bluuebunny/crossref_metadata_2025_split huggingface dataset:
Establishment of a novel lysosomal signature for the diagnosis of gastric cancer with in-vitro and in-situ validation
Authors: Wang Qi , Liu Ying , Li Zhangzuo , Tang Yidan , Long Weiguo , Xin Huaiyu , Huang Xufeng , Zhou Shujing , Wang Longbin , Liang Bochuan , Li Zhengrui , Xu Min 
Published: May 2023

BackgroundGastric cancer (GC) represents a malignancy with a multi-factorial combination of genetic, environmental, and microbial factors. Targeting lysosomes presents significant potential in the treatment of numerous diseases, while lysosome-related genetic markers for early GC detection have not yet been established, despite implementing this process by assembling artificial intelligence algorithms would greatly break through its value in translational medicine, particularly for immunotherapy.MethodsTo this end, this study, by utilizing the transcriptomic as well as single cell data and integrating 20 mainstream machine-learning (ML) algorithms. We optimized an AI-based predictor for GC diagnosis. Then, the reliability of the model was initially confirmed by the results of enrichment analyses currently in use. And the immunological implications of the genes comprising the predictor was explored and response of GC patients were evaluated to immunotherapy and chemotherapy. Further, we performed systematic laboratory work to evaluate the build-up of the central genes, both at the expression stage and at the functional aspect, by which we could also demonstrate the reliability of the model to guide cancer immunotherapy.ResultsEight lysosomal-related genes were selected for predictive model construction based on the inclusion of RMSE as a reference standard and RF algorithm for ranking, namely ADRB2, KCNE2, MYO7A, IFI30, LAMP3, TPP1, HPS4, and NEU4. Taking into account accuracy, precision, recall, and F1 measurements, a preliminary determination of our study was carried out by means of applying the extra tree and random forest algorithms, incorporating the ROC-AUC value as a consideration, the Extra Tree model seems to be the optimal option with the AUC value of 0.92. The superiority of diagnostic signature is also reflected in the analysis of immune features.ConclusionIn summary, this study is the first to integrate around 20 mainstream ML algorithms to construct an AI-based diagnostic predictor for gastric cancer based on lysosomal-related genes. This model will facilitate the accurate prediction of early gastric cancer incidence and the subsequent risk assessment or precise individualized immunotherapy, thus improving the survival prognosis of GC patients.
A linear B-cell epitope close to the furin cleavage site within the S1 domain of SARS-CoV-2 Spike protein discriminates the humoral immune response of nucleic acid- and protein-based vaccine cohorts
Authors: Lorenz Peter , Steinbeck Felix , Mai Franz , Reisinger Emil C. , Müller-Hilke Brigitte 
Published: May 2023

BackgroundUnderstanding the humoral immune response towards viral infection and vaccination is instrumental in developing therapeutic tools to fight and restrict the viral spread of global pandemics. Of particular interest are the specificity and breadth of antibody reactivity in order to pinpoint immune dominant epitopes that remain immutable in viral variants.MethodsWe used profiling with peptides derived from the Spike surface glycoprotein of SARS-CoV-2 to compare the antibody reactivity landscapes between patients and different vaccine cohorts. Initial screening was done with peptide microarrays while detailed results and validation data were obtained using peptide ELISA.ResultsOverall, antibody patterns turned out to be individually distinct. However, plasma samples of patients conspicuously recognized epitopes covering the fusion peptide region and the connector domain of Spike S2. Both regions are evolutionarily conserved and are targets of antibodies that were shown to inhibit viral infection. Among vaccinees, we discovered an invariant Spike region (amino acids 657-671) N-terminal to the furin cleavage site that elicited a significantly stronger antibody response in AZD1222- and BNT162b2- compared to NVX-CoV2373-vaccinees.ConclusionsUnderstanding the exact function of antibodies recognizing amino acid region 657-671 of SARS-CoV-2 Spike glycoprotein and why nucleic acid-based vaccines elicit different responses from protein-based ones will be helpful for future vaccine design.
Development of an AlphaLISA assay for sensitive and accurate detection of influenza B virus
Authors: Zong Huijun , Zhang Shengwei , Shang Xueyi , Jiang Hua , Zhao Zhongpeng , Chen Shaolong , Wang Xin , Wang Ye , Jiang Yongqiang , Li Xinyu , Tan Lingyun , Liu Peng , Lv Qingyu , Li Yan 
Published: May 2023

