bluuebunny/crossref_metadata_2025 huggingface dataset:
Guided Self‐Help Treatment for Children and Young People With Eating Disorders: A Proof‐Of‐Concept Pilot Study
Authors: Davey Emily , Bryant‐Waugh Rachel , Bennett Sophie D. , Micali Nadia , Baudinet Julian , Konstantellou Anna , Clark‐Stone Sam , Green Amelia , Shafran Roz
Published: January 2025

Objective

To conduct a proof‐of‐concept pilot study of a CBT guided self‐help intervention for children and young people with eating disorders.

Method

Children and young people were recruited from two outpatient eating disorder services in England. They received a CBT guided self‐help intervention consisting of eight modules and weekly support sessions. Clinical outcomes (eating disorder psychopathology and associated impairment, changes in %median BMI, depression, anxiety, and behavioural difficulties) were assessed at baseline and post‐intervention (12 weeks). Qualitative data were collected for future intervention refinement.

Results

Six female adolescents (aged 13–17) received the CBT guided self‐help intervention. All participants completed a minimum of six modules and six support sessions. Quantitative and qualitative feedback suggested that the intervention was acceptable. From baseline to post‐intervention, there was a reduction in eating disorder psychopathology and impairment, along with an increase in %median BMI. Outcomes for depression, anxiety and behavioural difficulties were mixed.

Conclusions

The CBT guided self‐help intervention was feasibly implemented, acceptable to participants, and showed potential to produce clinical benefits. While promising, these findings are preliminary and derived from a small, non‐randomised sample of White female adolescents. More rigorous evaluation with a randomised design and a larger, representative sample is warranted.
Using Family History Data to Improve the Power of Association Studies: Application to Cancer in UK Biobank
Authors: Wilcox Naomi , Tyrer Jonathan P. , Dennis Joe , Yang Xin , Perry John R. B. , Gardner Eugene J. , Easton Douglas F.
Published: January 2025

In large cohort studies the number of unaffected individuals outnumbers the number of affected individuals, and the power can be low to detect associations for outcomes with low prevalence. We consider how including recorded family history in regression models increases the power to detect associations between genetic variants and disease risk. We show theoretically and using Monte‐Carlo simulations that including a family history of the disease, with a weighting of 0.5 compared with true cases, increases the power to detect associations. This is a powerful approach for detecting variants with moderate effects, but for larger effect sizes a weighting of > 0.5 can be more powerful. We illustrate this both for common variants and for exome sequencing data for over 400,000 individuals in UK Biobank to evaluate the association between the burden of protein‐truncating variants in genes and risk for four cancer types.
Safety and efficacy of a pharmacist‐driven protocolized transition from insulin infusion to subcutaneous insulin in patients undergoing cardiothoracic surgery
Authors: Bird Shaina A. , Thuyns Michael R.
Published: January 2025

Introduction

Few validated approaches exist for the transition from intravenous (IV) insulin infusion to subcutaneous (SQ) insulin post‐operatively in cardiothoracic surgery patients.

Objective

This study aimed to assess whether a pharmacist‐driven protocol utilizing basal, prandial, correctional, or correctional‐only SQ insulin is safe and efficacious for post‐operative glycemic control following 24 h of IV insulin administration.

Methods

A retrospective, single‐center, observational study investigating outcomes associated with a pharmacist‐driven protocol utilizing basal, prandial, correctional, or correctional‐only insulin from May 2023 through July 2023 when compared with a historical nursing‐driven protocol observed from May 2021 through July 2021. Adult cardiac intensive care unit patients who received an insulin infusion within 24 h of cardiothoracic surgery and subsequently transitioned to SQ insulin were observed. The primary outcome was percentage of blood glucose (BG) readings at goal (140–180 mg/dL). Secondary outcomes included percentage of BG readings in a clinically acceptable range (110–180 mg/dL), hypoglycemia (<70 mg/dL), severe hypoglycemia (<40 mg/dL), administration of rescue dextrose, reinitiation of insulin infusion following transition, and surgical site infection.

