bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pan-cancer analysis of the transcriptional expression of histone acetylation enzymes in solid tumors defines a new classification scheme for gliomas
Authors: Zhang Junhao , Li Lingbo , Tang Aiwei , Wang Chucheng , Wang Yupeng , Hu Yongqi , He Guangting , Liao Wangjun , Zhou Rui 
Published: January 2025

IntroductionThe altered expression of genes encoding histone acetyltransferases (HATs) and histone deacetylases (HDACs) has been implicated in the tumorigenesis and progression of various solid tumors. However, systematic characterization of the transcriptomic landscape and clinical relevance of HATs and HDACs in pan-cancer contexts remains lacking.MethodsTranscriptome and clinical data of 9,483 patients across 31 tumor types from The Cancer Genome Atlas were collected for systematic pan-cancer analysis. Additional glioma-specific datasets (Chinese Glioma Genome Atlas, GlioVis, GSE43378, and GSE182109) were also collected to validate the transcriptional characteristics of HATs and HDACs in gliomas. Consensus clustering analysis was applied to identify distinct expression patterns of HATs and HDACs.ResultsBased on the transcriptomic data of 25 genes encoding 9 HATs and 16 HDACs, we identified five major subtypes across 31 cancer types (AC-I to AC-V). Notably, the AC-V subtype comprised over 95% of glioma patients, suggesting glioma patients exhibited distinct expression patterns of histone acetylation-modifying enzymes compared to patients with other solid tumors. Therefore, we re-conducted the consensus clustering analysis specifically within the context of gliomas and identified five subtypes, denoted “AC-GI” to “AC-GV”, which were characterized by differences in HATs/HDACs expression patterns, biological and immune status, genetic alterations, and clinical outcomes. The AC-GII patients exhibited the best prognosis and were sensitive to temozolomide, while AC-GV patients had the poorest prognosis and the lowest sensitivity to temozolomide among all subtypes. Moreover, based on the Connectivity Map database analysis and experimental verification, we identified several pan-HDAC inhibitors that could serve as sensitizers for temozolomide therapy in AC-GV patients, such as panobinostat and scriptaid. Considering the distinctive clinical characteristics of patients with AC-GII and AC-GV, we constructed the “ACG score” model capable of effectively recognizing patients with these subtypes and predicting patient prognosis.ConclusionHerein, we established novel biologically and clinically relevant molecular classifications for pan-solid tumors and gliomas based on transcriptional expression profiles of HATs and HDACs. Moreover, the ACG score model, calculated by the transcriptional expression of 29 genes, was not only an independent prognostic factor for glioma patients, but can also provide valuable references for promoting more effective therapeutic strategies.
Serum decorin and biglycan levels as predictive biomarkers for lung fibrosis severity and mortality risk in COVID-19 patients
Authors: Ahmad Shaaf , Maqsood Kaleem , Liaqat Farwa , Roohi Nabila 
Published: January 2025

IntroductionIndividuals experiencing severe symptoms of COVID-19 are at the greatest risk of developing post-COVID lung fibrosis, which significantly impacts long-term health outcomes. This study aims to investigate the predictive potential of serum biomarkers, specifically decorin and biglycan, in assessing the severity and mortality risk among COVID-19 patients.MethodsFor this study, healthy controls and COVID-19 patients (n = 240) among them 186 with moderate and 54 with severe symptoms from Ittefaq Hospital and Mayo Hospital, Lahore, Pakistan were recruited satisfying the inclusion and exclusion criteria. Patients were followed up for 2 months. Serum level of decorin and biglycan was evaluated by ELISA. One-way ANOVA and Independent sample “t”-test were applied at significance level p &lt; 0.05 by using GraphPad Prism.ResultsDecorin levels significantly decreased from controls (43.36 ± 1.14 ng/mL) to moderate (40.24 ± 0.64 ng/mL) and severe COVID-19 patients (35.49 ± 1.00 ng/mL) (p = 0.0059). Biglycan levels increased from controls (66.15 ± 2.22 pg/mL) to moderate (70.02 ± 1.57 pg/mL) and severe patients (75.88 ± 1.97 pg/mL) (p = 0.0042). In follow-up, survivors had higher decorin (39.6 ± 0.59 ng/mL) than non-survivors (35.84 ± 1.61 ng/mL) (p = 0.0319). Biglycan levels were similar between survivors (70.98 ± 1.41 pg/mL) and non-survivors (73.99 ± 3.24 pg/mL) (p = 0.459). Higher decorin levels correlate with survival in COVID-19 patients.ConclusionSerum decorin and biglycan levels are valuable biomarkers for predicting severity and mortality in COVID-19 patients. Lower decorin and higher biglycan levels correlate with increased disease severity, emphasizing their potential to identify patients at risk for lung fibrosis and guide clinical management.
Identification of nuclear valosin-containing-protein-like as a target of anti-nuclear autoantibodies in systemic sclerosis
Authors: Zeng Zitao , Miske Ramona , Scharf Madeleine , Denno Yvonne , Ott Anthonina , Brakopp Stefanie , Teegen Bianca , Stöcker Winfried , Siegert Elise , Saschenbrecker Sandra , Probst Christian , Komorowski Lars 
Published: January 2025

