bluuebunny/crossref_metadata_2025 huggingface dataset:
Haplotype analysis incorporating ancestral origins identified novel genetic loci associated with chicken body weight using an advanced intercross line
Authors: Bu Lina , Wang Yuzhe , Tan Lizhi , Wen Zilong , Hu Xiaoxiang , Zhang Zhiwu , Zhao Yiqiang
Published: December 2024

Background

The genome-wide association study (GWAS) is a powerful method for mapping quantitative trait loci (QTL). However, standard GWAS can detect only QTL that segregate in the mapping population. Crossing populations with different characteristics increases genetic variability but F2 or back-crosses lack mapping resolution due to the limited number of recombination events. This drawback can be overcome with advanced intercross line (AIL) populations, which increase the number recombination events and provide a more accurate mapping resolution. Recent studies in humans have revealed ancestry-dependent genetic architecture and shown the effectiveness of admixture mapping in admixed populations.

Results

Through the incorporation of line-of-origin effects and GWAS on an F9 AIL population, we identified genes that affect body weight at eight weeks of age (BW8) in chickens. The proposed ancestral-haplotype-based GWAS (testing only the origin regardless of the alleles) revealed three new QTLs on GGA12, GGA15, and GGA20. By using the concepts of ancestral homozygotes (individuals that carry two haplotypes of the same origin) and ancestral heterozygotes (carrying one haplotype of each origin), we identified 632 loci that exhibited high-parent (the heterozygote is better than both parents) and mid-parent (the heterozygote is better than the median of the parents) dominance across 12 chromosomes. Out of the 199 genes associated with BW8, EYA1, PDE1C, and MYC were identified as the best candidate genes for further validation.

Conclusions

In addition to the candidate genes reported in this study, our research demonstrates the effectiveness of incorporating ancestral information in population genetic analyses, which can be broadly applicable for genetic mapping in populations generated by ancestors with distinct phenotypes and genetic backgrounds. Our methods can benefit both geneticists and biologists interested in the genetic determinism of complex traits.
A comprehensive guide to study the agreement and reliability of multi-observer ordinal data
Authors: Vanbelle Sophie , Engelhart Christina Hernandez , Blix Ellen
Published: December 2024

Background

A recent systematic review revealed issues in regard to performing and reporting agreement and reliability studies for ordinal scales, especially in the presence of more than two observers. This paper therefore aims to provide all necessary information in regard to the choice among the most meaningful and most used measures and the planning of agreement and reliability studies for ordinal outcomes.

Methods

This paper considers the generalisation of the proportion of (dis)agreement, the mean absolute deviation, the mean squared deviation and weighted kappa coefficients to more than two observers in the presence of an ordinal outcome.

Results

After highlighting the difference between the concepts of agreement and reliability, a clear and simple interpretation of the agreement and reliability coefficients is provided. The large sample variance of the various coefficients with the delta method is presented or derived if not available in the literature to construct Wald confidence intervals. Finally, a procedure to determine the minimum number of raters and patients needed to limit the uncertainty associated with the sampling process is provided. All the methods are available in an R package and a Shiny application to circumvent the limitations of current software.

Conclusions

The present paper completes existing guidelines, such as the Guidelines for Reporting Reliability and Agreement Studies (GRRAS), to improve the quality of reliability and agreement studies of clinical tests. Furthermore, we provide open source software to researchers with minimum programming skills.
Partial-linear single-index Cox regression models with multiple time-dependent covariates
Authors: Lee Myeonggyun , Troxel Andrea B. , Kwon Sophia , Crowley George , Schwartz Theresa , Zeig-Owens Rachel , Prezant David J. , Nolan Anna , Liu Mengling
Published: December 2024

Background

In cohort studies with time-to-event outcomes, covariates of interest often have values that change over time. The classical Cox regression model can handle time-dependent covariates but assumes linear effects on the log hazard function, which can be limiting in practice. Furthermore, when multiple correlated covariates are studied, it is of great interest to model their joint effects by allowing a flexible functional form and to delineate their relative contributions to survival risk.