Results

Use of a pharmacist‐driven protocol improved the percentage of BG readings in goal range when compared with a nursing driven protocol (24.4% vs. 12.4%, p = 0.001). More BG readings were in the clinically acceptable range in the pharmacist‐driven group: 69.6% of readings versus 58.5% in the nursing‐driven group (p = 0.011). There were fewer hypoglycemic events in the pharmacist‐driven group. There were no reports of severe hypoglycemia, further IV insulin requirements, or surgical site infections in either group. Pharmacist compliance to the protocol was high at 92.4%.

Conclusions

A pharmacist‐driven protocolized approach to the transition to SQ insulin post‐operatively in cardiothoracic patients is both safe and efficacious. The pharmacist‐driven protocol resulted in an improved percentage of BG readings in goal range and fewer hypoglycemic events when compared with the historical nursing‐driven protocol.
Real‐world observations of using compounded GLP‐1 ± GIP agonists within a clinical pharmacist‐managed cardiometabolic clinic
Authors: Finks Shannon W. , Benavides Diego , Martin Andrea G. , Carmon Alex S.
Published: January 2025

Introduction

The long‐acting glucagon‐like peptide‐1 (GLP‐1) agonist semaglutide and the GLP‐1/glucose‐dependent insulinotropic polypeptide (GIP) agonist tirzepatide have demonstrated efficacy in reducing cardiometabolic risk factors in individuals with diabetes and obesity. Popularity of these agents has led to increased demand, even among patients with cardiometabolic risk factors beyond type 2 diabetes mellitus (T2DM). The growing demand and supply chain disruptions have resulted in a shortage of therapies. As a direct consequence, patients are exploring alternative options including compounded GLP‐1 ± GIP formulations.

Objective

This study reports real‐world observations on the safety and efficacy of compounded semaglutide and tirzepatide within a clinical pharmacist‐managed cardiometabolic clinic.

Methods

This retrospective cohort included 50 patients with cardiometabolic risk who had received a prescription for compounded GLP‐1 ± GIP therapy between July 2022 and July 2023. Observations were reported for this cohort with changes from baseline to 12 weeks and out to 24 weeks. Primary outcomes were changes in weight/body mass index (BMI) and hemoglobin A1c (HbA1c). Secondary outcomes included changes in waist circumference, blood pressure, triglyceride levels, inflammatory markers, medication adherence, and the incidence of adverse events and/or dropout rates.

Results

Fifty patients (18 males and 32 females) completed the 12‐week follow‐up, with an additional subset of patients (n = 40) continuing to 24 weeks of therapy. The average weight loss observed at 12 weeks was 16.06 ± 7.6 pounds (p = 0.001) and 38.82 ± 11.4 pounds at 24 weeks. HbA1c decreased on average from 5.5 ± 0.3 at baseline to 5.3 ± 0.3 at 12 weeks (p < 0.0001) and to 5.2 ± 0.027 (p < 0.001) at 24 weeks. All secondary cardiometabolic outcomes improved significantly throughout the study.

Conclusion

This study demonstrates a significant positive impact on cardiometabolic outcomes from utilizing compounded GLP‐1 ± GIP agonists when branded products could not be obtained. These observations also support the use of compounded GLP‐1 ± GIP agonists under pharmacist supervision as an alternative during drug shortages.
Thymoquinone and Metabolic Reprogramming in Breast Cancer: A New Dimension From Proteomic Analysis
Authors: Korak Tuğcan , Bal Albayrak Merve Gulsen , Kasap Murat , Akpinar Gurler
Published: January 2025