ObjectiveTo identify the target antigen of an anti-nuclear autoantibody (ANA) from a patient with a suspected systemic autoimmune disease and to study the autoantibody’s clinical association.MethodsThe index patient serum was screened for autoantibodies using indirect immunofluorescence assay (IFA) and line blots (membrane strips coated with parallel lines of different purified antigens). Immunoprecipitation with fixed HEp-2 cells followed by SDS-PAGE and MALDI-TOF mass spectrometry was used to identify the autoantigen, which was verified by competitive inhibition experiments, recombinant HEK293 cell-based IFA, and Western and line blots based on the recombinant antigen. The prevalence of autoantibodies against this antigen was studied in 693 patients with systemic autoimmune rheumatic diseases (SARD) and 150 healthy controls.ResultsThe index patient serum displayed a homogeneous nucleolar staining pattern on HEp-2 cells and monkey liver by IFA but did not react with 27 known nuclear antigens. Nuclear valosin-containing-protein-like (NVL) was identified as the ANA target antigen. Preincubation with recombinant NVL abolished the reactivity of the patient serum with HEp-2 cells in IFA. Additionally, the patient serum reacted with recombinant NVL in cell-based IFA and Western blot analysis, whereas sera from 15 healthy controls were nonreactive. Using line blots coated with recombinant NVL, anti-NVL autoantibodies were exclusively found in four out of 378 patients with systemic sclerosis, but neither in 315 patients with other SARD nor in 150 healthy controls.ConclusionThese findings indicate that autoantibodies against NVL may be a suitable marker to help narrowing the serological gap in systemic sclerosis.
Effect of continuous theta burst stimulation on the glymphatic system, brain network and cognitive function in patients with cerebral small vessel disease
Authors: Dai Pei , Yu Hui-xian , Wang Zhao-xia , Liu Si-hao , Liu Chang-bin , Xu Guang-qing 
Published: January 2025

ObjectiveWe aim to investigate the impact of continuous theta burst stimulation (cTBS) on glymphatic system (GS), brain network (BN) and cognition in cerebral small vessel disease (CSVD).MethodsThis exploratory study included a small cohort of 11 patients, divided into a cTBS group (6 patients) and a sham-cTBS group (5 patients). Over a period of 2 weeks, all participants underwent cTBS to the right dorsolateral prefrontal cortex (DLPFC). The efficiency of the GS was assessed by along the perivascular space (ALPS) index. BN was measured using global efficiency (GE), characteristic path length (CPL) and clustering coefficient (Cp). Cognition was evaluated by Montreal Cognitive Assessment (MoCA).ResultsIn the cTBS group, the ALPS index increased 4 out of 6 after treatment, compared to an increase in only 2 out of 5 in the control. Improvements in GE, CPL and Cp were observed in 4 out of 6 patients in the cTBS group, whereas no improvements were noted in the control group. The MoCA scores for all patients in the cTBS improved after treatment. Additionally, completion times of the Stroop color and word test C (Stroop C) were reduced for all individuals in the cTBS group, while the control saw an increase in one case. The Digital Span Test-backward (DST-backward) scores were significantly higher in the cTBS group than those in the control.ConclusionApplying cTBS to the DLPFC in CSVD may enhance the efficiency of brain glymphatic clearance, optimize network connectivity and improve cognitive function to a certain extent.
Genome-wide identification and expression analysis of bHLH gene family revealed their potential roles in abiotic stress response, anthocyanin biosynthesis and trichome formation in Glycyrrhiza uralensis
Authors: Ding Guohua , Shi Yanping , Xie Kerui , Li Hongbin , Xiao Guanghui 
Published: January 2025

