bluuebunny/crossref_metadata_2025_split huggingface dataset:
Practical solutions to resolve social barriers to hepatitis C treatment initiation among people who inject drugs: a qualitative study
Authors: Aung Phyo , Hellard Margaret , Dietze Paul , Petrovic Bek , Higgs Peter , Stoové Mark 
Published: December 2024

Abstract
Background
We aimed to identify motivators for people who inject drugs to pursue treatment for hepatitis C virus (HCV) infection and uncover opportunities that could make treatment more appealing.

Methods
Between November 2023 and January 2024, we conducted semi-structured interviews with 15 HCV RNA-positive individuals with a history of injecting drug use and self-reported as either untreated or treated but delayed treatment for more than 6 months. Thematic and framework data analysis was employed and interpreted using the Capability, Opportunity and Motivation (COM-B) framework of behaviour change.

Results
The findings suggest that a combination of stability through secure housing, mental readiness and overcoming drug dependence supported by OAT (Capability), accessible and convenient healthcare like mobile outreach services coupled with financial incentives (Opportunity), and supportive relationships (Motivation) could serve to help people who inject drugs take up HCV treatment.

Conclusion
Alcohol and other drug and primary care services for people who use drugs should adopt person-centred approaches and recognise the gradual nature of behavioural change to foster empathy and supportive relationships to promote engagement in HCV care. Additionally, integrating HCV treatment with mobile outreach services and providing practical assistance, such as housing and financial incentives, are critical to ensuring that individuals remain engaged in HCV care.
Developing an ethical framework for the recruitment of people who inject drugs experiencing incarceration in HIV prevention research: a qualitative study
Authors: Murphy Matthew , Gomes Nyx , Kane Kimberly , Rich Josiah D. , Goldsamt Lloyd , Ahluwalia Jasjit S. , Guthrie Kate M. , Ramsey Susan E. , Vargas Sara 
Published: December 2024

Abstract
Background
HIV disproportionately impacts people who experience incarceration. Incarceration represents an opportunity to engage in HIV prevention care for individuals who often experience a number of barriers accessing health services in the community. The development of evidence-based practices promoting pre-exposure prophylaxis for HIV prevention (PrEP) is crucial for ending the HIV epidemic within this highly marginalized population. However, PrEP research within carceral facilities has been limited and is hampered in part by the lack of ethical guidance on conducting HIV prevention research in this unique setting where incarcerated individuals are categorized as a vulnerable population requiring specific protections. This lack of knowledge is particularly striking when considering the lack of input from incarcerated individuals themselves on the responsible conduct of research, which is critical to understanding ways to ensure participant autonomy while avoiding coercive practices in research activities.

Methods
In order to gain a better understanding of ethical approaches to the conduct of HIV prevention research among incarcerated individuals, we conducted qualitative interviews with 21 incarcerated men who reported injecting drugs and met clinical criteria for PrEP use. The interview topics included HIV knowledge, PrEP knowledge, stigma, and perceptions related to ethical research practices.

Results
Themes identified included how forced abstinence during incarceration can negatively affect research participation, the importance of participant comfort as it relates to ensuring autonomy in decision making, a desire for person centred approaches in research activities, study staff characteristics impacting participant experience, and perceptions of carceral staff as members of research teams.

Conclusions
The results of this study indicate that conducting research focused on improving PrEP use in a carceral environment has support among those experiencing incarceration. However, researchers should place the participant experience at the center of research protocol development.
Prognostic impact of lymphovascular invasion in node-negative gastric cancer: a retrospective cohort study
Authors: Alangari Abdullah Ibrahim , Kim Sojung , Lee Han Hong , Song Kyo Young , Seo Hoseok 
Published: December 2024

Abstract
Background
Lymphovascular invasion (LVI) has been identified as a prognostic factor in various cancers, but its significance in node-negative gastric cancer remains unclear. Gastric cancer prognosis is notably affected by lymph node metastasis, with LVI potentially indicating metastatic spread.

Methods
A retrospective review was conducted on 5,699 patients who underwent curative radical gastrectomy for gastric cancer between 1989 and 2018. The median follow-up duration was 62 months (0–362 months). Overall, disease-specific, and disease-free survival were compared based on LVI status and stratified by T stage. Additionally, patients with stage IIA or T2N0 were further evaluated to clarify the clinical significance of LVI in the T2N0 group.

