bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combined novel homozygous variants in both SGPL1 and STAT1 presenting with severe combined immune deficiency: case report and literature review
Authors: Roa-Bautista Adriel , Sohail Mahreen , Wakeling Emma , Gilmour Kimberly C. , Davis Mark , Gait Anthony , Lucchini Giovanna , Cox David , Elfeky Reem , Kusters Maaike 
Published: June 2023

BackgroundSphingosine phosphate lyase insufficiency syndrome (SPLIS) is associated with biallelic variants in SGPL1, comprising a multisystemic disease characterized by steroid resistant nephrotic syndrome, primary adrenal insufficiency, neurological problems, skin abnormalities and immunodeficiency in described cases. Signal transducer and activator of transcription 1 (STAT1) plays an important role in orchestrating an appropriate immune response through JAK-STAT pathway. Biallelic STAT1 loss of function (LOF) variants lead to STAT1 deficiency with a severe phenotype of immunodeficiency with increased frequency of infections and poor outcome if untreated.Case presentationWe report novel homozygous SGPL1 and STAT1 variants in a newborn of Gambian ethnicity with clinical features of SPLIS and severe combined immunodeficiency. The patient presented early in life with nephrotic syndrome, severe respiratory infection requiring ventilation, ichthyosis, and hearing loss, with T-cell lymphopenia. The combination of these two conditions led to severe combined immunodeficiency with inability to clear respiratory tract infections of viral, fungal, and bacterial nature, as well as severe nephrotic syndrome. The child sadly died at 6 weeks of age despite targeted treatments.ConclusionWe report the finding of two novel, homozygous variants in SGPL1 and STAT1 in a patient with a severe clinical phenotype and fatal outcome early in life. This case highlights the importance of completing the primary immunodeficiency genetic panel in full to avoid missing a second diagnosis in other patients presenting with similar severe clinical phenotype early in life. For SPLIS no curative treatment is available and more research is needed to investigate different treatment modalities. Hematopoietic stem cell transplantation (HSCT) shows promising results in patients with autosomal recessive STAT1 deficiency. For this patient’s family, identification of the dual diagnosis has important implications for future family planning. In addition, future siblings with the familial STAT1 variant can be offered curative treatment with HSCT.
PD-1/PD-L1 immune checkpoint inhibitors in metastatic triple-negative breast cancer: a systematic review and meta-analysis
Authors: Yu Yinan , Jin Xueying , Zhu Xiaoling , Xu Yan , Si Wei , Zhao Jianguo 
Published: June 2023

BackgroundPD-1/PD-L1 immune checkpoint inhibitors (ICIs) have been controversial in the treatment of metastatic triple negative breast cancer (mTNBC). We collected randomized controlled trials in accordance with the study and carried out meta-analysis to comprehensively evaluate the efficacy and safety of immune checkpoint inhibitors in mTNBC.AimTo systematically evaluate the efficacy and safety of PD-1/PD-L1 ICIs (hereinafter referred to as ICIs) in the treatment of mTNBC.MethodsAs of 2023.2.5, Medline, PubMed, Embase, Cochrane library database and Web of Science were searched to determine the study in accordance with the trial of ICIs in the treatment of mTNBC. The assessment endpoints included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. Meta-analysis of the included studies was performed using Revman 5.4.ResultsA total of six trials with 3172 patients were included in this meta-analysis. The ORR of ICIs combined with chemotherapy was significantly improved compared with chemotherapy (HR=0.88, 95%CI: 0.81-0.94, I2 = 0%). For PFS, the experimental group were better than the control group in both intention-to-treat (ITT) population and PD-L1 positive population, showing statistical significance (ITT: HR=0.81, 95%CI: 0.74-0.89, P&lt;0.05, I2 = 0%; PD-L1 positive: HR=0.72, 95%CI: 0.63-0.82, P&lt;0.05, I2 = 18%); For OS, in the ITT population, no statistical difference was observed in either ICIs combined with chemotherapy(HR=0.92, 95%CI: 0.83-1.02, P=0.10)or immune monotherapy(HR=0.78, 95%CI: 0.44-1.36, P=0.37), in the PD-L1 positive population, ICIs group had better OS than chemotherapy group (HR=0.83, 95%CI: 0.74-0.93, P &lt; 0.05); In safety, serious adverse event (SAE) was no statistically significant difference between the ICIs group and the chemotherapy group; however, the incidence of immune-related adverse event (irAE) was significantly higher in the ICIs group than in the chemotherapy group (HR=2.15, 95%CI: 1.45-3.19, P &lt; 0.05).ConclusionICIs combined with chemotherapy significantly improved the PFS of mTNBC, however, ICIs only improved the OS in PD-L1 positive people, and no statistical difference was observed in ITT population; while benefiting from ICIs, we found that irAE in ICIs group increased significantly, and its high rate of adverse events still needs to be taken seriously.
EEG and peripheral markers of viewer ratings: a study of short films
Authors: Kosonogov Vladimir , Shelepenkov Danila , Rudenkiy Nikita 
Published: June 2023

