bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of neoadjuvant immunotherapy and traditional neoadjuvant therapy for resectable esophageal cancer: a systematic review and single-arm and network meta-analysis
Authors: Wang Hesong , Song Chunyang , Zhao Xiaohan , Deng Wenzhao , Dong Jing , Shen Wenbin 
Published: May 2023

ObjectiveThis systematic review and meta-analysis aimed to investigate the role of neoadjuvant immunochemotherapy with or without radiotherapy [NIC(R)T] compared to traditional neoadjuvant therapies, without immunotherapy [NC(R)T].Summary background dataNCRT followed by surgical resection is recommended for patients with early-stage esophageal cancer. However, it is uncertain whether adding immunotherapy to preoperative neoadjuvant therapy would improve patient outcomes when radical surgery is performed following neoadjuvant therapy.MethodsWe searched PubMed, Web of Science, Embase, and Cochrane Central databases, as well as international conference abstracts. Outcomes included R0, pathological complete response (pCR), major pathological response (mPR), overall survival (OS) and disease-free survival (DFS) rates.ResultsWe included data from 5,034 patients from 86 studies published between 2019 and 2022. We found no significant differences between NICRT and NCRT in pCR or mPR rates. Both were better than NICT, with NCT showing the lowest response rate. Neoadjuvant immunotherapy has a significant advantage over traditional neoadjuvant therapy in terms of 1-year OS and DFS, with NICT having better outcomes than any of the other three treatments. There were no significant differences among the four neoadjuvant treatments in terms of R0 rates.ConclusionsAmong the four neoadjuvant treatment modalities, NICRT and NCRT had the highest pCR and mPR rates. There were no significant differences in the R0 rates among the four treatments. Adding immunotherapy to neoadjuvant therapy improved 1-year OS and DFS, with NICT having the highest rates compared to the other three modalities.Systematic Review Registrationhttps://inplasy.com/inplasy-2022-12-0060/, identifier INPLASY2022120060.
Identification of the shared gene signatures and molecular mechanisms between multiple sclerosis and non-small cell lung cancer
Authors: Yang Jingyun , Hu Xiaofei , Wang Yu , Liu Wenying , Zhang Mengjie , Zhang Anmei , Ni Bing 
Published: May 2023

IntroductionThe association between multiple sclerosis (MS) and non-small cell lung cancer (NSCLC) has been the subject of investigation in clinical cohorts, yet the molecular mechanisms underpinning this relationship remain incompletely understood. To address this, our study aimed to identify shared genetic signatures, shared local immune microenvironment, and molecular mechanisms between MS and NSCLC.MethodsWe selected multiple Gene Expression Omnibus (GEO) datasets, including GSE19188, GSE214334, GSE199460, and GSE148071, to obtain gene expression levels and clinical information from patients or mice with MS and NSCLC. We employed Weighted Gene Co-expression Network Analysis (WGCNA) to investigate co-expression networks linked to MS and NSCLC and used single-cell RNA sequencing (scRNA-seq) analysis to explore the local immune microenvironment of MS and NSCLC and identify possible shared components.ResultsOur analysis identified the most significant shared gene in MS and NSCLC, phosphodiesterase 4A (PDE4A), and we analyzed its expression in NSCLC patients and its impact on patient prognosis, as well as its molecular mechanism. Our results demonstrated that high expression of PDE4A was associated with poor prognoses in NSCLC patients, and Gene Set Enrichment Analysis (GSEA) revealed that PDE4A is involved in immune-related pathways and has a significant regulatory effect on human immune responses. We further observed that PDE4A was closely linked to the sensitivity of several chemotherapy drugs.ConclusionGiven the limitation of studies investigating the molecular mechanisms underlying the correlation between MS and NSCLC, our findings suggest that there are shared pathogenic processes and molecular mechanisms between these two diseases and that PDE4A represents a potential therapeutic target and immune-related biomarker for patients with both MS and NSCLC.
Relative importance of ENSO and IOD on interannual variability of Indonesian Throughflow transport
Authors: Li Aojie , Zhang Yongchui , Hong Mei , Shi Jian , Wang Jing 
Published: May 2023

