bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential inclusion ofNEBexons 143 and 144 provides insight intoNEB-related myopathy variant interpretation and disease manifestation
Authors: Silverstein Sarah , Orbach Rotem , Syeda Safoora , Reghan Foley A , Gorokhova Svetlana , Meilleur Katherine G. , Leach Meganne E. , Uapinyoying Prech , Chao Katherine R , Donkervoort Sandra , Bönnemann Carsten G. 
Published: March 2024

AbstractBiallelic pathogenic variants in the gene encoding nebulin (NEB) are a known cause of congenital myopathy. We present two individuals with congenital myopathy and compound heterozygous variants (NM_001271208.2: c.2079C>A; p.(Cys693Ter) and c.21522+3A>G) inNEB.Transcriptomic sequencing on patient muscle revealed that the extended splice variant c.21522+3A>G causes exon 144 skipping. Nebulin isoforms containing exon 144 are known to be mutually exclusive with isoforms containing exon 143, and these isoforms are differentially expressed during development and in adult skeletal muscles. Patients MRIs were compared to the known pattern of relative abundance of these two isoforms in muscle. We propose that the pattern of muscle involvement in these patients better fits the distribution of exon 144-containing isoforms in muscle than with previously published MRI findings inNEB-related disease due to other variants. To our knowledge this is the first report hypothesizing disease pathogenesis through the alteration of isoform distributions in muscle.
Results of a nationally representative seroprevalence survey of chikungunya virus in Bangladesh
Authors: Allen Sam W. , Dos Santos Gabriel Ribeiro , Paul Kishor K , Paul Repon , Rahman Ziaur , Alam Mohammad Shafiul , Rahman Mahmudur , Al-Amin Hasan Mohammad , Vanhomwegen Jessica , Smull Taylor , Lee Kyu Han , Gurley Emily S. , Salje Henrik 
Published: March 2024

AbstractChikungunya virus (CHIKV) is responsible for a rapidly increasing but poorly understood infection burden globally. Bangladesh experienced its first reported outbreak in 2008. Despite a number of subsequent isolated outbreaks, culminating in an enormous nationwide epidemic in 2017, very little is known about the burden or dynamics of chikungunya within the country, and the risk factors for infection. We conducted a nationally representative seroprevalence survey in 2016 in 70 randomly selected communities across the country. Individuals provided blood samples, which were tested for the presence of IgG antibodies to CHIKV. We also trapped and speciated mosquitoes. We found that 69/2,938 (2.4%) of individuals were seropositive to CHIKV. Seropositive individuals were concentrated in the centre and south of the country. We found that being seropositive to dengue virus (aOR 3.11 [95% CIs: 1.17 – 24.45]) and male sex (aOR 0.29 [95% CIs: 0.01 – 0.96]), were significantly associated with CHIKV seropositivity, however,Aedespresence, income, and travel history were not. Using a spatial prediction model, we estimate that at the time of the study, 4.99 million people in the country had been infected with CHIKV. These findings highlight high population susceptibility prior to the major outbreak in 2017 and that historic outbreaks must have been spatially isolated.
Risk of Inflammatory Bowel Disease Following Hospitalisation with Infectious Mononucleosis: A Danish Nationwide Cohort Study (1977-2021)
Authors: Ebert Anthony , Harper Shania , Vestergaard Marie V. , Mitchell Wayne , Jess Tine , Elmahdi Rahma 
Published: March 2024

