bluuebunny/crossref_metadata_2025_split huggingface dataset:
Isogenic pairs of induced-pluripotent stem-derived endothelial cells identify DYRK1A/PPARG/EGR1 pathway is responsible for Down syndrome-associated pulmonary hypertension
Authors: Suginobe Hidehiro , Ishida Hidekazu , Ishii Yoichiro , Ueda Kazutoshi , Yoshihara Chika , Ueyama Atsuko , Wang Renjie , Tsuru Hirofumi , Hashimoto Kazuhisa , Hirose Masaki , Ishii Ryo , Narita Jun , Kitabatake Yasuji , Ozono Keiichi 
Published: October 2023

Abstract
Down syndrome (DS) is the most prevalent chromosomal disorder associated with a higher incidence of pulmonary arterial hypertension (PAH). The dysfunction of vascular endothelial cells (ECs) is known to cause pulmonary arterial remodeling in PAH, although the physiological characteristics of ECs harboring trisomy 21 (T21) are still unknown. In this study, we analyzed the human vascular ECs by utilizing the isogenic pairs of T21-induced pluripotent stem cells (iPSCs) and corrected disomy 21 (cDi21)-iPSCs. In T21-iPSC-derived ECs, apoptosis and mitochondrial reactive oxygen species (mROS) were significantly increased, and angiogenesis and oxygen consumption rate (OCR) were significantly impaired as compared with cDi21-iPSC-derived ECs. The RNA-sequencing identified that EGR1 on chromosome 5 was significantly upregulated in T21-ECs. Both EGR1 suppression by siRNA and pharmacological inhibitor could recover the apoptosis, mROS, angiogenesis, and OCR in T21-ECs. Alternately, the study also revealed that DYRK1A was responsible to increase EGR1 expression via PPARG suppression, and that chemical inhibition of DYRK1A could restore the apoptosis, mROS, angiogenesis, and OCR in T21-ECs. Finally, we demonstrated that EGR1 was significantly upregulated in the pulmonary arterial ECs from lung specimens of a patient with DS and PAH. In conclusion, DYRK1A/PPARG/EGR1 pathway could play a central role for the pulmonary EC functions and thus be associated with the pathogenesis of PAH in DS.
Early Initiation of Antiretroviral Therapy Preserves the Metabolic Function of CD4+ T Cells in Subtype C Human Immunodeficiency Virus 1 Infection
Authors: Naidoo Kewreshini K , Highton Andrew J , Baiyegunhi Omolara O , Bhengu Sindiswa P , Dong Krista L , Bunders Madeleine J , Altfeld Marcus , Ndung’u Thumbi 
Published: October 2023

Abstract

Background
Immune dysfunction often persists in people living with human immunodeficiency virus (HIV) who are on antiretroviral therapy (ART), clinically manifesting as HIV-1-associated comorbid conditions. Early ART initiation may reduce incidence of HIV-1–associated immune dysfunction and comorbid conditions. Immunometabolism is a critical determinant of functional immunity. We investigated the effect of HIV-1 infection and timing of ART initiation on CD4+ T cell metabolism and function.

Methods
Longitudinal blood samples from people living with HIV who initiated ART during hyperacute HIV-1 infection (HHI; before peak viremia) or chronic HIV-1 infection (CHI) were assessed for the metabolic and immune functions of CD4+ T cells. Metabolite uptake and mitochondrial mass were measured using fluorescent analogues and MitoTracker Green accumulation, respectively, and were correlated with CD4+ T cell effector functions.

Results
Initiation of ART during HHI prevented dysregulation of glucose uptake by CD4+ T cells, but glucose uptake was reduced before and after ART initiation in CHI. Glucose uptake positively correlated with interleukin-2 and tumor necrosis factor-α production by CD4+ T cells. CHI was associated with elevated mitochondrial mass in effector memory CD4+ T cells that persisted after ART and correlated with PD-1 expression.

