bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinicians’ use of Health Information Exchange technologies for medication reconciliation in the U.S. Department of Veterans Affairs: a qualitative analysis
Authors: Snyder Margie E. , Nguyen Khoa A. , Patel Himalaya , Sanchez Steven L. , Traylor Morgan , Robinson Michelle J. , Damush Teresa M. , Taber Peter , Mixon Amanda S. , Fan Vincent S. , Savoy April , Dismore Rachel A. , Porter Brian W. , Boockvar Kenneth S. , Haggstrom David A. , Locke Emily R. , Gibson Bryan S. , Byerly Susan H. , Weiner Michael , Russ-Jara Alissa L. 
Published: October 2024

Abstract
Background
Medication reconciliation is essential for optimizing medication use. In part to promote effective medication reconciliation, the Department of Veterans Affairs (VA) invested substantial resources in health information exchange (HIE) technologies. The objectives of this qualitative study were to characterize VA clinicians’ use of HIE tools for medication reconciliation in their clinical practice and to identify facilitators and barriers.

Methods
We recruited inpatient and outpatient prescribers (physicians, nurse practitioners, physician assistants) and pharmacists at four geographically distinct VA medical centers for observations and interviews. Participants were observed as they interacted with HIE or medication reconciliation tools during routine work. Participants were interviewed about clinical decision-making pertaining to medication reconciliation and use of HIE tools, and about barriers and facilitators to use of the tools. Qualitative data were analyzed via inductive and deductive approaches using a priori codes.

Results
A total of 63 clinicians participated. Over half (58%) were female, and the mean duration of VA clinical experience was 7 (range 0–32) years. Underlying motivators for clinicians seeking data external to their VA medical center were having new patients, current patients receiving care from an external institution, and clinicians’ concerns about possible medication discrepancies among institutions. Facilitators for using HIE software were clinicians’ familiarity with the HIE software, clinicians’ belief that medication information would be available within HIE, and their confidence in the ability to find HIE medication-related data of interest quickly. Six overarching barriers to HIE software use for medication coordination included visual clutter and information overload within the HIE display; challenges with HIE interface navigation; lack of integration between HIE and other electronic health record interfaces, necessitating multiple logins and application switching; concerns with the dependability of HIE medication information; unfamiliarity with HIE tools; and a lack of HIE data from non-VA facilities.

Conclusions
This study is believed to be the first to qualitatively characterize clinicians’ HIE use with respect to medication reconciliation. Results inform recommendations to optimize HIE use for medication management activities. We expect that healthcare organizations and software vendors will be able to apply the findings to develop more effective and usable HIE information displays.
Time-varying exposure to food retailers and cardiovascular disease hospitalization and mortality in the netherlands: a nationwide prospective cohort study
Authors: Pinho Maria Gabriela M. , Koop Yvonne , Mackenbach Joreintje D. , Lakerveld Jeroen , Simões Mariana , Vermeulen Roel , Wagtendonk Alfred J. , Vaartjes Ilonca , Beulens Joline W. J. 
Published: October 2024

Abstract

Background
Very few studies to date investigated the prospective association of changes in exposure to the food environment with cardiovascular disease (CVD) risk. We aim to explore if time-varying exposure to the food environment was associated with hospitalization and mortality due to total and specific types of CVD in The Netherlands.

Methods
In this prospective cohort study, 4,641,435 Dutch adults aged 35 + years who did not change residence in 2002–2018 were identified through registry data. Exposure to the food environment was defined as time-varying Food Environment Healthiness Index (FEHI) scores (range: − 5 to 5) and time-varying kernel density of specific food retailers (e.g., fast food outlets, supermarkets) around the home location between 2004 and 2018. The main outcome measures were hospitalization and mortality due to overall CVD, stroke, HF, and CHD occurring between 2004 and 2020, based on hospital and death registries.

