bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thermo-sensitive hydrogel combined with SHH expressed RMSCs for rat spinal cord regeneration
Authors: Gu Jun , Gao Biao , Zafar Hajra , Chu Bo , Feng Xiaojun , Ni Yinjie , Xu Lin , Bao Rui 
Published: October 2022

Purpose: Spinal cord injury (SCI) has a damaging impact on patients, amid being a worldwide problem with no effective treatment. Herein, we reported a method for functional therapy of SCI in rats, wherein we combined thermo-sensitive hydrogel with Sonic Hedgehog (SHH) expressed in rat bone-marrow derived mesenchymal stem cells (RMSCs).Methods: Bone marrow-derived mesenchymal stem cells (BMSCs) were isolated from Sprague-Dawley (SD) female rats. The SHH was optimized and transferred into RMSCs via cationic liposomes, while thermo-sensitive hydrogel was reformed with hyaluronate (HA) and Pluronic F127. Then, a rat model with SCI was established accordingly by male SD rats and randomized into sham, model, RMSCs with hydrogel and SHH-RMSCs with hydrogel. The evaluation of SCI repair based on Basso, Beattie Bresnahanlocomotor rating scale (BBB scale) and inclined plate score. Immunofluorescence, immunohistochemistry and hematoxylin-eosin were utilized to explore the expression of protein (GFAP, GAP43, NF200 and MBP) and histopathology.Results: It was demonstrated that transfection of SHH with cationic liposomes exhibited more effect in RMSCs than lipofectamine 2000. As shown in SEM, 3.5% HA-F127 demonstrated porous structure. In the MTT and dead/live assay, 3.5% HA-F127 showed good biocompatibility for RMSCs. Both RMSCs and SHH-RMSCs groups could significantly promote BBB and inclined plate scores (p &lt; 0.01) compared with the model. Furthermore, the SHH-RMSC group was significantly improved than RMSC with the expression of related proteins, where NF200, MBP, and GAP43 were principally enhanced with the GFAP expression being virtually down-regulated.Conclusion: All in all, the results suggested that transplantation of RMSCs with SHH could improve the function of SCI and promote nerve regeneration.
A novel near-infrared fluorescent probe for visualization of intracellular hydrogen peroxide
Authors: An Baoshuai , Pang Shude , Zhang Yanru , Wei Ningning 
Published: October 2022

Hydrogen peroxide (H2O2) as a crucial reactive oxygen species (ROS) plays a crucial role in redox signaling in physiological and pathological processes of living cells. Its normal production is closely related to signal transduction of living cells. Overproduction of H2O2in vivo has been proved to be related to many diseases. Some were developed to reveal the roles of H2O2. However, current fluorescent probes for the detection of H2O2 are restricted in their short emission wavelengths and small Stokes shifts that significantly decrease the sensitivity of detection and cellular visualization. In this work, a novel fluorescent probe BC-B was designed and synthesized with pinacol phenylboronic acid ester as a recognition group and near-infrared fluorophore BC-OH as a reporter group. BC-B probe exhibits a large Stokes shift (122 nm) and near-infrared emission (672 nm), showing an excellent selectivity and sensitivity in detection of H2O2 with the limit of 0.003 μmol/L. Confocal fluorescence imaging further demonstrates that BC-B can be used for detecting endogenous H2O2 in living cells.
Clinical performance of metagenomic next-generation sequencing for the rapid diagnosis of talaromycosis in HIV-infected patients
Authors: Mao Yuhuan , Shen Hui , Yang Caili , Jia Qunying , Li Jianying , Chen Yong , Hu Jinwei , Huang Weiliang 
Published: October 2022

