bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence and factors associated with cutaneous immune-related adverse events to immune check point inhibitors: An ambispective cohort study
Authors: Luangnara Athitaya , Kiratikanon Salin , Ketpueak Thanika , Suksombooncharoen Thatthan , Charoentum Chaiyut , Chewaskulyong Busyamas , Tovanabutra Napatra , Chiewchanvit Siri , Nochaiwong Surapon , Chuamanochan Mati 
Published: October 2022

BackgroundAlthough immune checkpoint inhibitors (ICIs) have become the frontline treatment option for patients with various advanced cancers due to improved survival, they can be associated with a spectrum of cutaneous immune-related adverse events (cirAEs). However, little is known regarding the occurrence and patterns of cirAE-related ICI therapy in patients of different races other than white populations. Therefore, we investigated the incidence and associated factors of cirAEs among cancer patients in northern Thailand.MethodsA referral-center-based ambispective cohort study was conducted from January 1, 2017, to March 31, 2021. Based on a linked database and merged patient-level data, adult patients with pathologically confirmed cancer who were diagnosed and received ICI therapy regardless of cancer type and followed up through August 31, 2021, were included. All cirAE-related ICI therapy was based on clinical evaluation and ascertainment by a board-certified dermatologist. The incidence of cirAE-related ICI therapy with confidence intervals (CIs) across cancer- and ICI therapy-specific groups was estimated. Factors associated with cirAEs were evaluated using multivariable modified Poisson regression to estimate risk ratios (RRs) and 95% CIs.ResultsThe study included 112 patients (67 men [59.8%]; mean age, 65.0 [range, 31.0-88.0] years), who were mainly diagnosed with lung cancer (56.3%), followed by liver cancer (19.6%). The overall incidence of cirAE-related ICI therapy was 32.1% (95% CI, 24.1-41.4); however, there was no substantial difference in sex, cancer type, or individual ICI therapy. The two identified prognostic risk factors of cirAE-related ICI therapy were age &gt;75 years (adjusted RR, 2.13; 95% CI, 1.09-4.15; P=0.027) and pre-existing chronic kidney disease stages 3-4 (adjusted RR, 3.52; 95% CI, 2.33-5.31; P&lt;0.001).ConclusionsThe incidence of cirAE-related ICI therapy among Thai cancer patients was comparable to that in white populations. Early identification, particularly in elderly patients and those with CKD, should be implemented in clinical practice to help optimize therapeutic decision-making and patient health outcomes.
Identification of serum glycobiomarkers for Hepatocellular Carcinoma using lectin microarrays
Authors: Zhang Yue , Zhang Sihua , Liu Jianhua , Zhang Yunli , Liu Yanjie , Shen Shuang , Tian Fangfang , Yan Gaobo , Gao Yongqing , Qin Xiaosong 
Published: October 2022

ObjectiveHepatocellular carcinoma (HCC) is the sixth most commonly occurring cancer and ranks third in mortality among all malignant tumors; as a result, HCC represents a major human health issue. Although aberrant glycosylation is clearly implicated in HCC, changes in serum immunoglobulin (Ig)G and IgM glycosylation have not been comprehensively characterized. In this study, we used lectin microarrays to evaluate differences in serum IgG and IgM glycosylation among patients with HCC, hepatitis B cirrhosis (HBC), or chronic hepatitis B (CHB), and healthy normal controls (NC) and aimed to establish a model to improve the diagnostic accuracy of HCC.MethodsIn total, 207 serum samples collected in 2019–2020 were used for lectin microarray analyses, including 97 cases of HCC, 50 cases of HBC, 30 cases of CHB, and 30 cases of NC. Samples were randomly divided into training and validation groups at a 2:1 ratio. Training group data were used to investigate the diagnostic value of the relative signal intensity for the lectin probe combined with alpha-fetoprotein (AFP). The efficacy of models for HCC diagnosis were analyzed by receiver operating characteristic (ROC) curves.ResultsIn terms of IgG, a model combining three lectins and AFP had good diagnostic accuracy for HCC. The area under the ROC curve was 0.96 (P &lt; 0.05), the sensitivity was 82.54%, and the specificity was 100%. In terms of IgM, a model including one lectin combined with AFP had an area under the curve of 0.90 (P &lt; 0.05), sensitivity of 75.41%, and specificity of 100%.ConclusionEstimation of serum IgG and IgM glycosylation could act as complementary techniques to improve diagnosis and shed light on the occurrence and development of the HCC
IL7RA single nucleotide polymorphisms are associated with the size and function of the MAIT cell population in treated HIV-1 infection
Authors: Han Fei , Gulam Muhammad Yaaseen , Zheng Yichao , Zulhaimi Nurul Syuhada , Sia Wan Rong , He Dan , Ho Amanda , Hadadi Leila , Liu Zhenyu , Qin Peiwu , Lobie Peter E. , Kamarulzaman Adeeba , Wang Lin-Fa , Sandberg Johan K. , Lewin Sharon R. , Rajasuriar Reena , Leeansyah Edwin 
Published: October 2022

