bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of long‐acting cabotegravir safety and pharmacokinetics in pregnant women in eastern and southern Africa: a secondary analysis of HPTN 084
Authors: Delany‐Moretlwe Sinead , Hanscom Brett , Guo Xu , Nkabiito Clemensia , Mandima Patricia , Nahirya Patricia Ntege , Mpendo Juliet , Bhondai‐Mhuri Muchaneta , Mgodi Nyaradzo , Berhanu Rebecca , Farrior Jennifer , Piwowar‐Manning Estelle , Ford Susan L. , Hendrix Craig W. , Rinehart Alex R. , Rooney James F. , Adeyeye Adeola , Landovitz Raphael J. , Cohen Myron S. , Hosseinipour Mina C. , Marzinke Mark A. ,   the HPTN 084 Study Team
Published: January 2025

AbstractIntroductionLong‐acting injectable cabotegravir (CAB‐LA) for pre‐exposure prophylaxis significantly reduced HIV acquisition in HPTN 084. We report on the safety and CAB‐LA pharmacokinetics in pregnant women during the blinded period of HPTN 084.MethodsParticipants were randomized 1:1 to either active cabotegravir (CAB) plus tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) placebo or active TDF/FTC plus CAB placebo. Pregnancy testing was performed at each visit; participants with a positive test had study product withheld and were offered open‐label TDF/FTC. Pregnancies were confirmed on two tests at least 4 weeks apart. All participants with a positive pregnancy test prior to November 5, 2020 are included in this analysis. Pregnancy incidence, maternal adverse event (AE) incidence, pregnancy outcomes (including composite outcome of spontaneous abortion <20 weeks, intrauterine foetal death or stillbirth ≥20 weeks, premature birth <37 weeks, or small for gestational age) were assessed. The apparent terminal phase half‐life (t1/2app) of CAB‐LA in pregnant women in HPTN 084 was compared to non‐pregnant women from the phase 2a HPTN 077 trial. Multivariable models assessed associations with t1/2app.ResultsFifty‐seven pregnancies (30 CAB‐LA, 27 TDF/FTC) were confirmed over 3845 person‐years [py] (incidence 1.5/100 py, 95% CI 1.1−1.9). CAB‐LA group participants had a median 342 days (IQR 192, 497) of CAB‐LA exposure prior to pregnancy detection. Grade 2 or higher maternal AE incidence did not differ by study arm (CAB 157, 95% CI 91−271 per 100 py vs. TDF/FTC 217, 95% CI 124–380 per 100 py; p = 0.256). Most pregnancies (81%) resulted in live births (25 CAB‐LA, 22 TDF/FTC). Composite poor pregnancy outcomes did not differ significantly by group (CAB 6/30 vs. TDF/FTC 4/27; p = 0.476). No congenital anomalies were observed. The CAB t1/2app geometric mean was 52.8 days (95% CI 40.7−68.4) in pregnant women compared to 60.3 days (95% CI 47.7−76.3; p = 0.66) in non‐pregnant women; neither pregnancy nor body mass index were significantly associated with t1/2app.ConclusionsCAB‐LA concentrations post‐cessation of injections were generally well tolerated in pregnant women. The t1/2app was comparable between pregnant and non‐pregnant women. Ongoing studies will examine the safety and pharmacology of CAB‐LA in women who choose to continue CAB‐LA through pregnancy and lactation.
Simple GCM Simulations of Rainfall Over Northeast Brazil, Part 2: Model Performance for Historical Seasonal Forecasts
Authors: Vasconcelos Junior Francisco das Chagas , Hall Nicholas M. J. , Cardoso Leticia , Hounsou‐Gbo Aubains , Martins Eduardo S. P. R. 
Published: January 2025