ABSTRACTBackgroundInfectious mononucleosis (IM) is a largely self-limiting syndrome mainly affecting adolescents and young adults but can present as a more severe disease requiring hospitalisation. The infectious agent most commonly causing IM, Epstein-Barr virus (EBV) has been associated with the development of several immune-mediated and inflammatory diseases.ObjectiveTo investigate the risk of inflammatory bowel disease (IBD) following hospitalisation with severe IM.MethodsDanish nationwide registries were used to identify severe IM patients and sex-, age- and municipality-matched non-IM hospitalised controls, from 1st January 1977 to 31st December 2022. We undertook Cox regression modelling to calculate the hazards (HR) and 95% CI of IBD diagnosis, including Crohn’s disease (CD) and ulcerative colitis (UC). Analyses were stratified by sex and age at IM hospitalisation.ResultsWe identified 39,684 patients with severe IM who were sex-, age-, and municipality-matched to 396,840 non-IM hospitalised controls. Severe IM was significantly associated with the development of IBD (HR:1.35; 95% CI: 1.22-1.49) and this was seen particularly in CD (HR: 1.56; 95% CI: 1.34-1.83) and to a lesser extent in UC (HR: 1.23; 95% CI: 1.08-1.40). Sex at severe IM diagnosis was not found to be a significant modifier to the risk of IBD development with risk increased in both females (HR: 1.36; 95% CI: 1.20-1.55) and males (HR: 1.34; 95% CI: 1.17-1.54). Only those receiving a severe IM diagnosis at 10-16 years (HR: 1.42; 95% CI:1.22-1.64) or 17-29 years (HR: 1.34; 95% CI:1.15-1.56) were at increased risk of IBD development.ConclusionThis study demonstrated an association between IM hospitalisation and later IBD development, indicating an association between severe EBV disease and IBD development. Further exploration of factors contributing to IBD susceptibility following EBV infection is warranted.
A Three-Year Retrospective Review of Gynecologic Oncology Referrals to the Specialist Palliative Care Team in a Tertiary Referral Centre: Population, Characteristics, and Outcomes
Authors: Goodings Anthony James , Pastrak Mila , Kajitani Sten , Cunningham Elaine , O’Brien Hannah , Weadick Catherine , Dennehy Karie 
Published: March 2024

AbstractBackgroundThe early integration of a specialist palliative care team is demonstrated to have numerous benefits for patients. These extend beyond end-of-life care to include reducing depressive symptoms, improving quality of life, and reducing unnecessary interventions.AimsThis study aims to characterize the patient population referred to the specialist palliative care service with a diagnosis of gynecological cancer. It also assesses referral frequency and response time in order to understand palliative care utilization in an acute hospital setting.MethodsA retrospective chart review and database analysis was performed to extract data on demographics, cancer diagnoses, and referral reasons for patients referred to the specialist palliative care service over three years. The study focuses on identifying patterns in the characteristics of the referred patient population.ResultsAnalysis of 162 patients revealed a distribution across cancer subtypes: 62% ovarian, 22% endometrial, 12% cervical, and 4% vulvar. A notable finding was that the outcomes for patients with ovarian cancer were more likely to be discharged home with or without community care (61.8%) compared to those with endometrial cancer (41.0%). A rapid response to referrals was observed, with 70% reviewed within three days and 98% within a week. This highlights the service’s efficiency and the demographic and diagnostic profile of the patient served.ConclusionsThis study gives insight into the demographic and diagnostic profiles of gynecological cancer patients referred for palliative care, alongside demonstrating rapid response to such referrals. Despite the rapid assessment times, the research importantly identifies differences in outcomes among different cancer subtypes, with a particular emphasis on the variance in discharge destinations. These findings reflect both patient preference and medical need, demonstrating the role of tailoring palliative care approaches to meet the individual needs and desires of this diverse patient population.
Algorithmic Individual Fairness and Healthcare: A Scoping Review
Authors: Anderson Joshua W. , Visweswaran Shyam 
Published: March 2024

AbstractObjectiveStatistical and artificial intelligence algorithms are increasingly being developed for use in healthcare. These algorithms may reflect biases that magnify disparities in clinical care, and there is a growing need for understanding how algorithmic biases can be mitigated in pursuit of algorithmic fairness. Individual fairness in algorithms constrains algorithms to the notion that “similar individuals should be treated similarly.” We conducted a scoping review on algorithmic individual fairness to understand the current state of research in the metrics and methods developed to achieve individual fairness and its applications in healthcare.MethodsWe searched three databases, PubMed, ACM Digital Library, and IEEE Xplore, for algorithmic individual fairness metrics, algorithmic bias mitigation, and healthcare applications. Our search was restricted to articles published between January 2013 and September 2023. We identified 1,886 articles through database searches and manually identified one article from which we included 30 articles in the review. Data from the selected articles were extracted, and the findings were synthesized.ResultsBased on the 30 articles in the review, we identified several themes, including philosophical underpinnings of fairness, individual fairness metrics, mitigation methods for achieving individual fairness, implications of achieving individual fairness on group fairness and vice versa, fairness metrics that combined individual fairness and group fairness, software for measuring and optimizing individual fairness, and applications of individual fairness in healthcare.ConclusionWhile there has been significant work on algorithmic individual fairness in recent years, the definition, use, and study of individual fairness remain in their infancy, especially in healthcare. Future research is needed to apply and evaluate individual fairness in healthcare comprehensively.
Resonant breathing improves self-reported symptoms and wellbeing in people with Long COVID
Authors: Polizzi Jessica , Tosto-Mancuso Jenna , Tabacof Laura , Wood Jamie , Putrino David 
Published: March 2024