IntroductionThe Indonesian Throughflow (ITF) connects the Pacific Ocean and the Indian Ocean. It plays an important role in the global ocean circulation system. The interannual variability of ITF transport is largely modulated by climate modes, such as Central-Pacific (CP) and Eastern-Pacific (EP) El Niño and Indian Ocean Dipole (IOD). However, the relative importance of these climate modes importing on the ITF is not well clarified.MethodsDominant roles of the climate modes on ITF in specific periods are quantified by combining a machine learning algorithm of the random forest (RF) model with a variety of reanalysis datasets.ResultsThe results reveal that during the period from 1993 to 2019, the average ITF transport derived from high-resolution reanalysis datasets is -14.97 Sv with an intensification trend of -0.06 Sv year-1, which mainly occurred in the upper layer. Four periods, which are 1993–2000, 2002–2008, 2009–2012 and 2013–2019, are identified as Niño 3.4, Dipole Mode Index (DMI), no significant dominant index, and DMI dominated, respectively.DiscussionThe corresponding sea surface height differences between the Northwest Tropical Pacific Ocean (NWP) and Southeast Indian Ocean (SEI) in these three periods when exist dominant index are -0.50 cm, 0.99 cm and -3.22 cm, respectively, which are responsible for the dominance of the climate modes. The study provides a new insight to quantify the response of ITF transport to climate drivers.
Research on the fluid dynamics interaction between submarine sand waves and seawater by seismic oceanography
Authors: Han Tonggang , Chen Jiangxin , He Bingshou , Azevedo Leonardo 
Published: May 2023

IntroductionThe seafloor is an important interface between the lithosphere and the hydrosphere, where processes related to circulation and energy exchange happen along with various marine processes widely developed in the water column near the seafloor. These processes are still not yet completely understood as there are constraints of submarine detection technology and the interdisciplinary nature of these complex environments. Seismic reflection data have been a preferable tool to study and image these processes due to their characteristics in terms of spatial resolution. In seismic reflection data, submarine sand waves show hair-like reflection configurations with low continuity and wearing-hair style, appearing with an angle with the seafloor. Investigation of the relationship between the characteristics of submarine sand waves induced hair-like reflection configuration and hydrodynamics is crucial for understanding hair-like reflection configuration generation and spatiotemporal evolution. MethodsThis study combines fluid dynamics numerical simulation and seismic oceanography to discuss the seismic response characteristics and formation mechanisms of the hair-like reflection configuration. First, we create a seawater time-variant fluid-dynamical model followed by the numerical simulation of seismic oceanography data. This procedure results in seismic oceanography numerical simulation sections with hair-like reflection configurations for different constant flow conditions forced on the boundary. Optimal matching method is then applied to interpret field seismic reflection sections given the results obtained with the numerical experiments. Results and discussionAs consequence, the fluid dynamic explanation for the formation mechanism of the hair-like reflection configuration due to differences in seawater thermohaline is proposed. The study provides additional comprehension and further insights into the dynamic process of submarine sand waves induced hair-like reflection configuration using the seismic oceanography method.
Emergency residents' self-perceived readiness for practice: the association of milestones, entrustable professional activities, and professional identities—a multi-institutional survey
Authors: Chang Yu-Che , Khwepeya Madalitso , Nkambule Nothando S. , Chuang Renee S. , Chaou Chung-Hsien 
Published: May 2023