MAIT cells are persistently depleted and functionally exhausted in HIV-1-infected patients despite long-term combination antiretroviral therapy (cART). IL-7 treatment supports MAIT cell reconstitution in vivo HIV-1-infected individuals and rescues their functionality in vitro. Single-nucleotide polymorphisms (SNPs) of the IL-7RA gene modulate the levels of soluble(s)IL-7Rα (sCD127) levels and influence bioavailability of circulating IL-7. Here we evaluate the potential influence of IL-7RA polymorphisms on MAIT cell numbers and function in healthy control (HC) subjects and HIV-1-infected individuals on long-term cART. Our findings indicate that IL-7RA haplotype 2 (H2*T), defined as T-allele carriers at the tagging SNP rs6897932, affects the size of the peripheral blood MAIT cell pool, as well as their production of cytokines and cytolytic effector proteins in response to bacterial stimulation. H2*T carriers had lower sIL-7Rα levels and higher MAIT cell frequency with enhanced functionality linked to higher expression of MAIT cell-associated transcription factors. Despite an average of 7 years on suppressive cART, MAIT cell levels and function in HIV-1-infected individuals were still significantly lower than those of HC. Notably, we observed a significant correlation between MAIT cell levels and cART duration only in HIV-1-infected individuals carrying IL-7RA haplotype 2. Interestingly, treatment with sIL-7Rα in vitro suppressed IL-7-dependent MAIT cell proliferation and function following cognate stimulations. These observations suggest that sIL-7Rα levels may influence MAIT cell numbers and function in vivo by limiting IL-7 bioavailability to MAIT cells. Collectively, these observations suggest that IL-7RA polymorphisms may play a significant role in MAIT cell biology and influence MAIT cells recovery in HIV-1 infection. The potential links between IL7RA polymorphisms, MAIT cell immunobiology, and HIV-1 infection warrant further studies going forward.
Analysis of cross neutralizing activity of antibodies from sera of severe fever with thrombocytopenia syndrome patients to deal with different genotype strains
Authors: Xu Jiaxin , Liu Yuanni , Zhang Fan , Wang Xin , Huang Weijin , Wu Yulong , Li Boqing , Zhuang Jiapeng , Bing Yixing , Wang Youchun , Qiao Yuanyuan 
Published: October 2022

BackgroundSevere fever with thrombocytopenia syndrome bunyavirus (SFTSV) is a tick-borne virus that causes severe communicable fever with thrombocytopenia syndrome (SFTS) with an average case fatality rate of 10%. In the study, we aimed to identify the cross-neutralizing antibody (nAb) against different genotype strains from sera of SFTSV infected patients.MethodsFirstly the genotype of SFTSV was identified by constructing a phylogenetic tree based on the M segments epidemic in the Jiaodong area of Shandong province, then different sera of subjects cross reactive with recombinant Gn (rGn-Fc) or recombinant Gc (rGc-Fc) of 0921 strain were examined. The levels of polyclonal nAbs from sera of 25 convalescents were measured by a pseudovirus-based neutralizing experiment.ResultsWe found local endemic strains were mainly C2 and C3 isolates of SFTSV. 14 of 15 sera from donors reacted with 0921 rGn-Fc, and 9 of 15 sera from donors reacted with 0921 rGc-Fc. Cross nAbs were produced by 10 of 25 sera from donors during the period of 2019–2021. Among these, five nAbs (A2, A4, A5, L9, and L10) neutralized the pseudoviruses of HB29, Gangwon, HN13, HN20, SPL030A, and SD4 strains.ConclusionOur data suggested that epidemic strains showed relatively stable heredity. Some blood sources from patients produced cross nAbs that could neutralize all of the strains examined. These findings highlight the important role played by humoral immunity in combatting SFTSV.
Identifying tumor immunity-associated molecular features in liver hepatocellular carcinoma by multi-omics analysis
Authors: Shen Qianyun , He Yin , Qian Jiajie , Wang Xiaosheng 
Published: October 2022