AbstractIntroductionLong COVID involves debilitating symptoms, many of which mirror those observed with dysautonomia, and care must be taken with traditional autonomic rehabilitation to avoid post-exertional malaise/post-exertional symptom exacerbation. Resonant breathing exercises require less exertion and can potentially improve autonomic function. The objective of this work was to report on the impact of a resonant breathing program on self-reported symptoms and wellbeing in people with Long COVID.MethodsA retrospective analysis of de-identified data was completed in a convenience sample of people with Long Covid, who participated in the Meo Health (formerly known as Stasis HP) resonant breathing program. Participants completed baseline and follow up surveys.ResultsData were available for 99 participants. Most measures of symptoms and wellbeing improved at follow up, with the largest differences per participant seen in sense of wellness (47.3%, p<0.0001), ability to focus (57.5%, p<0.0001), ability to breathe (47.5%, p<0.0001), ability to control stress (61.8%, p<0.0001) and sleep quality (34.9%, p=0.0002). Most (92%) participants reported improvement at follow up on the Patient Global Impression of Change Scale.ConclusionSelf-reported symptoms and wellbeing improved in people with Long COVID completing resonant breathing. Resonant breathing can be considered as an option within the broader treatment plan of people with Long COVID.
Humoral Immunity Elicited by the XBB.1.5 Monovalent COVID-19 Vaccine
Authors: Nguyenla Xammy Huu , Bates Timothy A. , Trank-Greene Mila , Wahedi Mastura , Tafesse Fikadu G. , Curlin Marcel 
Published: March 2024

AbstractAs novel SARS-CoV-2 variants continue to emerge, the updated XBB.1.5 monovalent vaccines remain to be evaluated in terms of immunogenicity against live clinical isolates. We report boosting of IgG(2.1X), IgA(1.5X), and total IgG/A/M(1.7X) antibodies targeting the spike receptor-binding domain and neutralizing titers against WA1(2.2X), XBB.1.5(7.4X), EG.5.1(10.5X), and JN.1(4.7X) variants.
Prospective study ofCandida aurisnucleic-acids in wastewater solids in 190 wastewater treatment plants in the United States suggests widespread occurrence
Authors: Zulli Alessandro , Chan Elana M. G. , Shelden Bridgette , Duong Dorothea , Xu Xiang-Ru S. , White Bradley J. , Wolfe Marlene K. , Boehm Alexandria B. 
Published: March 2024

AbstractCandida aurisis an emerging, multidrug-resistant fungal pathogen that poses a significant public health threat in healthcare settings. Despite yearly clinical cases rapidly increasing from 77 to 8,131 in the last decade, surveillance data on its distribution and prevalence remains limited. We implemented a novel assay forC. aurisdetection on a nationwide scale prospectively from September 2023 to March 2024, analyzing a total of 13,842 samples from 190 wastewater treatment plants across 41 U.S. states. Assays were extensively validated through comparison to other known assays and internal controls. Of these 190 wastewater treatment plants,C. auriswas detected in the wastewater solids of 65 of them (34.2%) with 1.45% of all samples having detectable levels ofC. auris. Detections varied seasonally, with 2.00% of samples positive in autumn versus 1.01% in winter (p<0.0001). The frequency of detection in wastewater was significantly associated with states having older populations (p<0.001), sewersheds containing more hospitals (p<0.0001), and sewersheds containing more nursing homes (p<0.001). These associations are in agreement with knownC. aurisepidemiology. This nationwide study demonstrates the viability of wastewater surveillance forC. aurissurveillance, and further highlights the value of wastewater surveillance when clinical testing is constrained.
Defensive fungal symbiosis on insect hindlegs
Authors: Nishino Takanori , Mukai Hiromi , Moriyama Minoru , Hosokawa Takahiro , Tanahashi Masahiko , Tachikawa Shuji , Nikoh Naruo , Koga Ryuichi , Fukatsu Takema 
Published: March 2024

