bluuebunny/crossref_metadata_2025_split huggingface dataset:
RFC1 in an Australasian neurological disease cohort: extending the genetic heterogeneity and implications for diagnostics
Authors: Scriba Carolin K , Stevanovski Igor , Chintalaphani Sanjog R , Gamaarachchi Hasindu , Ghaoui Roula , Ghia Darshan , Henderson Robert D , Jordan Nerissa , Winkel Antony , Lamont Phillipa J , Rodrigues Miriam J , Roxburgh Richard H , Weisburd Ben , Laing Nigel G , Deveson Ira W , Davis Mark R , Ravenscroft Gianina 
Published: July 2023

Abstract
Cerebellar ataxia, neuropathy and vestibular areflexia syndrome is a progressive, generally late-onset, neurological disorder associated with biallelic pentanucleotide expansions in Intron 2 of the RFC1 gene. The locus exhibits substantial genetic variability, with multiple pathogenic and benign pentanucleotide repeat alleles previously identified. To determine the contribution of pathogenic RFC1 expansions to neurological disease within an Australasian cohort and further investigate the heterogeneity exhibited at the locus, a combination of flanking and repeat-primed PCR was used to screen a cohort of 242 Australasian patients with neurological disease. Patients whose data indicated large gaps within expanded alleles following repeat-primed PCR, underwent targeted long-read sequencing to identify novel repeat motifs at the locus. To increase diagnostic yield, additional probes at the RFC1 repeat region were incorporated into the PathWest diagnostic laboratory targeted neurological disease gene panel to enable first-pass screening of the locus for all samples tested on the panel. Within the Australasian cohort, we detected known pathogenic biallelic expansions in 15.3% (n = 37) of patients. Thirty indicated biallelic AAGGG expansions, two had biallelic ‘Māori alleles’ [(AAAGG)exp(AAGGG)exp], two samples were compound heterozygous for the Māori allele and an AAGGG expansion, two samples had biallelic ACAGG expansions and one sample was compound heterozygous for the ACAGG and AAGGG expansions. Forty-five samples tested indicated the presence of biallelic expansions not known to be pathogenic. A large proportion (84%) showed complex interrupted patterns following repeat-primed PCR, suggesting that these expansions are likely to be comprised of more than one repeat motif, including previously unknown repeats. Using targeted long-read sequencing, we identified three novel repeat motifs in expanded alleles. Here, we also show that short-read sequencing can be used to reliably screen for the presence or absence of biallelic RFC1 expansions in all samples tested using the PathWest targeted neurological disease gene panel. Our results show that RFC1 pathogenic expansions make a substantial contribution to neurological disease in the Australasian population and further extend the heterogeneity of the locus. To accommodate the increased complexity, we outline a multi-step workflow utilizing both targeted short- and long-read sequencing to achieve a definitive genotype and provide accurate diagnoses for patients.
Impact of the Introduction of a Package of Diagnostic Tools, Diagnostic Algorithm, and Training and Communication on Outpatient Acute Fever Case Management at 3 Diverse Sites in Uganda: Results of a Randomized Controlled Trial
Authors: Kapisi James , Sserwanga Asadu , Kitutu Freddy Eric , Rutebemberwa Elizeus , Awor Phyllis , Weber Stephan , Keller Thomas , Kaawa-Mafigiri David , Ekusai-Sebatta Deborah , Horgan Philip , Dittrich Sabine , Moore Catrin E , Salami Olawale , Olliaro Piero , Nkeramahame Juvenal , Hopkins Heidi 
Published: July 2023

Abstract

Background
Increasing trends of antimicrobial resistance are observed around the world, driven in part by excessive use of antimicrobials. Limited access to diagnostics, particularly in low- and middle-income countries, contributes to diagnostic uncertainty, which may promote unnecessary antibiotic use. We investigated whether introducing a package of diagnostic tools, clinical algorithm, and training-and-communication messages could safely reduce antibiotic prescribing compared with current standard-of-care for febrile patients presenting to outpatient clinics in Uganda.