IntroductionCinema is an important part of modern culture, influencing millions of viewers. Research suggested many models for the prediction of film success, one of them being the use of neuroscientific tools. The aim of our study was to find physiological markers of viewer perception and correlate them to short film ratings given by our subjects. Short films are used as a test case for directors and screenwriters and can be created to raise funding for future projects; however, they have not been studied properly with physiological methods.MethodsWe recorded electroencephalography (18 sensors), facial electromyography (corrugator superciliiandzygomaticus major), photoplethysmography, and skin conductance in 21 participants while watching and evaluating 8 short films (4 dramas and 4 comedies). Also, we used machine learning (CatBoost, SVR) to predict the exact rating of each film (from 1 to 10), based on all physiological indicators. In addition, we classified each film as low or high rated by our subjects (with Logistic Regression, KNN, decision tree, CatBoost, and SVC).ResultsThe results showed that ratings did not differ between genres.Corrugator superciliiactivity (“frowning” muscle) was larger when watching dramas; whereaszygomaticus major(“smiling” muscle) activity was larger during the watching of comedies. Of all somatic and vegetative markers, onlyzygomaticus majoractivity, PNN50, SD1/SD2 (heart rate variability parameters) positively correlated to the film ratings. The EEG engagement indices, beta/(alpha+theta) and beta/alpha correlated positively with the film ratings in the majority of sensors. Arousal (betaF3+ betaF4)/(alphaF3+ alphaF4), and valence (alphaF4/betaF4) - (alphaF3/betaF3) indices also correlated positively to film ratings. When we attempted to predict exact ratings, MAPE was 0.55. As for the binary classification, logistic regression yielded the best values (area under the ROC curve = 0.62) than other methods (0.51–0.60).DiscussionOverall, we revealed EEG and peripheral markers, which reflect viewer ratings and can predict them to a certain extent. In general, high film ratings can reflect a fusion of high arousal and different valence, positive valence being more important. These findings broaden our knowledge about the physiological basis of viewer perception and can be potentially used at the stage of film production.
Spike-frequency adaptation inhibits the pairwise spike correlation
Authors: Wang Jixuan , Deng Bin , Gao Tianshi , Wang Jiang , Tan Hong 
Published: June 2023

IntroductionThe spike train output correlation with pairwise neurons determines the neural population coding, which depends on the average firing rate of individual neurons. Spike frequency adaptation (SFA), which serves as an essential cellular encoding strategy, modulates the firing rates of individual neurons. However, the mechanism by which the SFA modulates the output correlation of the spike trains remains unclear.MethodsWe introduce a pairwise neuron model that receives correlated inputs to generate spike trains, and the output correlation is qualified using Pearson correlation coefficient. The SFA is modeled using adaptation currents to examine its effect on the output correlation. Moreover, we use dynamic thresholds to explore the effect of SFA on output correlation. Furthermore, a simple phenomenological neuron model with a threshold-linear transfer function is utilized to confirm the effect of SFA on decreasing the output correlation.ResultsThe results show that the adaptation currents decreased the output correlation by reducing the firing rate of a single neuron. At the onset of a correlated input, a transient process shows a decrease in interspike intervals (ISIs), resulting in a temporary increase in the correlation. When the adaptation current is sufficiently activated, the correlation reached a steady state, and the ISIs are maintained at higher values. The enhanced adaptation current achieved by increasing the adaptation conductance further reduces the pairwise correlation. While the time and slide windows influence the correlation, they make no difference in the effect of SFA on decreasing the output correlation. Moreover, SFA simulated by dynamic thresholds also decreases the output correlation. Furthermore, the simple phenomenological neuron model with a threshold-linear transfer function confirms the effect of SFA on decreasing the output correlation. The strength of the signal input and the slope of the linear component of the transfer function, the latter of which can be decreased by SFA, could together modulate the strength of the output correlation. Stronger SFA will decrease the slope and hence decrease the output correlation.ConclusionsThe results reveal that the SFA reduces the output correlation with pairwise neurons in the network by reducing the firing rate of individual neurons. This study provides a link between cellular non-linear mechanisms and network coding strategies.
Glutamine metabolism genes prognostic signature for stomach adenocarcinoma and immune infiltration: potential biomarkers for predicting overall survival
Authors: Li Hui , Wu Zixuan , Zhang Yu , Lu Xiaohui , Miao Lili 
Published: June 2023

