bluuebunny/crossref_metadata_2025_split huggingface dataset:
Open Disclosure Among General Practitioners as Second Victim of a Patient Safety Incident: A Cross-Sectional Study in Flanders (Belgium)
Authors: Neyens Laurens , Stouten Esther , Vanhaecht Kris , Mira José , Panella Massimiliano , Seys Deborah , Schoenmakers Birgitte 
Published: November 2024

Background
The impact of a patient safety incident (PSI) on nurses and doctors in hospital settings has been studied in depth. However, the impact of a PSI on general practitioners and how those health care professionals can be supported are less clear.

Objectives
The objective of this study is to investigate the prevalence of GPs (in training) being personally involved in a PSI, as well as the impact, the support needed, and open disclosure in the aftermath of these PSIs.

Methods
A cross-sectional study, conducted between January 3, 2022, and March 5, 2022, led to a sample of 78 GPs or GPs in training in Flanders (Belgium). Participants filled in more than 80% of a questionnaire that measured the involvement in a PSI during the prior year and their entire career, and the impact in terms of emotional symptoms, attitudes, the support needed, and open disclosure were included.

Results
In total, 78 responses of GPs (in training) filled in the questionnaire, of which 87.2% were involved in a PSI over the course of their entire career and 55.1% during the prior year. Often, such a PSI resulted in permanent patient harm or patient death. The PSI that stuck with the GPs the most had many negative consequences for the GP in question, such as hypervigilance (88.2%) and feelings of guilt (82.4%), stress (79.4%), and shame (75.0%). More than half of the respondents involved want substantive clarity (64.4%), and in case of 51.7% of the respondents, an open discussion with the patient and/or family took place afterwards.

Conclusions
This study shows that GPs, even in training, can be negatively impacted after a PSI. Only half of the respondents were involved in an open disclosure process, but the ones involved had a positive feeling after disclosure. More support is needed for health care professionals in the aftermath of a PSI in primary care, and this support could enhance their involvement in the open disclosure process.
HIV Pre-exposure Prophylaxis Prescription Initiation and Maintenance Among Homeless-Experienced People Who Use Drugs
Authors: Eger William H. , Shaw Leah C. , Biello Katie B. , Lopez Claudia , Brody Jennifer K. , Bazzi Angela R. 
Published: November 2024

Background:
HIV pre-exposure prophylaxis (PrEP) remains particularly underused among homeless-experienced people who use drugs (PWUD).

Setting:
Boston Health Care for the Homeless Program, a Federally Qualified Health Center serving homeless-experienced individuals in Boston, Massachusetts.

Methods:
To identify determinants of PrEP prescription initiation and continuation, we analyzed electronic medical records and pharmacy data between April 2018 and March 2022. Participants were HIV-negative and reported sexual, drug, or community-related HIV exposures. Adjusted multinomial logistic regression explored associations between sociodemographics, social vulnerabilities, behavioral factors (eg, injection drug use), and mental health and substance use disorder diagnoses with filling of 1 and more than 1 PrEP prescription.

Results:
Among 509 participants, mean age was 38 years, 28% were women, 19% were Black, and 24% were Hispanic/Latino. At program enrollment, most were experiencing homelessness (92%), injecting drugs (78%), and living with a mental health disorder (71%). In multivariable-adjusted models, injection drug use was positively associated with filling 1 and more than 1 PrEP prescription (adjusted odds ratio [AOR]: 2.88, 95% confidence interval [CI]: 1.33 to 6.26; and AOR: 3.60, 95% CI: 2.02 to 6.42, respectively). Participants with opioid use disorder and generalized anxiety disorder were more likely to fill 1 and more than 1 prescription, whereas those with bipolar disorder were less likely to fill 1 prescription. No sociodemographic characteristics, sexual behaviors, or other mental health or substance use disorders were associated with study outcomes.

Conclusions:
A low-threshold, harm reduction-oriented PrEP program supported prescription initiation and continuation for homeless-experienced PWUD. Implementation research is needed to facilitate scale-up of this approach.
Pharmacokinetics and Safety of Bictegravir in Pregnant and Postpartum Persons With HIV and Their Infants
Authors: Powis Kathleen M. , Pinilla Mauricio , McMorrow Flynn , Stek Alice , Brooks Kristina M. , Shapiro David E. , Knowles Kevin , Eke Ahizechukwu C. , Greene Elizabeth , Agwu Allison , Topete Lourdes , Browning Renee , Chakhtoura Nahida , Arora Priyanka , Huang Xiaoying , Best Brookie M. , Mirochnick Mark , Momper Jeremiah D. ,   the IMPAACT 2026 Protocol Team
Published: November 2024

Background:
Limited data exist on bictegravir pharmacokinetics in pregnancy among persons with HIV (PWH) and infant washout.

