bluuebunny/crossref_metadata_2025_split huggingface dataset:
SARS-CoV-2 excretion kinetics in nasopharyngeal and stool samples from the pediatric population
Authors: Khemiri Haifa , Gdoura Mariem , Ben Halima Samar , Krichen Henda , Cammà Cesare , Lorusso Alessio , Ancora Massimo , Di Pasquale Adriano , Cherni Asma , Touzi Henda , Sadraoui Amel , Meddeb Zina , Hogga Nahed , Ammi Radhia , Triki Henda , Haddad-Boubaker Sondes 
Published: October 2023

BackgroundThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for serious respiratory infections in humans. Even in the absence of respiratory symptoms, gastrointestinal (GI) signs were commonly reported in adults and children. Thus, oral–fecal transmission was suspected as a possible route of infection. The objective of this study was to describe RNA shedding in nasopharyngeal and stool samples obtained from asymptomatic and symptomatic children and to investigate virus viability.MethodsThis study included 179 stool and 191 nasopharyngeal samples obtained from 71 children, which included symptomatic (n = 64) and asymptomatic (n = 7) ones. They were collected every 7 days from the onset of the infection until negativation. Viral RNA was detected by real-time RT-PCR, targeting the N and ORF1 genes. Whole-genome sequencing was performed for positive cases. Viral isolation was assessed on Vero cells, followed by molecular detection confirmation.ResultsAll cases included in this study (n = 71) were positive in their nasopharyngeal samples. SARS-CoV-2 RNA was detected in 36 stool samples obtained from 15 out of 71 (21.1%) children; 13 were symptomatic and two were asymptomatic. Excretion periods varied from 7 to 21 days and 7 to 14 days in nasopharyngeal and fecal samples, respectively. Four variants were detected: Alpha (n = 3), B.1.160 (n = 3), Delta (n = 7), and Omicron (n = 1). Inoculation of stool samples on cell culture showed no specific cytopathic effect. All cell culture supernatants were negative for RT-qPCR.ConclusionOur study demonstrated nasopharyngeal and fecal shedding of SARS-CoV-2 RNA by children up to 21 and 14 days, respectively. Fecal shedding was recorded in symptomatic and asymptomatic children. Nevertheless, SARS-CoV-2 was not isolated from positive stool samples.
A diagnosis model for brain atrophy using deep learning and MRI of type 2 diabetes mellitus
Authors: Syed Saba Raoof , M. A. Saleem Durai 
Published: October 2023

ObjectiveType 2 Diabetes Mellitus (T2DM) is linked to cognitive deterioration and anatomical brain abnormalities like cerebral brain atrophy and cerebral diseases. We aim to develop an automatic deep learning-based brain atrophy diagnosis model to detect, segment, classify, and predict the survival rate.MethodsTwo hundred thirty-five MRI images affected with brain atrophy due to prolonged T2DM were acquired. The dataset was divided into training and testing (80:20%; 188, 47, respectively). Pre-processing is done through a novel convolutional median filter, followed by segmentation of atrophy regions, i.e., the brain shrinkage, white and gray matter is done through the proposed TRAU-Net model (Transfer Residual Attention U-Net), classification with the proposed Multinomial Logistic regression with Attention Swin Transformer (MLAST), and prediction of chronological age is determined through Multivariate CoX Regression model (MCR). The classification of Brain Atrophy (BA) types is determined based on the features extracted from the segmented region. Performance measures like confusion matrix, specificity, sensitivity, accuracy, F1-score, and ROC-AUC curve are used to measure classification model performance, whereas, for the segmentation model, pixel accuracy and dice similarity coefficient are applied.ResultsThe pixel accuracy and dice coefficient for segmentation were 98.25 and 96.41, respectively. Brain atrophy multi-class classification achieved overall training accuracy is 0.9632 ± 1.325, 0.9677 ± 1.912, 0.9682 ± 1.715, and 0.9521 ± 1.877 for FA, PA, R-MTA, and L-MTA, respectively. The overall AUC-ROC curve for the classification model is 0.9856. The testing and validation accuracy obtained for the proposed model are 0.9379 and 0.9694, respectively. The prediction model's performance is measured using correlation coefficient (r), coefficient determination r2, and Mean Square Error (MSE) and recorded 0.951, 0.904, and 0.5172, respectively.ConclusionThe brain atrophy diagnosis model consists of sub-models to detect, segment, and classify the atrophy regions using novel deep learning and multivariate mathematical models. The proposed model has outperformed the existing models regarding multi-classification and segmentation; therefore, the automated diagnosis model can be deployed in healthcare centers to assist physicians.
A transcriptional evaluation of the melanoma and squamous cell carcinoma TIL compartment reveals an unexpected spectrum of exhausted and functional T cells
Authors: Cameron Cheryl M. , Richardson Brian , Golden Jackelyn B. , Phoon Yee Peng , Tamilselvan Banumathi , Pfannenstiel Lukas , Thapaliya Samjhana , Roversi Gustavo , Gao Xing-Huang , Zagore Leah L. , Cameron Mark J. , Gastman Brian R. 
Published: October 2023