ObjectiveInfluenza B virus (IBV) is highly contagious, spreads rapidly, and causes seasonal epidemic respiratory disease in the human population, especially in immunocompromised people and young children. Clinical manifestations in this high-risk population are often more severe than in immunocompetent hosts and sometimes atypical. Therefore, rapid, and accurate detection of IBV is important.MethodsAn amplified luminescent proximity homogeneous assay linked immunosorbent assay (AlphaLISA) was developed for detection of IBV by optimizing the ratio of IBV antibody-labeled receptor beads, streptavidin-conjugated donor beads and biotinylated IBV antibody, as well as the optimal temperature and time conditions for incubation. Assay sensitivity, specificity and reproducibility were evaluated. A total of 228 throat swab samples and inactivated influenza B virus were tested by AlphaLISA and lateral flow colloidal gold-based immunoassay (LFIA).ResultsAlphaLISA produced the best results for detection of inactivated influenza B virus when IBV antibody-labeled acceptor beads were 50 μg/ mL, streptavidin-conjugated donor beads were 40 μg/mL, and biotinylated IBV antibody was 0.5 μg/mL at 37°C for 15–10 min. Under these conditions, AlphaLISA had a limit of detection of 0.24 ng/mL for the detection of influenza B nucleoprotein, did not cross react with other common respiratory viruses, and showed good reproducibility with inter-assay coefficient of variation (CV) and intra-assay CV &lt; 5%. The results of 228 clinical throat swab samples showed good agreement between AlphaLISA and LFIA (Kappa = 0.982), and AlphaLISA showed better sensitivity than LFIA for detecting inactivated influenza B virus.ConclusionAlphaLISA showed higher sensitivity and throughput in the detection of IBV and can be used for IBV diagnosis and epidemic control.
Implications of gut microbiota dysbiosis and fecal metabolite changes in psychologically stressed mice
Authors: Zhang Yi , Zhang Jing , Wu Jianmin , Zhu Qinwen , Chen Changrong , Li Yanning 
Published: May 2023

IntroductionPsychological stress can induce affective disorders. Gut microbiota plays a vital role in emotional function regulation; however, the association between gut microbiota and psychological stress is poorly understood. We investigated effects of psychological stress on the gut microbiome and fecal metabolites and assessed the relationship between affective disorder behavior and altered fecal microbiota.MethodsA psychological stress model was established in C57BL/6J mice using a communication box. Sucrose preference test, forced swim test, and open field test helped assess anxiety- and depression-like behaviors. Fecal microbiota transplantation (FMT) was conducted using fecal samples from stressed and non-stressed mice. Moreover, 16S rRNA gene sequencing and untargeted metabolomics were performedResultsAfter stress exposure for 14 days, a significant increase in anxiety- and depression-like behaviors was observed. FMT of “affective disorder microbiota” from psychologically stressed mice increased stress sensitivity relative to FMT of “normal microbiota” from non-stressed mice. 16S rRNA gene sequencing revealed decreased abundance of Bacteroides, Alistipes, and Lactobacillus and increased abundance of Parasutterella and Rikenellaceae_RC9_gut_group in stressed mice; furthermore, stressed mice showed differential metabolite profiles. KEGG pathway analysis indicated that differential metabolites were chiefly involved in the downregulated pathways of α-linolenic acid metabolism, taste transduction, and galactose metabolism. Alistipes and Bacteroides were mainly positively correlated and Parasutterella was mainly negatively correlated with diverse metabolites.DiscussionOur findings suggest that gut microbiome dysbiosis contributes to affective disorder development in response to psychological stress.
Exergaming in older adults: the effects of game characteristics on brain activity and physical activity
Authors: Müller Helen , Baumeister Jochen , Bardal Ellen Marie , Vereijken Beatrix , Skjæret-Maroni Nina 
Published: May 2023

