bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiparameter flow cytometric and transcriptional analyis of CD20 positive T-cells in bone marrow in patients of multiple myeloma and monoclonal gammopathy of undetermined significance
Authors: Forró Barbara , Kajtár Béla , Lacza Ágnes , Kereskai László , Vida Livia , Kőszegi Balázs , Urbán Péter , Kun József , Gyenesei Attila , Kosztolányi Szabolcs , Kehl Dániel , Jáksó Pál 
Published: February 2025

IntroductionCD20+ T-cells were described firstly in peripheral blood and later in bone marrow in patients with hematological tumors, and certain immune-mediated diseases. During our hematological diagnostic work, this peculiar subgroup of lymphocytes has been consistently observed associated with untreated monoclonal gammopathy of undetermined significance (MGUS) and myeloma (MM). Despite the expanding literature data, the exact function of CD20+ T cells remains unclear.MethodsWe investigated the incidence of CD20+ T-cells in MGUS (n=27), and MM using a larger cohort (n=125) and compared it with control bone marrow samples (n=39). We examined their presence before and after treatment in 32 cases with flow cytometry. Comprehensive flow cytometric analysis included the examination of functional (T-cell activation, cytotoxic molecules and T-cell exhaustion) and maturation markers in a large number of cases. In addition RNA sequencing and subsequent bioinformatics analyses were carried out to detect differentially expressed (DE) genes of FACS sorted CD20+ T-cells versus CD20- T-cells.Results and discussionWe found that CD20+ T-cells are phenotypically and transcriptionally different from CD20- T-cells. Elevated incidence of CD20+ T-cells in MGUS and MM and the expression of CD8, NKG2D, and CD28 suggests anti-tumor functionality. Increased PD-1 expression indicates T-cell exhaustion which was mostly detected in the samples of patients with a higher tumor percentage. The majority of CD20+ T-cells are effector or effector memory T-cells. Some of the differentially expressed genes suggest antitumor function via regulating T-cell activation pathways, while other genes involved in tumor escape from immune surveillance by suppressing T-cells or by reprogramming T-cells toward T-cell exhaustion. Our findings suggest that CD20+ T-cells may play a vital role both in immune surveillance and immune escape contributing to progression of multiple myeloma.
Cross-protectivity of henipavirus soluble glycoprotein in an in vivo model of Nipah virus disease
Authors: Findlay-Wilson Stephen , Thakur Nazia , Crossley Lucy , Easterbrook Linda , Salguero Francisco J. , Ruedas-Torres Ines , Fotheringham Susan , Kennedy Emma , Bailey Dalan , Dowall Stuart 
Published: February 2025

IntroductionNipah virus (NiV) is one of a group of highly pathogenic viruses classified within the Henipavirus genus. Since 2012 at least 11 new henipa-like viruses have been identified, including from new locations and reservoir hosts; the pathogenicity of these new viruses has yet to be determined, but two of them have been associated with morbidity, including fatalities.MethodsThe efficacy and cross-reactivity of two vaccine candidates derived from the soluble glycoproteins of both NiV and Hendra virus (HeV) was evaluated in our recently established hamster model.ResultsBoth vaccine preparations resulted in strong humoral responses against NiV antigenic targets, demonstrating cross-reactive immunity. Efficacy was determined through challenge of hamsters with NiV Malaysian (NiV-M) strain. 100% of the hamsters survived a lethal challenge dose after prime/boost immunisation with glycoproteins derived from both NiV and HeV in the presence of adjuvant, with clinical signs and pathology being significantly reduced in immunised animals.DiscussionThis is first time the NiV and HeV soluble glycoproteins have been compared in the NiV-M hamster challenge model in the presence of Alhydrogel and AddaVax, providing evidence that glycoproteins from closely related henipavirus species can provide cross-protectivity against infection from alternate henipaviruses, supporting the potential of an effective pan-henipavirus vaccine for use in a frontline outbreak response.
HLA allele and haplotype frequencies of eight Indian populations based on 130,518 registered stem cell donors
Authors: Solloch Ute V. , Kaniyath Madhusoodhanan Chinma , Lange Vinzenz , Sauter Jürgen , Jagannathan Latha , Paul Patrick , Fernández-Viña Marcelo A. , Schmidt Alexander H. 
Published: February 2025