BackgroundTalaromycosis is an invasive endemic mycosis caused by the dimorphic fungus Talaromyces marneffei (T. marneffei, TM). It mainly affects immunodeficient patients, especially HIV-infected individuals, which causes significant morbidity and mortality. Culture-based diagnosis takes a long turnaround time with low sensitivity, leading to treatment delay. In this study, we aimed to evaluate the performance of Metagenomic Next-Generation Sequencing (mNGS) for the rapid diagnosis of talaromycosis in HIV-infected patients.MethodsRetrospectively analysis was conducted in HIV-infected cases at Changsha First Hospital (China) from January 2021 to March 2022. Patients who underwent routine microbiological examination and mNGS testing in parallel were enrolled. The clinical final diagnosis was used as a reference standard, and cases were classified into the TM group (60 cases) and the non-TM group (148 cases). The clinical performances of mNGS were compared with culture and serum Galactomannan (GM). The mixed infections detected by mNGS were analyzed. The impact of mNGS detection on treatment was also investigated.ResultsThe sensitivity of mNGS test reached 98.3% (95% CI, 89.8-99.9), which was significantly higher than culture (66.7% [95% CI, 53.2-77.9], P &lt; 0.001) and serum GM (83.3% [95% CI, 71.0-91.2], P &lt; 0.05). The specificity of 98.6% (95% CI, 94.7-99.7) was similar to culture (100.0% [95% CI, 96.8-100.0], P = 0.156), and superior to serum GM (91.9% [95% CI, 85.9-95.5], P &lt; 0.05). In bronchoalveolar lavage fluid (BALF) samples, the positive rate of mNGS was 97.6%, which was significantly higher than culture (28.6%, P &lt;0.001). mNGS has excellent performance in the identification of mixed infection in TM group patients. Cytomegalovirus, Epstein-Barr virus and Pneumocystis jirovecii were the most common concurrent pathogens. In summary, 60.0% (36/60) patients were added or adjusted to antimicrobial therapy after mNGS test.ConclusionmNGS is a powerful technique with high specificity and sensitivity for the rapid diagnosis of talaromycosis. mNGS of BALF samples may be a good option for early identification of T. marneffei in HIV-infected individuals with manifestations of infection. Moreover, mNGS shows excellent performance in mixed infection, which benefits timely treatment and potential mortality reduction.
The influence of work values of college students on entrepreneurial intention: The moderating role of psychological capital
Authors: Tian Lijun 
Published: October 2022

PurposeThe aim of this study is to determine the influences of work values on entrepreneurial intention among college students. The moderating role of psychological capital was also examined.Materials and methodsA total of 723 college students were investigated with work values questionnaire, entrepreneurial intention scale and positive psychological capital Questionnaire.ResultsWork values was significantly and positively correlated with entrepreneurial intention (r = 0.23, P &lt; 0.001); Psychological capital was significantly and positively correlated with entrepreneurial intention (r = 0.33, P &lt; 0.001); Psychological capital did not moderate the relationship between work values and entrepreneurial intention (β = 0.02, P &gt; 0.05); Hope moderated the relationship between work values and unconditional entrepreneurial intention (β = 0.09, P &lt; 0.05). The relationship between work values and unconditional entrepreneurial intention was stronger in the high hope group (simple slope = 0.21, p &lt; 0.001) than in the low hope group (simple slope = 0.07, p &lt; 0.001).ConclusionHope moderates the relationship between work values and unconditional entrepreneurial intention. Improving the quality of hope can be used as an intervention to improve college students’ unconditional entrepreneurial intention.
Optical coherence tomography of the retina combined with color Doppler ultrasound of the tibial nerve in the diagnosis of diabetic peripheral neuropathy
Authors: Chen Weimiao , Wu Xiaohong , Li Shilin , Zhang Yan , Huang Yinqiong , Zhuang Yong , Bai Xuefeng , Chen Xiaoyu , Lin Xiahong 
Published: October 2022

ObjectiveTo investigate the value of the retinal nerve fiber layer (RNFL) thickness in the optic disc and the cross-sectional area (CSA) of lower limb nerves in the diagnosis of diabetic peripheral neuropathy (DPN) separately and in combination.MethodsA total of 140 patients with type 2 diabetes were enrolled, including 51 patients with DPN (DPN group) and 89 patients without DPN (NDPN group). Clinical data and biochemical parameters were collected. Electromyography/evoked potential instrument was performed for nerve conduction study. Optical coherence tomography was performed to measure the RNFL thickness of the optic disc. Color Doppler ultrasound was performed to measure CSA of lower limb nerves.ResultsThe RNFL thickness was lower and the CSA of the tibial nerve (TN) in the DPN group was larger than that in the NDPN group. The album/urine creatinine ratio, diabetic retinopathy, and CSA of TN at 3 cm were positively correlated with DPN. The RNFL thickness in the superior quadrant of the optic disc was negatively correlated with DPN. For RNFL thickness to diagnose DPN, the area under the curve (AUC) of the superior quadrant was the largest, which was 0.723 (95% confidence interval [CI]: 0.645–0.805), and the best cutoff value was 127.5 μm (70.5% sensitivity, 72.1% specificity). For CSA of TN to diagnose DPN, the AUC of the distance of 5 cm was the largest, which was 0.660 (95% CI: 0.575–0.739), and the best cutoff value was 13.50 mm2 (82.0% sensitivity, 41.6% specificity). For the combined index, the AUC was greater than that of the above two indicators, which was 0.755 (95% CI: 0.664–0.846), and the best cutoff value was 0.376 (64.3% sensitivity, 83.0% specificity).ConclusionsPatients with DPN have a reduction of the RNFL thickness and an increase in the CSA of TN, and these two changes are related to DPN. The RNFL thickness of the optic disc and the CSA of TN can be used as diagnostic indicators of DPN, and the combination of the two indicators has a higher diagnostic value.
CD146 is closely associated with the prognosis and molecular features of osteosarcoma: Guidance for personalized clinical treatment
Authors: Wang Jingkun , Wu Zhonghan , Zheng Meige , Yu Shuisheng , Zhang Xin , Xu XinZhong 
Published: October 2022

