bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vγ9Vδ2 T-cells Are Potent Inhibitors of SARS-CoV-2 Replication and Represent Effector Phenotypes in Patients With COVID-19
Authors: Gay Laetitia , Rouviere Marie-Sarah , Mezouar Soraya , Richaud Manon , Gorvel Laurent , Foucher Etienne , La Scola Bernard , Menard Amélie , Allardet-Servent Jérôme , Halfon Philippe , Frohna Paul , Cano Carla , Mege Jean-Louis , Olive Daniel 
Published: April 2024

Abstract
Vγ9Vδ2 T cells play a key role in the innate immune response to viral infections through butyrophilin 3A (BTN3A). Here, we report blood Vγ9Vδ2 T cells decreased in clinically mild COVID-19 compared to healthy volunteers, and this was maintained up to 28 days and in the recovery period. Terminally differentiated Vγ9Vδ2 T cells tended to be enriched on the day of diagnosis, 28 days after, and during the recovery period. These cells showed cytotoxic and inflammatory activities following anti-BTN3A activation. BTN3A upregulation and Vγ9Vδ2 T-cell infiltration were observed in a lung biopsy from a fatal SARS-CoV-2 infection. In vitro, SARS-CoV-2 infection increased BTN3A expression in macrophages and lung cells that enhanced the anti–SARS-CoV-2 Vγ9Vδ2 T-cell cytotoxicity and interferon-γ and tumor necrosis factor-α. Increasing concentrations of anti-BTN3A lead to viral replication inhibition. Altogether, we report Vγ9Vδ2 T cells are important in the immune response against SARS-CoV-2 infection and activation by anti-BTN3A antibody may enhance their response.
Clinical Trials Registration. NCT04816760.
Distinct and rich assemblages of giant viruses in Arctic and Antarctic lakes
Authors: Pitot Thomas M , Rapp Josephine Z , Schulz Frederik , Girard Catherine , Roux Simon , Culley Alexander I 
Published: March 2024

Abstract
Giant viruses (GVs) are key players in ecosystem functioning, biogeochemistry, and eukaryotic genome evolution. GV diversity and abundance in aquatic systems can exceed that of prokaryotes, but their diversity and ecology in lakes, especially polar ones, remain poorly understood. We conducted a comprehensive survey and meta-analysis of GV diversity across 20 lakes, spanning polar to temperate regions, combining our extensive lake metagenome database from the Canadian Arctic and subarctic with publicly available datasets. Leveraging a novel GV genome identification tool, we identified 3304 GV metagenome-assembled genomes, revealing lakes as untapped GV reservoirs. Phylogenomic analysis highlighted their dispersion across all Nucleocytoviricota orders. Strong GV population endemism emerged between lakes from similar regions and biomes (Antarctic and Arctic), but a polar/temperate barrier in lacustrine GV populations and differences in their gene content could be observed. Our study establishes a robust genomic reference for future investigations into lacustrine GV ecology in fast changing polar environments.
Compliance Agreements: Emergent Flexibility in the Inter-American Human Rights System
Authors: Pérez-Liñán Aníbal , Brocca Mariana , Orizaga Inzunza Isabel Anayanssi 
Published: April 2024

Abstract
Are agreements between states and victims an effective way to achieve reparations for human rights violations? We identify and evaluate a legal instrument hitherto ignored in analyses of the Inter-American Human Rights System: compliance agreements. These agreements emerged as a tool to negotiate the implementation of recommendations made by the Inter-American Commission on Human Rights to states responsible for human rights violations. In the first part of the paper, we theorize the role of agreements in securing state compliance, and discuss the problem of self-selection in legal settlements. We then document the emergence of this legal instrument and its novel role in the Inter-American System. In the third part, we provide statistical evidence from event history, matching, difference-in-differences, and sensitivity analyses showing that agreements increase the probability of compliance and cut the expected time to compliance by more than half. Agreements thus contribute to a potential solution for the perceived crisis of compliance in the Inter-American Human Rights System. However, the Commission must offer greater transparency to facilitate the evaluation of this mechanism.
Under No Circumstances? What the Chinese Really Think about the Wartime Use of Nuclear Weapons
Authors: Ju Changwook , Byun Joshua 
Published: April 2024