Conclusions
ART initiation in HHI largely prevented metabolic impairment of CD4+ T cells. ART initiation in CHI was associated with persistently dysregulated immunometabolism of CD4+ T cells, which was associated with impaired cellular functions and exhaustion.
Proline-rich transmembrane protein 2 knock-in mice present dopamine-dependent motor deficits
Authors: Hatta Daisuke , Kanamoto Kaito , Makiya Shiho , Watanabe Kaori , Kishino Tatsuya , Kinoshita Akira , Yoshiura Koh-Ichiro , Kurotaki Naohiro , Shirotani Keiro , Iwata Nobuhisa 
Published: October 2023

Abstract
Mutations of proline-rich transmembrane protein 2 (PRRT2) lead to dyskinetic disorders such as paroxysmal kinesigenic dyskinesia (PKD), which is characterized by attacks of involuntary movements precipitated by suddenly initiated motion, and some convulsive disorders. Although previous studies have shown that PKD might be caused by cerebellar dysfunction, PRRT2 has not been sufficiently analyzed in some motor-related regions, including the basal ganglia, where dopaminergic neurons are most abundant in the brain. Here, we generated several types of Prrt2 knock-in (KI) mice harboring mutations, such as c.672dupG, that mimics the human pathological mutation c.649dupC and investigated the contribution of Prrt2 to dopaminergic regulation. Regardless of differences in the frameshift sites, all truncating mutations abolished Prrt2 expression within the striatum and cerebral cortex, consistent with previous reports of similar Prrt2 mutant rodents, confirming the loss-of-function nature of these mutations. Importantly, administration of l-dopa, a precursor of dopamine, exacerbated rotarod performance, especially in Prrt2-KI mice. These findings suggest that dopaminergic dysfunction in the brain by the PRRT2 mutation might be implicated in a part of motor symptoms of PKD and related disorders.
A Review and Quality Assessment of TikTok Videos for Burn Education
Authors: Sheikh-Oleslami Sara , Tuen Young Ji , Courtemanche Rebecca , Hynes Sally 
Published: October 2023

Abstract
Social media platforms can serve as a readily accessible tool for burn education, potentially reducing the incidence and severity of burn injuries. Previous studies have investigated the quality of online burn education videos on platforms such as YouTube. Here, we review the quality of such videos on TikTok, a newer and rapidly growing platform. TikTok was searched for English videos using 29 keywords (hashtags) such as #burn, #education, #prevention, and #management. The first 30 videos per hashtag were screened. Videos were categorized by content and creator. Two independent reviewers assessed the quality of the included videos using the Global Quality Scale (GQS). Metrics such as views, commentary, and likes were also examined. Of 535 screened videos, 72 met inclusion criteria. 47% (n = 34) were on management, 33% (n = 31) education, and 10% (n = 7) prevention. Only 6% (n = 4) cited sources. The median GQS score was 3.0 (IQR: 2.0–3.0, max 4.0). 50% (n = 36) were made by healthcare professionals with a median GQS score of 3.0 (IQR: 2.0–3.0, max 4.0) compared to 2.0 (IQR: 2.0–3.0, max 4.0) in nonhealthcare professionals (n = 36). Viewership varied from 41 to 4.2 million views. Overall, there is a lack of high-quality educational information on TikTok. This rapidly expanding and dynamic platform may provide an opportunity to direct individuals to higher quality resources.
Introduction: Irregularized Humanitarian Migrants—Policies, Rationales, and the Search for More Durable Solutions
Authors: van Houte Marieke , Kaşlı Zeynep , Leerkes Arjen 
Published: October 2023

AbstractIn this special issue, we seek explanations for international- and local-level variations in policy approaches to ‘irregularized humanitarian migrants’, who left their country of citizenship in hopes of finding protection abroad but do not, or no longer, hold a permanent legal status. We shed light on different policy responses and experiences across Europe, Africa, and the wider Middle East by drawing on a wide array of political systems and migration patterns and different groups of humanitarian migrants. We explore to what extent the outcomes of various policies and practices can be regarded as better and more durable solutions, defined as increasingly taking into account the interests of migrants and the communities they live in. Ultimately, we stress the importance of gaining deeper and more comprehensive understandings of the historically informed context-specific circumstances that irregularized humanitarian migrants find themselves in, as well as the patterns that we see emerging in the comparison of these cases.
DNA mismatch repair protects the genome from oxygen-induced replicative mutagenesis
Authors: Lózsa Rita , Németh Eszter , Gervai Judit Z , Márkus Bence G , Kollarics Sándor , Gyüre Zsolt , Tóth Judit , Simon Ferenc , Szüts Dávid 
Published: October 2023

