bluuebunny/crossref_metadata_2025_split huggingface dataset:
Researcher views on returning results from multi-omics data to research participants: insights from The Molecular Transducers of Physical Activity Consortium (MoTrPAC) Study
Authors: Ormond Kelly E. , Stanclift Caroline , Reuter Chloe M. , Carter Jennefer N. , Murphy Kathleen E. , Lindholm Malene E. , Wheeler Matthew T. 
Published: February 2025

Abstract

Background
There is growing consensus in favor of returning individual specific research results that are clinically actionable, valid, and reliable. However, deciding what and how research results should be returned remains a challenge. Researchers are key stakeholders in return of results decision-making and implementation. Multi-omics data contains medically relevant findings that could be considered for return. We sought to understand researchers' views regarding the potential for return of results for multi-omics data from a large, national consortium generating multi-omics data.

Methods
Researchers from the Molecular Transducers of Physical Activity Consortium (MoTrPAC) were recruited for in-depth semi-structured interviews. To assess understanding of potential clinical utility for types of data collected and attitudes towards return of results in multi-omic clinical studies, we devised an interview guide focusing on types of results generated in the study for hypothetical return based on review of the literature and professional expertise of team members. The semi-structured interviews were recorded, transcribed verbatim and co-coded. Thematic trends were identified for reporting.

Results
We interviewed a total of 16 individuals representative of 11 sites and 6 research roles across MoTrPAC. Many respondents expressed positive attitudes regarding hypothetical multi-omics results return, citing participant rights to their data and perception of minimal harm. Ethical and logistical concerns around the return of multi-omics results were raised, and they often mirrored those in the published literature for genomic return of results including: uncertain clinical validity, a lack of expertise to communicate results, and an unclear obligation regarding whether to return multi-omics results. With the exception of privacy concerns, respondents were able to give examples within multi-omics of how each point was relevant. Further, researchers called for more guidance from funding agencies and increased researcher education regarding return of results.

Conclusion
Overall, researchers expressed positive attitudes toward multi-omic return of results in principle, particularly if medically actionable. However, competing ethical considerations, logistical constraints, and need for more external guidance were raised as key implementation concerns. Future studies should consider views and experiences of other relevant stakeholders, specifically clinical genomics professionals and study participants, regarding the clinical utility of multi-omics information and multi-omics results return.
Tumor-initiating and metastasis-initiating cells of clear-cell renal cell carcinoma
Authors: Pham Dinh-Xuan , Hsu Tien 
Published: February 2025

Abstract
Clear-cell renal cell carcinoma (ccRCC) is the most common subtype of kidney malignancy. ccRCC is considered a major health concern worldwide because its numbers of incidences and deaths continue to rise and are predicted to continue rising in the foreseeable future. Therefore new strategy for early diagnosis and therapeutics for this disease is urgently needed. The discovery of cancer stem cells (CSCs) offers hope for early cancer detection and treatment. However, there has been no definitive identification of these cancer progenitors for ccRCC. A majority of ccRCC is characterized by the loss of the von Hippel-Lindau (VHL) tumor suppressor gene function. Recent advances in genome analyses of ccRCC indicate that in ccRCC, tumor-initiating cells (TICs) and metastasis-initiating cells (MICs) are two distinct groups of progenitors. MICs result from various genetic changes during subclonal evolution, while TICs reside in the stem of the ccRCC phylogenetic tree of clonal development. TICs likely originate from kidney tubule progenitor cells bearing VHL gene inactivation, including chromatin 3p loss. Recent studies also point to the importance of microenvironment reconstituted by the VHL-deficient kidney tubule cells in promoting ccRCC initiation and progression. These understandings should help define the progenitors of ccRCC and facilitate early detection and treatment of this disease.
Prevalence of malaria and associated factors among febrile children under 15 years at Bududa General Hospital, Eastern Uganda
Authors: Okongo Benson , Asiimwe Daisy , Olong Clinton , Muwanguzi Enoch , Wagubi Robert 
Published: February 2025

Abstract

Background
A significant portion of malaria-related deaths occur in Africa, and Uganda is an endemic region where malaria remains a public health concern. This study aimed to determine the prevalence of malaria and its associated factors among febrile children under 15 years of age at Bududa General Hospital, Eastern Uganda.