Abstract
The idea of using nuclear weapons to kill noncombatants is said to evoke strong moral opprobrium among millions of individuals across the globe, such that national leaders should be constrained from using the weapons even when such a decision would be strategically sensible. Classical area scholarship and recent survey evidence suggest that this “nuclear taboo” is strong among the Chinese public, buttressed by culturally grounded preferences for moderation in warfare. Drawing on findings in cultural sociology and political behavior, we argue that previous studies mislead on the extent to which ordinary Chinese citizens might oppose the use of nuclear weapons in a real military clash, primarily due to a failure to distinguish baseline preferences for nuclear nonuse from the willingness to approve of governmental decisions to use these weapons. Results from an original survey experiment fielded in mainland China show that many individuals who personally dislike the idea of using nuclear weapons are nonetheless willing to support their leaders’ decision to do so. Our study contributes new and systematic knowledge about Chinese nuclear attitudes and highlights the value of harnessing interdisciplinary insights to inform the research agenda on the nuclear taboo.
Temporal development in the impacts of plant invasions: search for the underlying mechanisms
Authors: Dostál Petr 
Published: March 2024

Abstract
Many invasive plants have negative impacts on native populations and communities, but there remains much uncertainty about how these impacts develop over time. In this review, I describe the mechanisms that promote the initial dominance of invaders, the characteristics associated with large negative impacts, and present the processes that contribute to changes in invader abundance and impacts over time. Together with ecological processes such as ecosystem engineering or enemy accumulation, I show that temporal variation in impacts can be linked to evolution in both native and invasive species. I also show that multiple processes operating in the same invasion system can jointly shape long-term impacts. Finally, I present the framework of modern coexistence theory as a tool for predicting the effects of invaders on native populations, and how these effects change with processes ongoing within invaded communities.
Quantifying radiation exposure in the radiological investigation of non-arthritic hip pain
Authors: Mayne Alistair IW , Saad Ahmed , Botchu Rajesh , Gosling Lucie , Wall Peter , Politis Angelos , D’Alessandro Peter , McBryde Callum 
Published: April 2024

ABSTRACT
Radiological investigations are essential for evaluating underlying structural abnormalities in patients presenting with non-arthritic hip pain. The aim of this study is to quantify the radiation exposure associated with common radiological investigations performed in assessing patients presenting with non-arthritic hip pain. A retrospective review of our institutional imaging database was performed. Data were obtained for antero-posterior, cross-table lateral, frog lateral radiographs and low-dose CT hip protocol. The radiation dose of each imaging technique was measured in terms of dose-area product with units of mGy cm2, and the effective doses (ED, mSv) calculated. The effective radiation dose for each individual hip radiograph performed was in the range of 0.03–0.83 mSv [mean dose-area product 126.7–156.2 mGy cm2]. The mean ED associated with the low-dose CT hip protocol (including assessment of femoral anteversion and tibial torsion) was 3.04 mSv (416.8 mGy cm2). The radiation dose associated with the use of CT imaging was significantly greater than plain radiographs (P &lt; 0.005). Investigation of non-arthritic hip pain can lead to significant ionizing radiation exposure for patients. In our institution, the routine protocol is to obtain an antero-posterior pelvic radiograph and then a specific hip sequence Magnetic Resonance Imaging (MRI) scan which includes the assessment of femoral anteversion. This provides the necessary information in the majority of cases, with CT scanning reserved for more complex cases where we feel there is a specific indication. We would encourage the hip preservation community to carefully consider and review the use of ionizing radiation investigations.
A new measure of US public agency policy discretion
Authors: Smith Natalie L , Yackee Susan Webb 
Published: April 2024

