bluuebunny/crossref_metadata_2025_split huggingface dataset:
Can Winegrowing Cause Rural Development? Evidence from Baden-Württemberg
Authors: Huning Thilo R , Wahl Fabian 
Published: February 2025

Abstract
Historical winegrowing shaped modern rural development, even in areas in which its cultivation was given up after the early modern period. We provide evidence for this idea from municipality level data on Southwestern German viticulture over the last 1,300 years, and find a significant link between historical winegrowing and modern economic development. We rely on cross-sectional regressions and on an instrumental variable strategy using precipitation seasonality. Our findings highlight two mechanisms through which historical viticulture affected modern development: by leaving behind a more egalitarian inheritance norm, and a more collectivist society.
A deficiency screen of the X chromosome for Rap1 GTPase dominant interacting genes in Drosophila border cell migration
Authors: Messer C Luke , Burghardt Emily , McDonald Jocelyn A 
Published: February 2025

Abstract
Collective cell migration is critical to embryonic development, wound healing, and the immune response, but also drives tumor dissemination. Understanding how cell collectives coordinate migration in vivo has been a challenge, with potential therapeutic benefits that range from addressing developmental defects to designing targeted cancer treatments. The small GTPase Rap1 has emerged as a regulator of both embryogenesis and cancer cell migration. How active Rap1 coordinates downstream signaling functions required for coordinated collective migration is poorly understood. Drosophila border cells undergo a stereotyped and genetically tractable in vivo migration within the developing egg chamber of the ovary. This group of 6-8 cells migrates through a densely packed tissue microenvironment and serves as an excellent model for collective cell migration during development and disease. Rap1, like all small GTPases, has distinct activity state switches that link extracellular signals to organized cell behaviors. Proper regulation of Rap1 activity is essential for successful border cell migration yet the signaling partners and other downstream effectors are poorly characterized. Using the known requirement for Rap1 in border cell migration, we conducted a dominant suppressor screen for genes whose heterozygous loss modifies the migration defects observed upon constitutively active Rap1V12 expression. Here we identified seven genomic regions on the X chromosome that interact with Rap1V12. We mapped three genomic regions to single Rap1-interacting genes, frizzled 4, Ubiquitin specific protease 16/45, and strawberry notch. Thus, this unbiased screening approach identified multiple new candidate regulators of Rap1 activity with roles in collective border cell migration.
Bridging language barriers: Access to primary care for Medicaid Managed Care patients with limited English proficiency in three metropolitan areas
Authors: Bustamante Arturo Vargas , Melgoza Esmeralda , Ismail Ahmad , Majano Rosario , Félix Beltrán Lucía 
Published: February 2025

Abstract
This secret shopper study compares the wait times for scheduling a first-time primary-care appointment among adults enrolled in Medicaid Managed Care who speak English, Spanish, or Mandarin in the Los Angeles, Houston, and New York Metropolitan Statistical Areas. Primary-care practices in Medicaid Managed Care Organization directories were randomized by language. The objective of the secret shoppers was to schedule first-time primary-care appointments, either in person or via telehealth. We found that the average wait times for Spanish and Mandarin speakers were greater than for English speakers by 3.73 and 14 days in Los Angeles and 7.29 and 2.55 days in Houston, respectively. The average wait time among Spanish and Mandarin speakers was 2.22 and 1.76 days less compared with English speakers in New York. We discuss the importance of policies and provide recommendations to address disparities in health access and use among adults with limited English proficiency.
A Uniform Estimate for the Quaternionic Gauduchon Metric With Prescribed Volume Form
Authors: Zhang Jiaogen 
Published: February 2025

Abstract
The quaternionic Calabi conjecture, posed by Alesker and Verbitsky [1], predicts that the quaternionic Monge–Ampère equation can always be solved on any compact HKT manifold. Motivated by this conjecture, we will introduce a quaternionic version of the Gauduchon conjecture on any compact $SL(n,\mathbb{H})$-manifold, specifically addressing the existence of quaternionic Gauduchon metrics with prescribed volume form. We reframe this question as a special case of fully nonlinear elliptic equations of second order and subsequently establish a uniform estimate for the potential function.
Iranian Madrasa Historiographies on the Fate of Falsafa after Averroes: The Structure, Scope, and History of ‘Islamic Philosophy’ from Mīr Dāmād to ṬabāṬabāʾī and Āshtiyānī
Authors: Amin Beidokhti Hanif 
Published: February 2025