Thymoquinone (TQ) has shown antitumorigenic effects in breast cancer; however, its detailed impact on cell signaling mechanisms requires further investigation. This study aims to elucidate the molecular mechanisms behind TQ's antiproliferative effects in breast cancer by analyzing proteome‐level changes. MCF‐7 cells were treated with 15 µM TQ, the inhibitory concentration (IC50), for 48 h. Proteins from treated and untreated (control) groups were isolated and subjected to liquid chromatography–tandem mass spectrometry (LC–MS/MS) proteomic analysis. Identified proteins were functionally annotated, with hub proteins identified using Cytoscape software, and verification conducted through Western blot analysis. Label‐free quantitation identified 629 master proteins, with 104 upregulated and 477 downregulated in TQ‐treated samples compared to controls. Among these, 150 proteins showed dramatic regulation, including 11 upregulated and 139 downregulated proteins, with ribosomal proteins emerging as central. The heatmap demonstrated robust clustering of replicates. Functional annotations indicated that TQ significantly impacts crucial mechanisms such as carbon metabolism, amino acid biosynthesis, protein synthesis, and the citrate cycle, essential for metabolic reprogramming. This study identifies novel molecular targets associated with metabolic reprogramming, previously underexplored in TQ's effects, highlighting their pivotal role in TQ's anticancer mechanisms in breast cancer. These findings could lay the groundwork for developing future TQ‐based therapies.
Structural Dynamics of Neutral Amino Acid Transporter SLC6A19 in Simple and Complex Lipid Bilayers
Authors: Dehury Budheswar , Mishra Sarbani , Panda Sunita , Singh Mahender Kumar , Simha Nischal L. , Pati Sanghamitra
Published: January 2025

B0AT1 (SLC6A19) is a major sodium‐coupled neutral amino acid transporter that relies on angiotensin converting enzyme 2 (ACE2) or collectrin for membrane trafficking. Despite its significant role in disorders associated with amino acid metabolism, there is a deficit of comprehensive structure‐function understanding of B0AT1 in lipid environment. Herein, we have employed molecular dynamics (MD) simulations to explore the architectural characteristics of B0AT1 in two distinct environments: a simplified POPC bilayer and a complex lipid system replicating the native membrane composition. Notably, our B0AT1 analysis in terms of structural stability and regions of maximum flexibility shows consistency in both the systems with enhanced structural features in the case of complex lipid system. Our findings suggest that diacylglycerol phospholipids significantly alter the pore radius, hydrophobic index, and surface charge distribution of B0AT1, thereby affecting the flexibility of transmembrane helices TM7, TM12, and loop connecting TM7‐TM8, crucial for ACE2‐B0AT1 interaction. Pro41, Ser190, Arg214, Arg240, Ser413, Pro414, Cys463, and Val582 are among the most prominent lipid binding residues that might influence B0AT1 functionality. We also perceive notable lipid mediated deviation in the degree of tilt and loss of helicity in TM1 and TM6 which might affect the substrate binding sites S1 and S2 in B0AT1. Considerably, destabilization in the structure of B0AT1 in lipid environment was evident upon mutation in TM domain, associated with Hartnup disorder through various structure‐based protein stability tools. Our two‐tiered approach allowed us to validate the use of POPC as a baseline for initial analyses of SLC transporters. Altogether, our all‐atoms MD study provides a platform for future investigations into the structure‐function mechanism of B0AT1 in realistic lipid mimetic bilayers and offers a framework for developing new therapeutic agents targeting this transporter.
Significant Association Between Genetic Polymorphism of Insulin‐Like Growth Factor‐2 mRNA Binding Protein‐2 and Type 2 Diabetes Mellitus: A Population‐Based Case–Control Study
Authors: Elssaig Elmutuz H. , Ahmed‐Abakur Eltayib H. , Alnour Tarig M. S. , Alsubai Mohammed A. , Ali Abdalla Eltoum , Ullah Mohammad Fahad , Saeedi Nizar H. , Alenzi Fahad Daefalah
Published: January 2025

Objectives

To determine the association between IGF2BP2 polymorphisms and type 2 diabetes mellitus.

Methods

This study involved 422 individuals, 214 diabetes mellitus cases, and 208 healthy controls. The PCR‐RFLP technique was used to determine the genotype of the IGF2BP2 gene for the SNPs rs4402960 (G>T) and rs1470579 (A>C).

Results

The results showed that the C allele of the rs1470579 variant and the T allele of the rs440960 variant were significantly associated with type 2 diabetes mellitus group (p = 0.0029 and 0.0001) as reported for both alleles, respectively. High frequencies of haplotypes TA and TC were observed in type 2 diabetes patients.

