bluuebunny/crossref_metadata_2025_split huggingface dataset:
Case Report: Craniofacial deafness hand syndrome with unusual cardiovascular symptoms and lack of holistic care
Authors: Saenz Hinojosa Samantha , Reyes-Silva Carlos , Hosomichi Kazuyoshi , Romero Vanessa I. 
Published: January 2025

BackgroundDelays in diagnosing rare genetic disorders often arise due to limited awareness and systemic challenges in primary care. This case highlights the importance of a holistic approach to patient care, encompassing timely detection and comprehensive evaluation of clinical features.MethodsWe report the case of a 21-year-old Ecuadorian male with facial and hand dysmorphias, cardiomegaly, pulmonary hypertension, and patent ductus arteriosus (PDA). Whole-exome sequencing, performed using the Illumina NextSeq platform. We extensively analyzed over 100 genes linked to congenital structural heart diseases.ResultsThe genetic findings provided a definitive diagnosis of Craniofacial-Deafness-Hand Syndrome, an extremely rare autosomal dominant condition, but found no variants that explain the patient’s cardiac phenotype. We identified a novel pathogenic missense variant in the PAX3 gene (c.A91C, p. T31P).Discussion and conclusionsThis case underscores the necessity of integrating genetic testing into routine clinical practice to enhance diagnostic precision for rare diseases. It also highlights the need for multidisciplinary collaboration and a holistic care model to improve patient outcomes. The unique association of Craniofacial-Deafness-Hand Syndrome with cardiovascular anomalies due to a PAX3 variation provides valuable insights into the genetic underpinnings of this rare condition.
Mapping the use of cardiovascular genetic services in pediatric clinical care: challenges and opportunities for improvement
Authors: Hundal Kerstin , Scherr Courtney L. , Fakhari Hoda , Ramesh Sanjana , Dellefave-Castillo Lisa , Duquette Deb , Cherny Sara , McNally Elizabeth M. , Webster Gregory , Rasmussen-Torvik Laura J. 
Published: January 2025

PurposeClinical genetic testing is increasingly integrated in managing and diagnosing cardiac conditions and disease. It is important to identify ongoing challenges. This study aimed to better understand how genetic testing is integrated into pediatric cardiac care and identify barriers and opportunities for improvement.MethodsWe conducted qualitative interviews with pediatric cardiology clinicians (N = 12). Following a journey mapping approach to data analysis, we described genetic testing workflow phases, participants’ thoughts and behaviors within each phase, and barriers and opportunities for improvement.ResultsParticipants described several challenges across the genetic testing workflow, from identifying patients for testing to disclosing results to the patients. Testing logistics, decision-making, and collaboration emerged as the most prominent challenges. Variation remains in the utilization of genetic testing, partially driven by case complexity and type of testing and attributable to other factors, like the level of interaction with genetics experts and inconsistent processes within the electronic medical record.ConclusionClinical genetic pediatric cardiology requires more systematic integration of genetic testing and transparent processes. Major opportunities include the interplay between clinicians, genetic experts, and the EMR. Incorporating process mapping results into clinical logistics may eradicate some barriers experienced by pediatric cardiologists and increase clinical efficiency.
Dual disease co-expression analysis reveals potential roles of estrogen-related genes in postmenopausal osteoporosis and Parkinson’s disease
Authors: Yu Dongdong , Kang Jian , Ju Chengguo , Wang Qingyan , Qiao Ye , Qiao Long , Yang Dongxiang 
Published: January 2025