Background: Although current immunotherapies have achieved some successes for hepatocellular carcinoma (HCC) patients, their benefits are limited for most HCC patients. Therefore, the identification of biomarkers for promoting immunotherapeutic responses in HCC is urgently needed.Methods: Using the TCGA HCC cohort, we investigated correlations of various molecular features with antitumor immune signatures (CD8+ T cell infiltration and cytolytic activity) and an immunosuppressive signature (PD-L1 expression) in HCC. These molecular features included mRNAs, microRNAs (miRNAs), long non-coding RNAs (lncRNAs), proteins, and pathways.Results: We found that the mutations of several oncogenes and tumor suppressor genes significantly correlated with reduced antitumor immune signatures, including TTN, CTNNB1, RB1, ZFHX4, and TP53. It indicates that these genes’ mutations may inhibit antitumor immune responses in HCC. Four proteins (Syk, Lck, STAT5, and Caspase-7) had significant positive expression correlations with CD8+ T cell enrichment, cytolytic activity, and PD-L1 expression in HCC. It suggests that these proteins’ expression could be useful biomarkers for the response to immune checkpoint inhibitors Similiarly, we identified other types of biomarkers potentially useful for predicting the response to ICIs, including miRNAs (hsa-miR-511-5p, 150-3p, 342-3p, 181a-3p, 625-5p, 4772-3p, 155-3p, 142-5p, 142-3p, 155-5p, 625-3p, 1976, 7702), many lncRNAs, and pathways (apoptosis, cytokine-cytokine receptor interaction, Jak-STAT signaling, MAPK signaling, PI3K-AKT signaling, HIF-1 signaling, ECM receptor interaction, focal adhesion, and estrogen signaling). Further, tumor mutation burden showed no significant correlation with antitumor immunity, while tumor aneuploidy levels showed a significant negative correlation with antitumor immunity.Conclusion: The molecular features significantly associated with HCC immunity could be predictive biomarkers for immunotherapeutic responses in HCC patients. They could also be potential intervention targets for boosting antitumor immunity and immunotherapeutic responses in HCC.
Identification of cholinergic centro-cingulate topography as main contributor to cognitive functioning in Parkinson’s disease: Results from a data-driven approach
Authors: van der Zee Sygrid , Kanel Prabesh , Müller Martijn L. T. M. , van Laar Teus , Bohnen Nicolaas I. 
Published: October 2022

BackgroundDegeneration of the cholinergic system plays an important role in cognitive impairment in Parkinson’s disease (PD). Positron emission tomography (PET) imaging using the presynaptic vesicular acetylcholine transporter (VAChT) tracer [18F]Fluoroethoxybenzovesamicol ([18F]FEOBV) allows for regional assessment of cholinergic innervation. The purpose of this study was to perform a data-driven analysis to identify co-varying cholinergic regions and to evaluate the relationship of these with cognitive functioning in PD.Materials and methodsA total of 87 non-demented PD patients (77% male, mean age 67.9 ± 7.6 years, disease duration 5.8 ± 4.6 years) and 27 healthy control (HC) subjects underwent [18F]FEOBV brain PET imaging and neuropsychological assessment. A volume-of-interest based factor analysis was performed for both groups to identify cholinergic principal components (PCs).ResultsSeven main PCs were identified for the PD group: (1) bilateral posterior cortex, (2) bilateral subcortical, (3) bilateral centro-cingulate, (4) bilateral frontal, (5) right-sided fronto-temporal, (6) cerebellum, and (7) predominantly left sided temporal regions. A complementary principal component analysis (PCA) analysis in the control group showed substantially different cholinergic covarying patterns. A multivariate linear regression analyses demonstrated PC3, PC5, and PC7, together with motor impairment score, as significant predictors for cognitive functioning in PD. PC3 showed most robust correlations with cognitive functioning (p &lt; 0.001).ConclusionA data-driven approach identified covarying regions in the bilateral peri-central and cingulum cortex as a key determinant of cognitive impairment in PD. Cholinergic vulnerability of the centro-cingulate network appears to be disease-specific for PD rather than being age-related. The cholinergic system may be an important contributor to regional and large scale neural networks involved in cognitive functioning.
Celecoxib and Etoricoxib may reduce risk of ischemic stroke in patients with rheumatoid arthritis: A nationwide retrospective cohort study
Authors: Chen Acer I-Hung , Lee Yung-Heng , Perng Wuu-Tsun , Chiou Jeng-Yuan , Wang Yu-Hsun , Lin Lichi , Wei James Cheng-Chung , Tsou Hsi-Kai 
Published: October 2022