Conclusion

The present study showed that IGF2BP2 rs1470579 and rs4402960 polymorphism were significantly associated with the increased risk of T2DM in the Saudi Arabian population and presented a genetic model to screen the high‐risk individuals with further validations.
The Experiences of Hijab and Non‐Hijab‐Wearing Muslim Women Students: Exploring Social Isolation and Discrimination in Delhi, India
Authors: Khan Farhat , Kohli Simran , Potsangbam Eileen , Kharshiing Korsi Dorene
Published: January 2025

Research suggests that Muslim women wearing the hijab may be particularly vulnerable to the experiences of stigmatization as the hijab represents a dominant marker of “otherness.” Using the relational demography perspective, this paper explored the viewpoints of hijab and non‐hijab‐wearing Muslim women in Delhi regarding the different forms of discrimination and/or social isolation they may have experienced. Thematic analysis was used to explore the participant's narratives, gathered by means of six focus group discussions (n = 38). For the hijab‐wearing group, two emergent themes were evident: “Journey of my hijab” and “The two sides of the hijab.” For the non‐hijab‐wearing group, the emergent themes included: “My name is (un)safe” and “Not Muslim enough.” The study findings can inform the development of intervention strategies to integrate the community more meaningfully by preventing “othering” and providing agency and autonomy.
Advances in Aggrephagy: Mechanisms, Disease Implications, and Therapeutic Strategies
Authors: Zhuang Haixia , Ma Xinyu
Published: January 2025

The accumulation of misfolded proteins within cells leads to the formation of protein aggregates that disrupt normal cellular functions and contribute to a range of human pathologies, notably neurodegenerative disorders. Consequently, the investigation into the mechanisms of aggregate formation and their subsequent clearance is of considerable importance for the development of therapeutic strategies. The clearance of protein aggregates is predominantly achieved via the autophagy‐lysosomal pathway, a process known as aggrephagy. In this pathway, autophagosome biogenesis and lysosomal digestion provide necessary conditions for the clearance of protein aggregates, while autophagy receptors such as P62, NBR1, TAX1BP1, TOLLIP, and CCT2 facilitate the recognition of protein aggregates by the autophagy machinery, playing a pivotal role in their degradation. This review will introduce the mechanisms of aggregate formation, progression, and degradation, with particular emphasis on advances in aggrephagy, providing insights for aggregates‐related diseases and the development of novel therapeutic strategies.
KIF18A Is a Novel Target of JNK1/c‐Jun Signaling Pathway Involved in Cervical Tumorigenesis
Authors: Wang Yajie , Zhou Bowen , Lian Xiaoying , Yu Siqi , Huang Baihai , Wu Xinyue , Wen Lianpu , Zhu Changjun
Published: January 2025

Cervical cancer remains a significant global health concern. KIF18A, a kinesin motor protein regulating microtubule dynamics during mitosis, is frequently overexpressed in various cancers, but its regulatory mechanisms are poorly understood. This study investigates KIF18A's role in cervical cancer and its regulation by the JNK1/c‐Jun signaling pathway. Cell growth was assessed in vitro using MTT and colony formation assays, and in vivo using a nude mouse xenograft model with KIF18A knockdown HeLa cells. The Genomic Data Commons (GDC) data portal was used to identify KIF18A‐related protein kinases in cervical cancer. Western blot analysis was employed to analyze phosphor‐c‐Jun, c‐Jun, and KIF18A expression levels following JNK1 inhibition, c‐Jun knockdown/overexpression, and KIF18A knockdown in cervical cancer cells. Chromatin immunoprecipitation (ChIP) and luciferase reporter assays were performed to assess c‐Jun binding and transcriptional activity of the KIF18A promoter. KIF18A knockdown significantly impaired cervical cancer cell growth both in vitro and in vivo. A strong positive correlation was observed between JNK1 and KIF18A expression in cervical and other cancers. JNK1 inhibition decreased both KIF18A expression and c‐Jun phosphorylation. c‐Jun was found to directly bind to and activate the KIF18A promoter. Furthermore, c‐Jun knockdown inhibited cervical cancer cell growth, and this effect was partially rescued by KIF18A overexpression. This study demonstrates that the JNK1/c‐Jun pathway activates KIF18A expression, which is essential for cervical cancer cell growth. Targeting the JNK/c‐Jun/KIF18A axis may represent a promising novel therapeutic strategy for cancer treatment.
Virtual triple‐bundle ACL graft via femoral tunnels behind the resident's ridge on 3D CT demonstrates equivalent orientation to native ACL
Authors: Okazaki Narihiro , Shino Konsei , Yokoi Hiroyuki , Ohori Tomoki
Published: January 2025