Results
In Cox regression models, each unit increase in the FEHI was associated with a lower hospitalization and mortality of CVD (hospitalization hazard ratio (HRh) = 0.90 (0.89 to 0.91), mortality hazard ratio (HRm) = 0.85 (0.82 to 0.89)), CHD (HRh = 0.88 (0.85 to 0.91), HRm = 0.80 (0.75 to 0.86)), stroke (HRh = 0.89 (0.84 to 0.93)), HRm = 0.89 (0.82 to 0.98)), and HF (HRh = 0.90 (0.84–0.96), HRm = 0.84 (0.76 to 0.92)). Increased density of local food shops, fast food outlets, supermarkets, and convenience stores and decreased density of food delivery outlets and restaurants were associated with a higher risk of CVD, CHD, stroke, and HF hospitalization and mortality.

Conclusions
In this observational longitudinal study, changes in exposure to a healthier food environment over 14 years were associated with a risk reduction in CVD hospitalization and mortality, in particular in urbanized areas and for younger adults and those with higher incomes.
SSRI use during acute COVID-19 and risk of Long COVID among patients with depression
Authors: Butzin-Dozier Zachary , Ji Yunwen , Deshpande Sarang , Hurwitz Eric , Anzalone A. Jerrod , Coyle Jeremy , Shi Junming , Mertens Andrew , van der Laan Mark J. , Colford John M. , Patel Rena C. , Hubbard Alan E. ,   the National COVID Cohort Collaborative (N3C) Consortium
Published: October 2024

Abstract
Background
Long COVID, also known as post-acute sequelae of COVID-19 (PASC), is a poorly understood condition with symptoms across a range of biological domains that often have debilitating consequences. Some have recently suggested that lingering SARS-CoV-2 virus particles in the gut may impede serotonin production and that low serotonin may drive many Long COVID symptoms across a range of biological systems. Therefore, selective serotonin reuptake inhibitors (SSRIs), which increase synaptic serotonin availability, may be used to prevent or treat Long COVID. SSRIs are commonly prescribed for depression, therefore restricting a study sample to only include patients with depression can reduce the concern of confounding by indication.

Methods
In an observational sample of electronic health records from patients in the National COVID Cohort Collaborative (N3C) with a COVID-19 diagnosis between September 1, 2021, and December 1, 2022, and a comorbid depressive disorder, the leading indication for SSRI use, we evaluated the relationship between SSRI use during acute COVID-19 and subsequent 12-month risk of Long COVID (defined by ICD-10 code U09.9). We defined SSRI use as a prescription for SSRI medication beginning at least 30 days before acute COVID-19 and not ending before SARS-CoV-2 infection. To minimize bias, we estimated relationships using nonparametric targeted maximum likelihood estimation to aggressively adjust for high-dimensional covariates.

Results
We analyzed a sample (n = 302,626) of patients with a diagnosis of a depressive condition before COVID-19 diagnosis, where 100,803 (33%) were using an SSRI. We found that SSRI users had a significantly lower risk of Long COVID compared to nonusers (adjusted causal relative risk 0.92, 95% CI (0.86, 0.99)) and we found a similar relationship comparing new SSRI users (first SSRI prescription 1 to 4 months before acute COVID-19 with no prior history of SSRI use) to nonusers (adjusted causal relative risk 0.89, 95% CI (0.80, 0.98)).

Conclusions
These findings suggest that SSRI use during acute COVID-19 may be protective against Long COVID, supporting the hypothesis that serotonin may be a key mechanistic biomarker of Long COVID.
Oral administration of Sophora Flavescens-derived exosomes-like nanovesicles carrying CX5461 ameliorates DSS-induced colitis in mice
Authors: Zhang Manqi , Xu Xichao , Su Liqian , Zeng Yuqing , Lin Jingxiong , Li Wenwen , Zou Yigui , Li Sicong , Lin Boxian , Li Ziyuan , Chen Hu , Huang Yuheng , Xu Quanle , Chen Hongbo , Cheng Fang , Dai Dongling 
Published: October 2024