BackgroundStomach adenocarcinoma (STAD), caused by mutations in stomach cells, is characterized by poor overall survival. Chemotherapy is commonly administered for stomach cancer patients following surgical resection. An imbalance in tumor metabolic pathways is connected to tumor genesis and growth. It has been discovered that glutamine (Gln) metabolism plays a crucial role in cancer. Metabolic reprogramming is associated with clinical prognosis in various cancers. However, the role of glutamine metabolism genes (GlnMgs) in the fight against STAD remains poorly understood.MethodsGlnMgs were determined in STAD samples from the TCGA and GEO datasets. The TCGA and GEO databases provide information on stemness indices (mRNAsi), gene mutations, copy number variations (CNV), tumor mutation burden (TMB), and clinical characteristics. Lasso regression was performed to build the prediction model. The relationship between gene expression and Gln metabolism was investigated using co-expression analysis.ResultsGlnMgs, found to be overexpressed in the high-risk group even in the absence of any symptomatology, demonstrated strong predictive potential for STAD outcomes. GSEA highlighted immunological and tumor-related pathways in the high-risk group. Immune function and m6a gene expression differed significantly between the low- and high-risk groups. AFP, CST6, CGB5, and ELANE may be linked to the oncology process in STAD patients. The prognostic model, CNVs, single nucleotide polymorphism (SNP), and medication sensitivity all revealed a strong link to the gene.ConclusionGlnMgs are connected to the genesis and development of STAD. These corresponding prognostic models aid in predicting the prognosis of STAD GlnMgs and immune cell infiltration in the tumor microenvironment (TME) may be possible therapeutic targets in STAD. Furthermore, the glutamine metabolism gene signature presents a credible alternative for predicting STAD outcomes, suggesting that these GlnMgs could open a new field of study for STAD-focused therapy Additional trials are needed to validate the results of the current study.
Zika virus-like particles (VLPs) produced in insect cells
Authors: de Mello Renata Gois , Bernardino Thaissa Consoni , Guardalini Luis Giovani Oliveira , Astray Renato Mancini , Antoniazzi Marta Maria , Jared Simone Gonçalves Silva , Núñez Eutimio Gustavo Fernández , Jorge Soraia Attie Calil 
Published: June 2023

