bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing the performance of the family folder system for collecting community-based health information in Tigray Region, North Ethiopia: a capture–recapture study
Authors: Derbew Atakelti Abraha , Debeb Hagos Godefay , Kinsman John , Myléus Anna , Byass Peter 
Published: February 2024

ObjectivesTo assess completeness and accuracy of the family folder in terms of capturing community-level health data.Study designA capture–recapture method was applied in six randomly selected districts of Tigray Region, Ethiopia.ParticipantsChild health data, abstracted from randomly selected 24 073 family folders from 99 health posts, were compared with similar data recaptured through household survey and routine health information made by these health posts.Primary and secondary outcome measuresCompleteness and accuracy of the family folder data; and coverage selected child health indicators, respectively.ResultsDemographic data captured by the family folders and household survey were highly concordant, concordance correlation for total population, women 15–49 years age and under 5-year child were 0.97 (95% CI 0.94 to 0.99, p<0.001), 0.73 (95% CI 0.67 to 0.88) and 0.91 (95% CI 0.85 to 0.96), respectively. However, the live births, child health service indicators and child health events were more erratically reported in the three data sources. The concordance correlation among the three sources, for live births and neonatal deaths was 0.094 (95% CI −0.232 to 0.420) and 0.092 (95% CI −0.230 to 0.423) respectively, and for the other parameters were close to 0.ConclusionThe family folder system comprises a promising development. However, operational issues concerning the seamless capture and recording of events and merging community and facility data at the health centre level need improvement.
Insight into Private General Physicians’ Practices: an Exploratory Qualitative Study in a Rural District of Pakistan
Authors: Akber Pradhan Nousheen , Zaidi Tahani Waqar , Siddiqi Sameen 
Published: February 2024

ObjectiveThe study aimed to assess private general physicians’(GPs) healthcare practices, identifying perceived malpractices, the support they receive, and barriers they experience in providing healthcare services.DesignQualitative exploratory study.SettingRural district, Thatta in Province of Sindh, Pakistan.Participants15 GPs.ResultsOur results include increased motivation among GPs for continued professional development, the high influence of pharmaceutical companies on providers’ prescribing practices, perceived malpractices by GPs, and the prevalence of quackery and ineffective regulatory mechanisms for private GPs in a rural district.ConclusionOur findings have implications for the capacity building of GPs by academic institutions, enforcement of regulatory measures by the authorities, and the introduction of measures to curb practices by unqualified practitioners. Finally, more research will be needed to further understand the perceptions of GPs, their needs and the service delivery interventions that will enhance the quality of care they provide.
Comparative effectiveness of biologics in patients with rheumatoid arthritis stratified by body mass index: a cohort study in a Swiss registry
Authors: Vallejo-Yagüe Enriqueta , Burkard Theresa , Finckh Axel , Burden Andrea Michelle 
Published: February 2024

ObjectivesObesity is associated with lower treatment response in patients with rheumatoid arthritis (RA). In patients with obesity, abatacept was suggested as a preferable option to tumour necrosis factor-alpha inhibitors. We aimed to assess the comparative effectiveness of etanercept, infliximab and abatacept, compared with adalimumab, in patients with RA with obesity. Secondarily, we also investigated this in patients with overweight and normal weight for completeness.DesignObservational cohort study.SettingSwiss Clinical Quality Management in Rheumatic Diseases (SCQM) registry (1997–2019).ParticipantsAdult patients with RA from the SCQM registry who received etanercept, infliximab, abatacept or adalimumab as their first biological or targeted synthetic disease-modifying antirheumatic drug were classified based on their body mass index (BMI) at the start of that treatment in three cohorts: obese, overweight, normal weight. They were followed for a maximum of 1 year.ExposureThe study exposure of interest was the patients’ first biological, particularly: etanercept, infliximab and abatacept, compared with adalimumab.Primary and secondary outcome measuresThe primary study outcome was remission within 12 months, defined as 28-joint Disease Activity Score (DAS28) <2.6. Missingness was addressed using confounder-adjusted response rate with attrition correction. Logistic regression was used to compare the effectiveness of etanercept, infliximab and abatacept versus adalimumab. Each BMI cohort was addressed and analysed separately.ResultsThe study included 443 obese, 829 overweight and 1243 normal weight patients with RA. There were no statistically significant differences in the odds of DAS28-remission at ≤12 months for etanercept, infliximab and abatacept, compared with adalimumab, in any of the BMI cohorts.ConclusionsNo differences in DAS28-remission were found between the study drugs and adalimumab as first biologic in patients with RA, independently of the BMI cohort. We did not find evidence that treatment with abatacept increased the likelihood of remission compared with adalimumab among obese patients with RA.
Kharameh cohort study (KHCS) on non-communicable diseases and preliminary findings of 3-year follow-up
Authors: Rezaianzadeh Abbas , Niazkar Hamid Reza , Rezaeianzadeh Ramin , Jafari Fatemeh , Rahimikazerooni Salar , Ghoddusi Johari Masoumeh , Zare Marjan , Hosseini Seyed Vahid 
Published: February 2024

