bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neutralization of recent SARS-CoV-2 variants by genetically and structurally related mAbs of the pemivibart lineage
Authors: Powers Colin , Williams Braedon , Kreher Alex , Gao Feng , West Brandyn , Chupp Daniel , Allen Robert 
Published: November 2024

AbstractPemivibart is a monoclonal antibody therapy currently under Emergency Use Authorization for the for the pre-exposure prophylaxis of coronavirus disease 2019 (COVID-19) in adults and adolescents over 12 years of age with certain immunocompromised conditions. As a part of the overall monitoring strategy for the activity of pemivibart, the antibody is regularly evaluated against emerging variants of SARS-CoV-2 using pseudovirus neutralization assays. Recent clinical data from Invivyd demonstrates that the PhenoSense pseudovirus assays carried out at Monogram Biosciences have been a reliable and consistent predictor of continued pemivibart clinical activity against SARS-COV-2 variants that have predominated across the timespan that includes the CANOPY clinical trial and the post-EUA authorization period. Additionally, new potential antibodies based upon the structural framework of pemivibart are continuously under evaluation. Fifteen of these yeast-produced “pemivibart-like” antibodies were tested for neutralization activity against recent variants KP.3 and KP.3.1.1. Like pemivibart, all 15 maintained activity against KP.3.1.1, with the change in IC50averaging 2.51-fold +/-0.7 compared to KP.3. Four pemivibart-like antibodies were also tested against the XEC variant, with the change in IC50averaging 3.01-fold compared to KP.3. These data suggest continued activity for pemivibart and pemivibart-like antibodies against KP.3.1.1 and XEC, recent variants containing N-terminal domain modifications.
Ventilatory Burden Predicts Change in Sleepiness Following Positive Airway Pressure in Sleep Apnea
Authors: Staykov Eric , Mann Dwayne L. , Kainulainen Samu , Leppänen Timo , Töyräs Juha , Azarbarzin Ali , Sands Scott A. , Terrill Philip I. 
Published: November 2024

AbstractRationaleExcessive daytime sleepiness, an important symptom of obstructive sleep apnea (OSA), is commonly quantified using the Epworth Sleepiness Scale score (ESS). Baseline OSA severity measures (ventilatory burden, flow limitation, and hypoxemia) provide insights into OSA pathophysiology and could predict changes in sleepiness (i.e. change-in-ESS) following continuous positive airway pressure (CPAP) treatment.ObjectivesWe hypothesized that change-in-ESS following CPAP treatment can be predicted from baseline polysomnography.MethodsAssociations between OSA severity measures and ESS were evaluated in 2332 participants, adjusting for age, sex, BMI, and total sleep time. Change-in-ESS prediction was evaluated using 213 CPAP treatment studies (HomePAP, BestAIR, and ABC) in three steps: severity measures were compared (adjusted regression,n=64), a prediction model was developed using baseline ventilatory burden and baseline ESS (n=139), and then evaluated in holdout participants (n=74).Measurements and Main ResultsIn cross-sectional analysis, ESS was associated with ventilatory burden (0.45 points/SD; 95% CI 0.23−0.67), hypoxic burden (0.39; 0.17−0.62), the apnea-hypopnea index (AHI) (0.36; 0.14−0.59), and flow limitation severity (0.22; 0.01−0.43). Comparison analysis revealed that change-in-ESS was most strongly associated with baseline ventilatory burden (-1.08 points/SD; -2.13 to -0.05) and baseline ESS (-2.75; -3.83 to -1.69); the AHI association was weaker (-0.97; -2.01−0.05). Predicted change-in-ESS and actual change-in-ESS were correlated in holdout participants (adjustedR²=0.313); median [IQR] actual change-in-ESS of predicted responders (≥2-point ESS improvement,n=54, 73.0%) was -5.0 [-10.0 to -2.0] and non-responders was 0.0 [-1.0−1.0] (P<0.001).ConclusionsBaseline ventilatory burden and baseline ESS were independently associated with change-in-ESS and could be used together to inform clinicians whether CPAP treatment will likely improve a patient’s sleepiness.
MUSCLE: Muscle Understanding through Synthetic Computation and Lesion Evaluation A Semi-Synthetic Dataset for Hamstring Injury Prediction Using Electrical Impedance
Authors: Youssef Baby Lea , Shehayib Reem , Maalouf Noel 
Published: November 2024