Abstract
Iranian philosophers train in a living tradition of falsafa that gives them a different perspective from that of modern European scholars. They call their profession philosophy, and philosophy for them is not a historical phenomenon, though it has a past. Contemporary falsafa has a narrative of its past, which I outline in this article, calling it the madrasa narrative. It is presented in the form of historiographies of falsafa, which, though less than a century old, form an extensive body of texts. After introducing this narrative, I focus on Mīr Dāmād’s (d. 1631) conception of the course of falsafa and his relation to his predecessors. I argue that he should be credited as the initiator of ‘Islamic philosophy’, both conceptually and terminologically. I emphasize the continuous line he draws linking himself to Fārābī (d. ca. 950-1) through Avicenna (d. 1037). Thereafter, I outline the formative contributions of Muḥammad Ḥusayn Ṭabāṭabāʾī (1904–81) in the contemporary practice of falsafa, and in historiography of Jalāl al-Dīn Āshtiyānī (1925–2005) who, together with Henry Corbin (1903–78), shaped the modern madrasa narrative. I show that Āshtiyānī’s historiographical effort was a reaction to what he considered Europeans’ unawareness of the continuity and vitality of falsafa in the Islamic East. I conclude with some observations on the scope, structure, and historiography of contemporary falsafa in Iran.
Challenges to and considerations of designing cancer prevention trials
Authors: Enserro Danielle M , Gunn Heather J , Elsaid Mohamed I , Duan Fenghai , Pugh Stephanie L 
Published: February 2025

Abstract
Prevention trials in oncology are some of the most important cancer clinical trials that can be designed, implemented, analyzed, and interpreted. They are pivotal in the goal of stopping the development of cancer before it starts. Prevention trials are unique in that they not only have some of the same requirements and challenges as treatment trials but also have challenges that may make their design more complex. This paper aims to discuss some types of prevention trials and highlight their most common design challenges, including large sample size requirements, slow accrual rates with long accrual duration, extended follow-up periods with trial adherence issues and missing data, endpoints that require extended follow-up or have a high level of confounding, and problems with optimizing study design. This article provides real study examples and suggestions for designing prevention clinical trials while mitigating the known issues they face.
Parental autonomy and children’s health: a patriarchal dilemma in the Middle East, with particular emphasis on Kuwait
Authors: Al Majed Bashayer 
Published: February 2025

Abstract
In 2020, Kuwaiti mothers won legal medical guardianship over their children, enabling them to authorize medical treatment, this despite still not having autonomy for their own medical care, yet being vicariously liable for potential tort caused by their child. This dichotomy raises questions over the implementation of the new legislation, if the mother and the male guardian had opposing views over the child’s health. Recent years have seen the UK cases of Charlie Gard and Alfie Evans initiate passionate ethical debate when courts invoked Parens Patriae, superseding parental autonomy and supporting clinicians’ decisions to withdraw life support. Middle Eastern courts tend to support parental decisions; however, strict civil laws exist regarding the continuation and cessation of life support. This article examines the patriarchal culture in the Middle East and explores whether a Kuwaiti mother’s medical autonomy would be upheld in the event of a parental dispute over their child’s treatment and end-of-life care, within the framework of the Kuwaiti Civil Code No. 67 of 1980. The article concludes that matriarchal guardianship would likely be undermined; however, legislative changes are the first step and advances in palliative care across the Middle East are introducing a changing culture towards open parental discussions and shared decision-making, slowly making the mother’s decisive voice a part of the norm.
Levofloxacin to prevent bacterial infection in patients with acute myeloid leukemia treated by venetoclax and azacitidine: a Toulouse-Bordeaux DATAML registry study
Authors: Brousse Xavier , Rasandisona Nicolas , Bérard Emilie , Leroy Harmony , Delavigne Karen , Mottal Nathan , Tavitian Suzanne , Leguay Thibaut , Lapierre Léopoldine , Delabesse Eric , Bidet Audrey , Gauthier Martin , Lara Diane , Banos Anne , Guiraud Jennifer , Floch Pauline , Ghenim Leila , Sarry Audrey , de Grande Anne-Charlotte , Béranger Clémentine , Récher Christian , Pigneux Arnaud , Bertoli Sarah , Dumas Pierre-Yves 
Published: February 2025

Abstract

Objectives
Antibiotic prophylaxis for patients with cancer remains a controversial issue and is not broadly recommended for hematological malignancies. The venetoclax (VEN) and azacitidine (AZA) combination allows for high rates of complete remission in acute myeloid leukemia (AML) but enhances the incidence of febrile neutropenia (FN) compared to AZA alone, making primary antibiotic prophylaxis a relevant question.

