bluuebunny/crossref_metadata_2025_split huggingface dataset:
Newborn screening for hypophosphatasia: development of a high-throughput tissue nonspecific alkaline phosphatase activity assay using dried blood spots
Authors: Noda Yusuke , Kido Jun , Sawada Takaaki , Tanaka Kenichi , Kumeda Kousuke , Yoshida Shinichiro , Sugawara Keishin , Nakamura Kimitoshi 
Published: December 2024

Abstract
Hypophosphatasia (HPP) is an inherited metabolic disease caused by deficiency of tissue nonspecific alkaline phosphatase (TNAP) caused by pathogenic variants of the ALPL gene (MIM 171760). The clinical manifestations of HPP vary, ranging from a lethal perinatal-onset type to a moderate late-onset type presenting with nonspecific symptoms, such as arthropathy and musculoskeletal pain. HPP is characterized by low TNAP activity and defective bone mineralization, leading to bone deformity and skeletal abnormalities. Moreover, this disease can cause systemic complications, such as muscle weakness, seizures, pain, and respiratory failure, leading to premature death in infants. This study aimed to evaluate whether measuring TNAP activity in dried blood spots (DBSs) can identify patients with HPP. We developed an assay to assess TNAP activity using DBSs and screened 45 632 newborns born between February 2019 and March 2022 in Kumamoto Prefecture in Japan for HPP. We detected a single heterozygous variant of the ALPL gene in 5 newborns. During the clinical course follow-up, one newborn presented with HPP-related clinical manifestations. This is the first study on newborn screening (NBS) for HPP worldwide. NBS for HPP using DBSs may be practical and beneficial, as it is a high-throughput method. Moreover, the DBSs used for the TNAP assay are the same as those used for public-funded NBS worldwide. In the future, this system may be implemented as standard NBS for HPP.
Decoding Cattle (Bos taurus) Diacylglycerol Acyltransferase (DGAT) Gene Families: A Pathway to Functional Understanding
Authors: Esfahani Effat Nasre , Ansari Mahyari Saeid , Davoodi Peymaneh , Ghaderi-Zefrehei Mostafa , Lesch Bluma J 
Published: December 2024

Abstract
Diacylglycerol acyltransferases (DGAT) are key enzymes in fat storage, converting diacylglycerol and fatty acyl CoA into triacylglycerol. In cattle (Bos taurus), the DGAT1 and DGAT2 genes are well-known for their significant influence on milk production traits, particularly milk fat yield and percentage. However, the cattle genome contains twelve other DGAT gene family members that remain largely uncharacterized. The research examined the genetic makeup of these DGAT proteins, revealing differences in exon count, isoforms, amino acid composition, molecular weight, isoelectric points, and predicted SNP locations. The genes are distributed across five chromosomes (2, 14, 15, 25, and X), and the expansion of this gene family in cattle is likely the result of gene duplication events, driven by specific motifs that favor such duplication. By identifying these distinctions, the study provides foundational insights into the lesser-known DGAT genes, which could be involved in regulating important traits like milk fat production. This comprehensive in silico analysis of the DGAT gene family offers valuable insights into the genetic and structural diversity of these enzymes in cattle. It also establishes a platform for future research into functional SNPs and their potential role in improving milk fat production traits, contributing to the advancement of cattle genetics and dairy production optimization. To this end, the identification of previously uncharacterized DGAT genes and their possible involvement in milk fat synthesis could pave the way for innovative breeding strategies focused on improving both milk yield and fat content in dairy cattle.
Application of nanomedicines in tumor immunotherapy
Authors: Gao Zirui , Wan Dandan , Luo Min , Wei Xiawei 
Published: December 2024

Abstract
Tumor immunotherapy has emerged as a formidable strategy, demonstrating substantial achievements in the field of cancer treatment. Despite its remarkable success, intrinsic limitations such as insufficient targeting capabilities, side effects, and resistance to immunotherapy hinder its efficacy. To address these challenges, the utilization of nanomedicines in tumor immunotherapy has been broadly explored, capitalizing on their advantages of targeting delivery capability, loading capacity, modifiability, and biocompatibility. Through rational design approaches, nanomedicines are engineered to meet diverse delivery requirements and synergize with different regimens to maximize therapeutic efficacy while alleviating side effects. This review initially discusses the challenges associated with tumor immunotherapy and underscores the pivotal role played by nanomedicines in overcoming these obstacles. Subsequently, representative types of nanoparticles are systematically introduced based on their structural properties, advantages, potential limitations, and future research directions. Special emphasis is placed on recent advancements in a range of nanomedicines designed for specific tumor immunotherapy strategies. Finally, the clinical applications as well as prospects of nanomedicines are discussed.
Cancer outcomes and cardiopulmonary toxicities for Black patients with breast cancer treated with proton therapy
Authors: Singh Gurbani , Koduri Sravya , Rao Manaahil , Kidorf Meira , Ruff Sarah , Patel Akshar , Bentzen Søren M , Nichols Elizabeth , McAvoy Sarah , Vyfhuis Melissa A L 
Published: December 2024

