically relevant fungal pathogens. A machine learning algorithm (ML) was trained to automatically classify these 19 fungal melt curves and detect novel melt curves. Performance was assessed on 73 clinical bronchoalveolar lavage (BAL) samples from patients suspected of IMI. Novel curves were identified by micropipetting U-dHRM reactions and Sanger sequencing amplicons.ResultsU-dHRM achieved an average of 97% fungal organism identification accuracy and a turn-around-time of 4hrs. Pathogenic molds (Aspergillus, Mucorales, LomentosporaandFusarium)were detected by U-dHRM in 73% of BALF samples suspected of IMI. Mixtures of pathogenic molds were detected in 19%. U-dHRM demonstrated good sensitivity for IMI, as defined by current diagnostic criteria, when clinical findings were also considered.ConclusionsU-dHRM showed promising performance as a separate or combination diagnostic approach to standard mycological tests. The speed of U-dHRM and its ability to simultaneously identify and quantify clinically relevant mold pathogens in polymicrobial samples as well as detect emerging opportunistic pathogens may provide information that could aid in treatment decisions and improve patient outcomes.
Glutamate inputs send prediction error of reward but not negative value of aversive stimuli to dopamine neurons
Authors: Amo Ryunosuke , Uchida Naoshige , Watabe-Uchida Mitsuko 
Published: November 2023

SummaryMidbrain dopamine neurons are thought to signal reward prediction errors (RPEs) but the mechanisms underlying RPE computation, particularly contributions of different neurotransmitters, remain poorly understood. Here we used a genetically-encoded glutamate sensor to examine the pattern of glutamate inputs to dopamine neurons. We found that glutamate inputs exhibit virtually all of the characteristics of RPE, rather than conveying a specific component of RPE computation such as reward or expectation. Notably, while glutamate inputs were transiently inhibited by reward omission, they were excited by aversive stimuli. Opioid analgesics altered dopamine negative responses to aversive stimuli toward more positive responses, while excitatory responses of glutamate inputs remained unchanged. Our findings uncover previously unknown synaptic mechanisms underlying RPE computations; dopamine responses are shaped by both synergistic and competitive interactions between glutamatergic and GABAergic inputs to dopamine neurons depending on valences, with competitive interactions playing a role in responses to aversive stimuli.
m6A RNA modification of mHttintron 1 regulates the generation ofHtt1ain Huntington’s Disease
Authors: Pupak Anika , Navarro Irene Rodríguez , Sathasivam Kirupa , Essmann Amelie , Singh Ankita , del Toro Daniel , Ginés Silvia , Bates Gillian P. , Vang Ørom Ulf Andersson , Marti Eulalia , Brito Verónica 
Published: November 2023

ABSTRACTHuntington’s disease (HD) is a dominantly inherited neurodegenerative disorder caused by an expanded, somatically unstable CAG repeat in the first exon of the huntingtin gene (HTT). In the presence of an expanded CAG repeat, huntingtin mRNA undergoes an aberrant processing that generatesHTT1atranscripts with exon 1 and intron 1 sequences, which encodes the aggregation-prone and pathogenic HTTexon 1 protein. The regulatory mechanisms that contribute to the production ofHTT1aare not fully understood. In a previous transcriptome-wide m6A landscape study performed inHdh+/Q111knock-in mice, we have found that the proximal region of intron 1 to exon1-intron 1 splice site inHttRNA is highly modified by m6A. Several pieces of evidence have demonstrated that m6A is involved in RNA processing and splicing. Therefore, in this study we set out to explore the impact of m6A RNA modifications in the generation ofHtt1a. We show in the striatum ofHdh+/Q111mice that m6A is enriched in intronic sequences 5’ to the cryptic poly (A) sites (IpA1 and IpA2) at 680 and 1145 bp into intron 1 as well as inHtt1apolyadenylated mRNA. We also verified the presence of specific m6A-modified sites near the 5’ exon1-intron1 splice donor site. IntronicHTTm6A methylation was recapitulated in human samples showing a significantly increased methylation ratio in HD putamenpost-mortemsamples and in HD fibroblast cell lines from pre-symptomatic and symptomatic patients. In order to test the hypothesis that the m6A modification is involved in mutantHttRNA processing, we performed a pharmacological inhibition of METTL3 and a targeted demethylation ofHttintron 1 in HD cells using a dCas13-ALKBH5 system. We found thatHtt1atranscript levels in HD cells are regulated by METTL3 and by methylation status inHttintron 1. Site-specific manipulation with an RNA editing system resulted in decreased expression levels ofHtt1a, which was accompanied by a reduction in DNA damage, a major hallmark in HD. Finally, we propose that m6A methylation in intron 1 is likely dependent on the expanded CAG repeats. These findings provide insight into the role of m6A in the generation of the aberrantly spliced mutantHtttranscripts with important implications for therapeutic strategies.
Debt maturity structure, credit ratings and audit fees: new evidence
Authors: Opare Solomon , Bhuiyan Md. Borhan Uddin 
Published: November 2023

Purpose
This research aims to revisit Gul and Goodwin (2010), which focuses on exploring the relationship between debt maturity structure, credit ratings and audit fees. Furthermore, the authors investigate whether this association varies based on firm size, firm life cycle and financial reporting quality.

Design/methodology/approach
To investigate the research question, the authors use an extended sample period, 2004–2017, in comparison to the sample period, 2003–2006, used in Gul and Goodwin (2010). The authors use ordinary least squares regression as a baseline methodology along with two-stage least-squares regression and change analysis to control for endogeneity concerns.

Findings
According to Gul and Goodwin (2010), auditors charge lower audit fees for firms with higher short-maturity debt and better credit ratings, indicating a lower likelihood of financial misreporting. Further, Gul and Goodwin (2010) find that lower credit rated firms benefit more from short-term debt. Primarily, the findings are consistent with Gul and Goodwin (2010) and provide further evidence that the beneficial effects of short-maturity debt for firms with poor ratings are evident for small firms, firms in the growth stage of their life cycle and firms with poor earnings quality.

Practical implications
The findings imply that practitioners in the audit profession and investors should take a more nuanced and comprehensive approach to varied firm and financial factors, taking into consideration the intricate relationships between many elements impacting a firm’s financial health. As a result, audit professionals may give more accurate appraisals of a firm’s financial condition, and investors can make better investment decisions.

Originality/value
The authors reconfirm the findings of Gul and Goodwin (2010) using an extended sample. The findings are novel, which evidence that the lower audit fees for rated firms with short-maturity debt are moderated by firm size, life cycle and financial reporting quality.