Results
The T2N0 LVI-positive group exhibited significantly poor prognosis than those in the T2N0 LVI-negative group, with no significant differences observed on comparing the T2N0 LVI-positive group with the T2N1 LVI-negative or LVI-positive groups. Furthermore, although the T2N0 LVI-negative group demonstrated better prognosis compared to the IIA group, the T2N0 LVI-positive group exhibited worse survival. In addition, LVI positivity was an independent risk factor for overall survival in T2N0 patients.

Conclusions
LVI in node-negative gastric cancer has clinical significance as a prognostic indicator, indicating an increased risk of disease recurrence and poor survival especially in T2 cohort. This indicates an increased likelihood of lymph node involvement and may influence treatment decisions and follow-up strategies.
From bench to bedside: cutting-edge applications of base editing and prime editing in precision medicine
Authors: Xu Weihui , Zhang Shiyao , Qin Huan , Yao Kai 
Published: December 2024

AbstractCRISPR-based gene editing technology theoretically allows for precise manipulation of any genetic target within living cells, achieving the desired sequence modifications. This revolutionary advancement has fundamentally transformed the field of biomedicine, offering immense clinical potential for treating and correcting genetic disorders. In the treatment of most genetic diseases, precise genome editing that avoids the generation of mixed editing byproducts is considered the ideal approach. This article reviews the current progress of base editors and prime editors, elaborating on specific examples of their applications in the therapeutic field, and highlights opportunities for improvement. Furthermore, we discuss the specific performance of these technologies in terms of safety and efficacy in clinical applications, and analyze the latest advancements and potential directions that could influence the future development of genome editing technologies. Our goal is to outline the clinical relevance of this rapidly evolving scientific field and preview a roadmap for successful DNA base editing therapies for the treatment of hereditary or idiopathic diseases.
Clinical and functional characterization of a novel STUB1 mutation in a Chinese spinocerebellar ataxia 48 pedigree
Authors: Li Jiaqi , Xie Wenyi , Chen Jian-Min , Xu Chun-Zuan , Huang Ya-Li , Chen Sheng , Liu Chang-Yun , Lu Ying-Qian , Zou Zhang-Yu 
Published: December 2024

Abstract
Background
Spinocerebellar ataxias (SCAs) encompass a wide spectrum of inherited neurodegenerative diseases, primarily characterized by pathological changes in the cerebellum, spinal cord, and brainstem degeneration. Autosomal dominant spinocerebellar ataxia type 48 (SCA48) is a newly identified subtype of SCA, marked by early-onset ataxia and cognitive impairment, and is associated with mutations in the STIP1 homology and U-box-containing protein 1 (STUB1) gene. The STUB1 gene encodes the protein CHIP (C-terminus of HSC70-interacting protein) which functions as E3 ubiquitin ligase and is crucial to the development of neural systems.

Results
Here, we reported a Chinese SCA48 family exhibited typical features and defined a novel missense mutation STUB1 c.755A>C (CHIP p. Y252S) through whole-exome sequencing. The variant was interpreted as a variant of uncertain significance, so we conducted a series of experiments using minigene plasmids to evaluate the pathogenicity of the variant. We found that the variant STUB1 c.755A>C caused a significant reduction of CHIP level and the loss function of ubiquitin ligase activity as the pathogenic STUB1 mutations reported before. Besides, we also found that the CHIP p. Y252S could cause tau aggregation, which is considered to contribute to the progression of neurodegenerative disorders.

Conclusions
We diagnose the SCA48 pedigree in China and highlight the role of decreased ubiquitination and increased tau aggregation in the pathogenesis of the novel STUB1 c.755C>A mutation.
Glycogen storage disorder types IX: the mutation spectrum and ethnic distribution
Authors: Geramizadeh Bita , Ezgu Fatih , Beyzaei Zahra 
Published: December 2024