IntroductionIn hematopoietic stem cell transplantation, optimal results are achieved when donors and patients are matched regarding their human leukocyte antigen (HLA) genes. Population-specific HLA allele and haplotype frequency distributions determine the probabilities to find matched donors in a stem cell donor registry of given size and ethnic composition.MethodsTo evaluate the needs of Indian patients with regard to future donor recruitment, we analyzed a large data set of n=130,518 potential stem cell donors registered with DKMS-BMST, a Bangalore-based donor registry with nationwide donor recruitment activities. We defined 8 subpopulations by native language and state of origin of both parents. The subpopulations comprised four samples belonging to the Dravidian language family (native language: Kannada/state of origin: Karnataka, Tamil/Tamil Nadu, Telugu/Andhra Pradesh and Malayalam/Kerala), and four samples belonging to the Indo-Aryan language group (Bengali/West Bengal, Gujarati/Gujarat, Hindi/Uttar Pradesh, Marathi/Maharashtra). The precise definition of subpopulations and large sample sizes between n=5,808 (Telugu/Andhra Pradesh) and n=14,866 (Malayalam/Kerala) are strengths of our study. Our results regarding HLA allele and haplotype frequencies refine published data.Results and DiscussionIn terms of genetic relatedness, we observed a division of the subpopulations into a Southern and a Northwestern Indian cluster and the Bengali/West Bengal sample which differed significantly from the seven other subpopulations. Patients from Southern Indian populations are the main beneficiaries from the DKMS-BMST registry in the current ethnic composition. A more even nationwide coverage will be achieved in the future with the opening of local recruitment offices in different parts of India.
Development of a tertiary lymphoid structure-based prognostic model for breast cancer: integrating single-cell sequencing and machine learning to enhance patient outcomes
Authors: Zhang Xiaonan , Li Li , Shi Xiaoyu , Zhao Yunxia , Cai Zhaogen , Ni Ni , Yang Di , Meng Zixin , Gao Xu , Huang Li , Wang Tao 
Published: February 2025

BackgroundBreast cancer, a highly prevalent global cancer, poses significant challenges, especially in advanced stages. Prognostic models are crucial to enhance patient outcomes. Tertiary lymphoid structures (TLS) within the tumor microenvironment have been associated with better prognostic outcomes.MethodsWe analyzed data from 13 independent breast cancer cohorts, totaling over 9,551 patients. Using single-cell RNA sequencing and machine learning algorithms, we identified critical TLS-associated genes and developed a TLS-based predictive model. This model stratified patients into high and low-risk groups. Genomic alterations, immune infiltration, and cellular interactions within the tumor microenvironment were assessed.ResultsThe TLS-based model demonstrated superior accuracy compared to traditional models, predicting overall survival. High TLS patients had higher tumor mutation burden and more chromosomal alterations, correlating with poorer prognosis. High-risk patients exhibited a significant depletion of CD4+ T cells, CD8+ T cells, and B cells, as evidenced by single-cell and bulk transcriptomic analyses. In contrast, immune checkpoint inhibitors demonstrated greater efficacy in low-risk patients, whereas chemotherapy proved more effective for high-risk individuals.ConclusionsThe TLS-based prognostic model is a robust tool for predicting breast cancer outcomes, highlighting the tumor microenvironment’s role in cancer progression. It enhances our understanding of breast cancer biology and supports personalized therapeutic strategies.
Virological response and predictive factors for antiviral treatment in chronic HBV-related liver disease with low ALT and high HBV DNA
Authors: Ma Lei , Li Yan , Weng Lihan , Xing Huichun 
Published: February 2025