Background: Osteosarcoma (OSA), a focus for orthopedic surgeons, always results in severe death due to metastasis. CD146 is severely expressed in several tumors, indicating its potential as a biomarker for OSA.Method: Two OSA cohorts were enrolled in this study. A Therapeutically Applicable Research to Generate Effective Treatments-Osteosarcoma (TARGET-OS) cohort was used as a training cohort, and GSE21257 was used as the external validation cohort. The R package “limma” was used to discriminate the differentially expressed genes among CD146-high and CD146-low patients and was further annotated by the enriched signaling pathways. The R package MOVICS was used to evaluate immune infiltration and the response to chemotherapy and immunotherapy. All statistical analyses were performed by R version 4.0.2, and p &lt; 0.05 was considered statistically significant.Result: CD146 plays an important role in promoting the progression, invasion, and metastasis of several tumors. In the current study, we first revealed an integrative unfavorable prognosis in patients with tumors (p &lt; 0.01, HR: 1.10, 95% CI: 1.07-1.14). CD146 is tightly correlated with m5C RNA methylation modification genes in OSA. Furthermore, we revealed that CD146 acts as an oncogene in OSA patients and is linked to poor prognosis in both the TARGET-OS cohort (p = 0.019, HR: 2.61, 95% CI: 1.171-5.834) and the GSE21257 cohort (p = 0.005, HR: 3.61, 95% CI: 1.474-8.855), with a total of 137 patients, regardless of whether they were adjusted for clinical pathological features. Highly-expressed CD146 impacts the signaling pathways of cytokine‒cytokine receptor interactions and is associated with the high infiltration of immunocytes. Moreover, patients with high CD146 expression were more likely to be sensitive to anti-PD-1 immunotherapy, while patients with low expression of CD146 were more likely to be sensitive to cisplatin and doxorubicin chemotherapy.Conclusion: Overall, CD146 is an independent prognostic factor for OSA patients and can help doctors select clinical treatment strategies.
Caveolin-1 rs1997623 variant and adult metabolic syndrome—Assessing the association in three ethnic cohorts of Arabs, South Asians and South East Asians
Authors: Al Madhoun Ashraf , Hebbar Prashantha , Nizam Rasheeba , Haddad Dania , Melhem Motasem , Abu-Farha Mohamed , Thanaraj Thangavel Alphonse , Al-Mulla Fahd 
Published: October 2022

Background: Animal and cell model studies have implicated CAV1 in the pathophysiology of metabolic disorders. Our previous studies demonstrated a potential association of CAV1 rs1997623 C/A variant with pediatric metabolic syndrome (MetS) in Arab children. In the present study, we evaluate whether the CAV1 variant associates with MetS Arab adults as well. The association signal is further examined for ancestry-specific variation by considering cohorts of other ethnicities.Method: The CAV1 rs1997623 was genotyped in three cohorts of Arab (n = 479), South Asian (n = 660), and South East Asian (n = 362) ethnic adults from Kuwait. MetS status of the individuals was diagnosed using the IDF criteria (presence of central obesity and at least two abnormalities out of: elevated TG, low HDL, hypertension, or T2D). The quantitative measure of MetS was calculated as siMS = 2 × WC/Height + FBG/5.6 + TG/1.7 + SBP/130–HDL/1.02 for males or HDL/1.28 for females. Allelic associations with quantitative and dichotomous MetS traits were assessed using linear and logistic regression models adjusted for age and sex. In addition, empirical p-values (Pemp) were generated using max(T) permutation procedure based on 10,000 permutations.Results: The CAV1 variant was significantly associated with MetS status (OR = 1.811 [1.25–2.61]; p-value = 0.0015; Pemp = 0.0013) and with siMS (Effect size = 0.206; p-value = 0.0035; Pemp = 0.0028) in the cohort of Arab individuals. The association was weak and insignificant in the South Asian and South East Asian cohorts (OR = 1.19 and 1.11; p-values = 0.25 and 0.67, respectively).Conclusion: The reported association of CAV1 rs1997623 C/A with MetS in Arab pediatric population is now demonstrated in an adult Arab cohort as well. The weak association signal seen in the Asian cohorts lead us to propose a certain extent of ethnic-specificity in CAV1 rs1997623 association with MetS.
Modulating the microenvironment during FVIII uptake influences the nature of FVIII-peptides presented by antigen-presenting cells
Authors: Lubich Christian , Steinitz Katharina Nora , Hoelbl Brigitte , Prenninger Thomas , van Helden Pauline Maria , Weiller Markus , Reipert Birgit Maria 
Published: October 2022