AbstractGlycogen storage disorders (GSD) GSD-IX are characterized by deficiencies in muscular and/or hepatic phosphorylase enzymes. GSD type IX za is an X-linked disorder, while IXb and IXc are autosomal recessive disorders resulting from pathogenic variants in the genes encoding the Phosphorylase b Kinase regulatory subunit alpha (PHKA), beta (PHKB), and gamma (PHKG), respectively. Despite progress in understanding these diseases, there are still unclear questions regarding their clinical manifestations, genetic variations, and the relationship between genotype and phenotype. Therefore, this review focuses on variants of GSD IX subtypes and all clinical findings to establish a genotype–phenotype relationship as well as highlighting the wide spectrum of disease-causing variants. Such information is beneficial for the establishment of a privileged mutation screening process in a specific region or ethnic group. Diagnosis is based on clinical manifestations and laboratory test results, but molecular analysis is often necessary to distinguish the various forms with similar presentations.
Ring 18 chromosome associated with cleft palate: case report and comprehensive literature review of clinical symptoms
Authors: Matyskova Dominika , Richtrova Michaela , Novotna Alzbeta , Koskova Olga 
Published: December 2024

Abstract
Background
Ring 18 chromosome is a rare chromosomal aberration associated with a wide range of symptoms affecting all organ systems. One possible symptom associated with this condition is an orofacial cleft. However, to date, there are very few reported cases where the cleft has been surgically treated.

Case Description
In our case study, we present a female patient with Ring 18 chromosome who underwent cleft palate surgery at 14 months of age. Subsequently, a reoperation of the palate was necessary due to wound dehiscence. For the secondary reconstruction of the palate, the acellular dermal matrix (ADM) MatriDerm® was used to improve healing. The cleft palate surgery progressively improved her ability to take in food, allowing a transition from nasogastric tube feeding to oral intake.

Results
This is only the fourth reported case of a child with Ring 18 chromosome undergoing surgical correction of an orofacial cleft. Additionally, it is one of the first cases where an ADM MatriDerm® was used in the surgical correction of a cleft palate. In this study, we also present a comprehensive literature review, providing an overview of the various symptoms associated with this syndrome.

Conclusion
Cleft palate surgery had a very positive effect on improving food intake in the patient with Ring 18 chromosome. The use of an acellular dermal matrix during the secondary cleft palate surgery led to improved healing and a good outcome.
Perioperative methadone compared to placebo in elderly hip fracture patients: a study protocol for a randomized controlled trial (MetaHip trial)
Authors: Nygaard Kevin Heebøll , Strøm Thomas , Specht Kirsten , Petersen Sofie Ronja , Schønnemann Jesper Ougaard 
Published: December 2024

Abstract

Background

Hip fractures are a source of severe pain among the elderly population and pose challenges due to limited analgesic tolerance. Perioperative methadone has shown promise in our pilot study suggesting a safe dose of 0.10 mg/kg, prompting further investigation into its benefits for elderly hip fracture patients.

Methods
This study employs a double-blinded randomized controlled trial to assess the analgesic effects of a single dose of methadone during hip fracture surgery. Patients aged ≥ 60 years are consecutively enrolled and randomized to receive either perioperative methadone (treatment group) or a saline solution (placebo group). A sample size of 130 patients is required for 88% statistical power. The medication is administered intravenously at anesthesia induction and monitored until discharge. A follow-up observation is conducted 3 months post-surgery.

Discussion
Primary outcome: Daily consumption of opioids within the first 3 days after surgery. Secondary outcomes include pain, mobility, nausea, vomiting, time to discharge, need for antidote, delirium, and constipation. The 3-month follow-up includes opioid use, pain, EQ-5D-5L scores, mobility, and persistent side effects. If statistically significant advantages are found in the treatment group, perioperative methadone could be considered as standard care for hip fracture patients, potentially enhancing their pain management. The study’s outcomes will provide insights into the feasibility and effectiveness of incorporating methadone into routine clinical practices for this patient group.