AbstractUlcerative colitis (UC) belongs to chronic inflammatory disease with a relapsing characterization. Conventional oral drugs of UC are restricted in clinical by premature degradation in the gastrointestinal tract, modest efficacy, and adverse effects. CX5461 can treat autoimmune disease, immunological rejection, and vascular inflammation. However, low solubility, intravenous administration, and non-inflammatory targeting limited its clinical application. Herein, this work aims to develop Sophora Flavescens-derived exosomes-like nanovesicles carrying CX5461 (SFELNVs@CX5461) for efficient CX5461 oral delivery for UC therapy. We identified SFELNVs as nano-diameter (80 nm) with negative zeta potential (-32mV). Cellular uptake has shown that SFELNVs were targeted uptake by macrophages, thus increasing drug concentration. Additionally, oral SFELNVs@CX5461 exhibited good safety and stability, as well as inflammation-targeting ability in the gastrointestinal tract of dextran sodium sulfate (DSS)-induced colitis mice. In vivo, oral administration of SFELNVs and CX5461 could relieve mice colitis. More importantly, combined SFELNVs and CX5461 alleviated mice colitis by inhibiting pro-inflammatory factors (TNF-α, IL-1β, and IL-6) expression and promoting M2 macrophage polarization. Furthermore, SFELNVs promoted M2 polarization by miR4371c using miRNA sequencing. Our results suggest that SFELNVs@CX5461 represents a novel orally therapeutic drug that can ameliorate colitis, and a promising targeting strategy for safe UC therapy.
Use of a newly developed minimally invasive bilateral fixed angle locking system in the treatment of pathological pelvic fractures: a case series
Authors: Unthan Mark , Marintschev Ivan , Spiegel Christian , Hofmann Gunther O. , Weschenfelder Wolfram 
Published: October 2024

Abstract
Background
Metastatic bone disease (MBD) and its complications have a significant impact on patients’ quality of life. Pathological fractures are a particular problem as they affect patient mobility and pose a high risk of non-union. The pelvis is frequently affected by MBD and its fixation is challenging. We present a case series of three pathological sacral fractures treated with a new minimally invasive bilateral fixed angle locking system.

Case presentation
Case 1 and 2 suffered a pathological transforaminal sacral fracture without adequate trauma in stage 4 carcinomas (gastric cancer and breast cancer). Both were initially treated with non-surgical treatment, which had only a limited effect and led to imminent immobility. Both were operated on with fluoroscopic navigation and underwent transsacral SACRONAIL® stabilisation according to CT morphology (S1 + S2 and S1 respectively). Immediately after the operation, pain decreased and mobilisation improved. Case 3 had a pathological transalar sacral fracture during the 2nd cycle of chemotherapy due to non-Hodgkin’s lymphoma. He soon became immobile and could only move in a wheelchair. The operation was performed with CT navigation due to the very small corridors and an implant was inserted in S1 and S2. The patient reported immediate pain relief and his ability to walk improved over the following months. Despite continued chemotherapy, no wound complications occurred.

Conclusions
The cases show the advantages of the minimally invasive bilateral fixed angle locking system SACRONAIL® in the treatment of patients with pathological sacral fractures. It allows immediate full weight bearing and the risk of secondary surgical complications is low. All cases showed an improvement in pain scores and mobility.
Molecular quantification of fritillariae cirrhosae bulbus and its adulterants
Authors: Liu Ziyi , Pei Yifei , Chen Tiezhu , Yang Zemin , Jiang Wenjun , Feng Xue , Li Xiwen 
Published: October 2024

Abstract
Background
Fritillariae Cirrhosae Bulbus (FCB) is frequently adulterated with its closely related species due to personal or non-man made factors, leading to alterations in the composition of its constituents and compromising the efficacy of its products.

Methods
The specific single nucleotide polymorphisms (SNPs) were screened by comparing candidate barcodes of Fritillaria and verified by amplification and sequencing. Herb molecular quantification (Herb-Q) was established by detecting specific SNPs, and the methodological validation was performed. Quantitative standard curves were established for FCB mixed with each adulterated species, and the quantitative validity of this method was verified based on external standard substance. In addition, eight commercial Shedan Chuanbei capsules (SDCBs) randomly selected were detected.

Results
FCB and its five adulterants can be distinguished based on the ITS 341 site. The methodological investigation of Herb-Q shows optimal accuracy, and repeatability, which exhibited good linearity with an R2 of 0.9997 (> 0.99). An average bias in quantitative validity was 5.973% between the measured and actual values. Four of eight commercial SDCBs were adulterated with F. ussuriensis or F. thunbergia with adulteration levels ranging from 9 to 15% of the total weight.