Setting:
Nonrandomized, open-label, multicenter phase-IV prospective study of bictegravir pharmacokinetics and safety in pregnant PWH and their infants.

Methods:
Steady-state 24-hour pharmacokinetic sampling of oral bictegravir 50 mg once daily (a component of fixed-dose combination bictegravir/emtricitabine/tenofovir alafenamide) during the second and third trimesters and postpartum was performed. Cord blood and infant washout samples were collected. Total and free bictegravir concentrations were measured by validated liquid chromatography with tandem mass spectrometry methods. Within-participant geometric mean ratios (GMR) with 90% confidence intervals (CI) were calculated to compare pharmacokinetics between second and third trimester versus postpartum. Infant HIV testing results were obtained.

Results:
Twenty-seven maternal–infant pairs were enrolled. Bictegravir area under the concentration–time curve from time 0 through 24 hours post-dose was 46% lower in the second trimester (n = 12; P = 0.002; GMR 0.54; 90% CI: 0.43 to 0.69) and 52% lower in the third trimester (n = 24; P < 0.0001; GMR 0.48; 90% CI: 0.43 to 0.55), compared with postpartum. C24 concentrations were above the estimated bictegravir protein-adjusted 95% effective concentration of 0.162 μg/mL. The median ratio of cord-to-maternal blood concentration was 1.38 (n = 17; quartiles: 1.17–1.63). Median T1/2 for infant bictegravir washout was 33.2 hours (quartiles: 25.7–45.9) with a Cmax of 2.06 μg/mL (quartiles: 1.37–2.72). Overall, 88%–92% of participants maintained suppression <40 copies/mL throughout pregnancy and postpartum. All available infant HIV testing results were negative. The safety profile for pregnant PWH and infants was acceptable.

Conclusions:
Bictegravir exposure was lower during pregnancy compared with postpartum, yet C24 concentrations were greater than the bictegravir protein-adjusted 95% effective concentration.
Disseminated Extranodal Natural Killer/T-Cell Lymphoma Mimicking a Paraneoplastic Polymyositis
Authors: Mumtaz Mudassir , Rayamajhi Sampanna 
Published: November 2024

Abstract
Extranodal natural killer/T-cell lymphoma (ENKTCL) is an aggressive EBV-associated non-Hodgkin lymphoma, most commonly arising from within the mucosa of the upper aerodigestive tract, typically with nasal presentation. Here, we present an interesting case of a 36-year-old man with ENKTCL with an atypical pattern of disease progression despite 3 cycles of SMILE chemotherapy. Restaging 18F-FDG PET/CT demonstrated widespread uptake within the skeletal musculature in a distribution concerning for a paraneoplastic polymyositis. However, muscle biopsy confirmed ENKTCL dissemination.
Clinical Efficacy of Endoscopic Retrograde Cholangiopancreatography Combined With Traditional Chinese Medicine Comprehensive Nursing in the Treatment of Biliary Tract Complications After Liver Transplantation
Authors: Li Yingjia 
Published: November 2024

Objective:
This study explored the clinical efficacy of endoscopic retrograde cholangiopancreatography (ERCP) combined with traditional Chinese medicine (TCM) comprehensive nursing in treating biliary tract complications (BTCs) after liver transplantation (LT).

Materials and Methods:
A total of 124 patients with BTCs after LT were screened and randomly divided into a control group and an experimental group. Both groups of patients underwent ERCP treatment and patients in the control group received conventional nursing, and those in the experimental group received TCM comprehensive nursing on top of the control group. The clinical efficacy after 1 month of intervention was recorded. Before intervention and 1 month after intervention, fasting venous blood was collected to detect the levels of hepatic function indicators alanine aminotransferase (ALT) and aspartate aminotransferase (AST). The negative emotions of the patients were evaluated by using the Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS), and the quality-of-life scores were determined by using the Quality-of-Life Scale. Postintervention complications, such as pancreatitis, hyperamylasemia, and reflux cholangitis, were recorded.