Trial registration
ClinicalTrials.gov ID: NCT06086171, submitted 4. October 2023. EU-CT: 2023–506252-24–00, UTN: U1111-1294–6125.
Exploring Motivation and Barriers to Physical Activity Among Educated Adult Saudi Women at Taif University
Authors: Alajlan Sarah M. , Aljohani Obaidalah H. , Boughattas Wissal 
Published: December 2024

AbstractAlthough physical activity (PA) offers numerous mental and physical health benefits, adult Saudi women face unique social and cultural barriers to participating in PA. This study aimed to explore the motivational factors and obstacles influencing PA participation among adult Saudi women at Taif University. Using Self-Determination Theory (SDT) as the framework, a questionnaire was developed and administered to 706 participants, including students, administrators, and faculty members. Results indicated that psychological motivations were the strongest drivers of PA engagement, while physical and service-related limitations were the primary barriers to regular participation. Notably, women aged 30 to 40 showed a greater inclination toward regular physical activity than other age groups. The results indicate a requirement for focused initiatives and enhancements in infrastructure to overcome obstacles and promote physical activity engagement among women in Saudi Arabia. Further research is needed to validate these findings and to inform strategies for promoting PA among Saudi women.
Electric circuit element boundary conditions for electromagneto-quasistatic and full wave models in A, φ potentials and their finite element implementation
Authors: Ciuprina Gabriela , Sabriego Ruth V. 
Published: December 2024

AbstractElectric Circuit Element (ECE) boundary conditions (BC) defined for full-wave (FW) electromagnetic field allow a natural coupling between field devices and electric circuits. The novelty of this paper is that it shows how ECE BC can be implemented into a 3D-finite element method (FEM), when using A, a magnetic vector potential and φ, a scalar potential. Weak formulations are described and implemented in the free environment Open Numerical Engineering LABoratory(onelab). The validation is carried out on 3D examples solved both in frequency (FD) and time domain (TD), for FW formulations in potentials, as well as for corresponding Darwin approximations of Electromagneto-Quasistatic (EMQS) models. Results are compared with those obtained with a formulation in EV, where E is the electric field inside the domain and V is a scalar potential defined solely on the boundary. The results show that: 1) the use of potentials has some advantages over the EV formulation in TD only; 2) excitation type matters, the voltage excitation, here essential in FEM, proved to be the most robust one for the considered examples: a coplanar waveguide and a spiral inductor.
Single-cell multi-omics analysis reveals candidate therapeutic drugs and key transcription factor specifically for the mesenchymal subtype of glioblastoma
Authors: Yang Yufan , Liu Ziyuan , Wei Yerong , He Shuai , Gu Ancheng , Li Zhiyong , Li Jianlong , Xu Zhongyuan , Cen Bohong 
Published: December 2024

AbstractThe inherent heterogeneity of tumor cells impedes the development of targeted therapies for specific glioblastoma (GBM) subtypes. This study aims to investigate the mesenchymal subtype of GBM to uncover detailed characteristics, potential therapeutic strategies, and improve precision treatment for GBM patients. We integrated single-cell RNA sequencing (scRNA-seq), single-nucleus assay for transposase-accessible chromatin sequencing (snATAC-seq), and bulk RNA sequencing datasets to identify core gene modules, candidate therapeutic drugs, and key transcription factors specific to mesenchymal subtype GBM tumor cells which we validated in vitro and human samples. Our analysis encompassed a heterogeneous single-cell landscape of 55,845 cells from tumor and adjacent normal tissues, focusing on the mesenchymal subtype’s adverse prognosis and its association with hypoxia. We identified a core gene module composed of 38 genes and, through pharmacogenomic analysis, found that Trametinib and Dasatinib exhibit increased effectiveness against mesenchymal subtype GBM cells. Furthermore, by incorporating snATAC-seq data, we delineated a crucial regulatory network and pinpointed the key transcription factor CEBPG. Our research has highlighted the strong link between the mesenchymal-like (MES-like) properties of GBM and hypoxia, providing valuable insights into candidate drugs and pivotal targets for precision treatment of the mesenchymal subtype.
Graphical Abstract
Functional traits and adaptation of lake microbiomes on the Tibetan Plateau
Authors: Feng Xiaoyuan , Xing Peng , Tao Ye , Wang Xiaojun , Wu Qinglong L. , Liu Yongqin , Luo Haiwei 
Published: December 2024

Abstract
Background
Tibetan Plateau is credited as the “Third Pole” after the Arctic and the Antarctic, and lakes there represent a pristine habitat ideal for studying microbial processes under climate change.