IntroductionExergames are increasingly used in rehabilitation settings for older adults to train physical and cognitive abilities. To meet the potential that exergames hold, they need to be adapted to the individual abilities of the player and their training objectives. Therefore, it is important to know whether and how game characteristics affect their playing. The aim of this study is to investigate the effect of two different kinds of exergame (step game and balance game) played at two difficulty levels on brain activity and physical activity.MethodsTwenty-eight older independently living adults played two different exergames at two difficulty levels each. In addition, the same movements as during gaming (leaning sideways with feet in place and stepping sideways) were performed as reference movements. Brain activity was recorded using a 64-channel EEG system to assess brain activity, while physical activity was recorded using an accelerometer at the lower back and a heart rate sensor. Source-space analysis was applied to analyze the power spectral density in theta (4 Hz–7 Hz) and alpha-2 (10 Hz–12 Hz) frequency bands. Vector magnitude was applied to the acceleration data.ResultsFriedman ANOVA revealed significantly higher theta power for the exergaming conditions compared to the reference movement for both games. Alpha-2 power showed a more diverse pattern which might be attributed to task-specific conditions. Acceleration decreased significantly from the reference movement to the easy condition to the hard condition for both games.DiscussionThe results indicate that exergaming increases frontal theta activity irrespective of type of game or difficulty level, while physical activity decreases with increasing difficulty level. Heart rate was found to be an inappropriate measure in this population older adults. These findings contribute to understanding of how game characteristics affect physical and cognitive activity and consequently need to be taken into account when choosing appropriate games and game settings for exergame interventions.
Interhemispheric neural characteristics of noxious mechano-nociceptive stimulation in the anterior cingulate cortex
Authors: Aminitabar Amir , Mirmoosavi Mahnoosh , Ghodrati Mohammad Taghi , Shalchyan Vahid 
Published: May 2023

BackgroundPain is an unpleasant sensory and emotional experience. One of the most critical regions of the brain for pain processing is the anterior cingulate cortex (ACC). Several studies have examined the role of this region in thermal nociceptive pain. However, studies on mechanical nociceptive pain have been very limited to date. Although several studies have investigated pain, the interactions between the two hemispheres are still not clear. This study aimed to investigate nociceptive mechanical pain in the ACC bilaterally.MethodsLocal field potential (LFP) signals were recorded from seven male Wistar rats’ ACC regions of both hemispheres. Mechanical stimulations with two intensities, high-intensity noxious (HN) and non-noxious (NN) were applied to the left hind paw. At the same time, the LFP signals were recorded bilaterally from awake and freely moving rats. The recorded signals were analyzed from different perspectives, including spectral analysis, intensity classification, evoked potential (EP) analysis, and synchrony and similarity of two hemispheres.ResultsBy using spectro-temporal features and support vector machine (SVM) classifier, HN vs. no-stimulation (NS), NN vs. NS, and HN vs. NN were classified with accuracies of 89.6, 71.1, and 84.7%, respectively. Analyses of the signals from the two hemispheres showed that the EPs in the two hemispheres were very similar and occurred simultaneously; however, the correlation and phase locking value (PLV) between the two hemispheres changed significantly after HN stimulation. These variations persisted for up to 4 s after the stimulation. In contrast, variations in the PLV and correlation for NN stimulation were not significant.ConclusionsThis study showed that the ACC area was able to distinguish the intensity of mechanical stimulation based on the power activities of neural responses. In addition, our results suggest that the ACC region is activated bilaterally due to nociceptive mechanical pain. Additionally, stimulations above the pain threshold (HN) significantly affect the synchronicity and correlation between the two hemispheres compared to non-noxious stimuli.
Cognitive reserve index and long-term disability in patients with severe traumatic brain injury discharged from the intensive rehabilitation unit
Authors: Hakiki Bahia , Pancani Silvia , Romoli Anna Maria , Draghi Francesca , Maccanti Daniela , Mannini Andrea , Cecchi Francesca 
Published: May 2023