Results:
The total effective rate in the experimental group (90.32%) was higher than that in the control group (72.58%). ALT, AST, SAS, and SDS scores of the 2 groups after treatment were lower than before treatment, and the scores of quality of life were higher. Greater improvements were observed in the experimental group. The complication rate of the experimental group (3.23%) was lower than that of the control group (22.58%) (P<0.05).

Conclusion:
ERCP combined with TCM comprehensive nursing for patients with BTCs after LT can effectively reduce anxiety and depression, improve the quality of life, and reduce the incidence of complications.
Predicting morbidity and mortality after surgery for isolated traumatic spinal injury without spinal cord injury
Authors: Mohammad Ismail Ahmad , Forssten Maximilian Peter , Cao Yang , Ioannidis Ioannis , Forssten Sebastian Peter , Sarani Babak , Mohseni Shahin 
Published: November 2024

BACKGROUND
Traumatic spinal injuries are associated with a high risk of morbidity and mortality. The aim of this study is to investigate which variables best predict adverse outcomes in patients who had surgery for isolated traumatic spinal injury without spinal cord injury.

METHODS
The American College of Surgeons Trauma Quality Improvement Program database was used to identify adult (18 years or older) surgically managed patients with an isolated traumatic spinal injury, without spinal cord injury admitted between 2013 and 2021. An isolated injury was defined as a spine Abbreviated Injury Scale score ≥2 and an Abbreviated Injury Scale score ≤1 in the remaining body regions, as well as corresponding International Classification of Diseases, Ninth and Tenth Revision, codes. The predictive value of demographic, clinical, and comorbidity data was evaluated using logistic regression models and ranked using the permutation importance method.

RESULTS
A total of 39,457 patients were included in the study, of whom 554 died during hospitalization. The most important variables for predicting in-hospital mortality were age, sex, Glasgow Coma Scale on admission, Orthopedic Frailty Score, and cervical spine injury. The most important variables for predicting complications were age, cervical spine injury, the need for cervical spine surgery, Revised Cardiac Risk Index, and alcohol use disorder. Finally, age, cervical spine injury, sex, Glasgow Coma Scale on admission, and Orthopedic Frailty Score had the highest relative importance when predicting failure to rescue. Models based on the five most important variables for each outcome demonstrated an excellent predictive ability for in-hospital mortality (area under the receiver operating characteristic curve [AUROC], 0.84; 95% confidence interval [CI], 0.82–0.86) and failure to rescue (AUROC [95% CI], 0.86 [0.84–0.87]) as well as an acceptable predictive ability for complications (AUROC [95% CI], 0.72 [0.71–0.73]).

CONCLUSION
The most important factors identified to predict mortality, complications, and failure to rescue in traumatic spinal injury patients without spinal cord injury who undergo surgery were patients' age, sex, frailty, cervical spine injury that necessitated surgical intervention, and cardiovascular risk.

LEVEL OF EVIDENCE
Prognostic and Epidemiological; Level III.
Cardiorespiratory Fitness From Cardiopulmonary Exercise Testing Is a Comprehensive Risk-stratifying Tool in Liver Transplant Candidates
Authors: Hughes Dempsey L. , Lizaola-Mayo Blanca , Wheatley-Guy Courtney M. , Vargas Hugo E. , Bloomer Pamela M. , Wolf Cody , Carey Elizabeth J. , Forman Daniel E. , Duarte-Rojo Andres 
Published: November 2024

Background.
Cardiovascular disease and physical decline are prevalent and associated with morbidity/mortality in liver transplant (LT) patients. Cardiopulmonary exercise testing (CPX) provides comprehensive cardiopulmonary and exercise response assessments. We investigated cardiorespiratory fitness (CRF) and cardiac stress generated during CPX in LT candidates.

Methods.
LT candidates at 2 centers underwent CPX. Standard-of-care cardiac stress testing (dobutamine stress echocardiography, DSE) results were recorded. Physical function was assessed with liver frailty index and 6-min walk test. CPX/DSE double products were calculated to quantify cardiac stress. To better study the association of CPX-derived metrics with physical function, the cohort was divided into 2 groups based on 6-min walk test median (372 m).

Results.
Fifty-four participants (62 ± 8 y; 65% men, Model for End-Stage Liver Disease-Na 14 [10–18]) underwent CPX. Peak oxygen consumption was 14.1 mL/kg/min for an anerobic threshold of 10.2 mL/kg/min, with further CRF decline in the lower 6MWT cohort despite lack of liver frailty index-frailty in 90%. DSE was nondiagnostic in 18% versus 4% of CPX (P = 0.058). All CPX were negative for ischemia. A double product of ≥25 000 was observed in 32% of CPX and 11% of DSE (P = 0.020). Respiratory function testing was normal. No patient presented major cardiovascular events at 30 d post-LT.