Methods

Motivated by the World Trade Center (WTC)-exposed Fire Department of New York cohort study, we proposed a partial-linear single-index Cox (PLSI-Cox) model to investigate the effects of repeatedly measured metabolic syndrome indicators on the risk of developing WTC lung injury associated with particulate matter exposure. The PLSI-Cox model reduces the dimensionality of covariates while providing interpretable estimates of their effects. The model’s flexible link function accommodates nonlinear effects on the log hazard function. We developed an iterative estimation algorithm using spline techniques to model the nonparametric single-index component for potential nonlinear effects, followed by maximum partial likelihood estimation of the parameters.

Results

Extensive simulations showed that the proposed PLSI-Cox model outperformed the classical time-dependent Cox regression model when the true relationship was nonlinear. When the relationship was linear, both the PLSI-Cox model and classical time-dependent Cox regression model performed similarly. In the data application, we found a possible nonlinear joint effect of metabolic syndrome indicators on survival risk. Among the different indicators, BMI had the largest positive effect on the risk of developing lung injury, followed by triglycerides.

Conclusion

The PLSI-Cox models allow for the evaluation of nonlinear effects of covariates and offer insights into their relative importance and direction. These methods provide a powerful set of tools for analyzing data with multiple time-dependent covariates and survival outcomes, potentially offering valuable insights for both current and future studies.
Disability justice and collective access to labour and delivery care: a qualitative study
Authors: Evans Meredith , Tarasoff Lesley A. , Lunsky Yona , Welsh Kate , Proulx Laurie , Havercamp Susan M. , Parish Susan L. , Brown Hilary K.
Published: December 2024

Background

People with disabilities experience perinatal health disparities. This qualitative study examines disabled people’s experiences of labour and delivery care from a disability justice lens.

Methods

Semi-structured interviews were conducted between July 2019 and February 2020 with 31 women and transgender people aged 18–45 years with physical, sensory, and/or intellectual/developmental disabilities, who were living in in Ontario, Canada and had given birth in the previous five years.

Results

People with disabilities described negative experiences of provider-driven, disrespectful, and discriminatory labour and delivery care that can be interpreted as examples of disability injustice and obstetric ableism. People with disabilities also described positive experiences of collaborative, respectful, and disability-affirming labour and delivery care that can be interpreted as examples of disability justice, facilitated by what feminist disability justice scholars and activists call collective access.

Conclusions

Collective access to labour and delivery care can improve perinatal health care for people with disabilities and promote disability justice. Reimagining care-related decision-making as an interdependent, collaborative, respectful, and disability-affirming process shared between patients and providers can help to facilitate collective access to labour and delivery care.
The metabolome of male and female individuals with knee osteoarthritis is influenced by 18-months of weight loss intervention: the IDEA trial
Authors: Welhaven Hope D. , Welfley Avery H. , Bothner Brian , Messier Stephen P. , Loeser Richard F. , June Ronald K.
Published: December 2024

Background

The Intensive Diet and Exercise for Arthritis (IDEA) trial was a randomized trial conducted to evaluate the effects of diet and exercise on osteoarthritis (OA), the most prevalent form of arthritis. Various risk factors, including obesity and sex, contribute to OA’s debilitating nature. While diet and exercise are known to improve OA symptoms, cellular and molecular mechanisms underlying these interventions, as well as effects of participant sex, remain elusive.

Methods

Serum was obtained at three timepoints from IDEA participants assigned to groups of diet, exercise, or combined diet and exercise (n = 10 per group). A randomly selected subset of serum samples were extracted and analyzed via liquid chromatography-mass spectrometry combined with metabolomic profiling to unveil mechanisms associated with types of intervention and disease. Extracted serum was pooled and fragmentation patterns were analyzed to identify metabolites that statistically differentially regulated between groups.

Results

Changes in metabolism across male and female IDEA participants after 18-months of diet, exercise, and combined diet and exercise intervention mapped to lipid, amino acid, carbohydrate, vitamin, and matrix metabolism. The diverse metabolic landscape detected across IDEA participants shows that intervention type differentially impacts the serum metabolome of OA individuals. Moreover, dissimilarities in the serum metabolome corresponded with participant sex.

Conclusions

These findings suggest that intensive weight loss among males and females offers potential metabolic benefits for individuals with knee OA. This study provides a deeper understanding of dysregulation occurring during OA development in parallel with various interventions, potentially paving the way for improved interventions, treatments, and quality of life of those impacted by OA.