PurposeThe Kharameh cohort study (KHCS) is one branch of the ‘Prospective Epidemiological Research Studies in Iran’, located in the south of Iran. The enrolment phase of KHCS spanned from April 2015 to March 2017, during which urban and rural residents of Kharameh were enrolled in the study. KHCS aims to investigate the incidence of non-communicable diseases (NCDs) such as hypertension, diabetes mellitus, cardiovascular diseases and cancer, and its related risk factors in a 15-year follow-up.ParticipantsKHCS was designed to recruit 10 000 individuals aged 40–70 years old from both urban and rural areas of Kharameh. Thus, a total of 10 800 individuals aged 40–70 years of age were invited and, finally, 10 663 subjects were accepted to participate, with a participation rate of 98.7%.Findings to dateOf the 10 663 participants, 5944 (55.7%) were women, and 6801 (63.7%) were rural residents. The mean age of the participants was 51.9±8.2 years. 41.8% of the participants were aged 40–49, 35.2% were aged 50–59 and the remaining 23% were 60–70 years old. Until March 2020 (first 3 years of follow-up), the total number of patients diagnosed with NCDs was 1565. Hypertension, type 2 diabetes and acute ischaemic heart disease were the most common NCDs. Furthermore, the total number of deaths during the first 3 years of follow-up was 312, with cardiovascular diseases (38.7%) as the most common cause of death, followed by cerebrovascular diseases (11.8%) and cancer (16.2%).Future plansThe remaining 12 years of follow-up will inevitably shed light on the genetic, lifestyle/socioeconomic status, and environmental risk and protective factors of NCDs.
Comparison of industry payments to psychiatrists and psychiatric advanced practice clinicians in the USA, 2021: a cross-sectional study
Authors: Havlik John , Ososanya Lydia , Lee Megan S , Wahid Syed , Heyang Michael , Sun Qiwei Wilton , Ross Joseph S , Rhee Taeho Greg 
Published: February 2024

ObjectivesTo compare industry payment patterns among US psychiatrists and psychiatric advanced practice clinicians (APCs) and determine how scope of practice laws has influenced these patterns.DesignCross-sectional study.SettingThis study used the publicly available US Centers for Medicare and Medicaid Services Sunshine Act Open Payment database and the National Plan and Provider Enumeration System (NPPES) database for the year 2021.ParticipantsAll psychiatrists and psychiatric APCs (subdivided into nurse practitioners (NPs) and clinical nurse specialists (CNSs)) included in either database.Primary and secondary outcome measuresNumber and percentage of clinicians receiving industry payments and value of payments received. Total payments and number of transactions by type of payment, payment source and clinician type were also evaluated.ResultsA total of 85 053 psychiatric clinicians (61 011 psychiatrists (71.7%), 21 895 NPs (25.7%), 2147 CNSs (2.5%)) were reviewed; 16 240 (26.6%) psychiatrists received non-research payment from industry, compared with 10 802 (49.3%) NPs and 231 (10.7%) CNSs (p<0.001) for pairwise comparisons). Psychiatric NPs were significantly more likely to receive industry payments compared with psychiatrists (incidence rate ratio (IRR), 1.85 (95% CI 1.81 to 1.88); p<0.001)). Compared with psychiatrists, NPs were more likely to receive payments of > United States Dollars (US) $) 100 (33.9% vs 14.6%; IRR, 2.14 (2.08 to 2.20); p<0.001) and > US$ 1000 (5.3% vs 4.1%; IRR, 1.29 (1.20 to 1.38); p<0.001) but less likely to receive > US$ 10 000 (0.4% vs 1.0%; IRR, 0.39 (0.31 to 0.49); p<0.001). NPs in states with ‘reduced’ or ‘restricted’ scope of practice received more frequent payments (reduced: IRR, 1.22 (1.18 to 1.26); restricted: IRR, 1.26 (1.22 to 1.30), both p<0.001).ConclusionsPsychiatric NPs were nearly two times as likely to receive industry payments as psychiatrists, while psychiatric CNSs were less than half as likely to receive payment. Stricter scope of practice laws increases the likelihood of psychiatric NPs receiving payment, the opposite of what was found in a recent specialty agnostic study.
Neoantigen-specific CD4+tumor-infiltrating lymphocytes are potent effectors identified within adoptive cell therapy products for metastatic melanoma patients
Authors: Hall MacLean S. , Teer Jamie K. , Yu Xiaoqing , Branthoover Holly , Snedal Sebastian , Rodriguez-Valentin Madeline , Nagle Luz , Scott Ellen , Schachner Ben , Innamarato Patrick , Hall Amy M. , Blauvelt Jamie , Rich Carolyn J. , Richards Allison D. , Ceccarelli Jake , Langer TJ , Yoder Sean J. , Beatty Matthew S. , Cox Cheryl A. , Messina Jane L. , Abate-Daga Daniel , Mule James J. , Mullinax John E. , Sarnaik Amod A. , Pilon-Thomas Shari 
Published: February 2024

BackgroundAdoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TILs) is a promising immunotherapeutic approach for patients with advanced solid tumors. While numerous advances have been made, the contribution of neoantigen-specific CD4+T cells within TIL infusion products remains underexplored and therefore offers a significant opportunity for progress.MethodsWe analyzed infused TIL products from metastatic melanoma patients previously treated with ACT for the presence of neoantigen-specific T cells. TILs were enriched on reactivity to neoantigen peptides derived and prioritized from patient sample-directed mutanome analysis. Enriched TILs were further investigated to establish the clonal neoantigen response with respect to function, transcriptomics, and persistence following ACT.ResultsWe discovered that neoantigen-specific TIL clones were predominantly CD4+T cells and were present in both therapeutic responders and non-responders. CD4+TIL demonstrated an effector T cell response with cytotoxicity toward autologous tumor in a major histocompatibility complex class II-dependent manner. These results were validated by paired TCR and single cell RNA sequencing, which elucidated transcriptomic profiles distinct to neoantigen-specific CD4+TIL.ConclusionsDespite methods which often focus on CD8+T cells, our study supports the importance of prospective identification of neoantigen-specific CD4+T cells within TIL products as they are a potent source of tumor-specific effectors. We further advocate for the inclusion of neoantigen-specific CD4+TIL in future ACT protocols as a strategy to improve antitumor immunity.
Temporal trends in mortality location in patients with anal cancer in the USA: an analysis of the National Center for Health Statistics mortality data
Authors: Sohail Amir H , Williams Caroline E , Schiller Emily , Ye Ivan B , Orozco Ronald , Hakmi Hazim , Shahjehan Faisal , Ali Hassam , Gangwani Manesh K , Aziz Muhammad , Hayat Umar , Maan Soban , Akhtar Aisha , Symer Matthew 
Published: February 2024

ObjectivesInvestigate trends in where patients died of anal cancer in the USA.MethodsRetrospective cohort study using the US National Center for Health Statistics Wide-Ranging ONline Data for Epidemiologic Research platform from 2003 to 2020; all patients with death certificates listing anal cancer as the underlying cause of death in the USA. Main outcome measure of location of patient death: inpatient facility, home, hospice, nursing home/long-term care facility and other.ResultsThere were a total of 16 296 deaths with anal cancer as the underlying diagnosis during the study period. The crude rate increased from 0.191 per 100 000 deaths in 2003 to 0.453 per 100 000 deaths in 2020. Over the study period, 22.4% of patient deaths occurred in inpatient facilities, 44.9% at home, 12.2% at hospice facilities and 13.1% at nursing homes/long-term care facilities. The percentage of deaths occurring in hospice facilities increased from 1.0% to 13.3% during the study period. Deaths at home also increased from 42.7% in 2003 to 55.8% in 2020. Meanwhile, inpatient deaths decreased from 33.5% in 2003 to 14.4% in 2020.ConclusionsThere has been a significant increase in the proportion of patients with anal cancer dying at home or hospice from 2003 to 2020.
Ecological connectivity of invasive and native fishes in a historic navigation waterway
Authors: Bergman Jordanna N. , Bennett Joseph R. , Minelga Valerie , Vis Chantal , Fisk Aaron T. , Cooke Steven J. 
Published: February 2024