IntroductionLicorice stands out as an exceptional medicinal resource with a long history of application, attributed to its substantial pharmacological potential. The basic helix-loop-helix (bHLH) transcription factors (TFs) gene family, being the second-largest in plants, is vital for plant development and adapting to environmental shifts. Despite this, the comprehensive characteristics of licorice bHLH gene family are not well-documented.ResultsIn this study, a detailed and thorough genome-wide identification and expression analysis of Glycyrrhiza uralensis bHLH gene family was carried out, resulting in the identification of 139 licorice bHLH members. Our duplication analysis highlighted the significant contribution of segmental duplications to the expansion of G. uralensis bHLH genes, with GubHLH genes experiencing negative selection throughout evolution. It was discovered that GubHLH64 and GubHLH38 could be importantly linked to the licorice trichome initiation and anthocyanin biosynthesis and GubHLH64 was also involved in the abiotic stress response. Additionally, certain subfamily III (d+e) GubHLH members could be implicated in the licorice drought response. GubHLH108, GubHLH109, and GubHLH116 were suggested to form a tightly related cluster, initiating transcriptional responses via JA signaling pathway.DiscussionIn summary, our findings furnish a foundational understanding for future investigations of GubHLH gene functions and regulation mechanisms, shedding light on the potential applications of licorice in medicine and agriculture.
MOUD 2.0: a clinical algorithm and implementation evaluation protocol for sublingual and injectable buprenorphine treatment of opioid use disorder
Authors: Joa Brandon L. , Fung Eric N. , Weinstein Michael S. , Weinstein Lara C. 
Published: January 2025

BackgroundPrimary care is the initial contact point for most patients with opioid use disorder (OUD) but lacks tools for guiding treatment. Only a small fraction of patients access evidence-based care. Long-acting injectable buprenorphine has potential to improve medication adherence and program retention in low-barrier primary care treatment settings. We present the first clinical decision support algorithm incorporating long-acting buprenorphine (LAIB) in primary care. We include a protocol for a future evaluation of the algorithm’s implementation process, “Medication for Opioid Use Disorder (MOUD) 2.0,” at a housing and integrated care clinic at a Federally Qualified Health Center.MethodsLiterature review and expert consensus informed creation of the algorithm, which underwent iterative development with feedback from clinicians, staff, and patients. Patients are categorized by adherence to therapy and retention in the program, with recommendations for each category. Adherence is determined by urine screen supplemented by self-report. To ensure all patients in this high morbidity and mortality risk population are treated, we will treat patients as their own controls in the evaluation, with potential for multisite comparisons. We will present descriptive statistics for adherence proportion before and after MOUD 2.0 implementation, testing for differences using McNemar’s test. We will then present pre- and post-implementation unadjusted six-month survival curves for retention.DiscussionLAIB is incorporated as an alternative or adjunctive treatment for patients refractory to sublingual buprenorphine and as an initial treatment for selected patients. We developed an algorithm with 4-, 8-, and 12-week decision points to guide treatment for patients with varying levels of response to sublingual buprenorphine and LAIB. This clinical decision tool incorporates LAIB among treatment options for OUD in primary care settings. The protocol will evaluate the algorithm’s implementation, presenting a replicable method for assessing adherence and retention among high-risk patients in similar settings.
Dyadic examination of rumination and depressive symptoms in Chinese heterogeneous young couples: the differential role of gender
Authors: Liu Xiaoyu , Zhou Anji , Jin Zhuyun , Han Zhuo Rachel , Qian Jing , Wang Hui 
Published: January 2025