Trial Registration

clinicaltrials.gov Identifier NCT00381290, Registered, 9/25/2006.
Does the role of family meetings important at the end-of-life? A retrospective national study in Taiwan
Authors: Yu Tsung-Hsien , Wei Chung-Jen , Wu Wei-Wen , Lu Frank Leigh
Published: December 2024

Background

Numerous studies have pointed out the benefits of family meetings, but it is unclear who uses family meetings and what the effects are on use of the end-of-life care.

Aim

The purposes of this study were to explore which characteristics are associated with the use of the family meeting and what effects the family meeting has on end-of-life care.

Design

A retrospective observational study using 2012–2017 data from Taiwan’s National Health Insurance claims database, cancer registry, and death registry.

Setting/participants

People who died between 2013 and 2017 in Taiwan as the study population. The deceased people whose information on gender, marital status, or insured classification that was unknown were excluded from this study.

Results

A total of 792,947 people were included. All demographic characteristics were associated with the use of family meetings, and all demographic characteristics (except for gender and residence area) and hospital characteristics were associated with the initiation time of family meetings. We also found use of family meetings increased the use of hospice care (OR:4.949) and decreased the use of CPR (OR:0.208) at the end of life, initiation time was also associated with the hospice and CPR, but the effects were varied.

Conclusion

This study demonstrated that family meetings affected the care at end-of-life. Although the utilization of family meeting was increased by year, but also variation still existed among demographic and health characteristics, how to promote it is the next concern in the future.
Development and alpha-testing of a patient decision aid for patients with chronic myeloid leukemia regarding dose reduction
Authors: Lokhorst D. N. , Djodikromo M. F. , Hermens R. P. M. G. , Blijlevens N. M. A. , Bekker C. L.
Published: December 2024

Background

Dose reduction of tyrosine kinase inhibitors (TKIs) is an option for some chronic myeloid leukemia (CML) patients to minimize side effects while maintaining efficacy. Shared decision-making (SDM) and patient decision aids (PDAs) are advocated to make informed choices such as reducing the dose of TKIs. This paper describes the development and alpha-testing of a PDA for patients with CML receiving TKI dose reduction.

Methods

The PDA was iteratively developed following IPDAS guidelines. First, a needs assessment with semi-structured interviews was conducted to understand the needs and preferences of patients and healthcare providers. Second, through feedback cycles with the project team and steering group the scope, content, and format were defined. Third, three rounds of alpha-testing were performed via individual “think aloud” sessions with patients (round 1) and healthcare providers (round 2) to qualitatively assess the comprehensibility, acceptability, and desirability of the PDA. Round 3 included quantitative evaluation via an acceptability and usability questionnaire. Qualitative data were categorized, and quantitative data were descriptively analyzed.

Results

The majority valued the development of the PDA during the needs assessment (n = 30). The PDA included disease and treatment information, information about dose reduction, knowledge questions, and a value clarification section. During alpha-testing, the PDA was considered clear, balanced, and helpful for decision-making. A total of 76% of the patients (n = 17) and 100% of the healthcare providers (n = 9) recommended it with overall mean scores of 7.4 and 7.8, respectively. The above average usability score was 68.1.

Conclusion

A well-accepted online PDA for chronic phase CML patients to consider TKI dose reduction was developed.
Basement membranes’ role in immune cell recruitment to the central nervous system
Authors: Wright Shaun A. , Lennon Rachel , Greenhalgh Andrew D.
Published: December 2024

Basement membranes form part of the extracellular matrix (ECM), which is the structural basis for all tissue. Basement membranes are cell-adherent sheets found between cells and vascular endothelia, including those of the central nervous system (CNS). There is exceptional regional specialisation of these structures, both in tissue organisation and regulation of tissue-specific cellular processes. Due to their location, basement membranes perform a key role in immune cell trafficking and therefore are important in inflammatory processes causing or resulting from CNS disease and injury. This review will describe basement membranes in detail, with special focus on the brain. We will cover how genetic changes drive brain pathology, describe basement membranes’ role in immune cell recruitment and how they respond to various brain diseases. Understanding how basement membranes form the junction between the immune and central nervous systems will be a major advance in understanding brain disease.
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