IntroductionSignificant heterogeneity exists within the tumor-infiltrating CD8 T cell population, and exhausted T cells harbor a subpopulation that may be replicating and may retain signatures of activation, with potential functional consequences in tumor progression. Dysfunctional immunity in the tumor microenvironment is associated with poor cancer outcomes, making exploration of these exhausted T cell subpopulations critical to the improvement of therapeutic approaches.MethodsTo investigate mechanisms associated with terminally exhausted T cells, we sorted and performed transcriptional profiling of CD8+ tumor-infiltrating lymphocytes (TILs) co-expressing the exhaustion markers PD-1 and TIM-3 from large-volume melanoma tumors. We additionally performed immunologic phenotyping and functional validation, including at the single-cell level, to identify potential mechanisms that underlie their dysfunctional phenotype.ResultsWe identified novel dysregulated pathways in CD8+PD-1+TIM-3+ cells that have not been well studied in TILs; these include bile acid and peroxisome pathway-related metabolism and mammalian target of rapamycin (mTOR) signaling pathways, which are highly correlated with immune checkpoint receptor expression.DiscussionBased on bioinformatic integration of immunophenotypic data and network analysis, we propose unexpected targets for therapies to rescue the immune response to tumors in melanoma.
PLAC8 is an innovative biomarker for immunotherapy participating in remodeling the immune microenvironment of renal clear cell carcinoma
Authors: Sun Xu , Liu Zhanpeng , Yu Qian , Chen Yinwei , Sun Yunwen , Zhu Qingyi , Yang Jian , Jiang Rongjiang 
Published: October 2023

BackgroundPLAC8 has been identified in the progression of various cancers by inducing tumorigenesis, immune response, chemotherapy resistance and metastasis. Nevertheless, the precise biological function of PLAC8 in renal cancer remains unknown.MethodsWe obtained the expression profile and associated clinical characteristics of patients diagnosed with clear cell renal cell carcinoma (ccRCC) from The Cancer Genome Atlas database. The biological behavior of specific cell lines was detected using Cell Counting Kit-8 (CCK-8), colony formation, and 5-ethynyl-2’-deoxyuridine (EdU) assay. A prognostic model was constructed based on PLAC8-related molecules through a machine-learning algorithm.ResultsWe observed overexpression of PLAC8 in ccRCC patients. In addition, PLAC8 has been identified as being linked to unfavorable clinical characteristics and adverse prognosis outcomes. Biological enrichment analysis revealed the potential involvement of PLAC8 in cell cycle checkpoints, mitotic phase transformation, immunotherapy-predicted and reactive oxygen species (ROS) related pathways. In addition, immune analyses showed that PLAC8 was involved in remodeling the tumor microenvironment (TME) and affecting the effect of immunotherapy in ccRCC patients. In vitro experiments demonstrated a significant reduction in the proliferation, invasion and migration of renal cancer cells following the knockdown of PLAC8. Finally, LASSO logistics regression was applied to construct a prognosis model, which presented a favorable prediction ability on the prognosis of ccRCC.ConclusionOur results implied that PLAC8 may be a novel immunotherapy biomarker of ccRCC, which is a crucial molecule in remodeling the cancer microenvironment. PLAC8 can predict immunotherapy response and is expected to guide precise treatment.
Cost-effectiveness analysis of first-line tislelizumab plus chemotherapy for recurrent or metastatic nasopharyngeal cancer
Authors: Pei Zhengda , Xiao Ningping , Yang Pei 
Published: October 2023