Methods
This cross-sectional study was conducted between April and June 2023. Informed consent was obtained from parents/guardians before 250 febrile children below 15 years were enrolled in this study. A structured questionnaire was administered to parents/guardians to collect sociodemographic characteristics and identify factors associated with malaria. Venous blood samples were collected from the children and screened for the presence of malaria parasitaemia using blood smear microscopy. The data collected were entered into an Excel spreadsheet and analysed using STATA version 14. Logistic regression models were used to determine the factors associated with malaria, and we considered ≤ 0.05 as the level of significance.

Results
Out of the 250 study participants, the overall prevalence of malaria was 111(44.4%). Among the children who tested positive for malaria, 98 (88.3%) had Plasmodium falciparum, 11 (9.9%) had Plasmodium malariae, and (1.8%) had Plasmodium ovale infection. The mean parasite count was 21,951 parasites/µL of blood. The highest parasite count was 154,387 parasites/µL of blood, and the lowest count was 146 parasites/µL of blood. The prevalence rates of low, moderate, and high malaria parasitaemia were 46.8%, 28.0%, and 25.2%, respectively. In the multivariate analysis, the factors associated with malaria infections were older age; 1 to 5 years (p = 0.013), 6 to 10 years (p = 0.000), 11 to 15 years (p = 0.000), secondary education (p = 0.050), and no use of insecticide-treated bed nets (p = 0.002).

Conclusion
The prevalence of malaria among febrile children in this study was high, with nearly half of the participants showing severe infections. Health education on the correct use of insecticide-treated mosquito nets should be prioritized to help control malaria.
Deciphering TCOF1 mutations in Chinese Treacher Collins syndrome patients: insights into pathogenesis and transcriptional disruption
Authors: Jiang Zhuoyuan , Mao Ke , Wang Bingqing , Zhu Hao , Liu Jiqiang , Lang Ruirui , Xiao Baichuan , Shan Hailin , Chen Qi , Li Ying , Zhao Shouqin , Zhang Qingguo , Liu Huisheng , Zhang Yong-Biao 
Published: February 2025

Abstract

Background
Treacher Collins syndrome (TCS, MIM #154500), a severe congenital disorder, predominantly involves dysplasia of craniofacial bones and is characterized by features such as downslanting palpebral fissures, lower eyelid colobomas, microtia, and other craniofacial anomalies. Despite its clinical importance, the underlying pathogenic mutations in TCS remain largely uncharacterized, representing a critical knowledge gap for researchers in the field.

Results
To address this, we performed mutation screening on a familial TCS case (trio) and 11 sporadic cases from a Chinese population. We identified 11 mutations predominantly localized to the central repeat domain (CRD) and the C-terminal domain (CTD, including the nuclear localization sequence) of TCOF1. The de novo frameshift mutation identified in the trio led to TCOF1 truncation, disrupting the central repeat domain crucial for binding transcriptional factors. Immunoprecipitation assays revealed that this pathogenic mutation attenuates the interaction between TCOF1 and transcription-related proteins, such as Pol II. Furthermore, cellular luciferase assays demonstrated that the mutation compromises the nuclear localization capability of TCOF1.

Conclusions
Our findings establish TCOF1 as the primary pathogenic gene in this Chinese TCS cohort, with mutations predominantly in the CRD and CTD, thereby expanding the known mutation spectrum of TCS and informing its prevention strategies.
Loss of MEF2C function by enhancer mutation leads to neuronal mitochondria dysfunction and motor deficits in mice
Authors: Yousefian-Jazi Ali , Kim Suhyun , Chu Jiyeon , Choi Seung-Hye , Nguyen Phuong Thi Thanh , Park Uiyeol , Kim Min-gyeong , Hwang Hongik , Lee Kyungeun , Kim Yeyun , Hyeon Seung Jae , Rhim Hyewhon , Ryu Hannah L. , Lim Grewo , Stein Thor D. , Lim Kayeong , Ryu Hoon , Lee Junghee 
Published: February 2025

Abstract

Background
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the loss of both upper and lower motor neurons, leading to progressive paralysis. Both genetic alterations and epigenetic modifications contribute to neuronal dysfunction in the pathogenesis of ALS. However, the mechanism behind genetic mutations in the non-coding region of genes that affect epigenetic modifications remains unclear.