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

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

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

CRISPR-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

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

Glycogen 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

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

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

Although 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

Electric 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

The 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

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

We 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

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.
Development of a high-resolution ocean ensemble future projection dataset for the North Pacific incorporating simple biogeochemical processes
Authors: Nishikawa Shiro , Sugiyama Toru , Kurogi Masao , Tsujino Hiroyuki , Nakano Hideyuki , Ishikawa Yoichi
Published: December 2024

In this study, we developed a new version of the future ocean regional projection dataset in the North Pacific (FORP-NP10) by performing an ensemble of historical and multi-scenario future projection simulations from 1960 to 2100 using a high-resolution ocean downscaling model system driven by surface forcings based on the atmospheric data of the Coupled Model Intercomparison Project (Phase 5). This version is characterized by the inclusion of simple biogeochemical processes within the simulations of the multi-case (four forcing cases) and multi-future projection scenarios (representative concentration pathway 2.6 and 8.5) using a mesoscale eddy-resolving (approximately 10 km) horizontal resolution. The dataset reasonably represented the main biogeochemical properties in the North Pacific and around Japan, such as surface CO2 flux, pH, subsurface oxygen, surface nitrate, and chlorophyll, as well as the ocean physics of the regions, including the mesoscale/frontal structures of the Kuroshio, Kuroshio Extension, and mixed layer depth. We assessed the bias tendencies and structures of these properties by comparing them with observational reference data and the low-resolution model results. Our ensemble dataset consistently projected future upper-ocean warming, acidification, deoxygenation, and changes in nutrient and primary production in the twenty-first century (reported as global analyses in recent reports of the Intergovernmental Panel on Climate Change) in the regions surrounding Japan, revealing that the future changes exhibited spatial contrasts or varying tendencies in the regions.
A review on composites based on upconversion nanoparticles and graphene oxide: development and theranostic applications centered at solid tumors
Authors: Ghorpade Kabirdas B. , Kumar Manoj , Tiwari Sanjay
Published: December 2024

Upconversion nanoparticles (UCNPs) have attracted considerable interest for the imaging of solid tumors because of their unique optical features. These applications can be expanded towards anticancer therapeutics by developing UCNP-graphene oxide (GO) composites. This strategy addresses low loading capacity and poor dispersibility of UCNPs in physiological media. These aspects have been covered in this article. We begin by discussing the synthesis methods and challenges associated with UCNPs, along with their surface modification strategies. Next, we describe the approaches of designing UCNP-GO composites and their applications in imaging, biosensing, and different therapeutic platforms.

Graphical Abstract
Surface-activated bonding between a 3D-printed Ti-6Al-4V structure and bulk aluminum
Authors: Mercer Christopher , Hasegawa Akira , Hosoda Naoe
Published: December 2024

Surface-activated bonding (SAB) of a 3D-printed Ti-6Al-4V pillar structure (fabricated by selective laser melting) to pure bulk aluminum at room temperature has been investigated. Argon beam irradiation was used to remove surface contaminants and “activate” the surfaces prior to bonding. The surface chemistry of the Ti-6Al-4V surface was analyzed using Electron Spectroscopy for Chemical Analysis (ESCA) to make sure any oxides had been removed by the irradiation procedure. The two materials were successfully bonded via SAB using special bonding apparatus, and scanning transmission electron microscopy (STEM) observation revealed a flat well-bonded interface with no obvious porosity. Furthermore, no thick reaction layer that could compromise the strength of the bond was evident. An oxide layer approximately 2 nm in thickness was observed at the interface by high-resolution TEM, but this is not considered sufficient to have a detrimental effect on bond integrity. The results of the investigation show that 3D-printed materials and structures can be successfully joined to aluminum by SAB techniques.
Dietary methionine supplementation promotes mice hematopoiesis after irradiation
Authors: Zhang Wei-Wei , Xiang Yang , Chen Li , Liu Shao-Ting , Lin Chuan-Chuan , Li Jiu-Xuan , Xiang Li-Xin , Chen Nan-Xi , Shi Dong-Ling , Zhang Yang-Yang , Wang Xue-Ying , Hu Lan-Yue , Chen Sai , Luo Ya , Tan Cheng-Ning , Xue Pei-Pei , Jiang Yang-Zhou , Li Sheng-Wen Calvin , Yang Zhen-Xing , Dai Ji-Gang , Li Zhong-Jun , Ran Qian
Published: December 2024