AbstractTympanal organs as “insect ears” have evolved repeatedly. Dinidorid stinkbugs were reported to possess a conspicuous tympanal organ on female’s hindlegs. Here we report an unexpected discovery that the stinkbug’s “tympanal organ” is actually a novel symbiotic organ. The stinkbug’s “tympanum” is not membranous but a porous cuticle, where each pore connects to glandular secretory cells. In reproductive females, the hindleg organ is covered with fungal hyphae growing out of the pores. Upon oviposition, the females skillfully transfer the fungi from the organ to the eggs. The eggs are quickly covered with hyphae and physically protected against wasp parasitism. The fungi are mostly benign Cordycipitaceae entomopathogens and show considerable diversity among insect individuals and populations, indicating environmental acquisition of specific fungal associates. These results uncover a novel external fungal symbiosis in which host’s elaborate morphological, physiological and behavioral specializations underpin the selective recruitment of benign entomopathogens for a defensive purpose.
Widespread Horizontal Gene Transfer Among Animal Viruses
Authors: Buck Christopher B. , Welch Nicole , Belford Anna K. , Varsani Arvind , Pastrana Diana V. , Tisza Michael J. , Starrett Gabriel J. 
Published: March 2024

AbstractThe initial objective of this study was to shed light on the evolution of small DNA tumor viruses by analyzingde novoassemblies of publicly available deep sequencing datasets. The survey generated a searchable database of contig snapshots representing more than 100,000 Sequence Read Archive records. Using modern structure-aware search tools, we iteratively broadened the search to include an increasingly wide range of other virus families. The analysis revealed a surprisingly diverse range of chimeras involving different virus groups. In some instances, genes resembling known DNA-replication modules or known virion protein operons were paired with unrecognizable sequences that structural predictions suggest may represent previously unknown replicases and novel virion architectures. Discrete clades of an emerging group called adintoviruses were discovered in datasets representing humans and other primates. As a proof of concept, we show that the contig database is also useful for discovering RNA viruses and candidate archaeal phages. The ancillary searches revealed additional examples of chimerization between different virus groups. The observations support a gene-centric taxonomic framework that should be useful for future virus-hunting efforts.
Peptides from non-immune proteins target infections through antimicrobial and immunomodulatory properties
Authors: Torres Marcelo D. T. , Cesaro Angela , de la Fuente-Nunez Cesar 
Published: March 2024

SummaryEncrypted peptides have been recently described as a new class of antimicrobial molecules. They have been proposed to play a role in host immunity and as alternatives to conventional antibiotics. Intriguingly, many of these peptides are found embedded in proteins unrelated to the immune system, suggesting that immunological responses may extend beyond traditional host immunity proteins. To test this idea, here we synthesized and tested representative peptides derived from non-immune proteins for their ability to exert antimicrobial and immunomodulatory properties. Our experiments revealed that most of the tested peptides from non-immune proteins, derived from structural proteins as well as proteins from the nervous and visual systems, displayed potentin vitroantimicrobial activity. These molecules killed bacterial pathogens by targeting their membrane, and those originating from the same region of the body exhibited synergistic effects when combined. Beyond their antimicrobial properties, nearly 90% of the peptides tested exhibited immunomodulatory effects, modulating inflammatory mediators such as IL-6, TNF-α, and MCP-1. Moreover, eight of the peptides identified, collagenin 3 and 4, zipperin-1 and 2, and immunosin-2, 3, 12, and 13, displayed anti-infective efficacy in two different preclinical mouse models, reducing bacterial infections by up to four orders of magnitude. Altogether, our results support the hypothesis that peptides from non-immune proteins may play a role in host immunity. These results potentially expand our notion of the immune system to include previously unrecognized proteins and peptides that may be activated upon infection to confer protection to the host.
Pseudo-pac site sequences used by phage P22 in generalized transduction ofSalmonella
Authors: Maier Jessie L. , Gin Craig , Callahan Ben , Sheriff Emma K. , Duerkop Breck A. , Kleiner Manuel 
Published: March 2024