ABSTRACTA dynamical model is used as a simple GCM to perform historical forecasts for rainfall in northeastern Brazil for the years 1982–2020. The model is forced by empirically derived source terms and includes basic parameterisations to simulate vertical diffusion, convection and condensation. Ensemble forecasts with 38 members are initiated on 1st January using persisted tropical sea surface temperature anomalies (SSTAs). Rainfall forecast performance is evaluated for the February–April (FMA) rainy season. The model reproduces the climatological precipitation in the specified Nordeste region with a mainly dry bias as the model rainfall maximum is displaced in the the northwest. Hindcasts for interannual rainfall anomalies correlate with observed values (r = 0.46) and model variance is weaker than observed. A further set of forecast experiments with SSTAs restricted to the three major ocean basins reveals that most of the forecast skill can be attributed to the Pacific, despite the model's greater sensitivity to Atlantic SSTAs. The sum of results from the three ocean basins is close to the full hindcast result. Finally, a set of 128 forecast runs with idealised SSTAs placed regularly within the tropics is carried out to calibrate the response of modelled rainfall to remote influences. An influence function is diagnosed in the form of a tropical distribution of northeastern Brazil rainfall in mm/day per unit SSTA. It is strongly concentrated in the tropical Atlantic, with dry/wet conditions resulting from positive SSTAs in the northern/southern tropical Atlantic, in keeping with the observed covariance. The influence function is the used to construct a linear approximation to the forecast performance of the simple GCM. It has similar skill but stronger variance, and the skill is partitioned differently between Atlantic and Pacific influences.
Left ventricular trabecular complexity for risk stratification of cancer therapy–related cardiac dysfunction in breast cancer
Authors: Shen Hesong , Xu Qian , Tu Chunrong , Peng Yangling , Xie Yuhang , Miao Zhiming , Yang Rui , Zhang Jiuquan 
Published: January 2025

AbstractThe left ventricular trabecular fractal dimension (LVTFD) derived from cardiac magnetic resonance reflects myocardial trabecular complexity, which is associated with cardiovascular disease risk. Baseline risk stratification of cancer therapy–related cardiac dysfunction (CTRCD) in patients with breast cancer who received anthracycline is a very important clinical issue. In this study, we used the Cox model to derive and validate a new score system based on LVTFD for baseline risk stratification of CTRCD in breast cancer patients receiving anthracycline. We also compare the performance of LVTFD‐based score with the Heart Failure Association‐International Cardio‐Oncology Society (HFA‐ICOS) score using C‐index. This study enrolled 370 participants, of whom 73 participants developed CTRCD. The C‐indices of LVTFD‐based score integrating age, hypertension, previous cardiovascular disease, and maximal apical fractal dimension were higher than those of HFA‐ICOS score for stratifying CTRCD (0.834 vs. 0.642 and 0.834 vs. 0.633, respectively, in derivation and validation cohort). LVTFD‐based score can stratify the CTRCD risk, but HFA‐ICOS score cannot. The above results reveal that the LVTFD‐based score is an alternative method for baseline risk stratification of CTRCD in breast cancer who received anthracycline.
Genetic Landscape of Dystonia in Asian Indians
Authors: Saini Arti , Singh Inder , Kumar Mukesh , Radhakrishnan Divya Madathiparambil , Agarwal Ayush , Garg Divyani , Elavarasi Arunmozhimaran , Singh Rahul , Chouhan Vivek , Sandeep  , Gupta Anu , Vishnu Venugopalan Yamuna , Singh Mamta Bhushan , Bhatia Rohit , Garg Ajay , Gupta Neerja , Mir Riyaz Ahmad , Faruq Mohammed , Binukumar Balachandran Krishnamma , Srivastava Achal Kumar , Rajan Roopa 
Published: January 2025

AbstractBackgroundGenomic variations associated with dystonia in Asian Indians remain largely unknown.ObjectivesTo identify genomic alterations associated with dystonia in the Asian Indian population using next generation sequencing approaches.MethodsFrom September 2018 to December 2023, we enrolled 745 individuals including probands with dystonia and family members, in the Indian Movement Disorder Registry and Biobank. Clinical and demographic data were captured on a REDCap platform. We performed whole exome sequencing (WES) on DNA specimens obtained from 267 individuals with isolated, combined or complex dystonia. Variants were classified according to joint guidelines of American College of Medical Genetics and Genomics (ACMG) and Association of Molecular Pathology (AMP).ResultsThe mean age of the WES cohort was 33.8 ± 16.2 years, and mean age at onset (AAO) of dystonia was 25.6 ± 17.7 years. 62.2% had isolated dystonia, 7.9% combined and 29.2% had complex phenotypes. WES identified pathogenic/ likely pathogenic variants in 54 patients (20.2%) including 14 novel variants in known dystonia genes. Variants in THAP1 were most common followed by PANK2, GLB1, PLA2G6, TOR1A, ANO3, VPS16, SGCE, SPG7, FTL and other genes. Multifocal/generalized distribution of dystonia [OR: 4.1; 95% CI 1.4–12.2, P = 0.011] and family history [OR: 4.3; 95% CI 2.1–8.9, P < 0.001] were associated with positive yield on WES.ConclusionTHAP1 was the most frequent dystonia associated gene in this cohort. Singleton WES identifiedpotentially pathogenic variants in approximately one out of five patients tested, and contributed to management decisions in 4%.
Targeting the Progression of Lupus‐Like Disease in Humanized Mouse Model by Specific Dietary Components
Authors: Ralchev Nikola , Kechidzhieva Lidiya , Boneva Blagovesta , Tumangelova‐Yuzeir Kalina , Kyurkchiev Dobroslav , Kalinova Desislava , Monov Simeon , Tchorbanov Andrey , Nikolova‐Ganeva Kalina 
Published: January 2025