Background and purposePrevious studies reported conflicting results about the risk of ischemic stroke associated with the use of non-steroidal anti-inflammatory drugs (NSAIDs) in patients with rheumatoid arthritis (RA). We aimed to investigate two specific COX-2 inhibitors, Celecoxib and Etoricoxib, and their corresponding effects on the risk of ischemic stroke in patients with RA.Patients and methods10,857 patients newly diagnosed with RA were identified and sampled from the Taiwanese National Health Insurance Research Database during the period from 2001 to 2009. The identification of RA was based on the criteria of ICD-9-CM diagnosis code 714.0. Patients diagnosed with cerebrovascular disease and those receiving RA treatment prior to the first diagnosis of RA were excluded. Study endpoint was ischemic stroke, defined by ICD-9-CM code. Cox proportional hazard models and Kaplan Meier curves were used to reveal covariates and differences by drugs in the risk of ischemic stroke. Dosages for Celecoxib were defined as ≤ 200 and &gt;200 mg/day; those for Etoricoxib were 0 and &gt;0 mg/day.ResultsAmong 7,904 RA patients, 6,669 did not take Celecoxib and 564 (8.46%) of them experienced an ischemic stroke event. Of the 597 individuals who took ≤ 200 mg/day of Celecoxib, 58 (9.72%) had strokes. Of the 638 patients who took &gt;200 mg/day of Celecoxib, 38 (5.96%) eventually experienced a stroke. Among the 7,681 patients who did not take Etoricoxib, 654 (8.51%) experienced an ischemic stroke, while 6 (2.69%) in 223 patients who consumed Etoricoxib had a stroke event. Consuming more than 200 mg of Celecoxib per day for &lt;3.5 years lowered the incidence rate for strokes [hazard ratio (HR) 0.67, 95% Confidence Interval (CI) 0.48–0.93 for dosage and HR 0.22, 95% CI 0.10–0.46 for duration, both p &lt; 0.001], while consuming any dosage of Etoricoxib significantly decreases the possibility (HR 0.35, 95% CI 0.16–0.80, p &lt; 0.001). On the other hand, consuming Etoricoxib for 8 years might have a neutral or even a potentially protective effect compared to at 3.8 years.ConclusionThis population-based retrospective cohort study has shown that Celecoxib and Etoricoxib reduce the risk of ischemic stroke in patients with RA in a dose- and time-dependent manner.
The neutrophil-to-lymphocyte ratio is an important indicator correlated to early neurological deterioration in single subcortical infarct patients with diabetes
Authors: Fang Lijun , Wang Yali , Zhang Hong , Jiang Lingling , Jin Xuehong , Gu Yongquan , Wu Minya , Pei Shaofang , Cao Yongjun 
Published: October 2022

Background and purposeThis study aimed to investigate the relationship between neutrophil-to-lymphocyte ratio (NLR) and early neurological deterioration (END) among cases suffering from single subcortical infarction (SSI) and diabetes.MethodsWe collected the data of patients with SSI admitted to our hospital between January 2019 and December 2020 retrospectively. A score of ≥2 elevations in overall National Institutes of Health Stroke Scale (NIHSS) score or ≥1 increase in motor NIHSS score in 5-day post-admission was considered END. Furthermore, logistic regression was used to analyze the relationship between NLR and END among SSI cases.ResultsAltogether, we enrolled 235 consecutive SSI cases, of which 53 (22.5%) were diagnosed with END, while 93 (39.5%) were diabetic. In patients with diabetes, the value of NLR increased markedly among the patients with END (median, 3.59; IQR, 2.18–4.84) compared to patients without END (median, 2.64; IQR, 1.89–3.18; P = 0.032). Meanwhile, in patients without diabetes, NLR was not significantly associated with END. In the multivariate analysis, NLR values were positively related to END (adjusted odds ratio (OR), 1.768; 95% CI, 1.166–2.682, P = 0.007) upon adjusting age, SSI type, lesion diameter, initial NIHSS, fasting blood glucose (FBG), 2-h postprandial blood glucose (2hPBG), and estimated glomerular filtration rate (eGFR). The subgroup analysis showed that the relationship between NLR and END was more pronounced in the branch atheromatous disease (BAD) (adjusted OR, 1.819; 95% CI, 1.049–3.153, P = 0.033) and anterior SSI subgroups (adjusted OR, 2.102; 95% CI, 1.095–4.037, P = 0.026).ConclusionNLR value was significantly related to END among SSI patients with diabetes and was recognized as an independent factor in predicting the risk of END.
Two-dimensional ultrasound and two-dimensional shear wave elastography on femoral and saphenous neuropathy in patients with type 2 diabetes mellitus
Authors: Song Yang , Zhang Ying , Zhang Yuhong , Hu Bin 
Published: October 2022