AbstractHamstring Injuries (HSIs) are common among athletes and necessitate extended rehabilitation before Return to Sport (RTS). Post-injury, athletes undergo physical examinations, which often fall short in assessing injury severity or guiding rehabilitation. Therefore, imaging techniques such as Magnetic Resonance Imaging (MRI) are used to evaluate the injury more comprehensively, aiding in the assessment of optimal rehabilitation and RTS timelines. Given the significant impact of HSIs on athletic careers, early prediction is essential. This article investigates the use of Electrical Impedance Tomography (EIT) for HSI prediction. EIT, a noninvasive method, involves injecting a current or voltage into the affected area to detect property changes, allowing for real-time monitoring and supporting its role in HSI prediction. A semi-synthetic dataset was created using MRI scans of patients with hamstring injuries. The dataset was developed by mapping the boundaries of the hamstring muscles (semimembranosus, semitendinosus, and biceps femoris) with Electrical Impedance Tomography and Diffuse Optical Tomography Reconstruction Software (EIDORS). EIDORS generated EIT voltage measurements by defining muscle boundaries and setting appropriate properties, forming the basis for the dataset. Machine Learning (ML) models were then employed to validate the dataset by distinguishing between injured and healthy hamstrings. The best-performing model, Random Forest (RF), achieved an accuracy of 98%, demonstrating the potential of EIT in predicting HSIs.Abstract FigureFigure 1:Graphical Abstract
Usefulness of apparent diffusion coefficient values and magnetic resonance imaging histogram analysis for identifying histological types of preoperative testicular tumors
Authors: Yasuda Yuka , Osaka Akiyoshi , Izumi Keita , Iwahata Toshiyuki , Nakayama Akinori , Kubota Kazunori , Saito Kazutaka 
Published: November 2024

AbstractThis study aimed to evaluate the ability of magnetic resonance imaging (MRI), including diffusion-weighted imaging with apparent diffusion coefficient values, to differentiate histological types of testicular tumors. Of 156 testicular tumors diagnosed at our hospital between January 2010 and July 2023, 65 cases with MRI were included. Tumors were categorized as seminoma, non-seminoma, and malignant lymphoma. Apparent diffusion coefficient values were calculated and analyzed using the ratio to normal testes and histograms according to tumor subtypes. Among the 65 cases, 46 were seminomas, 14 non-seminomas, and 5 malignant lymphomas. The apparent diffusion coefficient value ratio of seminomas was significantly higher than that of malignant lymphomas (p = 0.013). Additionally, the apparent diffusion coefficient value ratio of non-seminomas was significantly higher than that of seminomas and malignant lymphomas (p = 0.0013 and p < 0.001, respectively). On apparent diffusion coefficient histograms, malignant lymphomas had significantly higher values of kurtosis and skewness than seminomas. Normal testes and non-seminomas had significantly higher kurtosis and skewness values than that of malignant lymphomas and seminomas. A scoring model for seminomas and malignant lymphomas, developed with age and apparent diffusion coefficient value ratios, discriminated against the probability of seminoma and malignant lymphomas. MRI using apparent diffusion coefficient values and histogram analysis may aid the histological typing of seminomas, non-seminomas, malignant lymphomas.
ER Ca2+-levels control neuromodulator secretion by regulating L-type Ca2+-channel activity
Authors: Hoogstraaten Rein I. , Toonen Ruud F. , Verhage Matthijs 
Published: November 2024

AbstractRegulated secretion typically depends on activity-induced Ca2+influx. However, in invertebrates, the endoplasmic reticulum (ER) plays a distinct role, particularly in the release of neuromodulators from dense-core vesicles (DCVs). Here, we investigated the role of the neuronal ER as a Ca2+source for neuromodulator secretion in primary mouse neurons by directly monitoring ER and cytosolic Ca2+dynamics, along with DCV exocytosis at single vesicle resolution. During neuronal activity, neurons with a low initial [Ca2+]ERtook up Ca2+into the ER, while those with a high initial [Ca2+]ERreleased ER Ca2+. These latter neurons showed more DCV exocytosis. Acute ER Ca2+release by caffeine or thapsigargin application, resulted in minute increases in bulk cytosolic free Ca2+that did not trigger DCV exocytosis. Remarkably, following ER Ca2+depletion levels, activity-dependent Ca2+influx and DCV exocytosis were reduced by 50-90%, while synaptic vesicle (SV) exocytosis was unaffected. L-type Ca2+-channel inhibition by nimodipine reduced DCV exocytosis and Ca2+influx by 80-90 % without affecting SV exocytosis, a phenocopy of ER store depletion. In addition, introducing L-type channels lacking STIM1 interaction sites restored DCV fusion following ER store depletion. We conclude that the ER functions as a dynamic Ca2+store serving both as a Ca2+source or sink. Moreover, ER depletion activates a feedback loop that controls L-type Ca2+channel activity, essential for DCV exocytosis.
Stakeholder perspectives on the effectiveness of the Ifakara-Lupiro-Mang’ula Wildlife Management Area in Southern Tanzania
Authors: Tarimo Lucia J. , Kavishe Deogratius R. , Butler Fidelma , Killeen Gerry F. , Mombo Felister 
Published: November 2024