Purpose

To clarify the femoral tunnel location for a virtual anterior cruciate ligament (ACL) graft to simulate the native ACL.

Methods

Three‐dimensional (3D) computed tomography (CT) and magnetic resonance imaging (MRI) were obtained in 14 normal knees in full extension. Two types of virtual triple bundle ACL grafts (VACLG) were created. In one type, the femoral tunnels for anteromedial bundle (AM = AMM/anteromedial bundle medial part + AML/anteromedial bundle lateral part) and posterolateral bundle (PL) were positioned behind the resident's ridge (RR) based on the bone landmark strategy (BR‐VACLG group). In the other type, the tunnels were placed on the RR (OR‐VACLG group). VACLG was displayed as three straight lines by connecting the two centres of the femoral attachment areas of AM and PL to those of the three tibial footprints of AMM, AML and PL attachments on 3D CT, and then superimposed on MRI. The ACL/ACL graft‐the tibial plateau (ACL‐TP) angles were compared among normal ACL (N‐ACL), BR‐VACLG and OR‐VACLG.

Results

The mean ACL‐TP angles of N‐ACL, BR‐VACLG and OR‐VACLG were 74.4 ± 3.4°, 75.2 ± 4.5° and 68.7 ± 5.0° for AMM, 81.9 ± 3.8°, 82.9 ± 5.1° and 76.3 ± 4.0° and for AML, 71.1 ± 6.4°, 70.0 ± 7.2° and 61.0 ± 4.7° for PL on the oblique‐coronal slices; 55.3 ± 4.9° 53.9 ± 4.4° and 50.5 ± 4.3° for AMM; 54.9 ± 4.5°, 54.7 ± 2.6° and 50.7 ± 3.2° for AML; 51.4 ± 3.3°, 51.2 ± 2.4° and 48.1 ± 2.0° for PL on the oblique‐sagittal slices. There was no significant difference in the angles between N‐ACL and BR‐VACLG, while those of AMM and PL in OR‐VACLG were significantly lower compared to N‐ACL.

Conclusion

The virtual triple bundle ACL graft via femoral tunnels behind the RR on 3D CT shows equivalent orientation to the native ACL on MRI in full extension.

Level of Evidence

Level III.
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

Introduction

Long‐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.

Methods

Participants 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.

Results

Fifty‐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.

Conclusions

CAB‐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

A 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

The 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

Background

Genomic variations associated with dystonia in Asian Indians remain largely unknown.

Objectives

To identify genomic alterations associated with dystonia in the Asian Indian population using next generation sequencing approaches.

Methods

From 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).

Results

The 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.

Conclusion

THAP1 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

Systemic 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

Introduction/Aims

Glucocorticoid (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.

Methods

Through 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.

Results

Statements 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.

Discussion

These 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

Background

Applicability of the virtual games has been increasingly added to rehabilitation treatments, including women's health interventions.

Objective

To 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.

Methods

Physiotherapy 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.

Results

The 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).

Conclusion

The 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

Objective

Vesicovaginal 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.

Methods

A 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.

Results

Ten 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.

Conclusions

Although 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

The 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

Objective

The 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.

Methods

This 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.

Results

Among 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.

Conclusions

This 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

Objective

This study aims to compare the effectiveness of 2 artificial saliva substitutes (Biotène vs HydraSmile) in the symptomatic management of radiation‐induced xerostomia.

Study Design

Randomized double‐blind cross‐over study.

Setting

Single tertiary care academic institution.

Methods

Included 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.

Results

A 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.