AbstractSalmonella entericaSerovar Typhimurium (Salmonella) and its bacteriophage P22 are a model system for the study of horizontal gene transfer by generalized transduction. Typically, the P22 DNA packaging machinery initiates packaging when a short sequence of DNA, known as the pac site, is recognized on the P22 genome. However, sequences similar to the pac site in the host genome, called pseudo-pac sites, lead to erroneous packaging and subsequent generalized transduction ofSalmonellaDNA. While the general genomic locations of theSalmonellapseudo-pac sites are known, the sequences themselves have not been determined. We used visualization of P22 sequencing reads mapped to hostSalmonellagenomes to define regions of generalized transduction initiation and the likely locations of pseudo-pac sites. We searched each genome region for the sequence with the highest similarity to the P22 pac site and aligned the resulting sequences. We built a regular expression (sequence match pattern) from the alignment and used it to search the genomes of two P22-susceptibleSalmonellastrains-LT2 and 14028S- for sequence matches. The final regular expression successfully identified pseudo-pac sites in both LT2 and 14028S that correspond with generalized transduction initiation sites in mapped read coverages. The pseudo-pac site sequences identified in this study can be used to predict locations of generalized transduction in other P22-susceptible hosts or to initiate generalized transduction at specific locations in P22-susceptible hosts with genetic engineering. Furthermore, the bioinformatics approach used to identify theSalmonellapseudo-pac sites in this study could be applied to other phage-host systems.ImportanceBacteriophage P22 has been a genetic tool and a key model for the study of generalized transduction inSalmonellasince the 1950s, yet certain components of the generalized transduction molecular mechanism remain unknown. Specifically, the locations and sequences of pseudo-pac sites, hypothesized to facilitate packaging ofSalmonellaDNA by P22, to date have not been determined. In this study, we identified the specific locations and sequences of the pseudo-pac sites frequently recognized by P22 inSalmonellagenomes. The identification of highly efficient pseudo-pac sites inSalmonellaprovides fundamental insights into the sequence specificity necessary for P22 pac site recognition and opens the door to more targeted use of generalized transduction with P22.
Beam dynamics driven design of powerful energy recovery linac for experiments
Authors: Bogacz S. A. , André K. D. J. , Brüning O. , Holzer B. J. , Hounsell B. R. , Klein M. , Militsyn B. L. , Williams P. H. , Segurana G. Pérez , Bailey I. , Apsimon R. , Setiniyaz S. , Abukeshek R. , Barbagallo C. , Abdillah M. Ben , Bruni C. , Duchesne P. , Duthil P. , Fomin A. , Guyot C. , Kaabi W. , Michaud J. , Olry G. , Perrot L. , Reynet D. , Roux R. , Stocchi A. , Wurth S. , Abualrob H. , Baylac M. , Bouly F. , Jacquot B. 
Published: March 2024

Powerful ERL for experiments (PERLE) is a novel energy recovery linac (ERL) test facility [1], designed to validate choices for a 50 GeV ERL foreseen in the design of the Large Hadron Electron Collider and the Future Circular Collider and to host dedicated nuclear and particle physics experiments. Its main goal is to demonstrate the high current, continuous wave, multipass operation with superconducting cavities at 802 MHz. With very high beam power (10 MW), PERLE offers an opportunity for controllable study of every beam dynamic effect of interest in the next generation of ERLs and becomes a “stepping stone” between the present state-of-the-art 1 MW ERLs and the future 100 MW scale applications.

Published by the American Physical Society
2024
Spectroscopy of hot electron pair emission from a driven quantum dot
Authors: Schulenborg Jens , Fletcher Jonathan D. , Kataoka Masaya , Splettstoesser Janine 
Published: March 2024

On-demand emission of individual electrons for the implementation of flying qubits and quantum electron-optics experiments requires precise knowledge and tunability of emission times and energies. Crucially, for confined electron sources such as driven quantum dots, the effect of local Coulomb interaction on these emission properties needs to be understood, in particular if multiple particles are emitted close in time or near simultaneously. This paper theoretically analyzes electron pair emission from an ac driven quantum dot, detailing the competing effects of the electron-electron interaction, the time-dependent potential forming the quantum dot, and of the quantum-state properties, such as degeneracy, on the emission times and energies. We complement a numerical analysis of the coherent Schrödinger evolution of two particles in a driven potential with a master-equation description for strongly interacting electrons tunneling stochastically into a weakly coupled conductor. This captures a broad range of different influences on the emitted particles and thereby guides the development of single-electron sources with higher control over two-particle emission properties.

Published by the American Physical Society
2024