IntroductionThe deficiency of estrogen correlates with a range of diseases, notably Postmenopausal osteoporosis (PMO) and Parkinson’s disease (PD). There is a possibility that PMO and PD may share underlying molecular mechanisms that are pivotal in their development and progression. The objective of this study was to identify critical genes and potential mechanisms associated with PMO by examining co-expressed genes linked to PD.MethodsInitially, pertinent data concerning PMO and PD were obtained from the GWAS database, followed by conducting a Bayesian colocalization analysis. Subsequently, co-expressed genes from the PMO dataset (GSE35956) and the PD dataset (GSE20164) were identified and cross-referenced with estrogen-related genes (ERGs). Differentially expressed genes (DEGs) among PMO, PD, and ERGs were subjected to an array of bioinformatics analyses, including Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses, in addition to protein-protein interaction (PPI) network analysis. The study also involved constructing TF-gene interactions, TF-microRNA coregulatory networks, interactions of hub genes with diseases, and validation through quantitative reverse transcription polymerase chain reaction (qRT-PCR).ResultsThe colocalization analysis uncovered shared genetic variants between PD and osteoporosis, with a posterior probability of colocalization (PPH4) measured at 0.967. Notably, rs3796661 was recognized as a shared genetic variant. A total of 11 genes were classified as DEGs across PMO, PD, and ERGs. Five principal KEGG pathways were identified, which include the p53 signaling pathway, TGF-beta signaling pathway, cell cycle, FoxO signaling pathway, and cellular senescence. Additionally, three hub genes—WT1, CCNB1, and SMAD7—were selected from the PPI network utilizing Cytoscape software. These three hub genes, which possess significant diagnostic value for PMO and PD, were further validated using GEO datasets. Interactions between transcription factors and genes, as well as between microRNAs and hub genes, were established. Ultimately, the expression trends of the identified hub genes were confirmed through qRT-PCR validation.ConclusionsThis study is anticipated to offer innovative approaches for identifying potential biomarkers and important therapeutic targets for both PMO and PD.
Disclosure of oral pre-exposure prophylaxis use for HIV prevention among women enrolled in a contraceptive study: qualitative findings from Durban, South Africa
Authors: Beesham Ivana , Beksinska Mags , Milford Cecilia , Mansoor Leila E. 
Published: January 2025

BackgroundDisclosure of oral pre-exposure prophylaxis (PrEP) use for HIV prevention may improve adherence to PrEP; however, disclosure can be challenging and may result in stigma. Here, we describe disclosure of PrEP use among young women enrolled in a contraceptive study.MethodsIn this qualitative study, we conducted semi-structured, in-depth, face-to-face interviews with 13 women aged 18–25 years who initiated oral PrEP for HIV prevention during the Evidence for Contraceptive Options and HIV Outcomes (ECHO) Trial. Interviews were conducted in 2021 with women from Durban, South Africa. In this analysis, we explore women's experiences of PrEP disclosure including whether they disclosed PrEP use, who they disclosed to and the reaction to disclosure, and the impact of disclosure on PrEP use. Interviews were conducted in English, audio-recorded and transcribed. Data were analysed thematically.ResultsAll women disclosed oral PrEP use to at least one individual, with some women disclosing to multiple individuals including family, friends, partners and community members. Few women did not disclose oral PrEP use to their partner due to anticipating a negative reaction from the partner, feeling that the partner would assume the woman has HIV and is taking antiretroviral therapy and fear that the partner would associate PrEP use with the woman having other partners. Reactions to oral PrEP disclosure were generally supportive or neutral, however, few women reported negative reactions that included distrust in the efficacy of PrEP to prevent HIV, discouraging the woman from using oral PrEP because of the assumption that PrEP is HIV treatment, and concern about the woman having oral PrEP side effects. Negative reactions to disclosure generally did not impact on oral PrEP use. Supportive disclosures sometimes resulted in reminders for oral PrEP dosing.ConclusionOur findings indicate that women are willing to disclose their PrEP use to at least one other person when supported. These study findings may contribute to future PrEP counselling guidelines and strategies.
Protective or limited? Maternal antibodies and RSV-associated lower respiratory tract infection in hospitalized infants aged 28-90 days
Authors: Li Shuanglian , Mei Chenghao , Chen Sainan , Wang Chenglin , Gao Yelei , Ma Jinhua , Zhong Li , Luo Tingting , Zhao Xin , Bu Huaqin , Lyu Ying , Kuang Xiaohu , Jia Zhenxing , Wang Xiaoli , Wang Yuqing , Tian Daiyin 
Published: January 2025