Methods
This was an open-label, multicenter, 2-arm randomized controlled trial conducted at 3 public health facilities (Aduku, Nagongera, and Kihihi health center IVs) comparing the proportions of antibiotic prescriptions and clinical outcomes for febrile outpatients aged ≥1 year. The intervention arm included a package of point-of-care tests, a diagnostic and treatment algorithm, and training-and-communication messages. Standard-of-care was provided to patients in the control arm.

Results
A total of 2400 patients were enrolled, with 49.5% in the intervention arm. Overall, there was no significant difference in antibiotic prescriptions between the study arms (relative risk [RR]: 1.03; 95% CI: .96–1.11). In the intervention arm, patients with positive malaria test results (313/500 [62.6%] vs 170/473 [35.9%]) had a higher RR of being prescribed antibiotics (1.74; 1.52–2.00), while those with negative malaria results (348/688 [50.6%] vs 376/508 [74.0%]) had a lower RR (.68; .63–.75). There was no significant difference in clinical outcomes.

Conclusions
This study found that a diagnostic intervention for management of febrile outpatients did not achieve the desired impact on antibiotic prescribing at 3 diverse and representative health facility sites in Uganda.
Coronary vasospasm during infusion of CD-19 directed chimeric antigen receptor T-cell therapy: a case report
Authors: Tao Jacqueline J , Roszkowska Natalia , Majure David T , Mahmood Syed S 
Published: July 2023

Abstract

Background
Cardiovascular events have been reported to occur in one in five patients receiving chimeric antigen receptor T-cell (CAR-T) therapy. Commonly reported effects including cardiomyopathy, heart failure, myocardial infarction (MI), and arrhythmia. Here, we present a novel case of a patient who developed acute ST segment elevations during CAR-T cell infusion.

Case summary
A 76-year-old man with diffuse large B cell lymphoma was admitted for an investigational CD-19 directed, autologous CAR-T cell therapy. Less than 5 min into the CAR-T cell infusion, he developed severe chest pain, dyspnea, flushing, hypotension, and tachycardia. Electrocardiogram (EKG) showed inferior ST elevations and reciprocal lateral ST depressions. Emergent coronary angiography revealed mild non-obstructive coronary disease. ST segment changes and patient symptoms resolved after catheterization.

Discussion
Given the complete resolution of symptoms and EKG abnormalities in the context of non-obstructive coronary artery disease, this clinical presentation was thought to be most consistent with ST elevation MI due to coronary vasospasm. The mechanism of this vasospasm is as yet not understood and may be related to an anaphylactic reaction or a cardiotoxicity related to the cell therapy agent. As the use of CAR-T therapy continues to expand, there is a need to further characterize the full spectrum of its cardiotoxic effects.
Housing Prices and Credit Constraints in Competitive Search
Authors: Díaz Antonia , Jerez Belén , Rincón-Zapatero Juan Pablo 
Published: July 2023

Abstract
Wealthier, risk-averse buyers pay more to speed up transactions in competitive search markets. This result is established in a dynamic housing model where households save to smooth consumption and build a down payment. ‘Block recursivity’ is ensured by the existence of risk-neutral housing intermediaries. In the long run, the calibrated benchmark features higher indebtedness and house prices than a Walrasian model, especially when housing supply elasticity is low. The long-run price effects of greater credit availability are much larger if rental and owner-occupied stocks are segmented, but even without segmentation they can be substantial when supply elasticity is low.
The evolutionary ecology of variation in labile traits: selection on its among- and within-individual components
Authors: Araya-Ajoy Yimen G , Dingemanse Niels J , Westneat David F , Wright Jonathan 
Published: July 2023

AbstractCloser integration between behavioral ecology and quantitative genetics has resulted in a recent increase in studies partitioning sources of variation in labile traits. Repeatable between-individual differences are commonly documented, and their existence is generally explained using adaptive arguments, implying that selection has shaped variation at the among- and within-individual level. However, predicting the expected pattern of non-adaptive phenotypic variation around an optimal phenotypic value is difficult, hampering our ability to provide quantitative assessments of the adaptive nature of observed patterns of phenotypic variation within a population. We argue that estimating the strength of selection on trait variation among and within individuals provides a way to test adaptive theory concerned with phenotypic variation. To achieve this aim, we describe a nonlinear selection analysis that enables the study of the selective pressures on trait means and their among- and within-individual variation. By describing an integrative approach for studying the strength of selection on phenotypic variation at different levels, we hope to stimulate empirical studies investigating the ecological factors that can shape the repeatability, heritability, and coefficients of variation of labile and other repeatedly expressed traits.
A qualitative study on the influence of COVID-19 on smoking behaviors through changing social and physical contexts
Authors: Kegler M , Owolabi S , Reilly K , Pouncy J , Kaufmann J , Marra A , Haardörfer R , Berg C 
Published: July 2023