Abstract

Background
Black women have a 40% higher breast cancer mortality rate than White women and are at a higher risk of acquiring cardiovascular disease. Proton therapy can be used to mitigate cardiac radiation exposure; however, proton therapy remains a scarce resource in the United States. We report on the cardiovascular profiles of patients undergoing proton therapy to determine the potential benefit of the therapy for Black women compared with patients of other races.

Methods
We retrospectively analyzed 599 patients with breast cancer who received proton therapy from June 2016 to December 2021 at the Maryland Proton Treatment Center. A variety of sociodemographic, disease, and treatment variables were analyzed using descriptive statistics.

Results
With a median follow-up of 26 months (range = 0.47-90 months), Black patients made up 31.6% of the population and presented with higher rates of hypertension (P &lt; .001), cardiopulmonary conditions (P &lt; .001), and a higher median body mass index (P = .015) compared with the other cohort, a trend that persisted at the time of post–proton therapy follow-up. Black women had higher rates of triple-negative disease (P &lt; .001), with subsequent greater receipt of neoadjuvant chemotherapy (P = .039). Pulmonary events were 2.6 times more likely to occur in Black patients than in the non-Black cohort after proton therapy (odds ratio = 2.60, 95% CI = 1.39 to 4.88; P = .003).

Conclusions
Black women presenting for proton therapy had higher baseline risks of cardiovascular co-morbidities combined with more aggressive breast cancer biology and a subsequent 2.6-fold increased risk of pulmonary events after proton therapy. Our findings support the use of advanced radiation techniques as a means of sparing important organs at risk, especially in historically marginalized populations.
Cytidine analogs in plant epigenetic research and beyond
Authors: Dvořák Tomaštíková Eva , Pecinka Ales 
Published: December 2024

Abstract
Cytosine (DNA) methylation plays important roles in silencing transposable elements, plant development, genomic imprinting, stress responses, and maintenance of genome stability. To better understand the functions of this epigenetic modification, several tools have been developed to manipulate DNA methylation levels. These tools include mutants of DNA methylation writers and readers, targeted manipulation of locus-specific methylation, and the use of chemical inhibitors. Here, we summarize the effects of commonly used cytidine analog chemical inhibitors, represented by zebularine, 5-azacytidine, and their related compounds, on plants. These analogs are incorporated into chromosomal DNA, where they block the activity of the replicative CG DNA methyltransferase 1 (MET1). This leads to manifold alterations in the plant epigenome, modified developmental programs, or suppression of hybridization barriers. We also highlight the DNA-damaging effects of cytidine analogs, particularly the formation of stable DNA–protein crosslinks between DNA and MET1. This phenomenon sheds new light on specific phenotypes observed upon treatment with cytidine analogs. In conclusion, cytidine analogs are a vital tool for plant genome research and have the potential to open new promising avenues for applications in plant biotechnology and breeding.
Autophagy modulates glioblastoma cell sensitivity to Selinexor-mediated XPO1 inhibition
Authors: Tang Yongjian , Sprinzen Lisa , Terada Yukinori , Kiang Karrie M , Li Chuntao , Zeng Yu , Liu Fangkun , Zhou Hongshu , Liang Xisong , Zhang Jianzhong , Pieper Russell O , Chen Bo , Zhang Liyang 
Published: December 2024

Abstract

Background
Selinexor is a selective inhibitor of exportin-1 (XPO1), a key mediator of the nucleocytoplasmic transport for molecules critical to tumor cell survival. Selinexor’s lethality is generally associated with the induction of apoptosis, and in some cases, with autophagy-induced apoptosis. We performed this study to determine Selinexor’s action in glioblastoma (GBM) cells, which are notoriously resistant to apoptosis.