Introduction: The RATIONALE-309 trial confirmed the significant efficacy and safety of tislelizumab plus chemotherapy in patients with recurrent or metastatic nasopharyngeal carcinoma (R/M NPC). However, the economic benefits of this regimen are unclear. Therefore, this study aimed to evaluate the cost-effectiveness of adding tislelizumab to chemotherapy for R/M NPC from the perspective of the Chinese healthcare system.Methods: A Markov model was established to simulate the costs and outcomes of tislelizumab plus chemotherapy versus chemotherapy. The survival data came from the RATIONALE-309 trial. Only direct medical costs were considered, and utility values were referred to the literature. The incremental cost-effectiveness ratio (ICER) was used as the main outcome measure. Sensitivity analysis was performed to assess the effect of parameter uncertainty on the model. Additionally, subgroup analyses were performed.Results: The basic analysis showed that the cost of tislelizumab plus chemotherapy ($33,693) was $17,711 higher than that of chemotherapy ($15,982), but it also gained 1.05 QALYs more (2.72 QALYs vs. 1.67 QALYs), with an ICER of $16,859/QALY, which was lower than the willing-to-pay (WTP) of $36,289/QALY. The factors that most influenced the model were the utility of PD, the cost of tislelizumab, and the risk of platelet count decreased in tislelizumab plus chemotherapy group. The subgroup analysis also demonstrated that tislelizumab plus chemotherapy was cost-effective in the whole population regardless of EBV DNA level and PD-L1 expression level.Conclusion: Compared with chemotherapy alone, tislelizumab plus chemotherapy was cost-effective for the treatment of R/M NPC in China.
Prediction of the mechanism for the combination of diallyl trisulfide and cisplatin against gastric cancer: a network pharmacology study and pharmacological evaluation
Authors: Lv Huaiyou , Jia Xiumei , Yang Huatian , Zhu Xiaosong , Zhao Zhongxi , Jiang Xiaoyan 
Published: October 2023

Background: In this research, we aimed to explore the efficacy of diallyl trisulfide (DATS) combined with cisplatin (DDP) for gastric cancer treatment and its underlying mechanism based on network pharmacology.Methods: First, the pharmacological mechanism by which DATS combined with DDP acts against gastric cancer was predicted using network pharmacology. The TTD, GeneCards, and OMIM databases were used to extract drug and disease targets. The David Bioinformatics Resources 6.8 database was used to conduct GO and KEGG analyses. We investigated the efficacy of DATS combined with DDP against gastric cancer in SGC7901 cells and a xenograft model. Furthermore, the specific mechanism of DATS combined with DDP, inferred by network pharmacology, was identified by Western blotting and immunohistochemistry.Results: The combination of DDP and DATS significantly increased cytotoxicity and cell apoptosis compared to the DATS or DDP treatment group in vitro. In addition, continuous intraperitoneal injection of DATS markedly improved the tumor inhibitory effect of DDP in the SGC-7901 tumor-bearing mouse model. Furthermore, network pharmacology and experimental validation studies revealed that the combination of DATS and DDP synergistically enhanced antitumor activity by regulating endoplasmic reticulum stress and inhibiting STAT3/PKC-δ and MAPK signaling pathways.Conclusion: Our study showed that the combination of DATS and DDP could exert outstanding therapeutic effects in gastric cancer. Moreover, network pharmacology coupled with experimental validation revealed the molecular mechanisms of combination therapy for gastric cancer. This study offers a new adjuvant strategy based on DATS and DDP for the treatment of gastric cancer.
Referential and inferential production across the lifespan: different patterns and different predictive cognitive factors
Authors: Fargier Raphaël , Laganaro Marina 
Published: October 2023

IntroductionThe ability to speak is grounded in general memory and control processes and likely changes across the lifespan. However, our knowledge on how word production abilities naturally evolve from childhood to old age remains marginally investigated. Our aim was to shed further light on this issue by exploiting the contrast between two ways to elicit word production: referential picture naming and inferential naming from definition.MethodsWe collected accuracy and production latencies in a picture naming task and in a naming from definition task from 130 participants ranging from 10 to 80 years old. Measures of vocabulary size, digit span memory, semantic and phonemic fluencies and processing speed were also collected. We used multivariate adaptative regression splines and regression models to characterize lifespan patterns of the two tasks.ResultsPatterns of increase in performance were similar for picture naming and naming from definition only from childhood to young adulthood. In the second half of the lifespan, significant decrease of performance was found in older adults for picture naming (from around 60 years-old) but not for naming from definition. Clearly, word production elicited with an inferential task (naming from definition) yields different age-related patterns than usually described in the literature with a referential task (picture naming).DiscussionWe discuss how cognitive processes such as visual-conceptual processes and lexical prediction may explain the differential pattern of results in aging in referential and inferential production tasks. We argue for more lifespan studies and the need to investigate language production beyond picture naming, in particular with respect to aging.
Conventional ovarian stimulation vs. delayed single dose corifollitropin alfa ovarian stimulation in oocyte donors: a prospective randomized study. Tail trial
Authors: Alvarado Franco Carlos Alberto , Bernabeu García Andrea , Suñol Sala Jordi , Guerrero Villena Jaime , Albero Amorós Sonia , Llacer Joaquin , Delgado Navas Ricardo Antonio , Ortiz José A. , Pitas Anna , Castillo Farfan Juan Carlos , Bernabeu Pérez Rafael 
Published: October 2023

