bluuebunny/crossref_metadata_2025_split huggingface dataset:
A replication study of novel fetal hemoglobin-associated genetic variants in sickle cell disease-only cohorts
Authors: Ilboudo Yann , Brosseau Nicolas , Lo Ken Sin , Belhaj Hicham , Moutereau Stéphane , Marshall Kwesi , Reid Marvin , Kutlar Abdullah , Ashley-Koch Allison E , Telen Marilyn J , Joly Philippe , Galactéros Frédéric , Bartolucci Pablo , Lettre Guillaume 
Published: January 2025

Abstract
Sickle cell disease (SCD) is the most common monogenic disease in the world and is caused by mutations in the β-globin gene (HBB). Notably, SCD is characterized by extreme clinical heterogeneity. Inter-individual variation in fetal hemoglobin (HbF) levels strongly contributes to this patient-to-patient variability, with high HbF levels associated with decreased morbidity and mortality. Genetic association studies have identified and replicated HbF levels-associated variants at three loci: BCL11A, HBS1L-MYB, and HBB. In SCD patients, genetic variation at these three loci accounts for ~ 50% of HbF heritability. Genome-wide association studies (GWAS) in non-anemic and SCD patients of multiple ancestries have identified 20 new HbF-associated variants. However, these genetic associations have yet to be replicated in independent SCD cohorts. Here, we validated the association between HbF levels and variants at five of these new loci (ASB3, BACH2, PFAS, ZBTB7A, and KLF1) in up to 3740 SCD patients. By combining CRISPR inhibition and single-cell transcriptomics, we also showed that sequences near non-coding genetic variants at BACH2 (rs4707609) and KLF1 (rs2242514, rs10404876) can control the production of the β-globin genes in erythroid HUDEP-2 cells. Finally, we analyzed whole-exome sequence data from 1354 SCD patients but could not identify rare genetic variants of large effect on HbF levels. Together, our results confirm five new HbF-associated loci that can be functionally studied to develop new strategies to induce HbF expression in SCD patients.
Measurement of Whole Blood Tacrolimus Concentrations by LC-MS/MS and Immunoassay Methods: Influence of Immediate-Release vs Extended-Release Tacrolimus Formulations
Authors: Alabi Adekunle , Ge Mengyuan , Momper Jeremiah D , Tsunoda Shirley M , Kelner Michael J , Fitzgerald Robert L , Suhandynata Raymond T 
Published: January 2025

Abstract

Background
Therapeutic drug monitoring of the immunosuppressant tacrolimus is commonly performed by immunoassay or LC-MS/MS. Measurement biases between these methodologies have been characterized for immediate-release tacrolimus (IR-tac; Prograf) but have not been performed for extended-release formulations such as Envarsus. These discrepancies can impact patient care, as appropriate dosing is required to maintain therapeutic concentrations and immunosuppression.

Methods
Validation of a whole-blood LC-MS/MS method for the simultaneous quantification of tacrolimus and its major metabolite, desmethyl tacrolimus, was performed using traceable calibrators (tacrolimus, ERM-DA110a) and quality control (QC) material for tacrolimus and standard material for desmethyl tacrolimus. Tacrolimus concentrations were determined by LC-MS/MS and the ARCHITECT immunoassay in patients receiving either IR-tac or Envarsus for clinical care.

Results
External calibration curves for both tacrolimus and desmethyl tacrolimus were linear (R2 &gt; 0.995), and the analytical measurement range (AMR) for tacrolimus spanned from 1.1 to 31.6 ng/mL. Calibrator/QC biases were within 15% of their spiked concentrations throughout the AMR, and within-run imprecision was &lt;10%, except at the lower limit of quantification (n = 25). Between-run imprecision for low, mid, and high QC levels was ≤11% over a 2-week period (n = 5 days). Comparative biases between immunoassay and LC-MS/MS were significantly lower (P = 0.0074) for patients receiving Envarsus (n = 20 specimens) relative to patients receiving IR-tac (n = 32 specimens).