Methods
Convolutional neural network was used to identify an ALS-associated SNP located in the intronic region of MEF2C (rs304152), residing in a putative enhancer element. To examine the alteration of MEF2C transcription by the SNP, we generated HEK293T cells carrying the major or minor allele by CRISPR-Cas9. To verify the role of MEF2C-knockdown (MEF2C-KD) in mice, we developed AAV expressing shRNA for MEF2C based on AAV-U6 promoter vector. Neuropathological alterations of MEF2C-KD mice with mitochondrial dysfunction and motor neuronal damage were observed by confocal microscopy and transmission electron microscope (TEM). Behavioral changes of mice were examined through longitudinal study by tail suspension, inverted grid test and automated gait analysis.

Results
Here, we show that enhancer mutation of MEF2C reduces own gene expression and consequently impairs mitochondrial function in motor neurons. MEF2C localizes and binds to the mitochondria DNA, and directly modulates mitochondria-encoded gene expression. CRISPR/Cas-9-induced mutation of the MEF2C enhancer decreases expression of mitochondria-encoded genes. Moreover, MEF2C mutant cells show reduction of mitochondrial membrane potential, ATP level but elevation of oxidative stress. MEF2C deficiency in the upper and lower motor neurons of mice impairs mitochondria-encoded genes, and leads to mitochondrial metabolic disruption and progressive motor behavioral deficits.

Conclusions
Together, MEF2C dysregulation by the enhancer mutation leads to mitochondrial dysfunction and oxidative stress, which are prevalent features in motor neuronal damage and ALS pathogenesis. This genetic and epigenetic crosstalk mechanism provides insights for advancing our understanding of motor neuron disease and developing effective treatments.
Dysbiosis and extraintestinal cancers
Authors: He Ruishan , Qi Pingqian , Shu Linzhen , Ding Yidan , Zeng Peng , Wen Guosheng , Xiong Ying , Deng Huan 
Published: February 2025

Abstract
The gut microbiota plays a crucial role in safeguarding host health and driving the progression of intestinal diseases. Despite recent advances in the remarkable correlation between dysbiosis and extraintestinal cancers, the underlying mechanisms are yet to be fully elucidated. Pathogenic microbiota, along with their metabolites, can undermine the integrity of the gut barrier through inflammatory or metabolic pathways, leading to increased permeability and the translocation of pathogens. The dissemination of pathogens through the circulation may contribute to the establishment of an immune-suppressive environment that promotes carcinogenesis in extraintestinal organs either directly or indirectly. The oncogenic cascade always engages in the disruption of hormonal regulation and inflammatory responses, the induction of genomic instability and mutations, and the dysregulation of adult stem cell proliferation. This review aims to comprehensively summarize the existing evidence that points to the potential role of dysbiosis in the malignant transformation of extraintestinal organs such as the liver, breast, lung, and pancreas. Additionally, we delve into the limitations inherent in current methodologies, particularly the challenges associated with differentiating low loads gut-derived microbiome within tumors from potential sample contamination or symbiotic microorganisms. Although still controversial, an understanding of the contribution of translocated intestinal microbiota and their metabolites to the pathological continuum from chronic inflammation to tumors could offer a novel foundation for the development of targeted therapeutics.
Childhood occasional hypertension and its association with size at birth and early growth: a population-based retrospective cohort study from China
Authors: Zhang Shuang , Wang Leishen , Zhang Tao , Qiao Yijuan , Li Wei , Li Weiqin 
Published: February 2025

Abstract

Background
Hypertension has recently shown a rapid rise in prevalence among children and adolescents. It can track into adulthood and tend to manifest at an earlier age. It should be prevented urgently and efficiently.