ABSTRACTSystemic lupus erythematosus (SLE) is a complex autoimmune disease with a number of immunological aberrations in the mechanisms of innate and adaptive immune responses. Spontaneous and induced mouse models of the disease have contributed significantly to the advancement in lupus treatments. The involvement of humanized models, engrafted with lupus patients’ immune cells, represented the possibility to study the development of SLE. In the current research, we engrafted NSG/Rag2‐γc‐ mice with PBMCs from lupus patients and put the mice on specific diet composed of extra amounts of methyl‐containing micronutrients and cofactors which are key participants in the DNA methylation processes. The results showed a decrease in anti‐dsDNA IgG antibody and in proteinuria levels, less glomerular proliferation and protected renal structures in all mice put on the supplemented diet compared to humanized mice fed with the control diet. The observed therapeutic effect may be related to possible alterations in the methylation level and to targeted suppression of gene expression in the immune cells, which correlate negatively with the development of the clinical SLE characteristics. These findings point to the significant immunomodulating role of methyl donors in human models of SLE and represent new therapeutic opportunities with clinical potential.
International Consensus Guidance for the Management of Glucocorticoid Related Complications in Neuromuscular Disease
Authors: Bacher Corey , Narayanswami Pushpa , Bromberg Mark , Buttgereit Frank , Dodig Dubravka , Flanagan Eoin P. , Gottlieb Chloe , Marshall John K. , McCoy Rozalina G. , Mitchell Sara , Tosh Pritish K. , Sinha Partha S. , Laughlin Ruple S. , Kassardjian Charles D. 
Published: January 2025

ABSTRACTIntroduction/AimsGlucocorticoid (GC)‐related adverse reactions and risks are commonly seen during the treatment of immune‐mediated and inflammatory neuromuscular disorders. There is wide variation in the management of associated complications. The aim of this study is to develop international consensus guidance on the management of GC‐related complications in neuromuscular disorders.MethodsThrough the American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM), an international task force of 15 experts was convened to develop clinical guidance for the management of GC‐related complications in neuromuscular patients. The RAND/UCLA appropriateness method (RAM) was used to develop consensus guidance statements. Initial guidance statements were crafted after a thorough literature review and were modified after anonymous panel input, with up to three rounds of voting via email to achieve consensus.ResultsStatements were developed and achieved consensus for general care, monitoring of patients while on GC, osteoporosis prevention, vaccinations, infection screening, and Pneumocystis jiroveci pneumonia prophylaxis. A multidisciplinary approach to the management of GC‐related complications was emphasized.DiscussionThese formal consensus statements provide guidance to clinicians who use GC in the treatment of neuromuscular diseases regarding prevention and management of the more common associated adverse events and risks that arise with long and short‐term GC use and serve as a springboard for investigation and updates.
Development, Validation, and Usability of a Virtual Game for Consciousness and Relaxation of the Pelvic Floor Muscles
Authors: Souza Robson Arruda , de Moura‐Filho Alberto Galvão , Melo Renato S. , Lemos Andrea 
Published: January 2025

ABSTRACTBackgroundApplicability of the virtual games has been increasingly added to rehabilitation treatments, including women's health interventions.ObjectiveTo develop a virtual interface designed to increase consciousness and relax the pelvic floor muscles, validate its content and appearance, and check the level of usability and satisfaction.MethodsPhysiotherapy specialists with experience in pelvic floor rehabilitation and database research were consulted to define the content. Thus, 13 physiotherapists specialized in the area participated in the content and appearance validation of the virtual game with a minimum agreement level of 80%. An evaluation of the usability level was conducted through MATCH (Checklist for Evaluation of the Usability of Applications for Touchscreen Phones) and the satisfaction level through a visual analog scale.ResultsThe game is presented in two‐dimensional (2D) configuration and is based on parachuting. The main activity required is muscle relaxation to open the parachute and descend to the target. The goal is to reach the target by traveling as long as possible with the parachute open. A physical exercise protocol from the American College of Sports Medicine was used to define the contraction/relaxation time. A total of 4 of the 15 items which represented the content and appearance for validation needed a second round to reach the desired level of agreement. The game showed a high level of usability M: 63.04 (±5.28) and the level of satisfaction of the virtual game showed an average of 9.7 (±0.55).ConclusionThe virtual game developed for the pelvic floor muscle relaxation training showed content validity and adequate appearance and a high level of usability and satisfaction.
Buccal Mucosal Graft as a Second Layer in the Vaginal Repair of Vesicovaginal Fistulas
Authors: Taha Kareem M. , Mohamed Mohamed Ismail , Desoky Esam , Seleem Mohammed M. , Fawzi Amr M. 
Published: January 2025