BackgroundAs a successful innovation, competency-based medical education and its assessment tools continue to be a key strategy in training future doctors and tracking their performance trajectories. Linked to professional identity, evidence suggests that clinical competence is related to thinking, acting and feeling like a physician. Thus, incorporating the values and attitudes of healthcare professions as part of their professional identity in the clinical workplace improves professional performance.MethodsThrough a cross-sectional study, we examined the association of milestone, entrustable professional activities (EPA) and professional identity using self-reported tools among emergency medicine residents from 12 teaching hospitals across Taiwan. Milestone, EPA and professional identity were assessed using the Emergency Medicine Milestone Scale, Entrustable Professional Activity Scale and Emergency Physician Professional Identity and Value Scale, respectively.ResultsThe results of a Pearson correlation indicated a significant positive correlation between milestone-based core competencies and EPAs (r = 0.40 ~ 0.74, p &lt; 0.01). The professional identity domain of skills acquisition, capabilities and practical wisdom was positively correlated with milestone-based core competencies of patient care, medical knowledge, practice-based learning and improvement, and system-based practice (r = 0.18 ~ 0.21, p ≤ 0.05), and six items of EPA (r = 0.16 ~ 0.22, p &lt; 0.05). Additionally, the professional identity domain of professional recognition and self-esteem was positively correlated with practice-based learning and improvement, and system-based practice milestone competencies (r = 0.16 ~ 0.19, p &lt; 0.05).ConclusionThis study demonstrates milestone and EPA assessment tools are highly linked and therefore, can be synergistically used by supervisors and clinical educators to evaluate clinical performance during residency training. Emergency physicians’ professional identity is partly influenced by the advancement of skills and a resident’s ability to learn, effectively perform tasks and make appropriate medical decisions at the system level in their clinical practice. Further research is warranted to understand the importance of residents’ competency in relation to their professional identity development trajectory during clinical training.
Pruritogenic molecules in the skin of patients with dermatomyositis
Authors: Vincze Anett , Herczeg-Lisztes Erika , Szabó Katalin , Béldi Tibor Gábor , Nagy-Vincze Melinda , Pór Ágnes , Varga József , Dankó Katalin , Biró Tamás , Tóth Balázs István , Griger Zoltán 
Published: May 2023

IntroductionPruritus is a common excruciating symptom in systemic autoimmune diseases such as dermatomyositis (DM) but the pathogenesis is not fully understood. We intended to investigate the targeted expression analysis of candidate molecules involved in the development of pruritus in lesional vs. non-lesional skin samples of patients affected with active DM. We looked for correlations between the investigated pruriceptive signaling molecules, disease activity, and itching sensation of DM patients.MethodsInterleukins (IL-33 and IL-6), tumor necrosis factor α (TNF-α), peroxisome proliferator-activated receptor γ (PPAR-γ), and ion channels belonging to the transient receptor potential (TRP) family were analyzed. The expression of TNF-α, PPAR-γ, IL-33, IL-6, and TRP channels in lesional DM skin was evaluated by RT-qPCR and immunohistochemistry and was compared with non-lesional DM skin samples. Pruritus, disease activity, and damage of DM were evaluated by the 5-D itch scale and Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI), respectively. Statistical analysis was performed with IBM SPSS 28 software.ResultsA total of 17 active DM patients participated in the study. We could show that the itching score was positively correlated with the CDASI activity score (Kendall's tau-b = 0.571; p = 0.003). TNF-α gene expression was significantly higher in lesional DM skin than in non-lesional DM skin (p = 0.009) and differed in the subgroups of patients with different itch intensities (p = 0.038). The mRNA expression of lesional IL-6 correlated positively with 5-D itch and CDASI activity score (Kendall's tau-b = 0.585; p = 0.008 and 0.45; p = 0.013, respectively). TRPV4 expressions were positively correlated with CDASI damage score (Kendall's tau-b = 0.626; p &lt; 0.001), but the mRNA expressions of the TRP family, PPAR-γ, IL-6, and IL-33 were not different in lesional and non-lesional samples. Immunohistochemistry analysis did not find significant alterations in the expressions of TNF-α, PPAR-γ, IL-6, and IL-33 in lesional and non-lesional regions.DiscussionOur results argue that cutaneous disease activity, TNF-α, and IL-6 might play a central role in DM-associated itch, while TRPV4 plays a central role in tissue regeneration.
Toll-like receptor 4 deficiency in mice impairs venous thrombus resolution
Authors: Yuan Haixin , Huang Xiaoxi , Ding Jie 
Published: May 2023