Background and aimsHemophilia A is a severe bleeding disorder caused by the deficiency of functionally active coagulation factor VIII (FVIII). The induction of neutralizing anti-drug antibodies is a major complication in the treatment of hemophilia A patients with FVIII replacement therapies. Why some patients develop neutralizing antibodies (FVIII inhibitors) while others do not is not well understood. Previous studies indicated that the induction of FVIII inhibitors requires cognate interactions between FVIII-specific B cells and FVIII-specific CD4+ T cells in germinal center reactions. In this study, we investigated the FVIII peptide repertoire presented by antigen-presenting cells (APCs) under different microenvironment conditions that are expected to alter the uptake of FVIII by APCs. The aim of this study was to better understand the association between different microenvironment conditions during FVIII uptake and the FVIII peptide patterns presented by APCs.MethodsWe used a FVIII-specific CD4+ T cell hybridoma library derived from humanized HLA-DRB1*1501 (human MHC class II) hemophilic mice that were treated with human FVIII. APCs obtained from the same mouse strain were preincubated with FVIII under different conditions which are expected to alter the uptake of FVIII by APCs. Subsequently, these preincubated APCs were used to stimulate the FVIII-specific CD4+ T cell hybridoma library. Stimulation of peptide-specific CD4+ T-cell hybridoma clones was assessed by analyzing the IL-2 release into cell culture supernatants.ResultsThe results of this study indicate that the specific microenvironment conditions during FVIII uptake by APCs determine the peptide specificities of subsequently activated FVIII-specific CD4+ T cell hybridoma clones. Incubation of APCs with FVIII complexed with von Willebrand Factor, FVIII activated by thrombin or FVIII combined with a blockade of receptors on APCs previously associated with FVIII uptake and clearance, resulted in distinct peptide repertoires of subsequently activated hybridoma clones.ConclusionBased on our data we conclude that the specific microenvironment during FVIII uptake by APCs determines the FVIII peptide repertoire presented on MHC class II expressed by APCs and the peptide specificity of subsequently activated FVIII-specific CD4+ T cell hybridoma clones.
Mining of immunological and prognostic-related biomarker for cervical cancer based on immune cell signatures
Authors: Wang Nana , Nanding Abiyasi , Jia Xiaocan , Wang Yuping , Yang Chaojun , Fan Jingwen , Dong Ani , Zheng Guowei , Ma Jiaxin , Shi Xuezhong , Yang Yongli 
Published: October 2022

BackgroundImmunotherapy has changed the therapeutic landscape of cervical cancer (CC), but has durable anti-tumor activity only in a subset of patients. This study aims to comprehensively analyze the tumor immune microenvironment (TIME) of CC and to mine biomarkers related to immunotherapy and prognosis.MethodsThe Cancer Genome Atlas (TCGA) data was utilized to identify heterogeneous immune subtypes based on survival-related immune cell signatures (ICSs). ICSs prognostic model was constructed by Cox regression analyses, and immunohistochemistry was conducted to verify the gene with the largest weight coefficient in the model. Meanwhile, the tumor immune infiltration landscape was comprehensively characterized by ESTIMATE, CIBERSORT and MCPcounter algorithms. In addition, we also analyzed the differences in immunotherapy-related biomarkers between high and low-risk groups. IMvigor210 and two gynecologic tumor cohorts were used to validate the reliability and scalability of the Risk score.ResultsA total of 291 TCGA-CC samples were divided into two ICSs clusters with significant differences in immune infiltration landscape and prognosis. ICSs prognostic model was constructed based on eight immune-related genes (IRGs), which showed higher overall survival (OS) rate in the low-risk group (P&lt; 0.001). In the total population, time-dependent receiver operating characteristic (ROC) curves displayed area under the curve (AUC) of 0.870, 0.785 and 0.774 at 1-, 3- and 5-years. Immunohistochemical results showed that the expression of the oncogene (FKBP10) was negatively correlated with the degree of differentiation and positively correlated with tumor stage, while the expression of tumor suppressor genes (S1PR4) was the opposite. In addition, the low-risk group had more favorable immune activation phenotype and higher enrichment of immunotherapy-related biomarkers. The Imvigor210 and two gynecologic tumor cohorts validated a better survival advantage and immune efficacy in the low-risk group.ConclusionThis study comprehensively assessed the TIME of CC and constructed an ICSs prognostic model, which provides an effective tool for predicting patient’s prognosis and accurate immunotherapy.
Low density Plasmodium infections and G6PD deficiency among malaria suspected febrile individuals in Ethiopia
Authors: Abagero Beka R. , Kepple Daniel , Pestana Kareen , Witherspoon Logan , Biruksew Abdissa , Adanew Abinet , Baharu Fetiya , Hansel Shantoy , Lopez Karen , Janies Daniel A. , Lo Eugenia , Yewhalaw Delenasaw 
Published: October 2022