AbstractIn Tanzania, Wildlife Management Areas (WMAs) are established on village lands, usually adjacent to centrally managed core protected areas like national parks and game reserves, and managed in a devolved manner by local village authorities. WMAs are intended to conserve wildlife outside such core protected areas, while also providing opportunities for local communities to derive tangible benefits from wildlife and other natural resources. This study evaluates the perceived effectiveness of the Ifakara-Lupiro-Mang’ula (ILUMA) WMA in southern Tanzania among various stakeholders, focusing on its conservation, livelihoods and community development functions. Based on thematic analysis of perspectives shared by stakeholders at national, regional, district and village levels through in-depth interviews, focus group discussions and a public stakeholders meeting, the WMA was considered to have succeeded to only a very modest extent in achieving its intended goals. Essentially all participants narrated that the area is heavily encroached by human activities, including livestock grazing, agriculture, illegal fishing, meat poaching, deforestation, charcoal burning, timber harvesting and even permanent settlements. Contributing factors include a recently growing influx of agro-pastoralist immigrants, top-down political interference, financial constraints, financial mismanagement, limited resources for operations, lack of conservation education, investors or government support, and recent displacement of encroachment pressure from newly upgraded, centrally-managed protected areas nearby. To ensure future success and sustainability of the WMA, participants recommended enhancing stakeholder involvement and community participation in WMA management, improved collaboration with nearby centrally-managed protected areas for implementing operations, overhaul of the WMA constitution to reflect current best practices, building capacity among relevant village leaders and elected WMA representatives and initiating conservation education initiatives for the local community. Overall, the WMA should explore alternative income sources beyond tourism, to ensure direct benefits for the community member through sustainable, carefully-regulated access to natural resources, and resolve ongoing conflict over land use between the long-established villages that govern ILUMA and agro-pastoralists immigrants who have moved into the area more recently.
Influenza A virus transcription generates capped cRNAs that activate RIG-I
Authors: Elshina Elizaveta , Pitre Emmanuelle , Mendes Marisa , Schweibenz Brandon , Fan Rebecca L.Y. , French Hollie , Park Ji Woo , Wang Wei , Poon Leo L.M. , Marcotrigiano Joseph , Russell Alistair B. , te Velthuis Aartjan J.W. 
Published: November 2024

AbstractDuring influenza A virus (IAV) infection, host pathogen receptor retinoic acid-inducible gene I (RIG-I) detects the partially complementary, 5ʹ-triphosphorylated ends of the viral genome segments and non-canonical replication products. However, it has also been suggested that innate immune responses may be triggered by viral transcription. In this study, we investigated whether an immunostimulatory RNA is produced during IAV transcription. We show that the IAV RNA polymerase can read though the polyadenylation signal during transcription termination, generating a capped complementary RNA (ccRNA), which contains the 5ʹ cap of an IAV mRNA and the 3ʹ terminus of a cRNA instead of a poly(A) tail. ccRNAs are detectablein vitroand in both ribonucleoprotein reconstitution assays and IAV infections. Mutations that disrupt polyadenylation enhance ccRNA synthesis and increase RIG-I-dependent innate immune activation. Notably, while ccRNA itself is not immunostimulatory, it forms a RIG-I agonist by hybridizing with a complementary negative-sense viral RNA. These findings thus identify a novel non-canonical IAV RNA species and suggest an alternative mechanism for RIG-I activation during IAV infection.
Identification of a novel begomovirus betasatellite and occurrence of a viral complex associated with leaf curl disease in Bhut Jolokia in Assam
Authors: Saikia Richita , Paswan Ricky Raj , Borah Basanta Kumar 
Published: November 2024