Abstract
The US bureaucracy routinely issues major public policy decisions that affect Americans’ lives. Government agency leaders make those decisions based on a subjective understanding of their agency’s available policy discretion. Over time, discretion has become a prominent theoretical construct in the bureaucratic politics and public administration literature, but it is rarely measured directly. In this article, we create a new measure of agency policy discretion. We draw on research suggesting that discretion is derived from the bureaucracy’s key political principals: the elected executive, legislators, and interest groups. We use data from the American State Administrators Project and trigonometry to calculate the discretion area scores for 8,955 state agencies between 1978 and 2018. We then evaluate the measure through a series of construct validation assessments. The article offers an innovative and generalizable way to operationalize discretion that will advance future scholarship in organizational behavior, public administration, and bureaucratic decision-making.
Biomarkers of immunotherapy in glioblastoma
Authors: Savage William M , Yeary Mitchell D , Tang Anthony J , Sperring Colin P , Argenziano Michael G , Adapa Arjun R , Yoh Nina , Canoll Peter , Bruce Jeffrey N 
Published: April 2024

Abstract
Glioblastoma (GBM) is the most common primary brain cancer, comprising half of all malignant brain tumors. Patients with GBM have a poor prognosis, with a median survival of 14–15 months. Current therapies for GBM, including chemotherapy, radiotherapy, and surgical resection, remain inadequate. Novel therapies are required to extend patient survival. Although immunotherapy has shown promise in other cancers, including melanoma and non-small lung cancer, its efficacy in GBM has been limited to subsets of patients. Identifying biomarkers of immunotherapy response in GBM could help stratify patients, identify new therapeutic targets, and develop more effective treatments. This article reviews existing and emerging biomarkers of clinical response to immunotherapy in GBM. The scope of this review includes immune checkpoint inhibitor and antitumoral vaccination approaches, summarizing the variety of molecular, cellular, and computational methodologies that have been explored in the setting of anti-GBM immunotherapies.
Dual MPO/PR3 ANCA positivity and vasculitis: insights from a 7-cases study and an AI-powered literature review
Authors: Bettacchioli Eléonore , Foulquier Jean-Baptiste , Chevet Baptiste , Cornec-Le Gall Emilie , Hanrotel Catherine , Lanfranco Luca , de Moreuil Claire , Lambert Yannick , Dueymes Maryvonne , Foulquier Nathan , Cornec Divi 
Published: March 2024

Abstract

Objectives
Anti-neutrophil cytoplasm antibodies (ANCA)-associated vasculitides (AAV) are rare conditions characterized by inflammatory cell infiltration in small blood vessels, leading to tissue necrosis. While most patients with AAV present antibodies against either myeloperoxidase (MPO) or proteinase 3 (PR3), rare cases of dual positivity for both antibodies (DP-ANCA) have been reported, and their impact on the clinical picture remains unclear. The goal of this study was to investigate the clinical implications, phenotypic profiles and outcomes of patients with DP-ANCA.

Methods
A retrospective screening for DP-ANCA cases was conducted at Brest University Hospital's immunology laboratory (France), analysing ANCA results from March 2013 to March 2022. Clinical, biological, imaging, and histological data were collected for each DP-ANCA case. Additionally, a comprehensive literature review on DP-ANCA was performed, combining an artificial intelligence (AI)-based search using BIBOT software with a manual PUBMED database search.

Results
The report of our cases over the last 9 years and those from the literature yielded 103 described cases of patients with DP-ANCA. We identified four distinct phenotypic profiles: (i) idiopathic AAV (∼30%); (ii) drug-induced AAV (∼25%); (iii) autoimmune disease associated with a low risk of developing vasculitis (∼20%); and (iv) immune-disrupting comorbidities (infections, cancers, etc) not associated with AAV (∼25%).