Patients and Methods
Patients with AML who received VEN-AZA were selected from the DATAML registry to investigate the use of levofloxacin (LEVO) prophylaxis, administered at 500 mg/day from day 10 following the first course of VEN-AZA, until neutrophil recovery (&gt;0.5x109/L).

Results
A cohort of 258 patients was identified (median age 69.8 years, IQR 20.4-87.4), 72 of them having received LEVO and 186 treated with standard of care (SOC). VEN-AZA was used for newly diagnosed AML in 52.7% of cases. FN occurred in 33.3% of LEVO patients vs. 37.1% of SOC patients (p=0.572). Time from day 10 VEN-AZA to FN was significantly delayed in LEVO patients (12.5 days vs 8 in SOC; p=0.037). Pulmonary infections were considerably reduced by LEVO (10.2% vs 1.4%, p=0.018) as well as those involving enterobacterales (9.1% vs 1.4%; p=0.029). No early increase in fluoroquinolone resistance was detected (p=0.142).

Conclusion
Levofloxacin as primary prophylaxis in patients with AML treated with VEN-AZA seems to decrease the rate of documented infections even if the incidence of FN was not significantly decreased. This prophylaxis shaped a different clinical and microbiological landscape without significant increase of antibiotic resistance.
A Cross-National Analysis of Trust and Support for Pandemic Response Measures
Authors: Bryan James D , LeVan A Carl 
Published: February 2025

Abstract
Even as COVID-19 threatened millions of lives, people in many countries resisted public health recommendations. In a cross-national study of pandemic response, we demonstrate that political trust across different institutions predicts support for policies to manage the health risks. We disaggregate political trust, creating separate measures for “partisan” and “nonpartisan” controlled institutions. Our empirical strategy utilizes data from Eurobarometer, Afrobarometer, and Arab Barometer surveys across 57 countries. Tests of a “vertical trust” hypothesis demonstrate that trust in partisan and nonpartisan institutions predict support for pandemic restrictions and willingness to get vaccinated. Interestingly, the strength of the relationships varies across and within countries. Tests of a “contingent solidarity” hypothesis reveal widespread politicization of the pandemic by democratic and autocratic incumbents alike. We conclude by exploring how infusing neutral, nonpartisan institutions with subjective political narratives stokes mistrust in “scientific authority” and harms democracy.
Abatacept and the risk of malignancy: a meta-analysis across disease indications
Authors: Zuckerman Benjamin P , Gibson Mark , Roy Ritika , Hughes Mark , Mehta Daksh , Yang Zijing , Adas Maryam , Ng Kenrick , Russell Mark D , Cope Andrew , Norton Sam , Galloway James 
Published: February 2025

Abstract

Objectives
To estimate the association between abatacept use and the incidence of malignancy excluding non-melanomatous skin cancers (NMSCs).

Methods
Systematic database searches were performed, to April 2024, to identify phase II/III/IV randomised clinical trials (RCTs), long-term extension (LTE) and observational cohort studies of abatacept in people with rheumatoid arthritis and psoriatic arthritis. Network and pairwise meta-analyses were performed to estimate incidence rate ratios (IRRs) for malignancy excluding NMSC, comparing abatacept with placebo and tumour necrosis factor inhibitors (TNFi) in RCT/LTE studies. Pairwise meta-analyses evaluated the same outcome in observational studies, comparing abatacept with conventional synthetic DMARDs (csDMARDs) and biologic/targeted synthetic disease modifying antirheumatic drugs (b/tsDMARDs).