ObjectiveTo investigate virological response and predictive factors for antiviral treatment in chronic HBV patients with low ALT and high HBV DNA.MethodsA retrospective study grouped chronic HBV patients by baseline ALT: ALT &gt; 80 U/L (significantly elevated group, SAG), 40-80 U/L (mildly elevated group, MAG), and ≤ 40 U/L (normal group, NG). Inverse probability treatment weighting balanced confounding factors. Complete virological response (CVR, HBV DNA &lt; 20 IU/mL) and partial virological response (PVR, HBV DNA ≥ 20 IU/mL) were defined. NG subgroup analyses were performed using baseline ALT (cutoff: 30 U/L for males, 19 U/L for females), HBV DNA (cutoff: 7.21 Log10 IU/mL), and Aspartate Aminotransferase to Platelet Ratio Index (cutoff: 0.32). Cox regression identified factors predicting CVR at week 48.ResultsAfter IPTW, the number of patients in the NG, MAG, and SAG groups was 92, 141, and 284, and the CVR rates at week 48 were 38.05%, 55.26%, and 7analyses 3.32% respectively (p &lt; 0.0001). Weighted Kaplan-Meier analysis showed that the NG group had the lowest probability of achieving CVR at week 48 (p &lt; 0.0001). Particularly, in the NG group, the high-normal ALT subgroup had a higher CVR rate (56.34% (40/71)) than the low-normal ALT subgroup (29.73% (11/37), p = 0.0103), similar to that of the MAG group (p = 0.9871). The low-HBV DNA (82.46% (47/57)) and high-APRI subgroup (63.79% (37/58)) had higher CVR rates than the high-HBV DNA (7.84% (4/51)) and low-APRI subgroup (28% (14/50)) respectively. High HBV DNA and low ALT patients in NG had a CVR of 0% (0/18). Cox regression identified baseline ALT ≤ 30 U/L (males) or ALT ≤ 19 U/L (females), HBV DNA &gt; 7.21 Log10 IU/mL, HBeAg positive state, APRI &lt; 0.32, and a decrease in HBV DNA &lt; 3.49 Log10 IU/mL at 12 weeks as independent adverse predictors of CVR.ConclusionThe NG group has lower CVR, but the high-normal ALT subgroup performs similarly to MAG. High HBV DNA and low ALT significantly reduce CVR. Key adverse predictors include low ALT, high HBV DNA, HBeAg positivity, low APRI, and suboptimal viral reduction at 12 weeks.
Choroidal metastases from thoracic cancer: a retrospective study on clinical characteristics and treatment efficacy
Authors: Lin Xiacheng , Zhong Yusheng , Li Haiping , Yang Yating , Liu Ahui , Shi Yajing , Liang Jianhong , Cheng Yong 
Published: February 2025

ObjectiveThis study aimed to examine the clinical characteristics of choroidal metastases (CMs) and assess the efficacy of various treatment strategies for CMs in a specific patient cohort.MethodsThis retrospective case series study included 32 patients (38 eyes) diagnosed with CM at the Department of Ophthalmology, Peking University People’s Hospital, between 2009 and 2022. The cohort included 10 male patients (10 eyes) and 22 female patients (28 eyes), with a mean age of 52.53 ± 10.81 years. Detailed medical histories and multiple ophthalmic examinations were performed for all patients, with diagnoses confirmed by two senior ophthalmologists. Clinical characteristics, treatment responses, and follow-up outcomes were analyzed.ResultsLung cancer was the most common primary tumor (53.1%), with six patients initially presenting with ocular symptoms. Initial ultrasound imaging revealed a mean tumor height of 3.02 mm and a mean basal diameter of 11.09 mm. Optical coherence tomography (OCT) revealed irregular, highly reflective foci with undulating anterior surfaces, and fluorescein angiography (FFA) revealed early choroidal tumor masking and late-phase mottled hyperfluorescence with occasional leakage. Indocyanine green angiography (ICGA) revealed hypofluorescence in early and late phases, with slightly mottled hyperfluorescence in the late phase. The follow-up period ranged from 3 months to 4 years (median 4 months), during which systemic and local treatments effectively controlled or delayed tumor progression in most patients.ConclusionLung and breast cancers are the leading sources of CMs, with bilateral or multifocal lesions more frequently linked to breast cancer. Treatment for CMs should be meticulously individualized and should take into account the patient’s overall condition, tumor burden, and precise tumor location. Local treatment is essential for patients with significant ocular symptoms. A combination of local and systemic treatments has been shown to lead to a more significant reduction in tumor burden.
Exploring the therapeutic potential of “Zhi-Zhen” formula for oxaliplatin resistance in colorectal cancer: an integrated study combining UPLC-QTOF-MS/MS, bioinformatics, network pharmacology, and experimental validation
Authors: Li Yongjing , Chen Ke , Li Qin , Liu Qiaoli , Han Huijie , Liu Hui , Wang Songpo 
Published: February 2025