ABSTRACTObjectiveVesicovaginal fistula (VVF) is a pathological communication between the urinary bladder and the vagina. The most common cause of VVF is hysterectomy, while less common causes include obstetric trauma and pelvic surgery. Most cases require surgical intervention. Although various techniques have been described for the management of VVF, none has been considered the gold standard of management. In this study, we describe our technique using buccal mucosal graft (BMG) as a second layer in the repair of VVF through a vaginal approach.MethodsA total of 10 patients underwent surgery between May 2023 and December 2023. Patients were scheduled for follow‐up 3 weeks after surgery or earlier for any new symptoms of urinary incontinence, overactive bladder, or dysuria. Before catheter removal, a CT cystogram was performed to confirm fistula closure. Additional follow‐up visits were scheduled at 3‐6 months after repair to assess outcome.ResultsTen patients with a mean age of 35.7 ± 7.18 years were operated with the described technique. All patients had no recurrence of the fistula at the 6‐month follow‐up. None of them had additional morbidity due to the procedure. There were no post‐operative complications.ConclusionsAlthough the success rates of simple VVF are very high, the interposition of a tissue graft between the bladder and the vagina is required in the treatment of VVF, especially in those recurrent, large complex and radiation‐induced fistulas. The buccal mucosa has a thick epithelium that provides strength to the graft and a thin submucosa that is important for revascularization, so its use as a second layer in VVF repair may be beneficial. Its harvesting is a relatively simple procedure. It is not time‐consuming and is associated with low morbidity compared to Martius flap harvesting.
Enhancing Efficiency in Multiscale Simulation: Comparing a Lagrange Multiplier Based Approach and a Weak Staggered Coupling With Optional SPML Interface for Wave Propagation
Authors: Grunwald Christoph , Sauer Martin , Stolz Alexander , Hiermaier Stefan 
Published: January 2025

ABSTRACTThe representation of material failure due to wave propagation is essential for the numerical analysis of engineering structures under high dynamic loading. Explicit time integration schemes are well established for this kind of application. In order to realistically model the failure of certain material classes, it is necessary to resolve lower scale features accurately. Concurrent multiscale approaches are therefore well suited to this task. However, they are often complex and computationally demanding. The introduction of interfaces between disparately meshed domains may additionally lead to emerging reflections for waves that contain high frequencies, which the coarse domain cannot resolve. In this article, we compare accuracy, computational efficiency, versatility, and effort for two finite element implementations of concurrent two‐scale schemes. Both offer the possibility of adding a Selected Perfectly Matched Layer (SPML) to dampen incompatible frequencies. One approach is the widely used conventional Lagrange multiplier (LM) approach; the second is a weak staggered (WS) coupling, which was designed to maintain direct solution schemes' efficiency with explicit time integration and diagonal mass matrices. It turns out that, for typical discretizations, the WS coupling achieves an accuracy comparable to the LM coupling but requires fewer computational operations and, relevant for parallel computer architectures, significantly less communication efforts. Adaptive changes of interface topology, for example, due to explicitly resolved cracks crossing the interface, can easily be represented in the WS approach, making it a suitable candidate for the application in scenarios where gross damage is expected.
Changes in abdominal adipose tissues and ectopic fat depots during pregnancy are dissociated from gestational weight gain
Authors: Mogensen Christina Sonne , Magkos Faidon , Chabanova Elizaveta , Mølgaard Christian , Geiker Nina Rica Wium 
Published: January 2025