Results
In 18 eligible RCTs and 10 LTE studies, there were 15 535 person-years of exposure to abatacept, 1495 to placebo, and 733 to TNFi. In network meta-analyses of combined RCT/LTE data, the incidence of all malignancies excluding NMSCs was not significantly different between abatacept and placebo (IRR 0.58; 95% CI 0.32–1.09) or TNFi (IRR 0.72; 95% 0.27–1.87). In observational data, the incidence of malignancy was higher with abatacept, relative to other b/tsDMARDs (IRR 1.21; 95% CI 1.15–1.28), but not significantly different compared with csDMARDs (IRR 0.97; 95% CI 0.90–1.06).

Conclusions
Abatacept was associated with a higher incidence of malignancy compared with other b/tsDMARDs in observational studies, but not when compared with placebo or TNFi in RCT/LTE data. Further pharmacovigilance data is essential to help elucidate whether abatacept modifies cancer risk.

PROSPERO registration number
CRD42023382314
Association of Electrocardiographic Patterns After Successfully Resuscitated Out-of-Hospital Cardiac Arrest With Significant Coronary Lesions and Mortality—A Predefined Angiography After Out-of-Hospital Cardiac Arrest Without ST-Segment Elevation (TOMAHAWK) Trial
Authors: Thevathasan Tharusan , Claus Julia , Roßberg Michelle , Skurk Carsten , Fichtlscherer Stephan , Akin Ibrahim , Fuernau Georg , Hassager Christian , Zeymer Uwe , Preusch Michael R. , Graf Tobias , Feistritzer Hans-Josef , Jobs Alexander , de Waha Suzanne , Thiele Holger , Desch Steffen , Pöss Janine , Freund Anne ,   on behalf of the Angiography after Out-of-Hospital Cardiac Arrest without ST-Segment Elevation (TOMAHAWK) Investigators
Published: February 2025

Objectives:
The use of electrocardiograms for predicting significant coronary lesions and mortality in patients with successfully resuscitated out-of-hospital cardiac arrest (OHCA) without ST-segment elevation has not been defined yet. The objective of this study was to investigate the association and predictive value of various standardized 12-lead electrocardiogram patterns in patients with successfully resuscitated OHCA and no ST-segment elevations on the presence of significant coronary lesions (diagnostic performance) and 30-day mortality (prognostic performance).

Design:
Predefined subanalysis of the Angiography after Out-of-Hospital Cardiac Arrest without ST-Segment Elevation (TOMAHAWK) trial.

Setting:
Multicenter, international randomized controlled trial across 31 centers.

Patients:
Adult patients with successfully resuscitated OHCA and no ST-segment elevations.

Interventions:
The first recorded electrocardiogram after the return of spontaneous circulation (ROSC) at hospital admission was analyzed by experienced physicians.

Measurements and Main Results:
Significant coronary lesions and 30-day mortality. In total, 412 patients with a coronary angiography were included, of which 163 (40%) had significant coronary lesions. No electrocardiogram pattern was identified as a predictor of significant coronary lesions. In the total cohort of patients with and without coronary angiography, right bundle branch blocks (BBBs), prolonged intrinsicoid deflection times, and intrinsicoid deflections in right BBB were strong, independent predictors of 30-day mortality. The “intrinsicoid deflection” is the sharp upward deflection in the QRS complex of an electrocardiogram. The “intrinsicoid deflection time” is the interval from the start of the QRS complex to the peak of the R wave. The predictive performance for significant coronary lesions was poor across all electrocardiogram patterns and better for 30-day mortality.

Conclusions:
Standardized 12-lead electrocardiogram patterns after ROSC at hospital admission in patients with successfully resuscitated OHCA without ST-segment elevations have poor predictive performance for the presence of significant coronary lesions. Different QRS-related patterns might identify patients with higher risk of short-term mortality.
Phenotypes of Functional Decline or Recovery in Sepsis ICU Survivors: Insights From a 1-Year Follow-Up Multicenter Cohort Analysis
Authors: Liu Keibun , Nakashima Takaya , Goto Tadahiro , Nakamura Kensuke , Nakano Hidehiko , Motoki Maiko , Kamijo Hiroshi , Ayaka Matsuoka , Ishii Kenzo , Morita Yasunari , Hongo Takashi , Shimojo Nobutake , Tanaka Yukiko , Hanazawa Manabu , Hamagami Tomohiro , Oike Kenji , Kasugai Daisuke , Sakuda Yutaka , Irie Yuhei , Nitta Masakazu , Akieda Kazuki , Shimakura Daigo , Katsukawa Hajime , Kotani Toru , Nydahl Peter , Schaller Stefan J. , Ogura Takayuki ,   on behalf of the Investigating Long term Outcomes of ICU patients with Sepsis or Septic shock (ILOSS) Study Group
Published: February 2025

Objective:
Sepsis often leads to heterogeneous symptoms of post-intensive care syndrome (PICS) composing physical, cognitive, and psychiatric disabilities, resulting in deteriorated quality of life (QoL), with limited interventions. This study aimed to identify phenotypes of sepsis-associated PICS by physical, cognitive, and psychiatric function and QoL at hospital discharge.