The present study compares two protocols for ovarian controlled stimulation in terms of number of cumulus-oocyte complexes and metaphase II oocytes. We employed a single injection of 150mcg of corifollitropin alfa after a 7-day oral contraceptive pill-free interval for TAIL group and a conventional administration of corifollitropin alfa after a 5-day OCP-free interval with additional rFSH from 8th of ovarian controlled stimulation. Prospective, randomized, comparative, non-inferiority, opened and controlled trial carried out in 180 oocyte donors 31 were excluded, 81 were randomized to the control group and 68 to the TAIL group. No differences were found in the number of follicles larger than 14 and 17 mm at triggering day. However, a lower number of cumulus-oocyte complexes and metaphase II oocytes were obtained in TAIL group compared to the control group, expressed as median (interquartile range): 10.5 (5.5–19) vs. 14 [11–21] and 9 (4–13) vs. 12 (9–17) respectively. Additionally, the incidence of failed retrieval or metaphase II oocytes = 0 was higher in TAIL group 7(10.3%) vs. 1(1.2%) p = 0.024. The use of a single injection of corifollitropin alfa after a 7-day oral contraceptive pill-free interval in oocyte donors resulted in a lower number of cumulus-oocyte complexes and metaphase II oocytes. No additional rFSH was administered in this group.Clinical Trial Registration:https://www.clinicaltrialsregister.eu/ctr-search/trial/2019-001343-44/results.
Amelioration of Rheumatoid Arthritis by Fragaria nubicola (Wild Strawberry) via Attenuation of Inflammatory Mediators in Sprague Dawley Rats
Authors: Mashaal Kiran , Shabbir Arham , Shahzad Muhammad , Mobashar Aisha , Akhtar Tasleem , Fatima Tabinda , Riaz Bushra , Alharbi Rana , Fatima Afreen , Alanezi Abdulkareem A. , Ahmad Ashfaq 
Published: October 2023

Background and Objectives: Fragaria nubicola has never been evaluated scientifically for its anti-arthritic potential despite its use in folkloric systems of medicine. The research was conducted to assess the potential of F. nubicola against rheumatoid arthritis. Materials and Methods: The current study provided scientific evidence by evaluating the effects of plants using an in vivo CFA-induced model of arthritic rats and subsequent microscopic histopathological evaluation of ankle joints along with the determination of paw edema using a digital water displacement plethysmometer. The study also gave insight by determining levels of pro-inflammatory cytokines, matrix metalloproteinase enzymes (MMPs), prostaglandin E2 (PGE2), nuclear factor kappa B (NF-κB), vascular endothelial growth factor (VEGF), and biochemical and hematological parameters. GCMS analysis was also conducted for the identification of possible anti-inflammatory plant constituents. Results: The data showed that F. nubicola-treated groups attenuated the progression of arthritis and paw edema. Microscopic histopathological evaluation validated the anti-arthritic potential by showing amelioration of bone erosion, infiltration of inflammatory cells, and pannus formation. RT-PCR analysis displayed that treatment with F. nubicola down-regulated IL1β, IL6, TNFα, NF-κB, VEGF, MMP2, MMP3, and MMP9 levels. Moreover, ELISA exhibited a reduction in levels of PGE2 levels in treatment groups. The levels of RBCs, platelets, WBCs, and Hb content were found to be nearly similar to negative control in the treated group. Statistically, a non-significant difference was found when all groups were compared for urea, creatinine, ALT, and AST analysis, indicating the safety of plant extract and fractions at test doses. GCMS analysis of extract and fractions showed the existence of many anti-inflammatory and antioxidant phytochemicals. Conclusion: In conclusion, F. nubicola possessed anti-arthritic properties that might be attributed to the amelioration of MMPs and pro-inflammatory cytokines.
Preventive interventions to improve older people’s health outcomes: systematic review and meta-analysis
Authors: Palapar Leah , Blom Jeanet W , Wilkinson-Meyers Laura , Lumley Thomas , Kerse Ngaire 
Published: October 2023