Conclusion
This analysis of over a hundred DP-ANCA cases suggests substantial diversity in clinical and immunopathological presentations. Approximatively 50% of DP-ANCA patients develop AAV, either as drug-induced or idiopathic forms, while the remaining 50%, characterized by pre-existing dysimmune conditions, demonstrates a remarkably low vasculitis risk. These findings underscore the complex nature of DP-ANCA, its variable impact on patient health, and the necessity for personalized diagnostic and management approaches in these cases.
Description of a novel splice site variant in UBA1 gene causing VEXAS syndrome
Authors: Ospina Cardona Daniela , Rodriguez-Pinto Ignasi , Iosim Sonia , Bonet Nuria , Mensa-Vilaro Anna , Wong Mei-Kay , Ho Gary , Tormo Marc , Yagüe Jordi , Shon Wonwoo , Wallace Daniel J , Casals Ferran , Beck David B , Abuav Rachel , Arostegui Juan I 
Published: March 2024

Abstract

Objective
Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is a complex immune disorder consequence of somatic UBA1 variants. Most reported pathogenic UBA1 variants are missense or splice site mutations directly impairing the translational start site at p.Met41, with recent studies showing that these variants are frequent causes of recurrent inflammation in older individuals. Here we aimed to characterize a novel UBA1 variant found in two patients clinically presenting with VEXAS syndrome.

Methods
Patients’ data were collected from direct assessments and from their medical charts. Genomics analyses were undertaken by both Sanger and amplicon-based deep sequencing, and mRNA studies were undertaken by both cDNA subcloning and mRNA sequencing.

Results
We report a novel, somatic variant in a canonical splice site of the UBA1 gene (c.346-2A&gt;G), which was identified in two unrelated adult male patients with late-onset, unexplained inflammatory manifestations including recurrent fever, Sweet syndrome-like neutrophilic dermatosis, and lung inflammation responsive only to glucocorticoids. RNA analysis of the patients’ samples indicated aberrant mRNA splicing leading to multiple in-frame transcripts, including a transcript retaining the full sequence of intron 4 and a different transcript with the deletion of the first 15 nucleotides of exon 5.

Conclusion
Here we describe abnormal UBA1 transcription as a consequence of the novel c.346-2A&gt;G variant, identified in two patients with clinical features compatible with VEXAS syndrome. Overall, these results further demonstrate the expanding spectrum of variants in UBA1 leading to pathology and provide support for a complete gene evaluation in those patients considered candidates for VEXAS syndrome.
Influence of Substrate Stiffness on iPSC-Derived Retinal Pigmented Epithelial Cells
Authors: Wendland Rion J , Tucker Budd A , Worthington Kristan S 
Published: April 2024

Abstract
Retinal degenerative diseases are a major cause of blindness involving the dysfunction of photoreceptors, retinal pigmented epithelium (RPE), or both. A promising treatment approach involves replacing these cells via surgical transplantation, and previous work has shown that cell delivery scaffolds are vital to ensure sufficient cell survival. Thus, identifying scaffold properties that are conducive to cell viability and maturation (such as suitable material and mechanical properties) is critical to ensuring a successful treatment approach. In this study, we investigated the effect of scaffold stiffness on human RPE attachment, survival, and differentiation, comparing immortalized (ARPE-19) and stem cell-derived RPE (iRPE) cells. Polydimethylsiloxane was used as a model polymer substrate, and varying stiffness (~12 to 800 kPa) was achieved by modulating the cross-link-to-base ratio. Post-attachment changes in gene and protein expression were assessed using qPCR and immunocytochemistry. We found that while ARPE-19 and iRPE exhibited significant differences in morphology and expression of RPE markers, substrate stiffness did not have a substantial impact on cell growth or maturation for either cell type. These results highlight the differences in expression between immortalized and iPSC-derived RPE cells, and also suggest that stiffnesses in this range (~12-800 kPa) may not result in significant differences in RPE growth and maturation, an important consideration in scaffold design.
Systems-Based Practice: Expert Perspectives on the Origin and Evolution of an Ambiguous Competency
Authors: DeWaters Ami L. , Miller Erin L. , Haidet Paul , Gonzalo Jed D. 
Published: April 2024

Abstract

Purpose
Systems-based practice (SBP) has been a core competency in graduate medical education in the United States since 1999, but it has been difficult to operationalize in residency programs due to its conceptual ambiguity. The authors explored the historical origin and subsequent development of the SBP competency from the perspective of individuals who were influential across critical phases of its implementation and ensuing development. The goal of this study was to elicit the history of SBP from the perspective of individuals who have expertise in it and to use those findings to inform the current SBP construct.