Conclusions
Biases between immunoassay and LC-MS/MS tacrolimus measurements in patients receiving immediate-release vs extended-release formulations indicate that their distinct pharmacokinetic profiles impact measurement accuracy. These assay biases should be considered when interpreting tacrolimus concentration measurements.
Psychotherapy research in the deaf community: pilot clinical trial lessons learned
Authors: Anderson Melissa L , Wilkins Alexander M , Hostovsky Sheri , Pici-D’Ottavio Emma , Aldalur Aileen , McGinnis Felicia , Meza Kayla 
Published: January 2025

Abstract
At the time of publication, there are no evidence-based psychotherapies to treat any behavioral health condition with Deaf clients. This article describes unique study design considerations for psychotherapy clinical trials conducted in the U.S. Deaf community. We synthesized emergent themes from participant exit interviews with feasibility data and real-life challenges that our team encountered when implementing the Signs of Safety pilot clinical trial, conducted from 2019 to 2022. Particularly illustrative participant accounts were selected to demonstrate five major lessons learned—expanding reach for recruitment; formally assessing participants’ ASL fluency; selecting ethically-sound control groups; streamlining video fidelity monitoring; and making crystallized outcome assessments ASL-accessible. These lessons learned informed the design of the first-ever full-scale psychotherapy trial in the U.S. Deaf community, to be conducted from late autumn 2024 through 2028. This trial will potentially validate the first evidence-based therapy for Deaf people and provide a vital roadmap for conducting Deaf community-engaged clinical trials.
Climate and evolutionary history shape latitudinal patterns of angiosperm wood density
Authors: Waris Kilara , Larjavaara Markku , Luo Ao , Lyu Tong , Li Yaoqi , Jia Wen , Wang Zhiheng 
Published: January 2025

Abstract
Wood density indicates important plant functions and plays a key role in carbon cycling of forest ecosystems by affecting wood decomposition. However, how wood density varies globally and how it evolved through the evolutionary history of angiosperms remain unclear. Here, by integrating data of wood density, phylogeny, and distributions for angiosperms worldwide, we estimated global spatiotemporal patterns of wood density and their relationships with modern climate and paleoclimate. We found that mean wood density decreased with latitude in the northern hemisphere but increased with latitude in the southern hemisphere. The interspecific wood density variation within each geographic unit did not show clear latitudinal gradients. Temperature was the best predictor of the global geographic pattern in mean wood density, while the geographic variation in mean wood density across high-temperature regions could be explained by geographic variation in precipitation and precipitation seasonality. Since the Cenozoic (66 million years ago (Mya)), wood density increased first (until 20 Mya) and then decreased. In general, the Cenozoic wood density was positively correlated with paleotemperature and negatively correlated with paleoprecipitation, especially during more arid periods. Interestingly, the evolutionary trends of wood density on different continents differed, which corresponded to the divergence in wood density patterns and their relationships with modern climate on different continents. Our results highlight the dominant effect of environmental temperature on global variation in angiosperm wood density with an additional strong effect of precipitation seasonality. Our study also demonstrates the critical role of aridity and biogeographic idiosyncrasies in driving angiosperm wood density evolution.
Anatomy of a fall: stationary and super-Keplerian spiral arms generated by accretion streamers in protostellar discs
Authors: Calcino Josh , Price Daniel J , Hilder Thomas , Christiaens Valentin , Speedie Jessica , Ormel Chris W 
Published: January 2025

ABSTRACT
Late-stage infall onto evolved protoplanetary discs is an important source of material and angular momentum replenishment and disc substructures. In this paper, we used 3D smoothed particle hydrodynamics simulations to model streamer–disc interactions for a prograde streamer. The initially parabolic streamer interacts with the disc material to excite disc eccentricity, which can last on the order of $10^5$ yr. We found that the spiral arms the streamer excited in the disc can have a variety of pattern speeds, ranging from stationary to super-Keplerian. Spiral arms with various pattern speeds can exist simultaneously, providing a way to diagnose them in observations. Streamer-induced spirals appear similar to those generated by a massive outer companion, where the pitch angle of the spiral increases towards the source of the perturbation. Additionally, the spiral arms can show large and sudden pitch angle changes. Streamer-induced spirals are long-lived, lasting approximately $3\!-\!4$ times longer than the initial streamer infall time-scale (${\sim} 10^4$ yr). After the initial interaction with the disc, a long-lasting low m azimuthal mode persists in the disc.
Quantitative analysis of ‘virtual’ SSP assessment clinics in the NHS bowel cancer screening programme in England
Authors: Nickerson Claire , Wright Suzanne , Pickering Lucy , Adams Lee , Mandli Nagamani , Hex Nick , Collins Cameron , Webb Anne , Rayment Jeffery , Emery-Downing Karen , Maclean Rebecca 
Published: January 2025

Abstract

Background
Bowel cancer screening in England is initially carried out using a home testing kit, with those who require further testing first being referred to an assessment clinic. During COVID-19, these assessment clinics became ‘virtual’ (telephone or video-call) where previously they had only been held face-to-face.