IntroductionThe relationship between rumination and depressive symptoms has been extensively studied over the past two decades. However, few studies have explored how rumination contributes to depressive symptoms within the context of heterogeneous romantic relationships, particularly regarding potential gender differences in these effects. The present study aims to investigate whether rumination is related to four key factors of depressive symptoms (i.e., depressed affect, positive affect, somatic and retarded activity, interpersonal distress) both on the intrapersonal and interpersonal levels among young couples.MethodsParticipants were 148 Chinese young couples (N = 296; males: M age = 21.94 years, SD = 2.40 years; females: M age = 21.62 years, SD = 2.26 years). Couples completed self-reported questionnaires assessing rumination and depressive symptoms separately, using the Ruminative Response Scale (RRS) and the Center for Epidemiologic Studies Depression Scale (CES-D).ResultsThe results of a series of actor-partner interdependence models (APIM) showed that, on the intrapersonal level, rumination was positively and significantly associated with an individual’s own depressed affect, somatic and retarded activity, and interpersonal distress. On the interpersonal level, higher levels of rumination in males were associated with increased depressed affect and interpersonal distress in their female partners. However, no such partner effect was observed for male partners of ruminative females.ConclusionsThese findings suggest that females in romantic relationships, as compared to males, may be more susceptible to the influence of their male partners’ rumination. This study is among the firsts to demonstrate the gender-specific effect in the relationship between rumination and depressive symptoms in young couples.
Resilience and vulnerability of post-ostomy patients with early-onset colorectal cancer from the perspective of social-ecological theory: a qualitative study
Authors: Yang Fangfang , Feng Fangming , Gu Hongming , Liang Han , Zhang Jin , Cheng Yusha , Zhang Weiying 
Published: January 2025

BackgroundThe incidence rate of colorectal cancer (CRC) is rising among adults under the age of 50 (early-onset colorectal cancer, EOCRC). Post-ostomy dysfunction, along with negative perceptions due to incorrect public views and a decline in quality of life, has a significant impact on these individuals, their families, and social relationships.ObjectiveBy understanding the adaptation process of post-ostomy EOCRC(POEOCRC) patients, this study aims to provide information for developing targeted nursing interventions for this population.MethodsBased on the social-ecological theory, semi-structured, in-depth interviews were conducted with 16 POEOCRC patients in China between May 2023 and January 2024.Colaizzi’s method of phenomenology was employed for data analysis.ResultsThis study found two aspects of adaptation experience in POEOCRC patients. For resilience, three themes emerged:(1) Micro-Positive individual psychological experiences, (2) Meso-Positive adjustment within the family and (3) Macro-Social resource integration and utilization. In terms of vulnerability, three themes were as follows:(1) Micro-Persistent negative experiences, (2) Meso-Family crisis caused by the ostomy and (3) Macro-Urgency and fragility of social support.ConclusionThis study based on the social-ecological theory and highlights different dimensions of resilience and vulnerability experienced by POEOCRC patients. Early and targeted interventions to promote patients’ coping skills and their ability to adapt to family and society.
The evolutionary journey to a new normal for learning and capacity building of healthcare workers to prepare and respond to health emergencies across Africa
Authors: Bonkoungou Boukaré , Mosha Fausta , Abianuru Amarachi , Okeibunor Joseph , Utunen Heini , Balaciano Giselle , Barbosa de Lima Ana C. , Burke Lauren , McKenna Shannon , Nag Sukriti , Gueye Abdou Salam , Struminger Bruce 
Published: January 2025