Abstract
DNA mismatch repair (MMR) corrects mismatched DNA bases arising from multiple sources including polymerase errors and base damage. By detecting spontaneous mutagenesis using whole genome sequencing of cultured MMR deficient human cell lines, we show that a primary role of MMR is the repair of oxygen-induced mismatches. We found an approximately twofold higher mutation rate in MSH6 deficient DLD-1 cells or MHL1 deficient HCT116 cells exposed to atmospheric conditions as opposed to mild hypoxia, which correlated with oxidant levels measured using electron paramagnetic resonance spectroscopy. The oxygen-induced mutations were dominated by T to C base substitutions and single T deletions found primarily on the lagging strand. A broad sequence context preference, dependence on replication timing and a lack of transcriptional strand bias further suggested that oxygen-induced mutations arise from polymerase errors rather than oxidative base damage. We defined separate low and high oxygen–specific MMR deficiency mutation signatures common to the two cell lines and showed that the effect of oxygen is observable in MMR deficient cancer genomes, where it best correlates with the contribution of mutation signature SBS21. Our results imply that MMR corrects oxygen-induced genomic mismatches introduced by a replicative process in proliferating cells.
CROST: a comprehensive repository of spatial transcriptomics
Authors: Wang Guoliang , Wu Song , Xiong Zhuang , Qu Hongzhu , Fang Xiangdong , Bao Yiming 
Published: October 2023

Abstract
The development of spatial transcriptome sequencing technology has revolutionized our comprehension of complex tissues and propelled life and health sciences into an era of spatial omics. However, the current availability of databases for accessing and analyzing spatial transcriptomic data is limited. In response, we have established CROST (https://ngdc.cncb.ac.cn/crost), a comprehensive repository of spatial transcriptomics. CROST encompasses high-quality samples and houses 182 spatial transcriptomic datasets from diverse species, organs, and diseases, comprising 1033 sub-datasets and 48 043 tumor-related spatially variable genes (SVGs). Additionally, it encompasses a standardized spatial transcriptome data processing pipeline, integrates single-cell RNA sequencing deconvolution spatial transcriptomics data, and evaluates correlation, colocalization, intercellular communication, and biological function annotation analyses. Moreover, CROST integrates the transcriptome, epigenome, and genome to explore tumor-associated SVGs and provides a comprehensive understanding of their roles in cancer progression and prognosis. Furthermore, CROST provides two online tools, single-sample gene set enrichment analysis and SpatialAP, for users to annotate and analyze the uploaded spatial transcriptomics data. The user-friendly interface of CROST facilitates browsing, searching, analyzing, visualizing, and downloading desired information. Collectively, CROST offers fresh and comprehensive insights into tissue structure and a foundation for understanding multiple biological mechanisms in diseases, particularly in tumor tissues.
A generalizable scaffold-based approach for structure determination of RNAs by cryo-EM
Authors: Langeberg Conner J , Kieft Jeffrey S 
Published: October 2023

Abstract
Single-particle cryo-electron microscopy (cryo-EM) can reveal the structures of large and often dynamic molecules, but smaller biomolecules (≤50 kDa) remain challenging targets due to their intrinsic low signal to noise ratio. Methods to help resolve small proteins have been applied but development of similar approaches to aid in structural determination of small, structured RNA elements have lagged. Here, we present a scaffold-based approach that we used to recover maps of sub-25 kDa RNA domains to 4.5–5.0 Å. While lacking the detail of true high-resolution maps, these maps are suitable for model building and preliminary structure determination. We demonstrate this method helped faithfully recover the structure of several RNA elements of known structure, and that it promises to be generalized to other RNAs without disturbing their native fold. This approach may streamline the sample preparation process and reduce the optimization required for data collection. This first-generation scaffold approach provides a robust system to aid in RNA structure determination by cryo-EM and lays the groundwork for further scaffold optimization to achieve higher resolution.
CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2016—2020
Authors: Ostrom Quinn T , Price Mackenzie , Neff Corey , Cioffi Gino , Waite Kristin A , Kruchko Carol , Barnholtz-Sloan Jill S 
Published: October 2023