Introdutcion: The Zika virus (ZIKV) infections are a healthcare concern mostly in the Americas, Africa, and Asia but have increased its endemicity area beyond these geographical regions. Due to the advances in infections by Zika virus, it is imperative to develop diagnostic and preventive tools against this viral agent. Virus-like particles (VLPs) appear as a suitable approach for use as antiviral vaccines.Methods: In this work, a methodology was established to produce virus-like particles containing the structural proteins, C, prM, and E of Zika virus produced in insect cells using the gene expression system derived from baculovirus. The vector pFast- CprME -ZIKV was constructed containing the gene sequences of Zika virus structural proteins and it was used to generate the recombinant bacmids (Bac- CprME -ZIKV) through transformation into DH10BacTM cells. The Bac- CprME -ZIKV was transfected in Spodoptera frugiperda (Sf9) insect cells and batches of BV- CprME -ZIKV were obtained by infection assays using a multiplicity of infection of 2. The Sf9 cells were infected, and the supernatant was collected 96 h post-infection. The expression of the CprME -ZIKV protein on the cell surface could be observed by immunochemical assays. To concentrate and purify virus-like particles, the sucrose and iodixanol gradients were evaluated, and the correct CprME -ZIKV proteins’ conformation was evaluated by the Western blot assay. The virus-like particles were also analyzed and characterized by transmission electron microscopy.Results and discussion: Spherical structures like the native Zika virus from 50 to 65 nm containing the CprME -ZIKV proteins on their surface were observed in micrographs. The results obtained can be useful in the development path for a vaccine candidate against Zika virus.
Metabolic changes in the plasma of mild Alzheimer’s disease patients treated with Hachimijiogan
Authors: Kainuma Mosaburo , Kawakatsu Shinobu , Kim Jun-Dal , Ouma Shinji , Iritani Osamu , Yamashita Ken-Ichiro , Ohara Tomoyuki , Hirano Shigeki , Suda Shiro , Hamano Tadanori , Hieda Sotaro , Yasui Masaaki , Yoshiiwa Aoi , Shiota Seiji , Hironishi Masaya , Wada-Isoe Kenji , Sasabayashi Daiki , Yamasaki Sho , Murata Masayuki , Funakoshi Kouta , Hayashi Kouji , Shirafuji Norimichi , Sasaki Hirohito , Kajimoto Yoshinori , Mori Yukiko , Suzuki Michio , Ito Hidefumi , Ono Kenjiro , Tsuboi Yoshio 
Published: June 2023

Background: Alzheimer’s disease (AD), the most prevalent form of dementia, is a debilitating, progressive neurodegeneration. Amino acids play a wide variety of physiological and pathophysiological roles in the nervous system, and their levels and disorders related to their synthesis have been related to cognitive impairment, the core feature of AD. Our previous multicenter trial showed that hachimijiogan (HJG), a traditional Japanese herbal medicine (Kampo), has an adjuvant effect for Acetylcholine estelase inhibitors (AChEIs) and that it delays the deterioration of the cognitive dysfunction of female patients with mild AD. However, there are aspects of the molecular mechanism(s) by which HJG improves cognitive dysfunction that remain unclear.Objectives: To elucidate through metabolomic analysis the mechanism(s) of HJG for mild AD based on changes in plasma metabolites.Methods: Sixty-seven patients with mild AD were randomly assigned to either an HJG group taking HJG extract 7.5 g/day in addition to AChEI or to a control group treated only with AChEI (HJG:33, Control:34). Blood samples were collected before, 3 months, and 6 months after the first drug administration. Comprehensive metabolomic analyses of plasma samples were done by optimized LC-MS/MS and GC-MS/MS methods. The web-based software MetaboAnalyst 5.0 was used for partial least square-discriminant analysis (PLS-DA) to visualize and compare the dynamics of changes in the concentrations of the identified metabolites.Results: The VIP (Variable Importance in Projection) score of the PLS-DA analysis of female participants revealed a significantly higher increase in plasma metabolite levels after HJG administration for 6 months than was seen in the control group. In univariate analysis, the aspartic acid level of female participants showed a significantly higher increase from baseline after HJG administration for 6 months when compared with the control group.Conclusion: Aspartic acid was a major contributor to the difference between the female HJG and control group participants of this study. Several metabolites were shown to be related to the mechanism of HJG effectiveness for mild AD.
Functional near-infrared spectroscopy of medical students answering various item types
Authors: Husain Syeda Fabeha , Wang Nixi , McIntyre Roger S. , Tran Bach X. , Nguyen Thao Phuong , Vu Linh Gia , Vu Giang Thu , Ho Roger C. , Ho Cyrus S. 
Published: June 2023