Objective: Toll-like receptor 4 (TLR4) is crucial to the development of sterile inflammatory responses. The deep venous thrombosis resolution (DVT) is similar to sterile inflammation, so we hypothesize that TLR4 is involved.Methods and Results: We evaluated the effects of TLR4 deficiency on thrombus lysis in vivo, and explored the mechanisms in vitro. DVT mouse model was established by inferior vena cava (IVC) ligation. After the IVC ligation (1, 3, and 7 d), the mice were euthanized to collect the venous thrombus. The Tlr4−/− mice had significantly elevated weight/length ratios of thrombi at 3 and 7 d and increased collagen content at 3 d after IVC ligation, in addition to significantly lesser intrathrombus infiltration of neutrophils and macrophages, lower monocyte chemoattractant protein-1 (MCP-1) and matrix metalloproteinase-9 (MMP-9) expression in thrombus tissue sections and homogenates, and lower pro-MMP-9 activity at 3 d after IVC ligation than wild-type mice. After 7 days of IVC ligation, VEGF, IFNβ, and MCP-5 protein expression were decreased in venous thrombus from Tlr4−/− mice. 2 ml of 3% thioglycolate was injected intraperitoneally and peritoneal exudate was collected 3 days later from Tlr4−/− and wild type mice respectively. The intraperitoneal macrophages were isolated from adherent culture after centrifugation. Lipopolysaccharide (LPS) can activate TLR4/NF-κB signalling pathway in a concentration-dependent manner, initiated p65 nuclear translocation, IκBα phosphorylation and degradation, MMP-9 and MCP-1 transcription in WT intraperitoneal macrophages but not in Tlr4−/− intraperitoneal macrophages.Conclusion: TLR4 is involved in venous thrombosis resolution through NF-κB pathway. Loss of TLR4 in mice impairs the process.
The relationship between protein modified folding molecular network and Alzheimer’s disease pathogenesis based on BAG2-HSC70-STUB1-MAPT expression patterns analysis
Authors: Yang Xiaolong , Guo Wenbo , Yang Lin , Li Xuehui , Zhang Zhengkun , Pang Xinping , Liu Ji , Pang Chaoyang 
Published: May 2023

BackgroundAlzheimer’s disease (AD) is the most common cause of dementia and cognitive decline, while its pathological mechanism remains unclear. Tauopathies is one of the most widely accepted hypotheses. In this study, the molecular network was established and the expression pattern of the core gene was analyzed, confirming that the dysfunction of protein folding and degradation is one of the critical factors for AD.MethodsThis study analyzed 9 normal people and 22 AD patients’ microarray data obtained from GSE1297 in Gene Expression Omnibus (GEO) database. The matrix decomposition analysis was used to identify the correlation between the molecular network and AD. The mathematics of the relationship between the Mini-Mental State Examination (MMSE) and the expression level of the genes involved in the molecular network was found by Neural Network (NN). Furthermore, the Support Vector Machine (SVM) model was for classification according to the expression value of genes.ResultsThe difference of eigenvalues is small in first three stages and increases dramatically in the severe stage. For example, the maximum eigenvalue changed to 0.79 in the severe group from 0.56 in the normal group. The sign of the elements in the eigenvectors of biggest eigenvalue reversed. The linear function of the relationship between clinical MMSE and gene expression values was observed. Then, the model of Neural Network (NN) is designed to predict the value of MMSE based on the linear function, and the predicted accuracy is up to 0.93. For the SVM classification, the accuracy of the model is 0.72.ConclusionThis study shows that the molecular network of protein folding and degradation represented by “BAG2-HSC70-STUB1-MAPT” has a strong relationship with the occurrence and progression of AD, and this degree of correlation of the four genes gradually weakens with the progression of AD. The mathematical mapping of the relationship between gene expression and clinical MMSE was found, and it can be used in predicting MMSE or classification with high accuracy. These genes are expected to be potential biomarkers for early diagnosis and treatment of AD.
Mendelian randomization analyses of smoking and Alzheimer’s disease in Chinese and Japanese populations
Authors: Zhu Yuan , Guan Ying , Xiao Xuewen , Jiao Bin , Liao Xinxin , Zhou Hui , Liu Xixi , Qi Feiyan , Peng Qiyuan , Zhou Lu , Xu Tianyan , Yang Qijie , Zhang Sizhe , Li Meng , Zhu Zhouhai , Lu Sheming , Li Jinchen , Tang Beisha , Shen Lu , Yao Jianhua , Zhou Yafang 
Published: May 2023