Conclusions.
CPX provided efficient and effective combined cardiopulmonary risk and frailty assessments of LT candidates in a 1-stop test. The CRF was found to be very low despite preserved physical function or lack of frailty.
Hypertension Management Dynamics in Pediatric CKD: Insights from the 4C Study
Authors: Doyon Anke , Bayazit Aysun Karabay , Duzova Ali , Thurn Daniela , Canpolat Nur , Kaplan Bulut Ipek , Azukaitis Karolis , Obrycki Lukasz , Ranchin Bruno , Shroff Rukshana , Candan Cengiz , Erdogan Hakan , Paripovic Dusan , Donmez Osman , Lugani Francesca , Arbeiter Klaus , Yilmaz Ebru , Zaloszyc Ariane , Wühl Elke , Melk Anette , Querfeld Uwe , Schaefer Franz ,   4C Study Consortium
Published: November 2024

AbstractRationaleTo investigate blood pressure (BP) trajectories, and the impact of pharmacological intervention in children with chronic kidney disease (CKD).MethodsAnalysis of antihypertensive treatment (AHT) and BP slopes in 320 patients of the 4C Study cohort with CKD prior to renal replacement therapy, based on a minimum of three individual observations and two years of follow-up.ResultsAt enrollment, 70 patients (22%) had uncontrolled or untreated hypertension, 130 patients (41%) had controlled hypertension, and 120 patients (37%) had normotension without antihypertensive treatment. AHT medication was prescribed in 53% of patients at baseline and initiated or added in 91 patients (AHT-I, 28%) during follow-up.Overall BP standard deviation score (SDS) remained stable over time in the cohort (ß= -0.037±0.034, p=0.34 and -0.029± 0.348, p=0.093 per year for systolic and diastolic BP SDS). In the AHT-I group, systolic and diastolic BP SDS was higher at baseline and decreased significantly during follow-up (−0.22±0.07, p<.003 and -0.12±0.05 SDS per year, p=0.01). Only 8/70 (11%) patients of the previously untreated/uncontrolled group remained untreated at the last observation, while 31 (44%) were controlled during follow-up. Of the 120 normotensive patients at baseline, 60% remained normotensive while 40% progressed to uncontrolled/untreated (n=23, 19%) or controlled (n=24, 20%) hypertension.ConclusionsThe study provides comprehensive real-world evidence on long-term management of blood pressure in children with CKD from the 4C Study. Although blood pressure control improved significantly with the intensification of antihypertensive therapy, a notable proportion of previously normotensive patients developed de novo hypertension over the observation period.
A TORC1-PHR1 signaling axis regulates phosphorus starvation and immunity signaling network in Arabidopsis
Authors: Awasthi Prakhar , Muhammed Jamsheer K , Kumar Manoj , Mishra Shruti , Tiwari Archna , Jindal Sunita , Saksena Harshita B. , Singh Dhriti , Vadassery Jyothilakshmi , Rouached Hatem , Meyer Christian , Laxmi Ashverya 
Published: November 2024

AbstractThe Target of Rapamycin Complex 1 (TORC1) is a crucial eukaryotic kinase that modulates growth in response to nutrient availability. Phosphorus (P) is an essential macronutrient, and its deficiency induces extensive reprogramming of growth and defense strategies in plants. This process involves Phosphate Starvation Response 1 (PHR1), a master regulator of the Phosphate Starvation Response (PSR). In this study, we identify a novel, non-canonical role for TORC1 in regulating P starvation responses in Arabidopsis. We demonstrate that P limitation activates TORC1, leading to the stabilization of PHR1. Inhibition of TORC1 increased sensitivity to P starvation, accompanied by disruption of starvation-induced transcriptional reprogramming. Additionally, our results reveal that the TORC1-PHR1 signaling axis plays a crucial role in reprogramming the expression of genes involved in the plant immune signaling network. This regulation is critical for the symbiotic association with the endophytic fungusPiriformospora indicaunder P starvation. These findings underscore the significant role of the TORC1-PHR1 module in orchestrating the PSR and highlight the evolutionary adaptation of TORC1 signaling pathways in plants.
Genomic rare variant mechanisms for congenital cardiac laterality defect: A digenic model approach
Authors: Rai Archana , Klonowski Jonathan , Yuan Bo , Coveler Karen J. , Dardas Zain , Egab Iman , Xu Jiaoyang , Lupo Philip J. , Agopian A. J. , Kostka Dennis , Lo Cecilia W. , Yi Stephen (Song) , Gelb Bruce D. , Seidman Christine E. , Boerwinkle Eric , Posey Jennifer E. , Gibbs Richard A. , Lupski James R. , Morris Shaine A. , Coban-Akdemir Zeynep 
Published: November 2024