Methods
Patient-derived GBM cells were treated with Selinexor, and drug response and autophagy levels were monitored. Homozygous C528S XPO1 mutant GBM43 cells were generated by CRISPR/Cas9 editing. Single Selinexor or combination treatment with autophagy inhibitors was evaluated. In addition, bulk-tissue, single-cell, and spatial transcriptome were analyzed, and molecular docking was performed.

Results
Although all cell lines exhibited a dose- and time-dependent reduction of cell viability, the most profound molecular response to Selinexor was induction of autophagy instead of apoptosis. Selinexor-induced autophagy was an on-target consequence of XPO1 inhibition, and could be mitigated by expression of a mutant, Selinexor-resistant form of XPO1, and Selinexor-induced autophagy was related at least in part to nuclear trapping of the transcription factor TFEB. Furthermore, genetic or pharmacologic suppression of autophagy sensitized the cells to Selinexor-induced toxicity in association with the induction of apoptosis. Finally, in intracranial PDX studies, the combination of Selinexor with the autophagy inhibitor chloroquine significantly impeded tumor growth and extended mouse survival relative to single-agent treatment.

Conclusion
These results suggest that activation of autophagy confers a protective mechanism against Selinexor in GBM cells, and that the combination of Selinexor with autophagy inhibitors may serve as a viable means to enhance Selinexor-induced cell death.
A machine learning–assisted systematic review of preclinical glioma modeling: Is practice changing with the times?
Authors: Hirst Theodore C , Wilson Emma , Browne Declan , Sena Emily S 
Published: December 2024

Abstract

Background
Despite improvements in our understanding of glioblastoma pathophysiology, there have been no major improvements in treatment in recent years. Animal models are a vital tool for investigating cancer biology and its treatment, but have known limitations. There have been advances in glioblastoma modeling techniques in this century although it is unclear to what extent they have been adopted.

Methods
We searched Pubmed and EMBASE using terms designed to identify all publications reporting an animal glioma experiment, using a machine learning algorithm to assist with screening. We reviewed the full text of a sample of 1000 articles and then used the findings to inform a screen of all included abstracts to appraise the modeling applications across the entire dataset.

Results
The search identified 26 201 publications of which 13 783 were included at screening. The automated screening had high sensitivity but limited specificity. We observed a dominance of traditional cell line paradigms and the emergence of advanced tumor model systems eclipsed by a large increase in the volume of cell line experiments. Few studies used more than 1 model in vivo and most publications did not verify critical genetic features.

Conclusions
Advanced models have clear advantages in terms of tumor and disease recapitulation and have largely not replaced traditional cell lines which have a number of critical deficiencies that limit their viability in modern animal research. The judicious use of advanced models or more relevant cell lines might improve the translational relevance of future animal glioblastoma experimentation.
Mapping the Geographic Distribution of Dimorphic Mycoses Using a U.S. Commercial Insurance Database
Authors: Goodman Reid , Rauseo Adriana M , Windham Samuel L , Zuniga-Moya Julio C , Powderly William G , Spec Andrej , Mazi Patrick B 
Published: December 2024

Abstract

Background
The dimorphic mycoses (DM) histoplasmosis, blastomycosis, and coccidioidomycosis are classically thought to be geographically restricted to specific regions of the United States. The current scientific consensus is that these geographic boundaries are expanding, but the extent of this expansion remains uncertain.

Methods
This study is a retrospective analysis of &gt;21 million (annually) commercially insured individuals within the United States during 2007-2016. Diagnosis of histoplasmosis, coccidioidomycosis, and blastomycosis were identified using International Classification of Diseases, 9th/10th Revision within the MerativeTM MarketScan® database.

Results
There were 37,513 histoplasmosis, 14,987 coccidioidomycosis, and 2,207 blastomycosis diagnoses during 2007-2016 within 387 Metropolitan Statistical Areas (MSAs). DM were consistently diagnosed outside their historical hyperendemic regions.