Abstract
The Central Brain Tumor Registry of the United States (CBTRUS), in collaboration with the Centers for Disease Control and Prevention and the National Cancer Institute, is the largest population-based registry focused exclusively on primary brain and other central nervous system (CNS) tumors in the United States (US) and represents the entire US population. This report contains the most up-to-date population-based data on primary brain tumors available and supersedes all previous CBTRUS reports in terms of completeness and accuracy. All rates are age-adjusted using the 2000 US standard population and presented per 100,000 population. The average annual age-adjusted incidence rate (AAAIR) of all malignant and non-malignant brain and other CNS tumors was 24.83 per 100,000 population (malignant AAAIR=6.94 and non-malignant AAAIR=17.88). This overall rate was higher in females compared to males (27.85 versus 21.62 per 100,000) and non-Hispanic persons compared to Hispanic persons (25.24 versus 22.61 per 100,000). Gliomas accounted for 26.3% of all tumors. The most commonly occurring malignant brain and other CNS histopathology was glioblastoma (14.2% of all tumors and 50.9% of all malignant tumors), and the most common predominantly non-malignant histopathology was meningioma (40.8% of all tumors and 56.2% of all non-malignant tumors). Glioblastomas were more common in males, and meningiomas were more common in females. In children and adolescents (ages 0-19 years), the incidence rate of all primary brain and other CNS tumors was 6.13 per 100,000 population. There were 86,030 deaths attributed to malignant brain and other CNS tumors between 2016 and 2020. This represents an average annual mortality rate of 4.42 per 100,000 population and an average of 17,206 deaths per year. The five-year relative survival rate following diagnosis of a malignant brain and other CNS tumor was 35.7%, for a non-malignant brain and other CNS tumor the five-year relative survival rate was 91.8%.
Testing spatial working memory in pigs using an automated T-maze
Authors: Allen L M , Murphy D A , Roldan V , Moussa M N , Draper A , Delgado A , Aguiar M , Capote M A , Jarome T J J , Lee K , Mattfeld A T , Prather R , Allen T A 
Published: October 2023

Abstract
Pigs are an important large animal model for translational clinical research but underutilized in behavioral neuroscience. This is due, in part, to a lack of rigorous neurocognitive assessments for pigs. Here, we developed a new automated T-maze for pigs that takes advantage of their natural tendency to alternate. The T-maze has obvious cross-species value having served as a foundation for cognitive theories across species. The maze (17′ × 13′) was constructed typically and automated with flanking corridors, guillotine doors, cameras, and reward dispensers. We ran nine pigs in (1) a simple alternation task and (2) a delayed spatial alternation task. Our assessment focused on the delayed spatial alternation task which forced pigs to wait for random delays (5, 60, 120, and 240 s) and burdened spatial working memory. We also looked at self-paced trial latencies, error types, and coordinate-based video tracking. We found pigs naturally alternated but performance declined steeply across delays (R2 = 0.84). Self-paced delays had no effect on performance suggestive of an active interference model of working memory. Positional and head direction data could differentiate subsequent turns on short but not long delays. Performance levels were stable over weeks in diverse strains and sexes, and thus provide a benchmark for future neurocognitive assessments in pigs.
Trends of disease activity in Japanese patients over 75 years with rheumatoid arthritis from 2014 to 2021: the ANSWER cohort study
Authors: Yamada Hirotaka , Jinno Sadao , Maeda Toshihisa , Hayashi Shinya , Yamamoto Wataru , Onishi Akira , Onizawa Hideo , Takeuchi Tohru , Hiramatsu Yuri , Okita Yasutaka , Ebina Kosuke , Son Yonsu , Yoshida Naofumi , Watanabe Ryu , Hara Ryota , Yamashita Mai , Nose Yoko , Yamamoto Yuzuru , Okano Takaichi , Nishimura Keisuke , Ueda Yo , Sendo Sho , Hashimoto Motomu , Kuroda Ryosuke , Saegusa Jun 
Published: October 2023

Abstract

Objectives
To investigate if disease activity among elderly RA patients &gt;75 years of age has changed over time in the real-world clinical setting.

Methods
Data from an observational multicentre registry of RA patients in Japan were analysed. The primary outcome was to evaluate the changes in the proportion of very elderly RA patients (&gt;75 years) who achieved remission and low disease activity (LDA), from 2014 to 2021. The secondary outcome was to identify factors associated with remission and LDA by comparing demographic and clinical characteristics among the patients who had a study visit within the study period, using multivariate logistic regression.

Results
A total of 32 161 patient visits were identified from 2014 to 2021. The proportion of patients &gt;75 years of age increased from 16.5% to 26.9%, with biologics and targeted synthetic DMARDs (b/tsDMARDs) use increasing and glucocorticoids use decreasing, while conventional synthetic DMARDs use remained relatively stable. The proportion of RA patients &gt;75 years of age achieving remission and LDA significantly increased from 62.2% to 78.2% (P for trend &lt; 0.001). A negative factor associated with achieving remission and LDA was glucocorticoid use, seropositivity and a history of previous b/tsDMARDs use while MTX use was associated positively, independent of other predictors.