Regulated waterways, interconnected by navigation barriers (locks and dams), are uniquely difficult to manage, given interest in enabling native species connectivity while minimizing invasions. Canada's historic Rideau Canal Waterway, a 202 km navigable route located in eastern Ontario and connected by 24 lockstations, embodies this challenge. The lock(s) and water-control dam that compose each lockstation may respectively offer a connectivity pathway, though to what extent is unclear. We used acoustic telemetry (native largemouth bass ( Micropterus nigricans) and northern pike ( Esox lucius), and invasive common carp ( Cyprinus carpio); n = 224) to evaluate fish connectivity relative to lock operations and environmental data over three years (2019–2021). Thirty-five passages by 23 native fishes were recorded, with 49% of passages through locks. No common carp passages were detected; movements indicate that they favour higher flow areas downstream of dams, regions with no pathway upstream. Most passages were downstream and, of concern to obligate upstream migrators, we found that multi-flight and higher-lift locks appear impassable to upstream movements. Our results suggest that these lockstations limit, but not entirely restrict, connectivity.
The fermionic greybody factor and quasinormal modes of hairy black holes, as well as Hawking radiation’s power spectrum and sparsity
Authors: Al-Badawi Ahmad , Jha Sohan Kumar , Rahaman Anisur 
Published: February 2024

AbstractA hairy black hole (HBH) emerges due to matter surrounding the Schwarzschild metric when using the Extended Gravitational Decoupling (GD) approach. The fermionic greybody factors (GFs) and quasinormal modes (QNMs) as well as Hawking spectra and sparsity of HBH solutions are investigated. We consider massive and massless spin-1/2 fermions, along with massless spin-3/2 fermions. The equations of the effective potential for fermions with different spins are derived in HBH spacetime. Then, the rigorous bound method is used to calculate the fermionic spin-1/2 and spin-3/2 GFs. With the time domain integration method at our disposal, we illustrate the impact of additional parameters on the ringdown waveform of the massless fermionic spin-1/2 and spin-3/2 fields and, in turn, on their quasinormal modes. We then delve into investigating the Hawking spectra and sparsity of the radiation emitted by an HBH. Hairy parameters significantly affect the sparsity of Hawking radiation as well. We observe that the total power emitted by the BH increases both with $$\alpha $$
α
and Q but decreases with $$l_{0}$$

l
0

. Our study conclusively shows the significant impact of the additional parameters on important astrophysical phenomena such as quasinormal modes, Hawking spectra, and sparsity.
Chromoplexy Is a Frequent Early Clonal Event in EWSR1-Rearranged Round Cell Sarcomas That Can Be Detected Using Clinically Validated Targeted Sequencing Panels
Authors: Dermawan Josephine K. , Slotkin Emily , Tap William D. , Meyers Paul , Wexler Leonard , Healey John , Vanoli Fabio , Vanderbilt Chad M. , Antonescu Cristina R. 
Published: February 2024

Abstract

Chromoplexy is a phenomenon defined by large-scale chromosomal chained rearrangements. A previous study observed chromoplectic events in a subset of Ewing sarcomas (ES), which was linked to an increased relapse rate. Chromoplexy analysis could potentially facilitate patient risk stratification, particularly if it could be detected with clinically applied targeted next-generation sequencing (NGS) panels. Using DELLY, a structural variant (SV) calling algorithm that is part of the MSK-IMPACT pipeline, we characterized the spectrum of SVs in EWSR1-fused round cell sarcomas, including 173 ES and 104 desmoplastic small round cell tumors (DSRCT), to detect chromoplexy and evaluate its association with clinical and genomic features. Chromoplectic events were detected in 31% of the ES cases and 19% of the DSRCT cases. EWSR1 involvement accounted for 76% to 93% of these events, being rearranged with diverse noncanonical gene partners across the genome, involving mainly translocations but also intrachromosomal deletions and inversions. A major breakpoint cluster was located on EWSR1 exons 8–13. In a subset of cases, the SVs disrupted adjacent loci, forming deletion bridges. Longitudinal sequencing and breakpoint allele fraction analysis showed that chromoplexy is an early event that remains detectable throughout disease progression and likely develops simultaneously with the driver fusion. The presence of chromoplexy was validated in an external ES patient cohort with whole exome sequencing. Chromoplexy was significantly more likely to be present in cases that were metastatic at presentation. Together, this study identifies chromoplexy as a frequent genomic alteration in diverse EWSR1-rearranged tumors that can be captured by targeted NGS panels.