Conclusions
New diagnoses of histoplasmosis, coccidioidomycosis, and blastomycosis were routinely made outside their historically defined regions of endemicity. While exposure to hyperendemic regions remains a risk factor for developing a DM infection, clinicians should consider testing any patient presenting with a compatible clinical syndrome, regardless of their geographic history. Increased suspicion of DM infection will lead to fewer missed or delayed diagnoses thereby improving patient outcomes.
Training and usage of language interpretation services among health care providers in a large Canadian pediatric centre
Authors: Brochez Nicholas , Islam Bonnieca , Mian Qaasim , Forbes Karen L 
Published: December 2024

Abstract

Objectives
Canada has a diverse population and one of the highest immigration rates in the world. Non-English or French language preference populations face barriers accessing health care, which leads to increased rates of adverse events. Adequate training of health care providers (HCPs) with language interpretation services (LIS) and having accessible LIS are crucial to improve the quality of patient care. We sought to identify HCPs’ prior training, and use of and attitudes toward LIS in a Canadian tertiary pediatric centre.

Methods
An electronic survey was developed and distributed to a diverse group of pediatric HCPs at the Stollery Children’s Hospital in Edmonton, Alberta between October 2022 and February 2023. Survey completion was anonymous and voluntary. Descriptive statistics were used for quantitative data and thematic analysis for free text responses.

Results
Three hundred forty-five HCPs accessed the survey and 281 (81%) completed it. Fifty-three percent of respondents encountered a pediatric non-English or French language preference patient/family once weekly or more and 51.5% reported no previous training in the use of LIS in patient care. In-person interpreters were perceived as the most effective LIS modality. Barriers to using LIS included: inability to access desired modality and/or language; insufficient time; and lack of comfort in effective usage.

Conclusions
HCPs perceive LIS as integral to patient care and convenient to use, yet most report no prior training. This study identifies multiple barriers to using LIS and suggested improvements include enhancing LIS accessibility, reliability, and LIS education. These results will help inform local LIS initiatives and resource allocation.
Evaluating in times of paradigmatic change: some reflections on how to conduct ex-post evaluations amidst the transformative turn in research and innovation policy
Authors: Wieser Harald 
Published: December 2024

Abstract
The transformative turn in research and innovation (R&I) policy calls for new approaches to monitoring and evaluation, yet most evaluands are still rooted in previous policy paradigms. For evaluators tasked with conducting ex-post evaluations, this situation creates multiple challenges that have received little attention to date. In this ‘voice from the field’, I argue that times of paradigmatic change require an increased awareness about discursive politics, heightened expectations, uncertainties, and the differences between the old and the new in evaluations. Based on recent experiences from an ex-post evaluation of the R&I programme City of Tomorrow, I provide some suggestions for coping with these challenges.
The startle response and prepulse inhibition in psychosis and violence: A combined electromyography and electroencephalography study
Authors: Bang Nina , Pettersen Johanne H , Nesset Merete Berg , Rasmussen Kirsten , Dahl Hilde , Tesli Natalia , Bell Christina  , Vaskinn Anja , Fischer-Vieler Thomas  , Friestad Christine , Andreassen Ole A , Jönsson Erik G , Elvsåshagen Torbjørn , Haukvik Unn K , Moberget Torgeir 
Published: December 2024

Abstract
There is a pressing need for biomarkers of violent behavior risk in psychosis. Previous research indicates that electrophysiological measures of automatic defensive reactions may have potential. The purpose of this study was to investigate associations between violent behavior in individuals with and without psychosis and electromyography (EMG) and electroencephalography (EEG) responses to startling auditory stimuli. EMG and EEG was recorded during an auditory startle paradigm from healthy controls (HC, n=211), individuals with psychosis and a history of violent behavior (violent-PSY, n=18), individuals with psychosis without a history of violence (nonviolent-PSY, n=32), and individuals with a history of violence without psychosis (violent non-PSY, n=22). We estimated the auditory startle response (ASR) and prepulse inhibition (PPI) using EMG (i.e., EMGASR and EMGPPI) and the auditory evoked potential (i.e., AEPASR and AEPPPI) of the EEG. There were no significant effects of group on the EMGASR (p = 0.10) or the 30-ms, 60-ms, and 120-ms prepulse + pulse EMGPPI amplitudes (p = 0.11, p = 0.19, and p = 0.50, respectively). The N1 amplitude of the AEPASR was reduced in the violent-PSY group (p = &lt;.001) and the nonviolent-PSY group (p = .015) compared to HC. The P2 amplitude of the AEPASR was reduced in violent-PSY relative to nonviolent-PSY (p = .003), violent non-PSY (p = .016), and HC (p &lt; .001). Together, these results show that EEG-based neural responses to startling auditory stimuli are promising biomarkers of violence risk in psychosis.
Prediction of phenoconversion into alpha-synucleinopathy in patients with isolated REM sleep behavior disorder using event-related potentials during visuospatial attention tasks
Authors: Choi Kang-Min , Cha Kwang Su , Noh Tae-Gon , Lee Seolah , Shin Yong Woo , Byun Jung-Ick , Jun Jin-Sun , Shin Jung Hwan , Kim Han-Joon , Jung Ki-Young 
Published: December 2024