Conclusions
In our cohort, disease activity among very elderly RA patients has improved over time. The study suggests the importance of using a treat-to-target approach in very elderly RA patients to improve clinical outcomes.
The potential role of upregulated PARP-1/RIPK1 expressions in amikacin-induced oxidative damage and nephrotoxicity in Wistar rats
Authors: El Latif Amera Abd , Zahra Abo Elnasr A , Badr AlShimaa , Elbialy Zizy I , Alghamdi Abdullah A A , Althobaiti Norah A , Assar Doaa H , Abouzed Tarek kamal 
Published: October 2023

Abstract
This study aimed to investigate the gene expression levels associated with nephrotoxic action of amikacin, as well as the post-treatment effect of diuretics on its nephrotoxic effects. Sixty male rats were divided equally into six groups, including the control group receiving saline intra-peritoneally (ip), and the five treated groups including therapeutic and double therapeutic dose groups, injected ip (15 and 30 mg/kg b.wt./day) respectively for seven days, and another two rat groups treated as therapeutic and double therapeutic dose groups then administered the diuretic orally for seven days and the last group received amikacin ip at a rate of 15 mg/kg/day for seven days, then given free access to water without diuretics for another seven days and was kept as a self-recovery group. Amikacin caused kidney injury, which was exacerbated by the double therapeutic dose, as evidenced by abnormal serum renal injury biomarkers, elevated renal MDA levels, inhibition of renal catalase and SOD enzyme activities, with renal degenerative and necrotic changes. Moreover, comet assays also revealed renal DNA damage. Interestingly, amikacin administration markedly elevated expression levels of the PARP-1, RIP1, TNF-α, IL-1β, and iNOS genes as compared to the control group. However, compared to the self-recovery group, post-amikacin diuretic treatment modulates amikacin-induced altered findings and alleviates amikacin nephrotoxic effects more efficiently. Our findings suggested the potential role of PARP-1 and RIPK1 expressions that influence the expression of proinflammatory cytokines such as IL-1β and TNF-α by exaggerating oxidative stress which may contribute to the pathogenesis of amikacin-induced nephrotoxicity.
Misophonia and Hearing Comorbidities in a Collegiate Population
Authors: Brennan Caroline R. , Lindberg Ragnar R. , Kim Gibbeum , Castro Ariana A. , Khan Rafay A. , Berenbaum Howard , Husain Fatima T. 
Published: October 2023

Objectives:
Misophonia is a little-understood disorder in which certain sounds cause a strong emotional response in those who experience it. People who are affected by misophonia may find that noises like loud chewing, pen clicking, and/or sniffing trigger intense frustration, anger, or discomfort. The relationship of misophonia with other auditory disorders including loudness hyperacusis, tinnitus, and hearing loss is largely underexplored. This project aimed to investigate the prevalence and hearing-health comorbidities of misophonia in a college-aged population by using an online survey.

Design:
A total of 12,131 undergraduate and graduate students between the ages of 18 and 25 were given the opportunity to answer an in-depth online survey. These students were sampled in a roughly 50 of 50 sex distribution. The survey was created using Qualtrics and included the following components: electronic consent, demographics questionnaire, Misophonia Questionnaire (MQ), Khalfa’s Hyperacusis Questionnaire (HQ), Tinnitus and Hearing Survey, and Tinnitus Functional Index (TFI). To be eligible for compensation, answers for each of the above components were required, with the exception of the TFI, which was only presented to students who indicated that they experienced tinnitus. Respondents were determined to have high or possible likelihood of having misophonia if they gave specific answers to the MQ’s Emotion and Behavior Scale or the MQ Severity Scale.

Results:
After excluding duplicate responses and age-related outliers, 1,084 responses were included in the analysis. Just over 20% (n = 217) of the sample was determined to have a high or probable likelihood of having misophonia. The sample was primarily White, female, and of mid-to-high socioeconomic status. There was a strong positive correlation between MQ total scores and HQ total scores. High likelihood misophonia status showed a significant relationship with self-reported hearing loss and tinnitus. No statistically significant relationship was found between misophonia and age, ethnicity, or socioeconomic status. MQ total scores differed significantly when separating respondents by sex, self-reported tinnitus, and loudness hyperacusis. White respondents had significantly higher MQ total scores than Asian/Asian American respondents.

Conclusions:
The estimated prevalence of misophonia was about 8% to 20% of the sample, which agrees with most of the currently published research examining misophonia symptoms in collegiate populations. Results of data analysis suggest that misophonia severity may be related to loudness hyperacusis, sex, and possibly tinnitus. Future studies are needed to further examine the characteristics of these relationships, possibly in populations more optimized to reflect the general population or those with hearing-health disorders.