Abstract
Globally, COVID-19 has been a major societal stressor and disrupted social and physical environments for many. Elucidating mechanisms through which societal disruptions influence smoking behavior has implications for future tobacco control efforts. Qualitative interviews were conducted among 38 adults who smoked combustible cigarettes in 2020 and 2021. The majority were women (75.7%), identified as Black (56.8%), were employed (61.3%), had a smoke-free home (66.7%) and lived in a small metro or rural (79.0%) county, primarily in rural southwest Georgia. Participants reported more time at home, increased isolation and less socializing, changed work and financial situations and altered household and family contexts. The vast majority of participants smoked more at some point during the pandemic with about half of these continuing to smoke more at the time of the interview. More time at home, multiple sources of stress and boredom were the main reasons for increased smoking. Decreases in smoking were attributed to financial strain, smoke-free home rules and nonsmoking family members, concerns about COVID-19 and less socializing with friends who smoke. Future tobacco control efforts during societal stressors such as pandemics should take into account specific psychosocial and environmental influences in attempts to minimize negative changes to smoking patterns.
Highlighting Potential Physical and Chemical Cues Involved in Conspecific Recognition System in a Predator Nematode,Seinura caverna
Authors: Ekino Taisuke , Yoshiga Toyoshi , Takeuchi-Kaneko Yuko , Ichihara Yu , Kanzaki Natsumi , Shinya Ryoji 
Published: July 2023

SynopsisConspecific recognition is the ability to distinguish and respond to individuals of the same species. In nematodes, this behavior can mediate aggregation, feeding behavior, or mating. Here, we investigated whether and how the predatory nematode Seinura caverna recognizes and avoids conspecifics to prey on. In predation assays, S. caverna did not kill conspecifics, but killed nematodes of three heterospecific species. Interestingly, S. caverna did not kill Ektaphelenchoides spondylis nematodes. Seinura caverna did not eject its stylet when encountering conspecifics or E. spondylis. The characterization of the internal cuticle structure of 13 nematode species suggested that the cuticle may play a role in the preying decision, as E. spondylis and S. caverna exhibited similar, type III, cuticle layers. Chemical extracts from S. caverna further repelled conspecifics. We discuss the potential hierarchical use of physical and chemical cues in S. caverna predation behavior and provide insights into the evolutionary adaptations and behavior of this organism.
Perspectives on Principles of Cellular Behavior from the Biophysics of Protists
Authors: Larson Ben T 
Published: July 2023

Synopsis
Cells are the fundamental unit of biological organization. Although it may be easy to think of them as little more than the simple building blocks of complex organisms such as animals, single cells are capable of behaviors of remarkable apparent sophistication. This is abundantly clear when considering the diversity of form and function among the microbial eukaryotes, the protists. How might we navigate this diversity in the search for general principles of cellular behavior? Here, we review cases in which the intensive study of protists from the perspective of cellular biophysics has driven insight into broad biological questions of morphogenesis, navigation and motility, and decision making. We argue that applying such approaches to questions of evolutionary cell biology presents rich, emerging opportunities. Integrating and expanding biophysical studies across protist diversity, exploiting the unique characteristics of each organism, will enrich our understanding of general underlying principles.
Reply to the comment by Filbee-Dexter et al. (2023) “Seaweed forests are carbon sinks that may help mitigate CO2 emissions”
Authors: Gallagher John B 
Published: July 2023