BackgroundSystematic reviews of preventive, non-disease-specific primary care trials for older people often report effects according to what is thought to be the intervention’s active ingredient.AimTo examine the effectiveness of preventive primary care interventions for older people and to identify common components that contribute to intervention success.Design and settingA systematic review and meta-analysis of 18 randomised controlled trials (RCTs) published in 22 publications from 2009 to 2019.MethodA search was conducted in PubMed, MEDLINE, Embase, Web of Science, CENTRAL, CINAHL, and the Cochrane Library. Inclusion criteria were: sample mainly aged ≥65 years; delivered in primary care; and non-disease-specific interventions. Exclusion criteria were: non-RCTs; primarily pharmacological or psychological interventions; and where outcomes of interest were not reported. Risk of bias was assessed using the original Cochrane tool. Outcomes examined were healthcare use including admissions to hospital and aged residential care (ARC), and patient-reported outcomes including activities of daily living (ADLs) and self-rated health (SRH).ResultsMany studies had a mix of patient-, provider-, and practice-focused intervention components (13 of 18 studies). Studies included in the review had low-to-moderate risk of bias. Interventions had no overall benefit to healthcare use (including admissions to hospital and ARC) but higher basic ADL scores were observed (standardised mean difference [SMD] 0.21, 95% confidence interval [CI] = 0.01 to 0.40) and higher odds of reporting positive SRH (odds ratio [OR] 1.17, 95% CI = 1.01 to 1.37). When intervention effects were examined by components, better patient-reported outcomes were observed in studies that changed the care setting (SMD for basic ADLs 0.21, 95% CI = 0.01 to 0.40; OR for positive SRH 1.17, 95% CI = 1.01 to 1.37), included educational components for health professionals (SMD for basic ADLs 0.21, 95% CI = 0.01 to 0.40; OR for positive SRH 1.27, 95% CI = 1.05 to 1.55), and provided patient education (SMD for basic ADLs 0.28, 95% CI = 0.09 to 0.48). Additionally, admissions to hospital in intervention participants were fewer by 23% in studies that changed the care setting (incidence rate ratio [IRR] 0.77, 95% CI = 0.63 to 0.95) and by 26% in studies that provided patient education (IRR 0.74, 95% CI = 0.56 to 0.97).ConclusionPreventive primary care interventions are beneficial to older people’s functional ability and SRH but not other outcomes. To improve primary care for older people, future programmes should consider delivering care in alternative settings, for example, home visits and phone contacts, and providing education to patients and health professionals as these may contribute to positive outcomes.
Older adults’ perceptions of navigating eye health care in Denmark: a qualitative study
Authors: Sandholdt Catharina Thiel , Jacobsen Marie Honoré , Mathiesen Olivia Hjulsager , Jønsson Alexandra Brandt Ryborg , Jensen Andrea Nedergaard , Steinbo Emma Katrine Frøhlke , Reventlow Susanne , Waldorff Frans Boch 
Published: October 2023

BackgroundVision impairment can have an impact on cognition, health, and social function. Vision loss may be avoided if detected early and treated promptly. Eye health is a minor topic in general practice, but the ongoing relationship between doctor and patient has the potential to assist the patient in navigating the healthcare system and guaranteeing timely healthcare service delivery.AimTo explore the attitudes of older members of the public (aged ≥60 years) towards navigating primary sector eye health care in Denmark, with a focus on optometrists, practising ophthalmologists (POs), and GPs.Design & settingQualitative study in Copenhagen, Denmark.MethodFocus group interviews were performed in the spring of 2022 with 21 older members of the public.ResultsOlder members of the public perceived optometrists and POs to be the most relevant health professionals to consult about eye health. Opportunities were identified for enhancing the function of general practice including detecting early signs of visual impairment, being in charge of further referrals, and managing issues affecting quality of life such as dry eyes.ConclusionOlder members of the public sought help from health professionals who are directly qualified to treat symptoms of vision impairment that patients are experiencing or expect to face in the near future. Participants identified a potential for GPs to address vision impairment. This included focusing on the patient’s general health and function, as well as potential comorbidities influencing treatment trajectories. The current denigration of general practice risks missing out on the potential benefits of robust engagement from general practice in eye health.