Abstract

Study Objectives
Isolated rapid eye movement sleep behavior disorder (iRBD) is recognized as a prodromal stage of alpha-synucleinopathies. Predicting phenoconversion in iRBD patients remains a key challenge. We aimed to investigate whether event-related potentials (ERPs) recorded during visuospatial attention tasks can serve as predictors of phenoconversion in iRBD patients.

Methods
We conducted a longitudinal study with 126 iRBD patients (aged 67.1 ± 6.4, 77 males) and 41 healthy controls (aged 66.1 ± 6.9, 29 males). Among the patients, those who further developed synucleinopathies during the follow-up period (average 6.3 years) were classified as converters (iRBD-CV), while the others were non-converters (iRBD-NC). Posner’s visuospatial cueing task was performed at baseline. The N2 and P3 components were acquired for both the cue and target (valid and invalid) stimuli. Based on group comparisons, Kaplan–Meier survival analysis was performed.

Results
Twenty-nine patients converted to alpha-synucleinopathies (aged 69.4 ± 7.1, 14 males). iRBD patients exhibited overall reductions in N2 components for cue, valid, and invalid stimuli compared to HC (p = 0.012, 0.047, and 0.001, respectively). iRBD-CV patients displayed a significant increase in cue-elicited P3 (p &lt; 0.001) and a decreasing trend in cue-elicited N2 (p = 0.079) compared to iRBD-NC. These ERP alterations were strongly associated with faster rate of phenoconversion (p &lt; 0.001 for both components).

Conclusion
Our findings suggest that altered cue-elicited ERPs could serve as early biomarkers for predicting phenoconversion in iRBD patients, likely reflecting attention-related neurodegeneration pathways. These biomarkers potentially enable the detection of preclinical phenotypes in alpha-synucleinopathies, facilitating timely intervention.
Risk perception and mpox vaccine acceptability among people living with HIV in northern Nigeria
Authors: Iliyasu Zubairu , Kwaku Aminatu A , Nass Nafisa S , Umar Amina A , Amole Taiwo G , Abdullahi Hadiza M , Tsiga-Ahmed Fatimah I , Jibo Abubakar M , Fontana Brittany R , Salihu Hamisu M , Aliyu Muktar H 
Published: December 2024

Abstract

Background
There is a dearth of information regarding mpox risk perception and vaccine acceptance among people living with human immunodeficiency virus (HIV), especially in countries with a dual burden of HIV and mpox, such as Nigeria.

Methods
We used an explanatory mixed methods design and structured questionnaires administered to a clinic-based sample of people living with HIV (n=430), followed by in-depth interviews with a purposive subsample (n=20). Data were analysed using binary logistic regression and the framework approach.

Results
More than one-third (38.1% [n=164]) of the respondents self-perceived a high risk of mpox and 64.4% (n=277) indicated a willingness to receive the vaccine. Willingness to accept the mpox vaccine was positively associated with male sex, older age, non-Muslim faith, unmarried status, post-secondary education and current civil service employment. The odds of accepting the mpox vaccine was also higher among respondents who perceived mpox as a serious disease (adjusted odds ratio [aOR] 1.41 [95% confidence interval {CI} 1.12 to 2.35]), self-assessed a higher risk (aOR 1.66 [95% CI 1.19 to 3.06]) and were concerned about contracting the disease (aOR 1.78 [95% CI 1.12 to 3.94]). Reasons for hesitancy included anxiety about vaccine–antiretroviral drug interactions, low risk perception, perceived protection from antiretroviral treatment, the newness of the vaccine, mistrust of authorities and pharmaceutical companies and concerns regarding vaccine safety.

Conclusions
Mpox risk perception and vaccine acceptance were suboptimal. Vaccine acceptance was influenced by sociodemographic, perceived susceptibility and health behaviour-related factors. Targeted risk communication will enhance acceptance of mpox vaccination among people living with HIV in Nigeria.