Design:
A prospective observational study.

Setting:
Twenty-one mixed ICUs.

Patients:
All consecutive adult patients between November 2020 and April 2022, diagnosed with sepsis at ICU admissions and survived discharge, were enrolled.

Interventions:
None.

Measurements and Main Results:
Phenotyping with clusters determined by three approaches was performed with following variables at hospital discharge: Barthel Index (≤ 90 defined physical PICS), Short Memory Questionnaire (< 40 defined cognitive PICS), Hospital Anxiety and Depression Scale (≥ 8 defined psychiatric PICS), Impact of Event Scale-Revised (≥ 25 defined psychiatric PICS), EuroQoL 5-dimension 5-level, Clinical Frailty Scale hand-grip strength, and Medical Research Council. Each disability, employment, destination, and survival, were followed over the first year of hospital discharge. In total, 220 ICU patients were included (median age: 72.5 yr, 129 males (59%), 166 septic shocks (75%), and median Sequential Organ Failure Assessment Score: 8). Four phenotypes were identified: group 1 (n = 62) with no PICS, group 2 (n = 55) with mild PICS (physical and cognitive), group 3 (n = 53) with moderate PICS (all domains), and group 4 (n = 50) with severe PICS (all domains). Functional decline and recovery significantly varied among the phenotypes. Physical and cognitive PICS in group 2 improved by the 3-month follow-up, whereas the disabilities in groups 3 and 4 remained over the year. Psychiatric PICS in groups 3 and 4 ameliorated, whereas depression symptoms in group 4 were still evident at the 12-month follow-up. All groups showed persistent moderate to severe reduced QoL and low employment (0–50%). The survival in group 4 continuously decreased.

Conclusions:
Four clinical phenotypes of ICU sepsis survivors might contribute to a deeper understanding of post-sepsis trajectories and an individualized treatment approach.
The impact of genetic variations in FPGS, MTHFR, and ATIC on methotrexate response among pediatric patients with acute lymphoblastic leukemia
Authors: Wang Shu-Mei , Zhao Dan-Qi , Kong Xiao-Yan , Li Miao 
Published: February 2025

Objectives
Genetic polymorphisms in FPGS, MTHFR, and ATIC have emerged as important modulators of methotrexate (MTX) metabolism and toxicity. We investigated the distribution of FPGS rs10106, MTHFR rs1801131, and ATIC rs2372536 polymorphisms in children with acute lymphoblastic leukemia (ALL) and assessed their influence on MTX concentrations, toxicity profiles, and clinical outcomes.

Methods
Genotyping of FPGS rs10106 G > A, MTHFR rs1801131 A > C, and ATIC rs2372536 C > G polymorphisms was conducted using the Sequenom MassARRAY iPLEX platform in 145 pediatric ALL patients.

Results
Significant ethnic differences were observed in the allelic and genotypic distributions of the three single nucleotide polymorphisms (SNPs) investigated. None of these three SNPs had a significant effect on MTX levels or toxicities. The frequencies of the ATIC rs2372536 CC genotype and C allele in ALL patients (44.8% and 68.6%, respectively) were significantly lower than those in Han Chinese in Beijing, China (58.3% and 78.2%, respectively; P = 0.036 and 0.019, respectively). Patients carrying the ATIC rs2372536 GG genotype (36.4%, 4/11) had a significantly higher relapse rate than the CC genotype carriers (6.2%, 4/65, P = 0.013). There, however, were no significant effects on relapse-free survival in Kaplan–Meier and Cox regression analyses for all three candidate SNPs.

Conclusion
Our findings offer valuable insights into the intricate interplay between genetic polymorphisms, MTX exposure, toxicities, and clinical outcomes in patients with ALL and have the potential to inform precision medicine strategies.