Conclusion
This study confirmed that Herb-Q can quantitatively detect both the mixed herbs and Chinese patent medicines (CPMs) containing FCB with high reproducibility and accuracy. This method provides technical support for market regulation and helps safeguard patient rights.
Integrating deep phenotyping with genetic analysis: a comprehensive workflow for diagnosis and management of rare bone diseases
Authors: Li Guozhuang , Xu Kexin , Yin Xiangjie , Yang Jianle , Cai Jihao , Yang Xinyu , Li Qing , Wang Jie , Zhao Zhengye , Mahesahti Aoran , Zhang Ning , Zhang Terry Jianguo , Wu Nan 
Published: October 2024

AbstractPhenotypes play a fundamental role in medical genetics, serving as external manifestations of underlying genotypes. Deep phenotyping, a cornerstone of precision medicine, involves precise multi-system phenotype assessments, facilitating disease subtyping and genetic understanding. Despite their significance, the field lacks standardized protocols for accurate phenotype evaluation, hindering clinical comprehension and research comparability. We present a comprehensive workflow of deep phenotyping for rare bone diseases from the Genetics Clinic of Skeletal Deformity at Peking Union Medical College Hospital. Our workflow integrates referral, informed consent, and detailed phenotype evaluation through HPO standards, capturing nuanced phenotypic characteristics using clinical examinations, questionnaires, and multimedia documentation. Genetic testing and counseling follow, based on deep phenotyping results, ensuring personalized interventions. Multidisciplinary team consultations facilitate comprehensive patient care and clinical guideline development. Regular follow-up visits emphasize dynamic phenotype reassessment, ensuring treatment strategies remain responsive to evolving patient needs. In conclusion, this study highlights the importance of deep phenotyping in rare bone diseases, offering a standardized framework for phenotype evaluation, genetic analysis, and multidisciplinary intervention. By enhancing clinical care and research outcomes, this approach contributes to the advancement of precision medicine in the field of medical genetics.
Current advances and challenges in Managing Hereditary Diffuse Gastric Cancer (HDGC): a narrative review
Authors: van der Sluis L. , van Dieren J.M. , van der Post R.S. , Bisseling T.M. 
Published: October 2024

AbstractMore than 25 years ago, CDH1 pathogenic variants (PVs) were identified as the primary cause of hereditary diffuse gastric cancer (HDGC), an inherited cancer syndrome that increases the lifetime risk of developing diffuse gastric cancer (DGC) and lobular breast cancer (LBC). Since DGC is associated with a poor prognosis, a prophylactic total gastrectomy (PTG) is currently the gold standard for reducing the risk of DGC in CDH1 PV carriers. However, as germline genetic testing becomes more widespread, many CDH1 PV carriers have been identified, including in families with lower penetrance levels or without a history of gastric cancer (GC). When including these families, recent findings suggest that the cumulative lifetime risk of developing advanced DGC is much lower than previously thought and is now estimated to be 13–19%. This lower risk, combined with the fact that around one third of the CDH1 PV carriers decline PTG due to potential lifelong physical and psychological consequences, raises critical questions about the current uniformity in recommending PTG to all CDH1 PV carriers. As a result, there is a growing need to consider alternative strategies, such as endoscopic surveillance. However, despite the currently lower estimated risk of infiltrative (advanced) DGC, almost every PTG specimen shows the presence of small low-stage (pT1a) signet ring cell (SRC) lesions of which the behaviour is unpredictable but often are considered indolent or premalignant stages of DGC. Therefore, the primary goal of surveillance should be to identify atypical, deeper infiltrating lesions rather than every SRC lesion. Understanding the progression from indolent to more infiltrative lesions, and recognizing their endoscopic and histological features, is crucial in deciding the most suitable management option for each individual.
Blood trauma in veno-venous extracorporeal membrane oxygenation: low pump pressures and low circuit resistance matter
Authors: Blum Christopher , Landoll Micha , Strassmann Stephan E. , Steinseifer Ulrich , Neidlin Michael , Karagiannidis Christian 
Published: October 2024

Abstract
Background
Veno-venous extracorporeal membrane oxygenation (VV ECMO) has become standard of care in patients with the most severe forms of acute respiratory distress syndrome. However, hemolysis and bleeding are one of the most frequent side effects, affecting mortality. Despite the widespread use of VV ECMO, current protocols lack detailed, in-vivo data-based recommendations for safe ECMO pump operating conditions. This study aims to comprehensively analyze the impact of VV ECMO pump operating conditions on hemolysis by combining in-silico modeling and clinical data analysis.