AbstractBhut Jolokia (Capsicum chinenseJacq.) is one of the hottest chillies and an economically important crop in the northeastern regions of India. A major problem in the cultivation of Bhut Jolokia is the occurrence of leaf curl disease, which causes huge annual economic losses. The present study reveals the viral complex associated with the leaf curl disease in Bhut Jolokia collected from different geographical locations in Assam. A novel begomovirus betasatellite component was identified in two Bhut Jolokia samples, which was phylogenetically distinct from known begomovirus betasatellites. DAS-ELISA and PCR analysis confirmed the presence of multiple plant viruses including Chilli leaf curl virus (ChiLCV), Cucumber mosaic virus (CMV), Potato virus Y (PVY) and Tomato leaf curl virus (ToLCV) in most of the naturally infected Bhut Jolokia samples. Phylogenetic analysis revealed that thecoat protein(CP) gene of ChiLCVs and ToLCVs were highly conserved compared to theCPof CMV.
Fibril fragmentation generates diversity in seed population
Authors: Pedrola Júlia Aragonès , Todorovska Marija , Singh Shalini , Friedler Assaf , Rüdiger Stefan G. D. 
Published: November 2024

AbstractNeurodegenerative diseases are characterised by the formation and accumulation of protein fibrils. The mechanism underlaying this aggregation process remains poorly understood. Fibril fragmentation, resulting in seed generation, plays a role in toxicity. Here we provide a quantitative picture of the impact of ultrasound on patient-derived and recombinant fibrils from various diseases. Fragmentation of recombinant Tau fibrils and patient-derived fibrils from Alzheimer’s Disease, Corticobasal Degeneration and Frontotemporal Dementia generates amyloid and non-amyloid species. Interestingly, patient-derived fibrils are more susceptible to ultrasound than artificial fibrils. Understanding fibril fragmentation and the generation and nature of seeds may provide insights to the molecular mechanism of the disease progression, contributing to the development therapeutic approaches.
Quantification of subcellular RNA localization through direct detection of RNA oxidation
Authors: Lo Hei-Yong G. , Goering Raeann , Kocere Agnese , Lo Joelle , Pockalny Megan C. , White Laura K. , Ramirez Haydee , Martinez Abraham , Jacobson Seth , Spitale Robert C. , Pearson Chad G. , Resendiz Marino J. E. , Mosimann Christian , Taliaferro J. Matthew 
Published: November 2024

ABSTRACTAcross cell types and organisms, thousands of RNAs display asymmetric subcellular distributions. The study of this process often requires quantifying abundances of specific RNAs at precise subcellular locations. To analyze subcellular transcriptomes, multiple proximity-based techniques have been developed in which RNAs near a localized bait protein are specifically labeled, facilitating their biotinylation and purification. However, these complex methods are often laborious and require expensive enrichment reagents. To streamline the analysis of localized RNA populations, we developed Oxidation-Induced Nucleotide Conversion sequencing (OINC-seq). In OINC-seq, RNAs near a genetically encoded, localized bait protein are specifically oxidized in a photo-controllable manner. These oxidation events are then directly detected and quantified using high-throughput sequencing and our software package, PIGPEN, without the need for biotin-mediated enrichment. We demonstrate that OINC-seq can induce and quantify RNA oxidation with high specificity in a dose- and light-dependent manner. We further show the spatial specificity of OINC-seq by using it to quantify subcellular transcriptomes associated with the cytoplasm, ER, nucleus, and the inner and outer membranes of mitochondria. Finally, using transgenic zebrafish, we demonstrate that OINC-seq allows proximity-mediated RNA labeling in live animals. In sum, OINC-seq together with PIGPEN provide an accessible workflow for the analysis of localized RNAs across different biological systems.
“I prefer a doctor on camera than none at all”: Participants’ Perspectives on the Implementation of Integrated Telehealth and Community Health Workers Services to Improve Access to Healthcare in Rural Communities
Authors: Perez-Ramos Jose G. , McIntosh Scott , Wei-Chen Joselyn , Alicea-Vellon Jessica , Rodriguez-Diaz Carlos 
Published: November 2024