BackgroundRespiratory syncytial virus (RSV) is a major cause of severe health problems in newborns and young children. The protective role and limitations of serum maternal RSV antibodies in infants under 3 months remain controversial.MethodsA two-center prospective study from 2020 to 2023 recruited infants (n=286) admitted to the respiratory departments of two children’s hospitals in southwestern and southeastern China during RSV epidemic. These infants were hospitalized with lower respiratory tract infections (LRTI). We evaluated the relationship between serum RSV Prefusion (Pre-F), postfusion (Post-F) IgG levels, subtype neutralizing antibodies, and the incidence of RSV infection, as well as the relationship between these maternal antibodies and severity of disease. Since this prospective study only included data from RSV epidemic, we retrospectively reviewed medical records from the Children’s Hospital of Chongqing Medical University for the years 2019 to 2023 (n=3467) to analyze population characteristics during both RSV epidemic and non-epidemic periods, using the same inclusion and exclusion criteria.ResultThere were no significant differences in RSV Pre-F IgG, Post-F IgG, or RSV A or B neutralizing antibody levels between the RSV infected and non-infected groups during the epidemic. While RSV Pre-F IgG antibody was inversely correlated with disease severity, RSV Post-F IgG, and RSV A and B neutralizing antibodies did not show a similar correlation across the three illness severity categories. Additionally, there were no differences in age, gender, or illness severity distribution among hospitalized patients during epidemic and non-epidemic periods.ConclusionSerum maternal antibody levels offer insufficient protection against RSV-associated LRTI in hospitalized infants aged 28 to 90 days.
Active withdrawal of corticosteroids using tocilizumab and its association with autoantibody profiles in relapsed Takayasu arteritis: a multicentre, single-arm, prospective study (the Ab-TAK study)
Authors: Shirai Tsuyoshi , Ishii Tomonori , Okazaki Soshi , Shirota Yuko , Ishii Yusho , Sato Hiroko , Fujii Hiroshi 
Published: January 2025

ObjectivesThe feasibility of corticosteroid withdrawal (CW) for Takayasu arteritis (TAK) remains uncertain. Two autoantibodies (Abs) are identified against endothelial protein C receptor (EPCR) and scavenger receptor class B type 1 (SR-BI) in TAK, determining its three subgroups. This study aimed to evaluate CW using tocilizumab (TCZ) and its association with the Ab profile.MethodsThis prospective study, lasted for 24 weeks, included patients with relapsed but stable TAK. Scheduled tapering of prednisolone (PSL) was performed with subcutaneous TCZ (CW at week 20). The primary endpoint was the difference in type A remission, defined by CW and the absence of inflammatory signs, according to the Ab profile at week 24.ResultsTwenty patients were included and 18 patients with a mean PSL dose of 4.9 ± 2.8 mg/day were analysed. Anti-EPCR Ab-positive (E+), anti-SR-BI Ab-positive (S+), and double-negative (DN) groups included four (22.2%), eight (44.4%), and six (33.3%) patients, respectively. At week 24, the mean PSL dose was 2.0 ± 2.7 mg/day. Type A remission was observed in eight patients (44.4%), with significant differences based on the Ab profile: E+ (three patients, 75%), S+ (five patients, 62.5%), and DN (zero patients, 0%) (P=0.018). Besides, age, disease duration, PSL dose, type V arterial lesion, arterial dilation, and C-reactive protein &gt;0.01 mg/dL were identified as risks for CW failure.ConclusionCW using TCZ was achieved in 44.4% of patients with TAK relapse and was significantly higher in E+ and S+ patients. CW can be a feasible target, and the precise selection of patients is critical.
Magnitude and dynamics of the T-cell response to SARS-CoV-2 infection at both individual and population levels
Authors: Snyder Thomas M. , Gittelman Rachel M. , Klinger Mark , May Damon H. , Osborne Edward J. , Taniguchi Ruth , Jabran Zahid H. , Kaplan Ian M. , Dines Jennifer N. , Noakes Matthew T. , Pandya Ravi , Chen Xiaoyu , Elasady Summer , Svejnoha Emily , Ebert Peter , Pesesky Mitchell W. , De Almeida Patricia , O’Donnell Hope , DeGottardi Quinn , Keitany Gladys , Lu Jennifer , Vong Allen , Elyanow Rebecca , Fields Paul , Al-Asadi Hussein , Greissl Julia , Baldo Lance , Semprini Simona , Cerchione Claudio , Nicolini Fabio , Mazza Massimiliano , Delmonte Ottavia M. , Dobbs Kerry , Laguna-Goya Rocio , Carreño-Tarragona Gonzalo , Barrio Santiago , Imberti Luisa , Sottini Alessandra , Quiros-Roldan Eugenia , Rossi Camillo , Biondi Andrea , Bettini Laura Rachele , D’Angio Mariella , Bonfanti Paolo , Tompkins Miranda F. , Alba Camille , Dalgard Clifton , Sambri Vittorio , Martinelli Giovanni , Goldman Jason D. , Heath James R. , Su Helen C. , Notarangelo Luigi D. , Paz-Artal Estela , Martinez-Lopez Joaquin , Howie Bryan , Carlson Jonathan M. , Robins Harlan S. 
Published: January 2025