BackgroundChemoresistance is a critical factor compromising the survival of patients with colorectal cancer (CRC). The “Zhi-Zhen” formula (ZZF), a traditional prescription developed by Chinese national medicine masters, has been extensively used in clinical practice to treat gastrointestinal cancer. Notably, ZZF has the potential to enhance tumor sensitivity to chemotherapy. Although previous in vitro studies have demonstrated the efficacy of ZZF in overcoming chemoresistance in colorectal cancer (CRC), its precise molecular mechanisms remain poorly understood.Materials and methodsWe used an integrated approach of bioinformatics and network pharmacology to predict the potential active ingredients and targets of ZZF in alleviating chemoresistance. The top five active ingredients identified by degree in the network analysis were validated using mass spectrometry. We then established an oxaliplatin-resistant CRC cell model to explore the potential targets and regulatory mechanisms through which ZZF overcomes chemoresistance at the cellular level.ResultsNetwork pharmacology and bioinformatics analyses jointly identified 29 active compounds and 13 potential key targets of ZZF, associated with chemoresistance. Among these targets, the differential expression of CASP7 significantly affected the progression-free survival of patients with CRC. We established two oxaliplatin-resistant CRC cell lines and observed an upregulation of CASP7 expression in these resistant cells. Furthermore, ZZF increases the expression and activation of CASP7 in resistant cells, promoting apoptosis, and thereby ameliorating chemoresistance. Additionally, β-catenin knockdown led to an upregulation of CASP7 expression, whereas activation of the Wnt/β-catenin signaling pathway reduced CASP7 protein levels. ZZF decreases the activity of the Wnt/β-catenin signaling pathway by decreasing β-catenin transcription and nuclear localization.ConclusionZZF has potential clinical value in the treatment of chemoresistance in CRC by inhibiting the transcription and nuclear localization of β-catenin, thereby increasing the expression of CASP7 and enhancing the apoptotic response in chemoresistant CRC cells.
Effects of cipepofol on breathing patterns, respiratory drive, and inspiratory effort in mechanically ventilated patients
Authors: Su Rui , Zhang Linlin , Wang Yu-Mei , Miao Ming-Yue , Wang Shuya , Cao Yong , Zhou Jian-Xin 
Published: February 2025

BackgroundCipepofol is a highly selective gamma-aminobutyric acid A receptor potentiator. As a new sedative drug, detailed studies on its respiratory effects are further needed. The present study aims to investigate the effects of cipepofol on breathing patterns, respiratory drive, and inspiratory effort in mechanically ventilated patients.MethodsIn this one-arm physiological study, cipepofol was initiated at 0.3 mg/kg/h and increased by 0.1 mg/kg/h every 30 min until reaching 0.8 mg/kg/h. Discontinuation criteria were Richmond Agitation and Sedation Scale (RASS) score ≤ −4 or respiratory rate (RR) &lt; 8 breaths/min or pulse oxygen saturation (SpO2) &lt; 90%. The primary outcomes were changes from baseline in respiratory variables [RR, tidal volume (VT), minute ventilation (Vmin), airway occlusion pressure at 100 msec (P0.1), pressure muscle index (PMI), expiratory occlusion pressure (Pocc)] at 30 min after 0.3 mg/kg/h cipepofol infusion. The secondary outcomes included changes in respiratory variables, cardiorespiratory variables, and RASS scores at rates of cipepofol from 0.3 to 0.8 mg/kg/h.Results20 patients were enrolled and all of them completed the cipepofol infusion rate at 0.3 mg/kg/h, achieving RASS score of −2 to +1. For the primary outcomes, there was a significant reduction in VT (390.9, [356.6–511.0] vs. 451.6 [393.5–565.9], p = 0.002), while changes in RR (16.7 ± 2.7 vs. 16.2 ± 3.4, p = 0.465) and Vmin (7.2 ± 1.8 vs. 7.5 ± 1.9, p = 0.154) were not significant. The reductions in P0.1 (p = 0.020), PMI (p = 0.019), and Pocc (p = 0.007) were significant. For secondary outcomes, as the infusion rate of cipepofol increased from 0.3 to 0.8 mg/kg/h, there was a further decrease in VT (p = 0.002) and an increase in RR (p &lt; 0.001), while the change in Vmin (p = 0.430) was not significant. RASS score (p &lt; 0.001) was further decreased.ConclusionCipepofol demonstrates the capability to achieve RASS score −2 to +1 in mechanically ventilated adult patients. The effect of cipepofol on breathing patterns was a decrease in VT, while changes in RR and Vmin were insignificant. The effect on respiratory drive and inspiratory effort significantly reduced P0.1, PMI, and Pocc.Clinical trial registrationClinicalTrials.gov, identifier NCT06287138. https://clinicaltrials.gov/study/NCT06287138
Healthy lifestyle behaviors and depressive symptoms: a national cross-sectional study of the older adults in China
Authors: Jiao Haojin , Ge-Zhang Shangjie , Yang Jingqi 
Published: February 2025