AbstractObjectiveThe study objective was to evaluate changes in abdominal adipose tissue and ectopic fat during pregnancy and their associations with gestational weight gain (GWG) in women with overweight/obesity.MethodsThis study was a secondary analysis of a randomized controlled trial. Magnetic resonance scans were performed during gestational week (GW) 15, GW 32, and around birth to measure abdominal subcutaneous (SAT) and visceral (VAT) adipose tissues, liver fat, and muscle fat. Linear mixed models and multivariable linear regression analyses were utilized, adjusting for prepregnancy BMI, parity, and randomization.ResultsAmong 119 women, VAT and SAT decreased from GW 15 to GW 32 but rebounded at birth; final levels were lower than at GW 15. Liver fat and muscle fat did not change significantly. GWG was positively associated with changes in SAT but not with those in VAT, liver fat, or muscle fat.ConclusionsThis study demonstrates dynamic changes in abdominal fat depots during pregnancy in women with overweight/obesity. The observed reduction in VAT and SAT during pregnancy and the association of GWG with SAT suggest that weight gain during pregnancy may be less metabolically harmful than outside pregnancy. Future research should investigate the mechanisms and long‐term effects on maternal and child health.
Biotène Versus HydraSmile for Radiation‐Induced Xerostomia: Randomized Double‐Blind Cross‐Over Study
Authors: Harley Randall J. , Bowers Eve , Li Jinhong , Bisignani Mikayla , Nilsen Marci L. , Johnson Jonas T. 
Published: January 2025

AbstractObjectiveThis study aims to compare the effectiveness of 2 artificial saliva substitutes (Biotène vs HydraSmile) in the symptomatic management of radiation‐induced xerostomia.Study DesignRandomized double‐blind cross‐over study.SettingSingle tertiary care academic institution.MethodsIncluded adult patients 6 months postradiotherapy (50‐70 gy) for squamous cell carcinoma of the oral cavity, oropharynx, or larynx. The primary endpoint was change in overall subjective xerostomia score from baseline, through use of HydraSmile versus Biotène. Scores were derived from a 100‐point visual analog scale, with higher scores indicating better symptomatic control. Analysis of covariance model was used to regress the difference in after‐treatment measurement between HydraSmile and Biotène, with respect to baseline differences.ResultsA total of 91 participants were included (mean age 63.0 years [SD 9.7]; 85.7% male; 97.8% White). Change in overall xerostomia score with respect to baseline was not significantly different between HydraSmile and Biotène (mean difference 1.24, 95% confidence interval [CI] −2.35 to 4.81). Compared to water alone, both HydraSmile (mean difference 7.45, 95% CI 3.61‐11.29) and Biotène (mean difference 7.24, 95% CI 3.06‐11.43) significantly improved overall xerostomia score. Forty (44%) patients reported a preference for Biotène, 46 (50.5%) preferred HydraSmile, and 5 (5.5%) had no preference. Patients who preferred Biotène did not significantly benefit from HydraSmile, whereas those who preferred HydraSmile did not significantly benefit from Biotène.ConclusionBiotène and HydraSmile significantly improved oral dryness among patients with radiation‐induced xerostomia. While neither product demonstrated treatment superiority, individual product preference was predictive of greatest treatment benefit.
Safety of electroconvulsive therapy in the context of physiological and medical complexity: A state‐of‐the art review
Authors: Elias Alby , Das Soumitra , Kirkland James , Loyal Sarabjit , Thomas Naveen 
Published: January 2025

AbstractMedical contraindications and complications pose challenges for electroconvulsive therapy (ECT). Most published reports are scattered across various physiological systems and individual disease conditions. This review aimed to evaluate the literature on physiological and medical complexities during ECT and discuss risk mitigation strategies in a comprehensive review. We searched PubMed and Embase for contraindications and precautions during ECT with relevant MeSH terms and appraised previous reviews on the same topic. The results suggest that mortality directly attributed to ECT is extremely rare. Instances of fatalities, including fetal deaths, have been reported after ECT in the presence of recent myocardial infarction, deep vein thrombosis, intracranial aneurysm and tumors, pheochromocytoma, sepsis, and pregnancy. However, there are no definite conclusions or consensus on attributions of the outcomes to ECT in all cases because of the time lag between the treatment and deaths and confounding factors. The risks can be mitigated with safety protocols, adequate stakeholder communication, collaboration with anesthetists and specialists, consultation‐liaison services, and ECT education. Overall, ECT remains a relatively safe treatment even in the presence of medical and physiological complexities. In rare instances, certain medical conditions may indicate a high risk for ECT, where practitioners avoid the treatment or administer it with precautions if the risk‐benefit ratio favors its use.