IntroductionT cells are involved in the early identification and clearance of viral infections and also support the development of antibodies by B cells. This central role for T cells makes them a desirable target for assessing the immune response to SARS-CoV-2 infection.MethodsHere, we combined two high-throughput immune profiling methods to create a quantitative picture of the T-cell response to SARS-CoV-2. First, at the individual level, we deeply characterized 3 acutely infected and 58 recovered COVID-19 subjects by experimentally mapping their CD8 T-cell response through antigen stimulation to 545 Human Leukocyte Antigen (HLA) class I presented viral peptides. Then, at the population level, we performed T-cell repertoire sequencing on 1,815 samples (from 1,521 COVID-19 subjects) as well as 3,500 controls to identify shared “public” T-cell receptors (TCRs) associated with SARS-CoV-2 infection from both CD8 and CD4 T cells.ResultsCollectively, our data reveal that CD8 T-cell responses are often driven by a few immunodominant, HLA-restricted epitopes. As expected, the T-cell response to SARS-CoV-2 peaks about one to two weeks after infection and is detectable for at least several months after recovery. As an application of these data, we trained a classifier to diagnose SARS-CoV-2 infection based solely on TCR sequencing from blood samples, and observed, at 99.8% specificity, high early sensitivity soon after diagnosis (Day 3–7 = 85.1% [95% CI = 79.9–89.7]; Day 8–14 = 94.8% [90.7–98.4]) as well as lasting sensitivity after recovery (Day 29+/convalescent = 95.4% [92.1–98.3]).DiscussionThe approaches described in this work provide detailed insights into the adaptive immune response to SARS-CoV-2 infection, and they have potential applications in clinical diagnostics, vaccine development, and monitoring.
Frailty assessment in adults undergoing allogeneic hematopoietic cell transplantation: insights from a multicenter GETH-TC study to optimize outcomes and care
Authors: Salas María Queralt , Solano María Teresa , Baile González Mónica , Acera Gómez Marina , Fox Laura , Pérez Artigas María del Mar , Santamaría Ana , Quintela González María del Carmen , Sánchez Salinas Andrés , Salmerón Camacho Joaquina M. , Illana Álvaro Verónica , Abdallahi-Lefdil Zahra , Cornago Navascues Javier , Pardo Laura , Fernández-Luis Sara , Vega Suárez Leddy Patricia , Villar Sara , Beorlegui-Murillo Patricia , Esquirol Albert , Izquierdo García Isabel , Rodríguez González Sonia , Mussetti Alberto , Lavilla Esperanza , Lopez-Marín Javier , Filaferro Silvia , Cedillo Ángel , Bento Leyre , Sureda Anna 
Published: January 2025

IntroductionThis multicenter prospective study sponsored by the Grupo Español de Transplante Hematopoyético y Terapia Celular (GETH-TC) explores the use of frailty assessments in allo-HCT candidates.MethodsFrailty was measured using the HCT Frailty Scale at first consultation and HCT admission in 404 adults from 15 HCT programs in Spain. Based on the results, patients were classified into fit, pre-frail and frail categories. Allo-HCT outcomes were analyzed according to the results obtained from the HCT Frailty Scale. Data was collected prospectively and all patients signed informed consent.ResultsAt first consultation, 102 (26.2%) patients were classified as fit, 248 (61.4%) as pre-frail, and 50 (12.4%) as frail. During the study, 62 (15.2%) patients participated in a pre-habilitation program. Among non-pre-habilitated patients (n=342), the proportion of fit patients decreased from 26.6% to 16.7%, while frail patients increased from 12.7% to 19.9%. In contrast, pre-habilitated patients (n=62) showed improvements, with fit patients increasing from 24.2% to 46.8%, and frail patients decreasing from 9.7% to 3.2%. Multivariate analysis confirmed lower OS (HR 2.52, P=0.002) and higher NRM (HR 2.69, P=0.013) in frail patients at HCT admission compared to fit ones, with a trend towards lower OS in pre-frail patients (HR 1.54, P=0.097).ConclusionThis study highlights the feasibility of incorporating the HCT Frailty Scale into clinical practice, confirms its negative impact of frailty on transplant outcomes, and suggests that frailty is dynamic and potentially reversible through pre-transplant interventions.
Single-cell RNA sequencing and immune microenvironment analysis reveal PLOD2-driven malignant transformation in cervical cancer
Authors: Lin Zhiheng , Wang Fengxin , Yin Renwu , Li Shengnan , Bai Yuquan , Zhang Baofang , Sui Chenlin , Cao Hengjie , Su Dune , Xu Lianwei , Wang Honghong 
Published: January 2025