Methodology
A before and after study design was constructed to examine the impact of this change in clinic type on key programme metrics.

Results and Conclusions
The data showed fewer people changed their specialist screening practitioner appointments when the modality was virtual, with the virtual group also having higher clinic uptake and shorter times to first offered and first attended clinics.
Despite clinical opinion that not being able to physically see a patient would negatively impact diagnostic test quality, suggesting that incomplete tests would rise, referrals to colonoscopy would fall, and bowel preparation quality would suffer, the data did not support any of these suppositions.
Whilst the data indicated that diagnostic test uptake was lower in the virtual group, the presence of COVID-19 is likely to have skewed findings.
The IT system is being developed to support virtual clinics, which will aid future data analysis/monitoring and assist staff with clinic management.
GPCR dimerization: Drug discovery aspects and targets in renin‐angiotensin systems
Authors: Faisal Tahmid , Hussain Tahir 
Published: January 2025

AbstractG protein‐coupled receptors (GPCRs), which play crucial roles in various physiological functions, often assembled into dimers and higher‐order oligomers. This oligomerization phenomenon has been observed in diverse physiological and pathological contexts, presenting promising opportunities for drug discovery targeting vital systems such as the cardiovascular, nervous, endocrine, and renal systems. This review offers a concise understanding of GPCR dimerization, its signaling mechanisms, and its implications. Furthermore, we explored therapeutic strategies aimed at modulating receptors involved in dimer/oligomer formation within the renin‐angiotensin system.
Rates of Minimally Invasive Surgery After Introduction of Robotic-Assisted Surgery for Common General Surgery Operations
Authors: Fong Zhi Ven , Wall-Wieler Elizabeth , Johnson Shaneeta , Culbertson Richard , Mitzman Brian 
Published: January 2025

Importance:
Many patients who would benefit from minimally invasive surgery (MIS) have open surgery; robotic-assisted surgery (RAS) addresses some of the limitations of laparoscopic surgery and could increase rates of MIS across different patient populations.

Objective:
To determine whether the introduction of RAS increases MIS rates and whether increases are seen across different patient populations undergoing common general surgery procedures.

Design:
A retrospective cohort study was performed to compare rates of MIS in the year before and after the index date for hospitals that did and did not introduce RAS. Generalized estimating equation regression models were used to compare rates in MIS over time.

Setting:
PINC AI Healthcare Database, an all-payor discharge database of hospitals in the United States.

Participants:
Hospitals that performed cholecystectomy, inguinal hernia repair, ventral hernia repair, and colorectal resection from 2016 to 2022.

Exposure:
RAS hospitals performing at least 1 common general surgery procedure using RAS.

Main Outcome and Measure:
The primary analysis examined rates of MIS, defined as the rate of common general surgeries that were minimally invasive (laparoscopic or RAS) in a hospital. The secondary analysis examined MIS rates for common general surgeries, across age, sex, race, ethnicity, and payor.

Results:
Of 408 hospitals included in the study, 153 (38%) introduced RAS for common general surgeries. The relative MIS rate for hospitals that introduced RAS compared with hospitals that did not went from 1.08 (95% confidence interval [CI], 1.02–1.14; P < 0.01) before the index date to 1.15 (95% CI, 1.09–1.22; P < 0.01) after the index date (P
interaction < 0.01), indicating a larger increase in MIS rates among hospitals introducing RAS. MIS rates increased significantly more in hospitals that introduced RAS across patient age, sex, ethnicity, race, and payor compared with hospitals that did not introduce RAS.

Conclusions and Relevance:
Hospitals that introduced RAS for common general surgery procedures were associated with an increase in MIS rates across different patient populations compared with hospitals that did not introduce RAS.
Validity and Reliability Study of the Turkish Adaptation of the “Medical Office Survey on Patient Safety Culture”
Authors: Mevsim Vildan , Erdem Mustafa , Çöme Oğulcan , Bezircioğlu İncim 
Published: January 2025

Introduction:
The safety culture within health care organizations is essential for ensuring patient well-being and optimizing health care delivery. This study addresses the pressing need to establish a culture of patient safety within primary health care settings. The aim is to conduct a comprehensive validity and reliability study for the Turkish adaptation of the “Medical Office Survey on Patient Safety Culture” (MOSPSC) scale, designed to assess patient safety culture in primary care medical offices.