Methods
This study assesses the prevalence of occasional hypertension (OHTN) at 5 ~ 6 years old and evaluates its association with size at birth and BMI at 2 and 5 ~ 6 years old in full-term children. We conducted a population-based cohort study of 12,564 children from 66 kindergartens in Tianjin, China. Information on birth weight, body mass index (BMI) at 2 and 5 ~ 6 years old, and blood pressure at 5 ~ 6 years old was retrospectively collected.

Results
The prevalence of childhood OHTN (SBP or DBP ≥ P95 percentile for sex, age, and height) was 17.0%. At birth, SGA has a high risk of OHTN (AOR 1.36, 95%CI 1.10–1.68). In the SGA subgroup, although children are of normal weight at 5 ~ 6 years old, excessive catch-up growth (BMI ≥75th at 2 years old) was still attributed to OHTN (OR 1.51, 95%CI 1.03–2.24). Obesity (BMI ≥2SD at 5 ~ 6 years old) was a vital risk factor for OHTN (AOR 2.93, 95%CI 2.56–3.36) unregarding with birthweight (OR 95%CI: SGA 3.23(1.66 ~ 6.27), AGA 2.83 (2.42–3.31), LGA 3.52 (2.65–4.68)). The co-presence of moderate or excessive catch-up growth before 2 years old and obesity at 5 ~ 6 years old significantly increased the risk of childhood OHTN (OR from 2.74 (1.65–4.54) to 6.53 (2.68–15.90)).

Conclusions
Preschool obesity, low birth weight, and excessive catch-up growth increased the risk of OHTN in childhood.
Molecular imprinted polymer-based potentiometric approach for the determination of carvedilol and ivabradine hydrochloride in dosage form, spiked human plasma and in presence of their oxidative degradates
Authors: Fares Nermine V. , El Fiky Haitham A. , Ahmed Dina A. , El Ghany Maha F. Abd , Badawey Amr M. , Tantawy Mahmoud A. 
Published: February 2025

Abstract
Carivalan® pharmaceutical formulation, which includes carvedilol and ivabradine hydrochloride, is commonly prescribed for alleviating pain associated with angina. Solid contact ion-selective electrodes with wide range of applications have been developed for analysis of these two active ingredients. Those types of electrodes have common drawbacks. Aside from development of aqueous layer, the incorporated ion exchanger in plasticized membrane is usually unable to differentiate in sensing between two similarly charged lipophilic organic ions. These flaws impeded simultaneous quantification of carvedilol and ivabradine hydrochloride in their dosage form. First, attempts were made to stabilize possible signals by synthesizing hydrophobic multiwall carbon nanotubes-based carbon paste. Precipitation polymerization was used to create molecular imprinted polymers (MIPs) for each drug. MIPs’ graved cavities serve as artificial host-tailored receptors that are able to recognize and bind to individual drugs. Carvedilol MIP-based sensor showed Nernstian slope of 55.30 mV/decade while the corresponding value for ivabradine one was 55.50 mV/decade. The respective LODs were 7.0 × 10− 8 M and 6.0 × 10− 7 M. Interference from excipients of pharmaceutical formulation, common plasma ions, and possible oxidation byproducts was not witnessed, permitting direct and simultaneous measurement of carvedilol and ivabradine in their tablet solution and spiked human plasma. Furthermore, the proposed technique was compared favorably with the official titrimetric and reported spectrophotometric methods for analyzing carvedilol and ivabradine, respectively.
Comparison of characteristics and immune responses between paired human nasal and bronchial epithelial organoids
Authors: Zhu Lu , Yang Wenhao , Luo Jiaxin , Lu Danli , Hu Yanan , Zhang Rui , Li Yan , Qiu Li , Chen Zelian , Chen Lina , Liu Hanmin 
Published: February 2025

Abstract

Background
The nasal epithelium, as part of a continuous and integrated airway epithelium, provides a more accessible sample source than the bronchial epithelium. However, the similarities and differences in gene expression patterns and immune responses between these two sites have not been extensively studied.