Background

With the increasing risk of nuclear exposure, more attention has been paid to the prevention and treatment of acute radiation syndrome (ARS). Although amino acids are key nutrients involved in hematopoietic regulation, the impacts of amino acids on bone marrow hematopoiesis following irradiation and the associated mechanisms have not been fully elucidated. Hence, it is of paramount importance to study the changes in amino acid metabolism after irradiation and their effects on hematopoiesis as well as the related mechanisms.

Methods

The content of serum amino acids was analyzed using metabolomic sequencing. The survival rate and body weight of the irradiated mice were detected after altering the methionine content in the diet. Extracellular matrix (ECM) protein analysis was performed via proteomics analysis. Inflammatory factors were examined by enzyme-linked immunosorbent assay (ELISA). Flow cytometry, Western blotting, and immunofluorescence were employed to determine the mechanism by which S100 calcium-binding protein A4 (S100A4) regulates macrophage polarization.

Results

The survival time of irradiated mice was significantly associated with alterations in multiple amino acids, particularly methionine. A high methionine diet promoted irradiation tolerance, especially in the recovery of bone marrow hematopoiesis, yet with dose limitations. Folate metabolism could partially alleviate the dose bottleneck by reducing the accumulation of homocysteine. Mechanistically, high methionine levels maintained the abundance of ECM components, including collagens and glycoproteins, in the bone marrow post-irradiation, among which the level of S100A4 was significantly changed. S100A4 regulated macrophage polarization via the STAT3 pathway, inhibited bone marrow inflammation and facilitated the proliferation and differentiation of hematopoietic stem/progenitor cells.

Conclusions

We have demonstrated that an appropriate elevation in dietary methionine enhances irradiation tolerance in mice and explains the mechanism by which methionine regulates bone marrow hematopoiesis after irradiation.
Does lifting female piglets by one hind leg increase the risk of umbilical and hind leg lesions?
Authors: Barington Kristiane , Hansen Marie Høy , Andersen Amanda Bastian , Pedersen Ken Steen , Larsen Inge
Published: December 2024

Background

Umbilical lesions in pigs have a negative impact on animal welfare and productivity. It has been suggested that lifting young piglets by one hind leg may be a risk factor for developing omphalitis and umbilical hernia. However, the hypothesis that lifting piglets by one hind leg should stretch the umbilical wall and impede the healing of the umbilicus has not yet been investigated. The present study examined if piglets caught, lifted, and carried by one hind leg have an increased risk of developing lesions in the umbilicus and the hind legs compared to piglets caught, lifted, and carried with support under the abdomen.

Materials and methods

In a commercial indoor sow herd, 1901 piglets were randomly allocated into two groups on the day of birth. Piglets in Group 1 (986 piglets) were caught, lifted, and carried by one hind leg (either left or right, as the same leg was not necessarily used each time). Piglets in Group 2 (915 piglets), were caught, lifted, and carried with support under the abdomen. All piglets were lifted 8–10 times during the first 14 days of life as a part of routine management procedures. From each group, 50 female piglets, 14 days old, were randomly selected and euthanised for necropsy and histopathological evaluation.

Results

The risk of having haemosiderophages in the umbilicus was 1.4 times higher in piglets caught, lifted, and carried by one hind leg compared to piglets caught, lifted, and carried with support under the abdomen (p = 0.01). No other variable differed significantly between the groups. Omphalitis was present in 68% and 58% of piglets in Groups 1 and 2, respectively. Moreover, umbilical herniation was present in 14% and 12% of piglets in Groups 1 and 2, respectively. Lesions were present in the hind legs of piglets in both groups and included synovial hyperplasia, neutrophilic granulocyte infiltration, oedema, and haemorrhage.

Conclusion

Female piglets caught, lifted, and carried by one hind leg did not have an increased risk of umbilical hernia, omphalitis, or joint lesions compared to piglets caught, lifted, and carried with support under the abdomen.