ObjectivesThe “cognitive reserve” (CR) theory posits that higher premorbid cognitive activities can mitigate the effects of brain damage. This study aimed to investigate the association between CR and long-term functional autonomy in patients surviving a severe traumatic brain injury (sTBI).SettingData were collected from the database of inpatients with severe acquired brain injury in a rehabilitation unit admitted from August 2012 to May 2020.ParticipantsPatients that had incurred an sTBI, aged 18+ years, completing the phone Glasgow Outcome Scale-Expanded at follow-up (pGOS-E) in absence of previous brain trauma or neurological disease, or cognitive disorders were included. Patients with severe brain injury from non-traumatic etiologies were not included in the study.DesignIn this longitudinal study, all patients underwent a multidimensional assessment including the cognitive reserve index questionnaire (CRIq), the coma recovery scale-revised, the level of cognitive functioning, the Disability Rating Scale (DRS), and the Galveston Orientation and Amnesia Test at admission. At discharge, functional scales were administered again together with the Glasgow Outcome Scale. The pGOS-E was assessed at follow-up.Main measurespGOS-E.ResultsA total of 106 patients/caregivers underwent the pGOS-E after 5.8 [3.6] years from the event. Among them, 46 (43.4%) died after discharge, and 60 patients [men: 48 (80%); median age: 54 years; median time post-onset: 37 days; median education level: 10 years; median CRIq total score: 91] were included in the analysis exploring the association between pGOS-E and demographic data, cognitive reserve surrogates, and clinical variables at admission and discharge from the rehabilitation unit. A younger age (B = −0.035, p = 0.004) and a lower DRS category at discharge (B = −0.392, p = 0.029) were significantly related to a higher long-term functional autonomy in the multivariate analysis.ConclusionLong-term functional autonomy was not influenced by CR as assessed through the educational level and the CRIq.
Case report: Persistent hypogammaglobulinemia in thymoma-associated myasthenia gravis: the impact of rituximab or Good's syndrome?
Authors: Ren Jingru , Wang Jianchun , Liu Ran , Guo Jing , Yao Yan , Luo Jingjing , Hao Hongjun , Gao Feng 
Published: May 2023

IntroductionRituximab (RTX) showed good efficacy and safety for patients with myasthenia gravis. However, the percentage of peripheral CD20+ B cell may be absent for years after low dose of RTX treatment. Persistent hypogammaglobulinemia and opportunistic infection may occur in patients under treatment of RTX with thymoma relapse.Case representationWe report a case of refractory myasthenia gravis. After two doses of 100 mg rituximab, the patient developed transient neutropenia. The peripheral blood CD20+ B cell percentage was 0 more than 3 years. Eighteen months later, the patient's symptoms relapsed with thymoma recurred. She had persistent hypogammaglobulinemia and multiple opportunistic infections.ConclusionIn MG patient under B cell depletion therapy had thymoma relapse, Good's syndrome may induce prolonged B cell depletion, hypogammaglobulinemia and opportunistic infections.
Remotely supervised at-home tDCS for veterans with persistent post-traumatic headache: a double-blind, sham-controlled randomized pilot clinical trial
Authors: Charvet Leigh , Harrison Adam T. , Mangold Kiersten , Moore Robert Davis , Guo Siyuan , Zhang Jiajia , Datta Abhishek , Androulakis X. Michelle 
Published: May 2023

BackgroundCurrently, there are no FDA approved therapies for persistent post-traumatic headache (PPTH) secondary to traumatic brain injury (TBI). As such neither headache nor TBI specialists have an effective means to manage PPTH. Thus, the objective of the present pilot trial was to evaluate the feasibility and preliminary efficacy of a four-week at-home remotely supervised transcranial direct current stimulation (RS-tDCS) intervention for veterans with PPTH.MethodsTwenty-five (m = 46.6 ± 8.7 years) veterans with PPTH were randomized into two groups and received either active (n = 12) or sham (n = 13) RS-tDCS, with anodal stimulation over left dlPFC and cathodal over occipital pole. Following a four-week baseline, participants completed 20–sessions of active or sham RS-tDCS with real-time video monitoring over a period of four-weeks. Participants were assessed again at the end of the intervention and at four-weeks post-intervention. Primary outcomes were overall adherence rate (feasibility) and change in moderate-to-severe headache days per month (efficacy). Secondary outcomes were changes in total number of headache days, and PPTH-related functional outcomes.ResultsAdherence rate was high with 88% of participants (active = 10/12; sham = 12/13) fully completing tDCS interventions. Importantly, there was no significant difference in adherence between active and sham groups (p = 0.59). Moderate-to-severe headache days were significantly reduced within the active RS-tDCS group (p = 0.004), compared to sham during treatment (−2.5 ± 3.5 vs. 2.3 ± 3.4), and 4-week follow-up (−3.9 ± 6.4 vs. 1.2 ± 6.5). Total number of headache days was significantly reduced within the active RS-tDCS (p = 0.03), compared to sham during-treatment (−4.0 ± 5.2 vs. 1.5 ± 3.8), and 4-week follow-up (−2.1 ± 7.2 vs. −0.2 ± 4.4).ConclusionThe current results indicate our RS-tDCS paradigm provides a safe and effective means for reducing the severity and number of headache days in veterans with PPTH. High treatment adherence rate and the remote nature of our paradigm indicate RS-tDCS may be a feasible means to reduce PPTH, especially for veterans with limited access to medical facilities.Clinical Trial Registration: ClinicalTrials.gov, identifier [NCT04012853].
Associations between vitamin D levels and dietary patterns in patients with Hashimoto’s thyroiditis
Authors: Kaličanin Dean , Cvek Maja , Barić Ana , Škrabić Veselin , Punda Ante , Boraska Perica Vesna 
Published: May 2023