Results
Four lines of matched nasal and bronchial airway epithelial cells obtained from the four patients were embedded in Matrigel and cultured in thechemically defined medium to generate patient-derived nasal organoids (NO) and bronchial organoids (BO). Histologic examination of nasal organoid tissue revealed high similarity and a reduced ciliary beat frequency compared to bronchial organoid tissue. Whole exome sequencing revealed that over 99% of single nucleotides were shared between the NO and matched BO and there was a 95% overlap in their RNA transcriptomes. RNA sequencing analysis of differentially expressed genes indicated a significant reduction in the immune response in NO. RSV infection revealed more productive replication in NO, with a downregulated immune pathway identified by RNA sequencing analysis and upregulated levels of pro-inflammatory cytokines in culture supernatants in NO compared to BO.

Conclusions
NO and BO serve as robust in vitro models, faithfully recapitulating the biological characteristics of upper respiratory epithelial cells. The different regions of respiratory epithelial cells exhibit distinct immune responses, underscoring their complementary roles in exploring airway immune mechanisms and disease pathophysiology.
Peer-assisted telemedicine hepatitis-C treatment for people who use drugs in rural communities: a mixed methods study
Authors: Hoffman Kim , Leichtling Gillian , Shin Sarah , Seaman Andrew , Gailey Tonhi , Spencer Hunter C. , Korthuis P. Todd 
Published: February 2025

Abstract

Background
The increase in opioid use disorder among young, nonurban people has fueled sharp rises in hepatitis C virus (HCV) infections. Innovative treatment models are needed that circumvent healthcare system barriers for people who use drugs (PWUD), particularly in rural areas. The Oregon HOPE TeleHCV study randomized PWUD living with HCV in rural Oregon to peer-facilitated and streamlined telemedicine HCV treatment (Peer TeleHCV) versus enhanced usual care (EUC) and assessed sustained virologic response at 12 weeks post treatment (SVR12). Peer Support Specialists (peers) conducted HCV screening in the community, facilitated pretreatment evaluation and linkage to telemedicine HCV treatment clinicians, and supported Peer TeleHCV study participants in HCV medication adherence. A qualitative investigation queried telemedicine clinicians and peers about their experiences with the implementation of the model and key drivers of implementation effectiveness.

Methods
Two remote audio/video recorded focus groups were conducted, one with the study’s clinicians and one with the peers. Participants were asked their views of key elements for successful implementation and outcomes of the Peer TeleHCV model. Group interviews lasted one hour. Recordings were professionally transcribed for thematic analysis with a mixed deductive and inductive framework, using Atlas.ti. Patients were surveyed about their interactions and satisfaction with peers.

Results
Quantitative data (n = 78) indicated patients had high levels of satisfaction with and support from the peers. Three themes were identified from the qualitative data (n = 12) including. (1) Key peer-level elements such as providing support during potentially difficult lab draws, creating a peer-facilitated “bubble of trust” between patients and clinicians, enabling technology access, conducting outreach to maintain contact and support treatment retention, and facilitating stabilizing wrap-around services (e.g., housing vouchers) (2) Key clinician-level factors such as capacity for unscheduled peer-facilitated appointments, having dedicated time for case consults with peers, and clinicians trained in working with PWUD and skilled in identifying related clinical concerns (3) Key systems-level elements such as standing lab orders, challenges related to specialty pharmacies and Medicaid managed care organizations, and streamlined communication strategies between peers and clinicians.

Conclusion
All participants reported that the Peer TeleHCV model built trust and eased barriers for PWUD initiating and remaining in HCV treatment. This low-barrier model makes space for PWUD to receive HCV treatment, regardless of drug use. Implementing support from peer specialists, telemedicine technology, and streamlined testing and treatment strategies may connect more rural PWUD living with HCV with the cure.