Conclusion

Biotène 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

Medical 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.
Gifted Identification Inventory for Teacher Awareness: Development, Validation, and Measurement Invariance
Authors: Özbaşi Durmuş , Yilmaz Defne
Published: January 2025

The purpose of this study is to develop a self‐awareness tool for teachers to help them in identification, and support the gifted and talented students in educational settings via more accurate nominations by educators. The Gifted Identification Inventory for Teacher Awareness (GIIFTA) was developed via fourth stages of writing essay (n = 5), Delphi method (n = 10), the exploratory factor analysis (EFA) (n = 273), and the confirmatory factor analysis (CFA) (as a different group from EFA, n = 286). The construct of GIIFTA consists of 22 items in three dimensions with a 5‐point Likert scale. The three dimensions of the inventory are: Noticing the Gifted Students, Distinguishing Cognitive Traits, and Distinguishing Emotional Social Traits. The fit index values of the CFA analysis were calculated (χ2/SD = 2.65; GFI = 0.86; CFI = 0.92; IFI = 0.86; NFI = 0.88; NNFI = 0.91; SRMR = 0.05 and RMSEA = 0.07). In addition, convergent and divergent validity were also examined and found to be within acceptable limits. The measurement invariance of the emerging dimensions was also examined in terms of gender variable and it was found that the structure did not change. The item‐total correlation values of the items in the measurement tool ranged from 0.51 to 077. Its structure does not change by gender. The reliability coefficients for the entire scale were calculated to range from 0.88 to 0.95. These results indicate that GIIFTA has good psychometric properties to assess teachers' awareness of gifted students in their classrooms.
Factors Influencing Body Image Among Chinese Secondary School Students: A Mixed Methods Approach
Authors: Liu Fangfang , Chen Fu , Li Guang , Li Xiaofei
Published: January 2025

This study aims to assess the current physical health status and levels of body image satisfaction among Chinese secondary school students and identify the influencing factors of student body image perception. Guided by a mixed‐methods research design, data was obtained through collecting 903 secondary student questionnaires and interviewing 15 students. The results identified various factors that influence the body image of Chinese secondary school students, including personal growth, academic stress, peers, families, and social media. However, there are no significant differences in the overall perception of body image between students of different grades or between males and females. The findings of this study can provide valuable insights for individuals, families, schools, and society, with the intention of assisting Chinese adolescents in cultivating positive body images, enhancing self‐satisfaction, and fostering a healthy state of mind and body. The findings hold significant implications for promoting overall well‐being and fostering a better future for secondary school students.
Mechanical properties of hemp fiber‐reinforced thermoset and thermoplastic polymer composites: A comprehensive review
Authors: Islam Shahidul , Hasan Md. Byzed , Kodrić Marija , Motaleb K. Z. M. Abdul , Karim Fahmida‐E‐ , Islam Md. Redwanul
Published: January 2025

Hemp fibers have mechanical characteristics similar to those of synthetic fibers, which makes them an attractive material for producing environmentally friendly composites. Hemp fibers have excellent mechanical properties and a unique hydrophilicity, requiring for extra attention in composite formulations. Hemp fibers are a very versatile vegetable fiber that is frequently utilized in structural composites. In addition, hemp has shown potential in a variety of other fields, including as sports goods, building, and lighter materials. The present article aims to give a comprehensive summary of the status of sophisticated studies in hemp fiber reinforced composites at present time. The most important research on thermoset and thermoplastic materials reinforced with hemp fiber is compiled and discussed in this publication. This document also provides an overview of the primary attributes of hemp fibers, talks about how to develop these attributes chemically, explains how to create and describe hemp fiber composites, and identifies areas that need more research. In summary, this study ends with several important recommendations and future approaches that draw attention to the issues that require further investigation and potential industrialization of composites.

Highlights

Advances in hemp fiber extraction and chemical treatments.

Performance traits of hemp‐reinforced thermoset and thermoplastic composites.

Tribological, and moisture absorption properties of hemp fiber composites.

SEM analysis revealing composite structural characteristics.

Future applications and sustainability of hemp fiber in polymers.