Methods:
The research model follows rigorous methodology, including a systematic translation and adaptation process aligned with World Health Organization guidelines. A diverse sample of 402 family physicians from primary health care centers across Turkey participated in the study. Descriptive results highlight participants’ characteristics, work environments, and experiences in primary care. The scale’s construct validity is evaluated using the Kaiser-Meyer-Olkin (KMO) and Bartlett tests, while its reliability is assessed through internal consistency analyses, including Cronbach α, split-half reliability, and item-total correlation.

Results:
Results indicate strong internal consistency, with Cronbach α values ranging from 0.42 to 0.91 for scale dimensions and an overall value of 0.89. Construct validity assessment attests to the scale’s appropriateness for assessing patient safety culture. Challenges in conducting factor analysis due to participant responses are discussed.

Conclusions:
The study contributes to the field by providing a validated and reliable tool specifically tailored for assessing patient safety culture in primary care medical offices. The Turkish adaptation of the MOSPSC scale offers health care professionals and organizations a valuable instrument for enhancing patient safety culture, identifying areas for improvement, and ultimately optimizing patient care within primary health care settings.
Pharmacovigilance Indicators in Health Services: A Systematic Review. Are There Still Relevant Gaps?
Authors: Pimentel Alessandra de Freitas , Lopes Luis P.N. , Alexandre Thaiane de Lima , Ferreira Adrielly de Barcellos Fernandes , Figueras Albert , Guaraldo Lusiele , de Matos Guacira C. 
Published: January 2025

Objective:
The aim of this study was to identify potentially applicable pharmacovigilance (PV) indicators for health services available in the literature.

Methods:
We searched MEDLINE, EMBASE, LILACS, IBECS, CUMED, SciELO, and Google Scholar bibliographic between January 1, 2004 and January 23, 2023, and 25 websites from different organizations for studies describing specific PV indicators in health services. The methodological quality of the included studies was assessed using the Appraisal of Indicators through the Research and Evaluation (AIRE) tool. The indicators were differentiated into structure, process and outcome, and also grouped according to the applicability of the PV activities carried out in health services, based on the domains proposed by the Centers for Disease Control and Prevention.

Results:
We identified 14 studies and 100 PV indicators classified as structural (51%), process (32%), and outcome (17%). The indicators classified according to the aspect of the PV activities they measure cover “Results of PV/ External impact” (45%); “How does the PV unit works/Management of their information” (32%); “The PV unit and team” (23%). According to AIRE, the methodological quality of the included studies varied considerably. In consensus, we selected 55 indicators that could potentially be useful to health services.

Conclusions:
This systematic review made it possible to identify a considerable number of indicators. Many of them aim to evaluate different aspects of PV activities that can be valuable from a public health and health system perspective. Therefore, we propose a new classification and a set of indicators useful for health services.
Validation of the PANAMA-Score for Survival and Benefit of Adjuvant Therapy in Patients with Resected Pancreatic Cancer After Neoadjuvant FOLFIRINOX
Authors: Rompen Ingmar F. , Stoop Thomas F. , van Roessel Stijn , van Veldhuisen Eran , Janssen Quisette P. , Alseidi Adnan , Balduzzi Alberto , Balzano Gianpaolo , Berrevoet Frederik , Bonds Morgan , Busch Olivier R. , Butturini Giovanni , Javed Ammar A , Del Chiaro Marco , Conlon Kevin C. , Falconi Massimo , Frigerio Isabella , Fusai Giuseppe K. , Gagnière Johan , Griffin Oonagh , Hackert Thilo , Sparrelid Ernesto , Halimi Asif , Labori Knut J. , Malleo Giuseppe , Marino Marco V. , Mortensen Michael B. , Nikov Andrej , Lesurtel Mickaël , Keck Tobias , Kleeff Jörg , Pandé Rupaly , Pfeiffer Per , Pietrasz Daniel , Roberts Keith J. , Sa Cunha Antonio , Salvia Roberto , Strobel Oliver , Tarvainen Timo , van Laarhoven Hanneke W. M. , Koerkamp Bas Groot , Loos Martin , Michalski Christoph , Besselink Marc G. , Hank Thomas 
Published: January 2025