ABSTRACTBackgroundRural and isolated communities, such as Culebra, Puerto Rico, face significant healthcare challenges due to geographic isolation, limited medical resources, and socioeconomic disadvantages. Chronic diseases, particularly diabetes and hypertension, are prevalent and contribute to poor health outcomes. Telehealth services (THS) and community health workers (CHWs) have been identified as effective interventions for improving healthcare access in underserved areas. This study aimed to explore the community perceptions and attitudes towards integrating THS with the support of CHWs to enhance chronic disease management in Culebra.MethodsA Qualitative Research approach involved 20 patients from Culebra’s Federally Qualified Health Center (FQHC). Semi-structured interviews were conducted, guided by the Socio-Ecological Model (SEM), to assess community perspectives toward THS and CHWs at individual, interpersonal, community, and societal levels. Thematic analysis revealed three primary themes: social determinants of health, the role of CHWs, and the benefits and challenges of THS.ResultsFindings indicate that CHWs play a critical role in improving healthcare access by assisting with medical appointments, medication management, and providing emotional support. THS was recognized for its potential to reduce transportation barriers and improve continuity of care, though concerns regarding convenience, technology access, and data privacy persist. The integration of CHWs and THS was viewed positively as a solution to healthcare access challenges, with participants expressing trust in this model for managing chronic diseases.DiscussionThis study highlights the need for further development of THS infrastructure and CHW support to ensure equitable healthcare access in rural areas like Culebra. The combination of THS and CHWs shows promise for reducing healthcare disparities and improving outcomes for isolated populations. Future efforts should focus on systemic changes to address broader social determinants of health, fostering sustainable and effective healthcare delivery in underserved communities.
Heterochromatin epimutations impose mitochondrial dysfunction to confer antifungal resistance
Authors: Fellas Andreas , Pidoux Alison L. , Tong Pin , Hewes Harriet H. , Wallace Emma C. , Allshire Robin C. 
Published: November 2024

AbstractGlobal health and food supply are endangered by an increasing frequency of antifungal resistance in pathogenic fungi. Wild-type fission yeast,Schizosaccharomyces pombe, can gain resistance to insults such as caffeine and antifungal compounds through reversible epimutations. Resistant epimutants exhibit histone H3K9 methylation-dependent heterochromatin islands at various chromosomal locations, reducing expression of underlying genes. Two genes whose heterochromatin island-induced repression causes resistance encode mitochondrial proteins: the LYR domain protein Cup1 and the Cox1 translation regulator Ppr4. Genetic mutations,cup1-ttandppr4Δ, that phenocopy their respective epimutants, cause mitochondrial dysfunction, including respiratory deficiency, poor growth on non-glucose carbon sources, and elevated reactive oxygen species. RNA-Seq analyses indicate thatcup1-ttandppr4Δcells activate the mitonuclear retrograde pathway and the Pap1 transcription factor-dependent oxidative stress response pathways. Both mutants show increased nuclear localisation of Pap1 and its recruitment to promoters of genes encoding oxidoreductases and membrane transporters, causing increased efflux activity.cup1andppr4epimutants also show mitochondrial dysfunction phenotypes and increased efflux, explaining how heterochromatin-island epimutations cause drug resistance. Thus, wild-type cells harness epimutations that impose mitochondrial dysfunction to bypass external insults. As mitochondrial dysfunction has been linked to antifungal resistance in several fungi, similar epimutations likely contribute to development of resistance in fungal pathogens.
Perceptions of CSR initiatives as a strategic driver in strengthening relationships among banks and Italian consumers: an empirical approach in the Italian banking context
Authors: Barone Marco , Bussoli Candida , Conte Danilo , Fattobene Lucrezia , Morrone Domenico 
Published: November 2024

PurposeCorporate social responsibility (CSR) activities are increasingly prominent in the current agendas of firms, regulatory agencies and consumers worldwide. It is vital for banks to understand how consumers perceive CSR activities, as such activities strengthen their brand equity building. This study examines the relationship between financial consumers’ perceptions of banks’ CSR initiatives and brand equity, identifying a mediating influence of consumer trust and satisfaction.Design/methodology/approachThe survey was conducted by distributing questionnaires to Italian banking consumers (941 valid responses). The research hypotheses were tested using structural equation modeling and confirmatory factor analysis.FindingsOur analysis reveals that consumers’ perceptions of banks’ CSR initiatives directly affect brand equity. Moreover, trust and satisfaction positively mediate the relationship between consumers’ perceptions of CSR initiatives and brand equity in the Italian banking industry.Originality/valueThese findings advance understanding by making a novel contribution to the literature; they also have managerial implications. In terms of literature advancement, we provide new evidence related to a context with specific features, namely Italy. From a managerial perspective, this study highlights the importance of informing Italian customers about and promoting awareness of sustainable activities. In turn, client perceptions affect the banks’ value.