Significance:
Chromoplexy is detectable using targeted NGS in a substantial portion of EWSR1-rearranged round cell sarcomas as an early and persistent clonal event, expanding the genomic complexity of fusion-associated sarcomas.
Development of Chromosome 1q+ Specific Treatment for Highest Risk Pediatric Posterior Fossa Ependymoma
Authors: Griesinger Andrea M. , Calzadilla Annaliese J. , Grimaldo Enrique , Donson Andrew M. , Amani Vladimir , Pierce Angela M. , Steiner Jenna , Kargar Soudabeh , Serkova Natalie J. , Bertrand Kelsey C. , Wright Karen D. , Vibhakar Rajeev , Hankinson Todd , Handler Michael , Lindsay Holly B. , Foreman Nicholas K. , Dorris Kathleen 
Published: February 2024

Abstract

Purpose:
There are no effective treatment strategies for children with highest-risk posterior fossa group A ependymoma (PFA). Chromosome 1q gains (1q+) are present in approximately 25% of newly diagnosed PFA tumors, and this number doubles at recurrence. Seventy percent of children with chromosome 1q+ PFA will die because of the tumor, highlighting the urgent need to develop new therapeutic strategies for this population.

Experimental Design:
In this study, we utilize 1q+ PFA in vitro and in vivo models to test the efficacy of combination radiation and chemotherapy in a preclinical setting.

Results:
5-fluorouracil (5FU) enhances radiotherapy in 1q+ PFA cell lines. Specifically, 5FU increases p53 activity mediated by the extra copy of UCK2 located on chromosome 1q in 1q+ PFA. Experimental downregulation of UCK2 resulted in decreased 5FU sensitivity in 1q+ PFA cells. In in vitro studies, a combination of 5FU, retinoid tretinoin (ATRA), and radiation provided the greatest reduction in cellular proliferation and greatest increase in markers of apoptosis in 1q+ PFA cell lines compared with other treatment arms. Similarly, in vivo experiments demonstrated significant enhancement of survival in mice treated with combination radiation and 5FU and ATRA.

Conclusions:
These results are the first to identify a chromosome 1q+ specific therapy approach in 1q+ PFA. Existing phase I studies have already established single-agent pediatric safety and dosages of 5FU and ATRA, allowing for expedited clinical application as phase II trials for children with high-risk PFA.
Tumor Burden Dictates the Neoantigen Features Required to Generate an Effective Cancer Vaccine
Authors: Garzia Irene , Nocchi Linda , Avalle Lidia , Troise Fulvia , Leoni Guido , Seclì Laura , Antonucci Laura , Cotugno Gabriella , Allocca Simona , Romano Giuseppina , Conti Laura , Caiazza Carmen , Mallardo Massimo , Poli Valeria , Scarselli Elisa , D'Alise Anna Morena 
Published: February 2024

Abstract
Tumor neoantigens (nAg) represent a promising target for cancer immunotherapy. The identification of nAgs that can generate T-cell responses and have therapeutic activity has been challenging. Here, we sought to unravel the features of nAgs required to induce tumor rejection. We selected clinically validated Great Ape–derived adenoviral vectors (GAd) as a nAg delivery system for differing numbers and combinations of nAgs. We assessed their immunogenicity and efficacy in murine models of low to high disease burden, comparing multi-epitope versus mono-epitope vaccines. We demonstrated that the breadth of immune response is critical for vaccine efficacy and having multiple immunogenic nAgs encoded in a single vaccine improves efficacy. The contribution of each single neoantigen was examined, leading to the identification of 2 nAgs able to induce CD8+ T cell–mediated tumor rejection. They were both active as individual nAgs in a setting of prophylactic vaccination, although to different extents. However, the efficacy of these single nAgs was lost in a setting of therapeutic vaccination in tumor-bearing mice. The presence of CD4+ T-cell help restored the efficacy for only the most expressed of the two nAgs, demonstrating a key role for CD4+ T cells in sustaining CD8+ T-cell responses and the necessity of an efficient recognition of the targeted epitopes on cancer cells by CD8+ T cells for an effective antitumor response. This study provides insight into understanding the determinants of nAgs relevant for effective treatment and highlights features that could contribute to more effective antitumor vaccines.
See related Spotlight by Slingluff Jr, p. 382.
The Siren Song of Synergy
Authors: Bhola Patrick D. , Letai Anthony 
Published: February 2024

Summary:
In ancient Greek mythology, sirens were creatures of stunning beauty whose mystical songs led sailors to sail their boats onto hidden rocks and into total destruction. In this issue, Mason-Osann and colleagues present data in the context of acute myelogenous leukemia to suggest that while synergy may show initial attractions in drug combinations, it may carry with it hazards previously unforeseen.
See related article by Mason-Osann et al., p. 95 (1).