BackgroundPrevious epidemiological studies have reported controversial results on the relationship between smoking and Alzheimer’s disease (AD). Therefore, we sought to assess the association using Mendelian randomization (MR) analysis.MethodsWe used single nucleotide polymorphisms (SNPs) associated with smoking quantity (cigarettes per day, CPD) from genome-wide association studies (GWAS) of Japanese population as instrumental variables, then we performed two-sample MR analysis to investigate the association between smoking and AD in a Chinese cohort (1,000 AD cases and 500 controls) and a Japanese cohort (3,962 AD cases and 4,074 controls), respectively.ResultsGenetically higher smoking quantity showed no statistical causal association with AD risk (the inverse variance weighted (IVW) estimate in the Chinese cohort: odds ratio (OR) = 0.510, 95% confidence interval (CI) = 0.149–1.744, p = 0.284; IVW estimate in the Japanese cohort: OR = 1.170, 95% confidence interval CI = 0.790–1.734, p = 0.434).ConclusionThis MR study, for the first time in Chinese and Japanese populations, found no significant association between smoking and AD.
Impaired rich-club connectivity in childhood absence epilepsy
Authors: Yu Yadong , Qiu Mengdi , Zou Wenwei , Zhao Ying , Tang Yan , Tian Jisha , Chen Xiaoyu , Qiu Wenchao 
Published: May 2023

IntroductionChildhood absence epilepsy (CAE) is a well-known pediatric epilepsy syndrome. Recent evidence has shown the presence of a disrupted structural brain network in CAE. However, little is known about the rich-club topology. This study aimed to explore the rich-club alterations in CAE and their association with clinical characteristics.MethodsDiffusion tensor imaging (DTI) datasets were acquired in a sample of 30 CAE patients and 31 healthy controls. A structural network was derived from DTI data for each participant using probabilistic tractography. Then, the rich-club organization was examined, and the network connections were divided into rich-club connections, feeder connections, and local connections.ResultsOur results confirmed a less dense whole-brain structural network in CAE with lower network strength and global efficiency. In addition, the optimal organization of small-worldness was also damaged. A small number of highly connected and central brain regions were identified to form the rich-club organization in both patients and controls. However, patients exhibited a significantly reduced rich-club connectivity, while the other class of feeder and local connections was relatively spared. Moreover, the lower levels of rich-club connectivity strength were statistically correlated with disease duration.DiscussionOur reports suggest that CAE is characterized by abnormal connectivity concentrated to rich-club organizations and might contribute to understanding the pathophysiological mechanism of CAE.
A novel sleep aid device to reduce sleep latency using air–CO2 mixed gas
Authors: Han Hyewon , Kim Dongsin , Kim Jin Seok , Kwac Lee Ku , Hyeon Janghun , Oh Junhyoung 
Published: May 2023

IntroductionSleep is an indispensable component of human life. However, in modern times, the number of people suffering from sleep disorders, such as insomnia and sleep deprivation, has increased significantly. Therefore, to alleviate the discomfort to the patient due to lack of sleep, sleeping pills and various sleep aids are being introduced and used. However, sleeping drugs are prescribed only to a limited extent due to the side effects posed by them and resistance to such drugs developed by patients in the long term, and the majority of sleep aids are scientifically groundless products. This study aimed to develop a device that induced sleep by spraying a mixed gas of carbon dioxide and air to create an environment that could induce sleep, similar to the inside of a sealed vehicle, to control oxygen saturation in the body.MethodsBased on the stipulated safety standards and the human tidal volume, the target concentration of carbon dioxide was determined to be of three types: 15,000, 20,000, and 25,000 ppm. After analyzing diverse structures for safely mixing gases, the most appropriate shape, the reserve tank, was selected as the best suited structure. Various variables, such as spraying angle and distance, flow rate, atmospheric temperature, and nozzle length, were comprehensively measured and tested. Furthermore based on this aspect, diffusion simulation of carbon dioxide concentration and actual experiments were conducted. To secure the stability and reliability of the developed product, an accredited test was performed to investigate the error rate of carbon dioxide concentration. Furthermore, clinical trials comprising polysomnography and questionnaires confirmed the effectiveness of the developed product not only in reducing sleep latency but also in enhancing the overall sleep quality.ResultsWhen the developed device was put to use in reality, sleep latency was decreased by 29.01%, on average, for those with a sleep latency of 5 min or more, compared to when the device was not in use. Moreover, the total sleep time was increased by 29.19 min, WASO was decreased by 13.17%, and sleep efficiency was increased by 5.48%. We also affirmed that the ODI and 90% ODI did not decrease when the device was used. Although different questions may be raised about the safety of using a gas such as carbon dioxide (CO2), the result that tODI was not reduced shows that sleep aids using CO2 mixtures do not adversely affect human health.DiscussionThe results of this study suggest a new method that can be used to treat sleep disorders including insomnia.