BackgroundFaced with the COVID-19 mobility restrictions, the WHO AFRO EPR program pioneered a collaborative initiative with Project ECHO to virtually educate health workers across Africa at scale. This initiative has evolved into a transformative learning journey. This paper aims to present the lessons learned.ResultsFrom April 2020 to February 2024, 287 virtual learning sessions were conducted with over 125,816 attendances from 173 countries and regions. This marked a significant increase compared to pre-pandemic face-to-face training, which targeted fewer than 2,000 participants annually. Survey responses (n = 43,221) indicated high relevance and applicability, with 97% of respondents planning to use the information in their work and 89% finding the sessions very or extremely relevant. Self-reported knowledge levels increased from 28 to 74% post-session.DiscussionIntegrating digital learning into WHO AFRO's education and training toolkit has facilitated immediate emergency responses and enhanced long-term resilience, adaptability, and equity among healthcare workers, especially in under-resourced regions. This initiative has reached more health professionals than pre-pandemic in-person training, facilitating more equitable access to essential knowledge and best practices.ConclusionThe WHO AFRO and Project ECHO partnership navigated a variety of challenges, while establishing a paradigm shift in learning strategies. Emphasizing a digital learning first approach, while retaining in-person elements, this collaborative initiative offers insights for future healthcare education, highlighting adaptability, cost-efficiency, equity, and new technologies in addressing global health challenges. However, to sustain this momentum and further expand access to critical knowledge, stakeholders must commit to continued investment in digital learning infrastructure, training, and technology.
Substance use and social influence as risk factors for nicotine and tobacco product use in adolescents and young adults who use electronic nicotine delivery systems
Authors: Hatz Laura E. , Courtney Kelly E. , Wallace Alexander L. , Wade Natasha E. , Baca Rachel , Doran Neal , Jacobus Joanna 
Published: January 2025

BackgroundNicotine and tobacco product (NTP) use in adolescence and young adulthood is associated with negative health and psychosocial outcomes. This study prospectively tested alcohol use, cannabis use, and peer and family NTP use as predictors of NTP use in adolescents and young adults (AYAs) who were NTP naïve or who primarily used electronic nicotine delivery systems (ENDS).MethodParticipants (N = 133) ages 16–22 completed a baseline laboratory visit and follow-up session 1 year later. Participants’ baseline alcohol use, cannabis use, and NTP use by peers and family were tested as risk factors for any and moderate to heavy (at least monthly) NTP use at follow-up. Logistic regressions were conducted for the full sample (N = 133) and in a subsample of participants reporting no to low NTP use at baseline (n = 76).ResultsBaseline alcohol use, cannabis use, and peer and family NTP use were associated with NTP use at 1-year follow-up, over and above baseline NTP use. Peer and family NTP use emerged as the most consistent predictor of AYA NTP use (ORs: 4.059–8.432), while recent cannabis and alcohol use exerted effects (ORs: 1.003–1.021) that varied by NTP use level.DiscussionA confluence of variables, including prior substance use and social and familial influences, act as risk factors for NTP use in AYAs who primarily use ENDS. Identification of risk and protective factors for NTP use is necessary to inform efforts to decrease NTP use in this developmentally vulnerable population.
IMAGINER 2—improving accuracy with augmented realIty navigation system during placement of external ventricular drains over Kaufman's, Keen's, Kocher's and Frazier's point
Authors: Vychopen Martin , Kropla Fabian , Winkler Dirk , Güresir Erdem , Grunert Ronny , Wach Johannes 
Published: January 2025

BackgroundExternal ventricular drain (EVD) placement is a routine neurosurgical procedure used to treat acute hydrocephalus and monitor intracranial pressure. Kocher's point is the most commonly used anatomical landmark, but other entry points can be challenging even for experienced neurosurgeons. Augmented reality (AR) may enhance the accuracy and safety of these procedures. Previous studies demonstrated improved ventriculostomy accuracy using AR among novices. This study evaluates AR's impact on EVD placement accuracy performed by experienced neurosurgeons.MethodsEighteen neurosurgical experts performed ventriculostomies on a Styrofoam head model using Kaufman's, Keen's, Kocher's, and Frazier's points. Punctures were performed freehand (Freehand group) and with AR assistance (AR group). Post-procedure CT scans were used to compare the actual catheter tip positions with the ideal positions. Accuracy was assessed by the distance between real and ideal catheter tips and by Kakarla grading.ResultsThe AR group had a mean tip distance of 16.93 ± 9.38 mm compared to 21.71 ± 9.69 mm in the Freehand group (p = 0.003). The AR group also showed better Kakarla grading outcomes (Grade 1: n = 26, Grade 3: n = 26) vs. the Freehand group (Grade 1: n = 7, Grade 3: n = 53; p &lt; 0.0001). Neurosurgeons with ≥7 years of experience demonstrated higher accuracy across both methods (p = 0.040).ConclusionAR significantly enhances the accuracy of EVD placement, particularly using Kaufman's, Keen's, Kocher's, and Frazier's points, with experienced neurosurgeons benefiting the most from AR assistance.