Results
Here, we collected 169 samples from 54 lakes including those from the central Tibetan region that was underrepresented previously, grouped them to freshwater, brackish, and saline lakes, and generated a genome atlas of the Tibetan Plateau Lake Microbiome. This genomic atlas comprises 8271 metagenome-assembled genomes featured by having significant phylogenetic and functional novelty. The microbiomes of freshwater lakes are enriched with genes involved in recalcitrant carbon degradation, carbon fixation, and energy transformation, whereas those of saline lakes possess more genes that encode osmolyte transport and synthesis and enable anaerobic metabolism. These distinct metabolic features match well with the geochemical properties including dissolved organic carbon, dissolved oxygen, and salinity that distinguish between these lakes. Population genomic analysis suggests that microbial populations in saline lakes are under stronger functional constraints than those in freshwater lakes. Although microbiomes in the Tibet lakes, particularly the saline lakes, may be subject to changing selective regimes due to ongoing warming, they may also benefit from the drainage reorganization and metapopulation reconnection.

Conclusions
Altogether, the Tibetan Plateau Lake Microbiome atlas serves as a valuable microbial genetic resource for biodiversity conservation and climate research.
Germline loss-of-function variant in the E3 ubiquitin ligase TRAF2 in a young adult patient with medulloblastoma: a case report
Authors: Vo Josh N. , Franson Andrea , Waszak Sebastian M. , Wu Yi-Mi , Becker Nicole , Chinnaiyan Arul M. , Robinson Dan R. 
Published: December 2024

AbstractWe identified a rare heterozygous germline loss-of-function variant in the tumor necrosis factor receptor-associated factor 2 (TRAF2) in a young adult patient diagnosed with medulloblastoma. This variant is located within the TRAF-C domain of the E3 ubiquitin ligase protein and is predicted to diminish the binding affinity of TRAF2 to upstream receptors and associated adaptor proteins. Integrative genomics revealed a biallelic loss of TRAF2 via partial copy-neutral loss-of-heterozygosity of 9q in the medulloblastoma genome. We further performed comparative analysis with an in-house cohort of 20 medulloblastomas sequenced using the same platform, revealing an atypical molecular profile of the TRAF2-associated medulloblastoma. Our research adds to the expanding catalog of genetic tumor syndromes that increase the susceptibility of carriers to MB.
Identification of D842V mutation in gastrointestinal stromal tumors based on CT radiomics: a multi-center study
Authors: Xie Zhenhui , Zhang Qingwei , Zhang Ranying , Zhao Yuxuan , Zhang Wang , Song Yang , Yu Dexin , Lin Jiang , Li Xiaobo , Suo Shiteng , Zhou Yan 
Published: December 2024

Abstract
Background
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Recent advent of tyrosine kinase inhibitors (TKIs) has significantly improved the prognosis of GIST patients. However, responses to TKI therapy can vary depending on the specific gene mutation. D842V, which is the most common mutation in platelet-derived growth factor receptor alpha exon 18, shows no response to imatinib and sunitinib. Radiomics features based on venous-phase contrast-enhanced computed tomography (CECT) have shown potential in non-invasive prediction of GIST genotypes. This study sought to determine whether radiomics features could help distinguish GISTs with D842V mutations.

Methods
A total of 872 pathologically confirmed GIST patients with CECT data available from three independent centers were included and divided into the training cohort ($$n = 487$$

n
=
487

) and the external validation cohort ($$n = 385$$

n
=
385

). Clinical features including age, sex, tumor size and location were collected. Radiomics features on the largest axial image of venous-phase CECT were analyzed and a total of two radiomics features were selected after feature selection. Random forest models trained on non-radiomics features only (the non-radiomics model) and on both non-radiomics and radiomics features (the combined model) were compared.

Results
The combined model showed better average precision (0.250 vs. 0.102, p = 0.039) and F1 score (0.253 vs. 0.155, p = 0.012) than the non-radiomics model. There was no significant difference in ROC-AUC (0.728 vs. 0.737, p = 0.836) and geometric mean (0.737 vs. 0.681, p = 0.352).

Conclusions
This study demonstrated the potential of radiomics features based on venous-phase CECT images to identify D842V mutation in GISTs. Our model may provide an alternative approach to guide TKI therapy for patients inaccessible to sequence variant testing, potentially improving treatment outcomes for GIST patients especially in resource-limited settings.