The identification and management of low parasitemia infections have become increasingly challenging for malaria control and elimination. Submicroscopic Plasmodium infections and G6PD deficiency among febrile patients require more sensitive diagnostic methods to improve detection and careful treatment regime of these infections. In Ethiopia, information on the low density submicroscopic malarial infections and frequency of G6PD deficiency (G6PDd) is scarce. In this study, 297 malaria suspected febrile patient samples were collected from health facilities of Bonga town in southwestern Ethiopia. The positivity rates of Plasmodium infection were determined by microscopy and quantitative PCR. G6PD activity level was determined by careSTART™ G6PD biosensor and the frequency of three common variants: G6PD*A (A376G), G6PD*A− (G202A) and Mediterranean (C563T) were investigated. G6PD gene sequencing was performed to detect mutations in exons 2–11 for both G6PD normal and deficient samples based on the phenotypic assay. More than twice Plasmodium infected samples was detected by qPCR (52/297; 17.4%) than microscopy (21/297; 7.0%). About 31 (10%) of the infections were submicroscopic. Bednet usage and age had a significant association with Plasmodium infection. Of the 271 participants who were tested for G6PD phenotype, 19 (7.0%) had low G6PD level. No mutations were observed in A376G, G202A, and C563T in the G6PDd samples, but three novel non-synonymous mutations in exon 2 including a C to T transition at position ChrX:6504 (Arg to Thr), G to T at ChrX:6369 (Ser to IIe), and G to C at ChrX:6664 (Gln to His) were detected. A high number of submicroscopic Plasmodium infections observed in this study pose a challenge for accurate and timely diagnosis, which could hinder malaria control efforts. G6PD deficiency in malaria patients pose danger when treating patients with primaquine. The three novel mutations detected in exon 2 of the G6PD gene merit further investigation on the hemolytic risk when exposed to oxidative antimalarials, their prevalence, and clinical significance.
Are we ready to collaborate? The interprofessional collaborative competencies of healthcare professionals in the Global South context
Authors: Soemantri Diantha , Findyartini Ardi , Werdhani Retno Asti , Koesnoe Sukamto , Dahlia Debie 
Published: October 2022

BackgroundCurrent evidence of interprofessional collaboration suggests the importance of measuring and identifying the current state of the health professions’ interprofessional competencies. Therefore, this study was aimed at measuring the interprofessional competencies of health professionals in the Global South context using the validated CICS29.Materials and methodsThis was a cross-sectional study involving 300 healthcare professionals of a newly established teaching hospital. Prior to the measurement of interprofessional competencies, the 29-items CICS29, which has been translated into Indonesian language, was revalidated using a confirmatory factor analysis (CFA). The 29 items of CICS29 were grouped into six subscales and each item was measured using a 5-point Likert scale. Data on gender, age, type of profession, and the length of working experience was also collected to identify whether discernible differences between grouping variables exists.ResultsPrior to measuring the interprofessional competencies, the validity of the instrument was established. Based on the CFA, the same six-factor model was found in the current study. The Indonesian CICS29 was reliable, with Cronbach alpha values of 0.921 for the whole instrument and that of each subscale ranged between 0.656 and 0.726. The mean total score of CICS29 was 128.53 (out of 145), ranged from 123 to 133.40 obtained by pharmacists and dentists respectively. No significant differences of CICS29 scores were found between grouping variables.ConclusionThe current study has revealed relatively good interprofessional competencies of healthcare professionals working in a newly established teaching hospital in the Global South healthcare context. Measuring the interprofessional competencies serves as baseline for further intervention to nurture and maintain collaborative practice. In addition, the current study has further proven the cross-cultural validity of CICS29, thus appropriate to be utilized in different setting and context.