IntroductionThis investigation assesses the impact of healthy lifestyle behaviors on depressive symptoms among older adults in China, utilizing data from the 2020 China Health and Retirement Longitudinal Study (CHARLS).MethodsThe analysis included 9,020 valid samples from individuals aged 60 and above. Sleep duration, social participation, and physical exercise were examined as independent variables. Depressive symptoms were measured using the CESD-10 scale, with relationships analyzed through an ordered logistic regression model.ResultsThe study reveals significant correlations between healthy lifestyle behaviors — specifically adequate sleep, regular physical exercise, and active social participation — and reduced prevalence of depressive symptoms in the elderly (p &lt; 0.05).DiscussionThese findings underscore the potential of healthy lifestyle interventions as key strategies in alleviating the mental health burden among China’s aging population. Integration of these results into public health policies is recommended to enhance the mental well-being of older adults.
Development of an enzyme-linked immunosorbent assay (ELISA) for determining neutrophil elastase (NE) – a potential useful marker of multi-organ damage observed in COVID-19 and post-Covid-19 (PCS)
Authors: Adamiec-Mroczek Joanna , Kluz Joanna , Chwałek Sandra , Rabczyński Maciej , Gostomska-Pampuch Kinga , Lewandowski Łukasz , Misiuk-Hojło Marta , Ponikowska Beata , Chourasia Goutam , Dumas Ilias , Gamian Andrzej , Fiodorenko-Dumas Żanna , Konopska Bogusława , Gola Agnieszka , Konikowska Klaudia , Strub Daniel , Bronowicka-Szydełko Agnieszka , Madziarska Katarzyna 
Published: February 2025

BackgroundThe ongoing post-COVID-19 syndrome (PCS) epidemic, causing complications of diverse etiology, necessitates the search for new diagnostic markers and the development of widely accessible methods for their detection. This would enable the prognosis of PCS progression and faster implementation of targeted treatments. One potential marker is neutrophil elastase (NE), whose elevated levels in the blood during PCS may result from organ damage caused by increased secretion of severe inflammatory mediators or amyloidosis resulting from the interaction of NE with SARS-CoV-2. The aim of this publication is to present a step-by-step method for designing an enzymatic ELISA test, enabling the quantitative assessment of NE in the blood serum of patients.MethodsNE was measured using the designed ELISA test.ResultsThe study outlines all the steps necessary for designing and optimizing the ELISA test, including the selection of standards, primary and secondary antibodies, and their dilutions. Using the test, elevated NE levels were demonstrated in patients with advanced-stage diabetic nephropathy after symptomatic COVID-19, compared to a relative group of patients sampled before COVID-19.ConclusionThe undertaken efforts enabled the development of a test with high performance parameters (initially set sensitivity: ≥40 pg/μL; intra-assay precision: 7%; inter-assay precision &lt;20%). No significant cross-reactivity with other tested proteins was observed. Serial dilution of plasma samples resulted in a proportional decrease in signal intensity.
Protective and risk factors in daily life associated with cognitive decline of older adults
Authors: Tong Fang , Yang Hao , Yu Haidong , Sui Le-wen , Yao Jing-yuan , Shi Chen-lei , Yao Qiao-yuan , Shi Mei-fang , Qian Cheng-lang , Li Gang , Zhao Chao , Wang Hui-jing 
Published: February 2025

BackgroundCognitive decline is a chronic condition which is characterized by a loss of the ability to remember, learn, and pay attention to complex tasks. Many older people are now suffering from cognitive decline, which decreases life quality and leads to disability. This study aimed to identify the risk and protective factors for cognitive decline of the older people from daily life and establish a predictive model using logistic regression.MethodsWe investigated 3,790 older people with health examination and questionnaires which included information associated with physical condition, lifestyle factors, and cognitive status. Single-factor comparison, principal component analysis with a Manova-Wilk test, multiple linear regression, and logistic regression were performed to filter the risk and protective factors regarding cognitive decline of older individuals. Then a predictive model using logistic regression was established based on the most significant protective and risk factors.ResultsWe found a significant separation along the coordinate axis between people with normal and declined cognition by principal component analysis, as confirmed by the Manover-Wilk test. Single-factor comparison, multiple linear regression and logistic regression implied that gender, age, hypertension level, height, dietary habit, physical-exercise duration, physical-exercise history, and smoking history could be closely linked with cognitive decline. We also observed significant differences in height, physical exercise duration, physical-exercise years, and smoking years between the male and female of the participants. ROCs of the predictive model by logistic regression were plotted, with AUC values of 0.683 and 0.682, respectively, for the training and testing sets. Although an effective predictive model is thought to have AUC over 0.7, we still believe that the present model is acceptable because the value is close to the threshold.ConclusionThe protective factors of cognitive decline for older people were male gender, height, keeping moderate exercising, and nicotine stimulation, and the risk factors included age, female gender, vegetarianism and hypertension. Except for the genetic factor, differences in lifestyle, such as smoking and exercise habits, may contribute to the observed differences in cognitive function between genders. The significant results could be utilized in the practice for the early intervention of cognitive decline in aged people.