BackgroundTraditionally, the effect of assessment item types including true/false questions (TFQs), multiple-choice questions (MCQs), short answer questions (SAQs), and case scenario questions (CSQs) is examined through psychometric qualities or student interviews. However, brain activity while answering such questions or items remains unknown. Functional near-infrared spectroscopy (fNIRS) can be used to safely measure cerebral cortex hemodynamic response during various tasks. Hence, this fNIRS study aimed to determine differences in frontotemporal cortex activity as medical students answered TFQs, MCQs, SAQs, and CSQs.MethodsIn total, 24 medical students (13 males and 11 females) were recruited in this study during their mid-psychiatry posting. Oxy-hemoglobin and deoxy-hemoglobin levels in the frontal and temporal regions were measured with a 52-channel fNIRS system. Participants answered 9–18 trials under each of the four types of tasks that were based on their psychiatry curriculum during fNIRS measurements. The area under the oxy-hemoglobin curve (AUC) for each participant and each item type was derived. Repeated measures ANOVA with post-hoc Bonferroni-corrected pairwise comparisons were used to determine differences in oxy-hemoglobin AUC between TFQs, MCQs, SAQs, and CSQs.ResultsOxy-hemoglobin AUC was highest during the CSQs, followed by SAQs, MCQs, and TFQs in both the frontal and temporal regions. Statistically significant differences between different types of items were observed in oxy-hemoglobin AUC of the frontal region (p ≤ 0.001). Oxy-hemoglobin AUC in the frontal region was significantly higher during the CSQs than TFQ (p = 0.005) and during the SAQ than TFQ (p = 0.025). Although the percentage of correct responses was significantly lower in MCQ than in the other item types, there was no correlation between the percentage of correct response and oxy-hemoglobin AUC in both regions for all four item types (p &gt; 0.05).ConclusionCSQs and SAQs elicited greater hemodynamic response than MCQs and TFQs in the prefrontal cortex of medical students. This suggests that more cognitive skills may be required to answer CSQs and SAQs.
Direct and indirect effects of self-directed learning on creativity in healthcare undergraduates: a chain mediation model of openness to challenge and diversity and creative self-efficacy
Authors: Qian Jiazhen , Li Xiang , Liu Ting , Zhang Mengfan , Li Kaiyan 
Published: June 2023

BackgroundCreativity and self-directed learning (SDL) are prominent for undergraduate healthcare students to provide quality patient care in an increasingly complex healthcare environment. Research suggested that SDL is linked with creativity, yet the mechanism underlying the relationship between SDL and creativity has not been fully understood.ObjectiveThis study examined the relationship between SDL and creativity and constructed a chain mediation model to identify the mediating effect of openness to diversity and challenge (ODC) and creative self-efficacy (CSE).MethodsThrough convenience sampling, 575 healthcare undergraduates (average age = 19.28 years, SD = 1.124 years) were surveyed from Shandong Province in China. Creativity, SDL, ODC, and CSE were assessed using corresponding scales. Pearson’s correlation analysis, hierarchical multiple linear regression analysis, a serial multiple mediation analysis, and bias-corrected percentile Bootstrap method were conducted by using structural equation modeling by AMOS 26.0.ResultsThe direct path between SDL and creativity was significant. SDL can positively predict both ODC and CSE, and the latter two variables can significantly and positively predict creativity. ODC and CSE played a significant partial mediating role in the relationship between SDL and creativity. The mediating effect consists of three indirect effects: SDL → ODC → creativity (the mediating effect value is 0.193, p = 0.012), SDL → CSE → creativity (the mediating effect value is 0.096，p = 0.001), and SDL → ODC → CSE → creativity (the mediating effect value is 0.035, p = 0.031).ConclusionSDL can positively predict creativity. ODC and CSE had significant mediating effects between SDL and creativity, including single partial mediating effects of ODC and CSE and chain mediating effects of ODC-CSE.
Teachers’ views on the effect of STEM education on the labor market
Authors: Akcan Ahmet Tayfur , Yıldırım Bekir , Karataş Ali Rauf , Yılmaz Mustafa 
Published: June 2023

IntroductionThis paper explores teachers’ views on the impact of STEM education on the labor market. This study focused on teachers’ views to investigate STEM education and the labor market and the relationship between the two.MethodsThe sample consisted of 32 teachers from different branches. Participants were recruited using purposive convenience sampling. This paper adopted a qualitative case study research design. Qualitative data were collected using a semi-structured interview form. The qualitative data were analyzed using inductive content and descriptive analysis.ResultsParticipants stated that STEM education offered new fields of work, promoted entrepreneurship, and increased job opportunities. They also noted that STEM education helped reduce social costs. They emphasized that STEM education made participants happy, prevented brain drain, and reduced social problems. On the other hand, they also noted that STEM education could lead to technological unemployment. The descriptive analyses showed that STEM education had a positive impact on employment, a reduction in social costs, and a positive impact on underemployment. In light of the results, we made recommendations for future research.