Aim:
To validate the prognostic value of the PAncreatic NeoAdjuvant MAssachusetts (PANAMA)-score and to determine its predictive ability for survival benefit derived from adjuvant treatment in patients after resection of pancreatic ductal adenocarcinoma (PDAC) following neoadjuvant FOLFIRINOX

Background:
The PANAMA-score was developed to guide prognostication in patients after neoadjuvant therapy and resection for PDAC. As this score focuses on the risk for residual disease after resection, it might also be able to select patients who benefit from adjuvant after neoadjuvant therapy.

Methods:
This retrospective international multicenter study is endorsed by the European-African Hepato-Pancreato-Biliary Association (E-AHPBA). Patients with PDAC who underwent resection after neoadjuvant FOLFIRINOX were included. Mantel-Cox regression with interaction analysis was performed to assess the impact of adjuvant chemotherapy.

Results:
Overall, 383 patients after resection of PDAC following neoadjuvant FOLFIRINOX were included of whom 187 (49%), 137 (36%), and 59 (15%) had a low-risk, intermediate-risk, and high-risk PANAMA-score, respectively. A discrimination in median OS was observed stratified by risk groups (48.5, 27.6, and 22.3 months, Log-Rank-Plow-intermediate=0.004, Log-Rank-Pintermediate-high=0.027). Adjuvant therapy was not associated with an OS difference in the low-risk group (HR 1.50, 95%CI:0.92-2.50), whereas improved OS was observed in the intermediate (HR 0.58, 95%CI:0.34-0.97) and high-risk groups (HR 0.47, 95%CI:0.24-0.94) (p-interaction=0.008).

Conclusions:
The PANAMA 3-tier risk groups (low-risk, intermediate-risk, and high-risk, available via pancreascalculator.com) correspond with differential survival in patients with resected PDAC following neoadjuvant FOLFIRINOX. The risk groups also differentiate between survival benefit associated with adjuvant treatment, with only the intermediate- and high-risk groups associated with improved OS.
Exploratory factor analysis as a validation tool in a questionnaire to evaluate the uptake of cataract surgery
Authors: Salowi Mohamad Aziz , Naing Nyi Nyi , Ahmad Rosdi Hajar , Wan Nawang Wan Radziah , Mustafa Norasyikin , Sharudin Siti Nurhuda , Che Omar Nor Anita , Mokhtar Azlina 
Published: January 2025

Background Exploratory Factor Analysis (EFA) evaluates construct validity by identifying underlying relationships among questionnaire items, helping determine the number of latent constructs. This study aimed to validate a newly developed questionnaire on cataract surgery uptake among the community by interviewing subjects aged 50 years and older. Methods A bilingual questionnaire, based on theoretical factors of knowledge, perception, attitude, and practice, was developed through literature review and expert interviews. It underwent forward-backward translation, content validity, and face validity assessment, followed by discussions with panels of eye care experts. Data for EFA were collected through interviews with subjects aged 50 and older, who had visual acuity worse than 6/18 due to cataracts or had undergone cataract surgery. Responses were analyzed for factor loadings and reliability. Principal Axis Factoring (PAF) was used for factor extraction, initially based on Eigenvalues > 1, and later fixed at eight factors. Factors were rotated using Varimax with Kaiser Normalization. Items with weak factor loadings were removed iteratively, with re-analysis conducted after each removal. Results A total of 287 subjects were recruited and consented to EFA. All 40 items in the questionnaire (knowledge, attitude, perception and practice) were combined and analysed. The Kaiser-Meyer-Olkin (KMO) test was 0.714, indicating that factor analysis was suitable for exploring the underlying structure. Bartlett's test of Sphericity was highly significant (p < 0.001), indicating that the variables (questions) were sufficiently interrelated for factor analysis. Factors 3 and 7 had only two questions, although they showed fairly good loading with satisfactory correlation. The Cronbach's alpha reliability of all the factors varies from 0.50 to 0.72 (total = 0.72). The final questionnaire consisted of six factors and 22 questions. Conclusions The developed and validated questionnaire demonstrated an acceptable factor structure related to knowledge, attitude, perception, and practice in evaluating cataract surgery uptake. This tool provides a reliable method for assessing cataract surgery uptake in the community.