ObjectiveThis study aims to examine the value of two-dimensional (2D) ultrasound and two-dimensional shear wave elastography (2D-SWE) in evaluating femoral nerve (FN) and saphenous nerve (SN) neuropathy in patients with type 2 diabetes mellitus (T2DM).Materials and methodsAccording to the diabetic peripheral neuropathy (DPN) diagnostic criteria, 60 patients with T2DM were enrolled and divided into 35 T2DM patients without DPN (non-DPN group) and 25 T2DM patients with DPN (DPN group). The control group consisted of another 15 healthy volunteers. The width, thickness, cross-sectional area (CSA), and perimeter of the FN and SN in the lower extremities were measured with 2D ultrasound. The average shear wave velocity (SWV) of the FN and SN was measured by 2D-SWE. Parameters of the left and right lower extremities were compared in each group, and the above parameters were compared among groups. The correlations between ultrasonographic and laboratory parameters were evaluated, and the independent influencing factors of SWV of the FN and SN were analyzed.ResultsThe width, thickness, CSA, perimeter, and SWV of FN and SN in the DPN group were greater than those in the non-DPN groups and control group (P &lt; 0.05). The width, thickness, CSA, perimeter, and SWV of the FN and SN in the non-DPN group were greater than those in the control group (P &lt; 0.05). The CSA of FN was positively correlated with FPG, HbA1c, and TG (r = 0.34–0.69, P &lt; 0.01). The perimeter of FN was positively correlated with FPG, HbA1c, and TG (r = 0.37–0.68, P &lt; 0.01). The perimeter of the FN was negatively correlated with IgF-1 (r = −0.31, P &lt; 0.05). The CSA of the SN was positively correlated with FPG and TG (r = 0.26–0.42, P &lt; 0.05). The perimeter of the SN was positively correlated with FPG and TG (r = 0.37–0.39, P &lt; 0.01). The SWV of FN and SN were positively correlated with FPG and TG (r = 0.35–0.57, P &lt; 0.01; r = 0.43–0.49, P &lt; 0.01). FPG and TG were independent influencing factors of the SWV of the FN and SN (P &lt; 0.05).Conclusion2D ultrasound and 2D-SWE could be used to non-invasively, objectively, and accurately evaluate the abnormal changes of the FN and SN in patients with T2DM. It has important clinical significance for the early diagnosis of DPN and the curative effect evaluation.
Hypertension, dietary fiber intake, and cognitive function in older adults [from the National Health and Nutrition Examination Survey Data (2011–2014)]
Authors: Zhang HuanRui , Tian Wen , Qi GuoXian , Sun YuJiao 
Published: October 2022

BackgroundDietary fiber was associated with hypertension (HYP) and cognitive function, but it was unknown whether the effect of HYP on cognitive function in older adults was modified by dietary fiber intake.MethodsWe recruited 2,478 participants from the 2011–2012 and 2013–2014 National Health and Nutrition Examination Survey (NHANES), with cognitive performance measured by Registry for Alzheimer's disease (CERAD), the Animal Fluency test (AFT), and the Digit Symbol Substitution test (DSST). Multivariate General linear model was used to estimate the interaction between dietary fiber intake and HYP status in association with low cognitive performance.ResultsAmong 2,478 participants, 36% was Controlled HYP, 25% was Low uncontrolled HYP, 11% was High uncontrolled HYP, and 86% was low dietary fiber intake. The association between HYP status and DSST impairment differed by dietary fiber intake for those with high uncontrolled HYP compared to those without HYP. Among participants with low dietary fiber intake, those with uncontrolled HYP had higher risk of DSST impairment compared to those without HYP [HYP ≥ 90/140: OR (95% CI), 1.68 (1.15–2.45); HYP ≥ 100/160: OR (95%CI), 2.05 (1.29–3.23)]; however, there was no association between HYP status and DSST impairment among participants with high dietary fiber intake. Moreover, the interaction of HYP status and dietary fiber intake on DSST was close to statistical significance (P for interaction = 0.057).ConclusionsUncontrolled HYP was associated with poorer cognitive performance in older adults with low, but not high dietary fiber intake. Sufficient dietary fiber intake might be as a new nutrition strategy for the prevention of cognitive impairment in older adults with uncontrolled HYP.