Abstract
Filbee-Dexter et al. provided commentary on Gallagher et al.’s assertion regarding the limitations of seaweed ecosystems in mitigating CO2 emissions. However, Filbee-Dexter et al. appear to have different understandings of several key aspects, and claims of heterotrophic bias contradict their cited literature upon which our analysis was based. Filbee-Dexter et al.’s reliance on net primary production fails to consider the consumption and remineralization of said production. Their endorsements of high levels of seaweed ecosystem autotrophy taken from the literature were either conceptually, temporally, or community assemblage-inappropriate. The existing literature does not substantiate their claim of methodological bias between different types of net ecosystem production (NEP) measurements. Additionally, all of these direct measurements account for any photo-re-assimilation of respiratory subsidies. Contrary to Filbee-Dexter et al.’s claim, Gallagher et al. consider the export of sequestered seaweed. The study revealed that respiratory subsidies offset the exported sequestration rates from an average of +173 million tonnes C yr−1 as a carbon sink to a carbon source of around −54 million tonnes C yr−1. Nonetheless, there are also points of consensus. It will be necessary to weight NEP for the types of seaweed ecosystems, and account for differences with a seaweeds’ particular degraded or alternative state as more data becomes available. Finally, more research is required to better understand the fate of export, and the impact of net calcification on the atmospheric exchange of CO2.
Contested Facts: The Politics and Practice of International Fact-Finding Missions
Authors: Lesch Max 
Published: July 2023

Abstract
International organizations (IOs) dispatch fact-finding missions to establish epistemic authority by objectively and impartially assessing contested facts. Despite this technocratic promise, they are often controversial and sometimes even fuel international disputes that challenge the epistemic authority of the dispatching organizations. Although the twenty-first century has witnessed a proliferation of United Nations (UN) commissions of inquiry, they have received surprisingly little attention in international relations (IR) scholarship. How can we explain this trend and the successes and failures of fact-finding missions, which sometimes even backfire on the IO authority? Drawing on IR theories of delegation, epistemic authority, and IO field operations as well as public international law scholarship on commissions of inquiry, this article develops an analytical framework for studying the delegation, implementation, and dissemination of fact-finding missions. It theorizes how and under what conditions international fact-finding missions close or widen credibility gaps and thus help to establish, maintain, or weaken the epistemic authority of IOs. The article illustrates this framework with a case study of the Ad Hoc Working Group on the Human Rights Situation in Chile, sent by the UN Commission on Human Rights in 1974 to investigate allegations of human rights violations and torture. The conclusion outlines a comparative research agenda on international fact-finding missions for IR that contributes to the study of knowledge production in IOs and the enforcement of international norms.
Recombinant GM-CSF enhances the bactericidal ability of PMNs by increasing intracellular IL-1β and improves the prognosis of secondary Pseudomonas aeruginosa pneumonia in sepsis
Authors: Tu Fuquan , Pan Lili , Wu Wenwei , Cai Yuanhua , Li Jinggang , Wang Xuechun , Lai Xiaolin , Chen Zhixiang , Ye Luya , Wang Shaoyuan 
Published: July 2023

Abstract
This study tested the hypothesis that recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) enhances polymorphonuclear neutrophils (PMNs) via interleukin (IL)-1β to improve the prognosis of secondary infection in sepsis. The latter stage of sepsis is prone to induce immunosuppression, resulting in secondary fatal infections. Recombinant GM-CSF has become a way for sepsis-induced immunosuppression due to its immunomodulatory effect. However, the functional impact of GM-CSF on PMNs in sepsis remains obscure. This study aimed to study the role of recombinant GM-CSF on the bactericidal ability of PMNs in septic mice, assessing its effect on the prognosis of secondary pneumonia, and explore the mechanism of recombinant GM-CSF by intervening PMNs in patients with sepsis. The C57BL/6J sepsis mouse model was induced by cecal ligation and puncture. Recombinant murine GM-CSF (rmGM-CSF) was used in vivo when mice developed immunosuppression, which was characterized by abnormal bactericidal function of PMNs in peripheral blood. rmGM-CSF improved the prognosis of secondary pneumonia and reversed the function of PMNs. PMNs isolated by Percoll from septic patients were treated by recombinant human GM-CSF (rhGM-CSF) in vitro. The expression of CD11b, reactive oxygen species, phagocytosis, and neutrophil extracellular trap release in PMNs were enhanced by rhGM-CSF treatments. Whole-transcriptomic sequencing of mouse PMNs indicated that recombinant GM-CSF increased the expression of Il1b gene in PMNs. Blocking and inhibiting IL-1β release effectively counteracted the enhancing effect of GM-CSF on the bactericidal function of PMNs. rmGM-CSF enhances the bactericidal function of PMNs in vivo and improves the prognosis of secondary pneumonia in septic mice, and recombinant GM-CSF increases IL-1β precursor reserves, which, if stimulated, can rapidly enhance the bactericidal capacity of PMNs.
Total temporomandibular joint replacement in recurrent temporomandibular joint ankylosis: a case report
Authors: Rauniyar Dilip , Upadhyaya Chandan , Chaurasia Nitesh , Shakya Mamata , Sharma Siddhartha 
Published: July 2023