Methods
We combined data from 580 patients treated with VV ECMO in conjunction with numerical predictions of hemolysis using computational fluid dynamics and reduced order modeling of the Rotaflow (Getinge) and DP3 (Xenios) pumps. Blood trauma parameters across 94,779 pump operating points were associated with numerical predictions of shear induced hemolysis.

Results
Minimal hemolysis was observed at low pump pressures and low circuit resistance across all flow rates, whereas high pump pressures and circuit resistance consistently precipitated substantial hemolysis, irrespective of flow rate. However, the lower the flow rate, the more pronounced the influence of circuit resistance on hemolysis became. Numerical models validated against clinical data demonstrated a strong association (Spearman’s r = 0.8) between simulated and observed hemolysis, irrespective of the pump type.

Conclusions
Integrating in-silico predictions with clinical data provided a novel approach in understanding and potentially reducing blood trauma in VV ECMO. This study further demonstrated that a key factor in lowering side effects of ECMO support is the maintenance of low circuit resistance, including oxygenators with the lowest possible resistance, the shortest feasible circuit tubing, and cannulae with an optimal diameter.
Integration of long-read sequencing, DNA methylation and gene expression reveals heterogeneity in Y chromosome segment lengths in phenotypic males with 46,XX testicular disorder/difference of sex development
Authors: Berglund Agnethe , Johannsen Emma B. , Skakkebæk Anne , Chang Simon , Rohayem Julia , Laurentino Sandra , Hørlyck Arne , Drue Simon O. , Bak Ebbe Norskov , Fedder Jens , Tüttelmann Frank , Gromoll Jörg , Just Jesper , Gravholt Claus H. 
Published: October 2024

Abstract
Background
46,XX testicular disorder/difference of sex development (46,XX DSD) is a rare congenital condition, characterized by a combination of the typical female sex chromosome constitution, 46,XX, and a variable male phenotype. In the majority of individuals with 46,XX DSD, a Y chromosome segment containing the sex-determining region gene (SRY) has been translocated to the paternal X chromosome. However, the precise genomic content of the translocated segment and the genome-wide effects remain elusive.

Methods
We performed long-read DNA sequencing, RNA sequencing and DNA methylation analyses on blood samples from 46,XX DSD (n = 11), male controls (46,XY; variable cohort sizes) and female controls (46,XX; variable cohort sizes), in addition to RNA sequencing and DNA methylation analysis on blood samples from males with Klinefelter syndrome (47,XXY, n = 22). We also performed clinical measurements on all 46,XX DSD and a subset of 46,XY (n = 10).

Results
We identified variation in the translocated Y chromosome segments, enabling subcategorization into 46,XX DSD (1) lacking Y chromosome material (n = 1), (2) with short Yp arms (breakpoint at 2.7–2.8 Mb, n = 2), (3) with medium Yp arms (breakpoint at 7.3 Mb, n = 1), and (4) with long Yp arms (n = 7), including deletions of AMELY, TBLY1 and in some cases PRKY. We also identified variable expression of the X-Y homologues PRKY and PRKX. The Y-chromosomal transcriptome and methylome reflected the Y chromosome segment lengths, while changes to autosomal and X-chromosomal regions indicated global effects. Furthermore, transcriptional changes tentatively correlated with phenotypic traits of 46,XX DSD, including reduced height, lean mass and testicular size.

Conclusion
This study refines our understanding of the genetic composition in 46,XX DSD, describing the translocated Y chromosome segment in more detail than previously and linking variability herein to genome-wide changes in the transcriptome and methylome.