BackgroundCervical cancer is the fourth most common cancer in women globally, and the main cause of the disease has been found to be ongoing HPV infection. Cervical cancer remains the primary cause of cancer-related death despite major improvements in screening and treatment approaches, especially in low- and middle-income nations. Therefore, it is crucial to investigate the tumor microenvironment in advanced cervical cancer in order to identify possible treatment targets.Materials and methodsIn order to better understand malignant cervical cancer epithelial cells (EPCs), this study used bulk RNA-seq data from UCSC in conjunction with single-cell RNA sequencing data from the ArrayExpress database. After putting quality control procedures into place, cell type identification and clustering analysis using the Seurat software were carried out. To clarify functional pathways, enrichment analysis and differential gene expression were carried out. The CIBERSORT and ESTIMATE R packages were used to evaluate the immune microenvironment characteristics, and univariate and multivariate Cox regression analyses were used to extract prognostic features. Furthermore, assessments of drug sensitivity and functional enrichment were carried out.ResultsEight cell types were identified, with EPCs showing high proliferative and stemness features. Five EPC subpopulations were defined, with C1 NNMT+ CAEPCs driving tumor differentiation. A NNMT CAEPCs Risk Score (NCRS) model was developed, revealing a correlation between elevated NCRS scores and adverse patient outcomes characterized by immune evasion. In vitro experiments validated that the prognostic gene PLOD2 significantly enhances proliferation, migration, and invasion of cervical cancer cells.ConclusionThis investigation delineated eight cell types and five subpopulations of malignant EPCs in cervical cancer, establishing the C1 NNMT+ CAEPCs as a crucial therapeutic target. The NCRS model demonstrated its prognostic capability, indicating that higher scores are associated with poorer clinical outcomes. The validation of PLOD2 as a prognostic gene highlights its therapeutic potential, underscoring the critical need for integrating immunotherapy and targeted treatment strategies to enhance diagnostic and therapeutic approaches in cervical cancer.
Positive end-expiratory pressure increases intracranial pressure but not pressure reactivity index in supine and prone positions: a porcine model study
Authors: Hammervold Rønnaug , Beqiri Erta , Smielewski Peter , Storm Benjamin S. , Nielsen Erik W. , Guérin Claude , Frisvold Shirin K. 
Published: January 2025

IntroductionPositive end-expiratory pressure (PEEP) and prone positioning can improve gas exchange by promoting uniform lung aeration. However, elevated ventilation pressures may increase intracranial pressure (ICP) and disrupt cerebral autoregulation. This study investigated the effects of PEEP on ICP and cerebral autoregulation in a porcine model with healthy lungs and normal ICP, comparing prone and supine positions. Cerebral autoregulation was assessed through cerebrovascular reactivity using the pressure reactivity index (PRx). We also explored whether other baseline variables influenced potential variances in ICP and PRx.MethodologyTwelve anesthetized pigs were randomized to begin in either supine or prone position, across PEEP of 5, 10, 15, and 20 cmH2O. Continuous monitoring included esophageal pressure to calculate end-inspiratory and end-expiratory transpulmonary pressures. The ICM+® software (University of Cambridge Enterprise, Cambridge, United Kingdom) was used for high-resolution data collection, signal processing and ICP curve analysis. Linear mixed-effects models and ANOVA were used to analyze changes in ICP and PRx and the influence of position. An exploratory correlation analysis was conducted on baseline variables potentially related to the ICP increase.ResultsMean ICP increase was 1.0 mmHg ± 0.9 at 10 cmH2O PEEP, 2.0 mmHg ± 1.7 at 15 cmH2O PEEP, and 3.1 mmHg ± 1.6 at 20 cmH2O PEEP compared to a baseline PEEP of 5 cmH2O (p &lt; 0.001). The effect of PEEP increase on ICP was not influenced by body position. PRx remained unaffected by PEEP. PEEP-induced increases in ICP were higher in cases of higher baseline ICP, higher central venous pressure, lower respiratory system elastance and lower end-inspiratory and end-expiratory transpulmonary pressures.ConclusionIncreasing PEEP elevates ICP regardless of body position without adversely affecting cerebral autoregulation in a healthy porcine model. Baseline ICP, central venous pressure, respiratory system elastance and end-inspiratory and end-expiratory transpulmonary pressure may influence the magnitude of ICP changes.