Method
Between March and July 2021, 24 physicians, nurses, educators, and leaders in the field of SBP were individually interviewed about the origin and meaning of SBP as practiced in U.S. medical education using a semistructured guide. Individuals were selected based upon their influence on the origin or evolution of the SBP competency. Data were iteratively collected and analyzed using real-time analytic memos, regular adjudication sessions with the research team, and thematic analysis. Researchers identified themes from participants’ perspectives and agreed upon the final results and quotations.

Results
Five themes were identified: SBP has many different definitions, SBP was intentionally designed to be vague, systems thinking was identified as the foundation of the SBP competency, the 6 core competencies established in the United States by the Accreditation Council for Graduate Medical Education were developed to be interdependent, and the SBP and practice-based learning and improvement competencies are uniquely related and synergistic.

Conclusions
Interview data indicate that since its inception, SBP has been a nuanced and complex competency, resulting in a lack of mutually shared understanding among stakeholders. This deliberate historical examination of expert perspectives provides insight into specific areas for improving how SBP is taught and learned.
The Relationship Between Program and Applicant Characteristics With Applicant Program Signals in the 2022 Residency Recruitment Cycle: Findings From 3 Specialties
Authors: LaFemina Jennifer , Rosman Ilana S. , Wallach Sara L. , Wise Paul E. , Smink Douglas S. , Fletcher Laura 
Published: April 2024

Abstract

Purpose
Continuing increases in application volume have driven a national dialogue to reform the residency recruitment process. Program signaling allows applicants to express interest in a program at the preinterview stage with the goal of helping programs identify applicants with more genuine interest in their programs. This study explored the relationship between program signals and program and applicant characteristics.

Method
Participating dermatology, general surgery, and categorical internal medicine (IM) programs and applicants of the 2022 supplemental ERAS application (SuppApp) were included. Data from the SuppApp, the MyERAS Application for Residency Applicants (MyERAS), and the 2020 GME Track Survey were used. Cohen’s h was used to determine effect size, and chi-squared was used to determine statistical significance.

Results
There was an uneven distribution of signals to programs, with 25% of programs receiving about half of the signals across all 3 specialties. Programs with larger numbers of both residents and applicants received greater numbers of program signals relative to their program density, although this effect was small (h < 0.50, P < .001). No meaningful differences were seen across genders for any specialty. Only Hispanic applicants in IM sent a higher proportion of signals to programs with more underrepresented in medicine residents than White only applicants (40% vs 26%, h = 0.30, P < .001). Across all specialties, there was a small-to-moderate effect for international medical graduate (IMG) applicants sending a larger proportion of signals to programs with more IMG residents (h < 0.80, P < .001).

Conclusions
This first-year pilot study (i.e., SuppApp) provided initial evidence that supports the feasibility and fairness of program signals in residency selection. As program signals become more common across specialties, future research should continue to evaluate trends in where applicants send signals, and possible relationships between program and application characteristics.
Teaching Trainees Effective Patient Communication Skills in the Clinical Environment: Best Practices Under Crisis Conditions
Authors: Dubosh Nicole M. , Carter Keme 
Published: April 2024

Abstract
Communication within the health care setting has significant implications for the safety, engagement, and well-being of patients and physicians. Evidence shows that communication training is variable or lacking in undergraduate and graduate medical education. Physician-patient communication presents a vulnerable point in patient care, which was heightened by the COVID-19 pandemic and its aftermath. Physicians have to adapt their strategies to meet new challenges, including communicating through the necessary barriers of personal protective equipment and telecommunication platforms. They also face uncharted challenges of facilitating discussions around proactive planning and scarce resources. Medical educators must be equipped to provide trainees with the skills needed to maintain empathy, facilitate trust and connection, and adapt communication behaviors under such crisis conditions. Using the Calgary-Cambridge model as a framework, the authors describe 3 new challenges to effective physician-patient communication for which COVID-19 was the impetus—face masks, visitor restrictions, and resource allocation/proactive planning discussions—and propose educational solutions.