Abstract
Total temporomandibular joint replacement (TMJR) is a surgical procedure in which end-stage temporomandibular joint disorders are replaced with an alloplastic prosthesis between the mandible and the base of the skull when autogenous grafts are inadvisable. These alloplastic prostheses may be available as stock or custom-made prostheses consisting of the mandibular condyle and glenoid fossa components. Although the first total temporomandibular joint prosthesis was used in the 1960s, we present the case of a 20-year-old female patient, probably the first case of total temporomandibular joint arthroplasty in Nepal, performed at Dhulikhel Hospital in Kavrepalanchok. The patient underwent bilateral TMJR with a custom joint prosthesis for recurrent TMJ ankylosis. Postoperatively, the patient noticed significant improvements in mouth opening, chewing ability, facial esthetics and, most importantly, her self-esteem and confidence.
Influence of management practices on water-related grain yield determinants
Authors: Echarte Laura , Alfonso Carla S , González Hugo , Hernández Mariano D , Lewczuk Nuria A , Nagore Luján , Echarte María M 
Published: July 2023

Abstract
Adequate management of N supply, plant density, row spacing, and soil cover has proved useful for increasing grain yields and/or grain yield stability of rainfed crops over the years. We review the impact of these management practices on grain yield water-related determinants: seasonal crop evapotranspiration (ET) and water use efficiency for grain production per unit of evapotranspired water during the growing season (WUEG,ET,s). We highlight a large number of conflicting results for the impact of management on ET and expose the complexity of the ET response to environmental factors. We analyse the influence of management practices on WUEG,ET,s in terms of the three main processes controlling it: (i) the proportion of transpiration in ET (T/ET), (ii) transpiration efficiency for shoot biomass production (TEB), and (iii) the harvest index. We directly relate the impact of management practices on T/ET to their effect on crop light interception and provide evidence that management practices significantly influence TEB. To optimize WUEG,ET,s, management practices should favor soil water availability during critical periods for seed set, thereby improving the harvest index. The need to improve the performance of existing crop growth models for the prediction of water-related grain yield determinants under different management practices is also discussed.
The ratio of auxin to cytokinin controls leaf development and meristem initiation in Physcomitrium patens
Authors: Cammarata Joseph , Roeder Adrienne H K , Scanlon Michael J 
Published: July 2023

Abstract
Crosstalk between auxin and cytokinin contributes to widespread developmental processes, including root and shoot meristem maintenance, phyllotaxy, and vascular patterning. However, our understanding of crosstalk between these hormones is limited primarily to angiosperms. The moss Physcomitrium patens (formerly Physcomitrella patens) is a powerful system for studying plant hormone function. Auxin and cytokinin play similar roles in regulating moss gametophore (shoot) architecture, to those in flowering plant shoots. However, auxin–cytokinin crosstalk is poorly understood in moss. Here we find that the ratio of auxin to cytokinin is an important determinant of development in P. patens, especially during leaf development and branch stem cell initiation. Addition of high levels of auxin to P. patens gametophores blocks leaf outgrowth. However, simultaneous addition of high levels of both auxin and cytokinin partially restores leaf outgrowth, suggesting that the ratio of these hormones is the predominant factor. Likewise, during branch initiation and outgrowth, chemical inhibition of auxin synthesis phenocopies cytokinin application. Finally, cytokinin-insensitive mutants resemble plants with altered auxin signaling and are hypersensitive to auxin. In summary, our results suggest that the ratio between auxin and cytokinin signaling is the basis for developmental decisions in the moss gametophore.