AbstractLaterality defects are defined by perturbations in the usual left-right asymmetry of organs. Due to low known genetic etiology of congenital heart disease (CHD) cases (less than 40%), we used a digenic model approach for the identification of contributing variants in known laterality defect genes (N = 115) in the exome/genome sequencing (ES/GS) data from individuals with clinically diagnosed laterality defects. The unsolved ES/GS data were analyzed from three CHD cohorts: Baylor College of Medicine-Genomics Research to Elucidate the Genetics of Rare Diseases (BCM-GREGoR; N = 247 proband ES), Gabriella Miller Kids First Pediatric Research program (Kids First; N = 158 trio GS), and Pediatric Cardiac Genomics Consortium (PCGC; N = 163 trio ES), and trans-heterozygous digenic variants were identified in 2.8% (inherited digenic variants in 0.4%), 8.2%, and 13.5% cases respectively, which was significantly higher as compared to 602 control trios provided by the 1000 Genomes Project(p =0.001, 1.4e-07, and 8.9e-13, respectively). Trans-heterozygous digenic variants were also identified in 0.4%, and 1.4% cases with non-laterality CHD in Kids First and PCGC datasets, respectively, which was not statistically significant as compared to control trios (p= 1, and 0.059, respectively). Altogether, in laterality cohorts, 23% of digenic pairs were in the same structural complex of motile cilia. Out of 39 unique digenic pairs in laterality CHD, 29 are more likely to be potential digenic hits as predicted by DiGePred tool. These findings provide further evidence that digenic epistatic interaction can contribute to the complex genetics of laterality defects.
Targeting STING in experimental peritoneal damage: a novel approach in peritoneal dialysis therapy
Authors: Marchant Vanessa , García-Giménez Jorge , González-Mateo Guadalupe T. , Sandoval Pilar , Tejedor-Santamaria Lucía , Rayego-Mateos Sandra , Ramos Ricardo , Jiménez-Heffernan José , Ortiz Alberto , Raby Anne-Catherine , López-Cabrera Manuel , Ramos Adrián M. , Ruiz-Ortega Marta 
Published: November 2024

AbstractPeritoneal dialysis (PD) is a widely used kidney replacement therapy for end-stage kidney disease (ESKD) patients. However, long-term exposure to PD fluids (PDF) can lead to peritoneal membrane (PM) damage, causing ultrafiltration failure and thus PD discontinuation. Investigating the molecular mechanisms underlying this damage is crucial for identifying new therapeutic targets to mitigate peritoneal deterioration in PD patients. Therefore, in this work we study the role of STING in peritoneal inflammation and fibrosis. To this aim, we performed different preclinical mouse models of peritoneal inflammation, fibrosis, and adhesions. In a chlorhexidine gluconate (CHX)-induced inflammation model, we found changes in the peritoneal transcriptomic profile, and cytosolic DNA-sensing signaling was one of the most enriched KEGG pathways. STING, as a conspicuous member of this pathway, was upregulated in CHX-and PDF-exposed mice, and in peritoneal biopsies from PD patients. STING genetic deficiency diminished peritoneal inflammation, by downregulating inflammatory gene expression, preventing NF-κB pathway activation, and decreasing cell infiltration, in early (10 days) and advanced (30 days) stages of the CHX model. STING absence also decreased PM thickness and fibrosis in the advanced CHX model, reduced adhesion scores in a post-surgical intra-abdominal adhesion model, and decreased inflammation in anS. epidermidis-induced peritonitis model. Furthermore, pharmacological inhibition of STING with C-176 decreased inflammation and macrophage-mediated mesothelial-to-mesenchymal transition in cultured mesothelial cells, and reduced CHX-induced PM thickness and inflammation in mice. Altogether, these findings highlight STING as a key mediator of peritoneal damage and suggest it may be a novel therapeutic target for preventing PD-associated peritoneal deterioration.