IntroductionVitamin D insufficiency is a global health problem affecting healthy and diseased individuals, including patients with Hashimoto’s thyroiditis (HT). Identifying dietary factors that may affect vitamin D levels and providing dietary guidelines accordingly can alleviate this problem. We therefore aimed to identify still unknown associations of dietary patterns, assessed through the Food Frequency Questionnaire (FFQ) with vitamin D blood levels.Materials and methodsFFQ was collected from 459 patients from Croatian Biobank of Patients with Hashimoto’s thyroiditis (CROHT), while total 25(OH)D was measured from their stored serum samples. We performed linear regression analysis between vitamin D levels and weekly intake of 24 food groups in 459 patients with HT (ALL), and in two disease-severity groups (MILD and OVERT).ResultsThe main results of our study are observations of: (1) an inverse association between vitamin D levels and coffee consumption (ALL: β = −0.433, p = 0.005; OVERT: β = −0.62, p = 0.008); (2) an inverse association between vitamin D levels and sweets consumption (ALL: β = −0.195, p = 0.034; OVERT: β = −0.431, p = 0.006); (3) positive association between vitamin D levels and vegetable consumption (ALL: β = 0.182, p = 0.019; OVERT, β = 0.311, p = 0.009). Importantly, effect sizes of all three associations were more prominent in HT patients with prolonged and more severe disease (OVERT).ConclusionFurther research into the functional and causal relationships of the observed associations is important to provide guidance regarding coffee/sugar intake on vitamin D status. A well-balanced diet can help prevent vitamin D deficiency and improve the quality of life of patients with HT, especially those in later stages of disease characterized by greater metabolic imbalance.
Interpretable deep learning survival predictive tool for small cell lung cancer
Authors: Zhang Dongrui , Lu Baohua , Liang Bowen , Li Bo , Wang Ziyu , Gu Meng , Jia Wei , Pan Yuanming 
Published: May 2023

BackgroundSmall cell lung cancer (SCLC) is an aggressive and almost universally lethal neoplasm. There is no accurate predictive method for its prognosis. Artificial intelligence deep learning may bring new hope.MethodsBy searching the Surveillance, Epidemiology, and End Results database (SEER), 21,093 patients’ clinical data were eventually included. Data were then divided into two groups (train dataset/test dataset). The train dataset (diagnosed in 2010–2014, N = 17,296) was utilized to conduct a deep learning survival model, validated by itself and the test dataset (diagnosed in 2015, N = 3,797) in parallel. According to clinical experience, age, sex, tumor site, T, N, M stage (7th American Joint Committee on Cancer TNM stage), tumor size, surgery, chemotherapy, radiotherapy, and history of malignancy were chosen as predictive clinical features. The C-index was the main indicator to evaluate model performance.ResultsThe predictive model had a 0.7181 C-index (95% confidence intervals, CIs, 0.7174–0.7187) in the train dataset and a 0.7208 C-index (95% CIs, 0.7202–0.7215) in the test dataset. These indicated that it had a reliable predictive value on OS for SCLC, so it was then packaged as a Windows software which is free for doctors, researchers, and patients to use.ConclusionThe interpretable deep learning survival predictive tool for small cell lung cancer developed by this study had a reliable predictive value on their overall survival. More biomarkers may help improve the prognostic predictive performance of small cell lung cancer.