bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of Complement Pathways in Kidney Tissue May Mediate Tubulointerstitial Injury in Diabetic Nephropathy
Authors: Jiang Shimin , Jiao Yuanyuan , Zou Guming , Gao Hongmei , Zhuo Li , Li Wenge 
Published: April 2022

IntroductionKey genes involved in tubulointerstitial injury may influence the development and progression of diabetic nephropathy (DN). We investigated whether complement-related genes are linked to the mechanism underlying tubulointerstitial injury in DN.MethodsWe analyzed the microarray data of 17 tubulointerstitial tissue samples from DN patients and 21 normal controls from the Gene Expression Omnibus. A gene co-expression network was constructed, and genes were divided into modules by weighted gene co-expression network analysis (WGCNA). We also investigated the association of C3 and C1q deposits in kidney tissues with a composite outcome of end-stage renal disease or a 50% reduction in the estimated glomerular filtration rate (eGFR) in DN patients. Finally, we performed immunohistochemical analyses of C3, C1q, C5b-9, mannose-binding lectin (MBL), and factor B in kidney tissues.ResultsNine co-expression modules were constructed using 12,075 genes from the 38 human tubulointerstitial tissue samples. Black module with more genes was positively correlated with tubulointerstitial injury in DN. C3, one of the top 10 genes in tubulointerstitial injury, was verified in an independent dataset; C3 was significantly overexpressed in tubulointerstitial tissue from patients with DN compared to the normal controls. The mRNA level of C3 in renal tubulointerstitium was negatively correlated with eGFR in DN patients (r = −0.75; p = 0.001). Analysis of the follow-up data of 54 DN patients demonstrated that codeposits of C3 and C1q in kidney tissues were independently associated with the renal outcome in DN (hazard ratio, 2.3, 95% confidence interval, 1.01–5.2, p &lt; 0.05). Immunohistochemical analysis showed that patients with higher C1q, C3, C5b-9, MBL, or factor B expression in renal tubulointerstitium were more likely to progress to kidney failure.ConclusionLocal complement activation of the classical, lectin and alternative pathways appears linked to tubulointerstitial injury and disease progression in DN.
Physical Activity and Mortality in Patients With Chronic Kidney Disease: A Protocol for Systematic Review and Dose-Response Meta-Analysis
Authors: Zhang Fan , Wang Hui , Huang Liuyan , Bai Yan 
Published: April 2022

ObjectiveTo examine the dose-response associations between total physical activity, different intensity of physical activity, and all-cause mortality in patients with chronic kidney disease (CKD).Methods and AnalysisPubMed, Embase, Web of Science, and the Cochrane library will be searched from inception to June 2022. Only cohort studies assessing physical activity associations with all-cause mortality among CKD patients will be considered for inclusion. The quality of included cohort studies will be evaluated according to the Newcastle-Ottawa Scale (NOS). The robust error meta-regression (REMR) model will be used to establish dose-response relationships between physical activity and mortality. Additional statistical analysis including Egger's test, subgroup analysis, sensitivity analysis. The strengths of evidence will be evaluated with the Grading of Recommendation, Assessment, Development, and Evaluation approach.Ethics and DisseminationEthics approval is not required as no private information from individuals is collected.PROSPERO Registration NumberCRD 42021283630.
Artificial Intelligence-Enabled Electrocardiogram Predicted Left Ventricle Diameter as an Independent Risk Factor of Long-Term Cardiovascular Outcome in Patients With Normal Ejection Fraction
Authors: Chen Hung-Yi , Lin Chin-Sheng , Fang Wen-Hui , Lee Chia-Cheng , Ho Ching-Liang , Wang Chih-Hung , Lin Chin 
Published: April 2022

BackgroundHeart failure (HF) is a global disease with increasing prevalence in an aging society. However, the survival rate is poor despite the patient receiving standard treatment. Early identification of patients with a high risk of HF is important but challenging. Left ventricular end-diastolic diameter (LV-D) increase was an independent risk factor of HF and adverse cardiovascular (CV) outcomes. In this study, we aimed to develop an artificial intelligence (AI) enabled electrocardiogram (ECG) system to detect LV-D increase early.ObjectiveWe developed a deep learning model (DLM) to predict left ventricular end-diastolic and end-systolic diameter (LV-D and LV-S) with internal and external validations and investigated the relationship between ECG-LV-D and echocardiographic LV-D and explored the contributions of ECG-LV-D on future CV outcomes.MethodsElectrocardiograms and corresponding echocardiography data within 7 days were collected and paired for DLM training with 99,692 ECGs in the development set and 20,197 ECGs in the tuning set. The other 7,551 and 11,644 ECGs were collected from two different hospitals to validate the DLM performance in internal and external validation sets. We analyzed the association and prediction ability of ECG-LVD for CV outcomes, including left ventricular (LV) dysfunction, CV mortality, acute myocardial infarction (AMI), and coronary artery disease (CAD).ResultsThe mean absolute errors (MAE) of ECG-LV-D were 5.25/5.29, and the area under the receiver operating characteristic (ROC) curves (AUCs) were 0.8297/0.8072 and 0.9295/0.9148 for the detection of mild (56 ≦ LV-D &lt; 65 mm) and severe (LV-D ≧ 65 mm) LV-D dilation in internal/external validation sets, respectively. Patients with normal ejection fraction (EF) who were identified as high ECHO-LV-D had the higher hazard ratios (HRs) of developing new onset LV dysfunction [HR: 2.34, 95% conference interval (CI): 1.78–3.08], CV mortality (HR 2.30, 95% CI 1.05–5.05), new-onset AMI (HR 2.12, 95% CI 1.36–3.29), and CAD (HR 1.59, 95% CI 1.26–2.00) in the internal validation set. In addition, the ECG-LV-D presents a 1.88-fold risk (95% CI 1.47–2.39) on new-onset LV dysfunction in the external validation set.ConclusionThe ECG-LV-D not only identifies high-risk patients with normal EF but also serves as an independent risk factor of long-term CV outcomes.
Health-Related Quality of Life Evaluation Using the Short Form-36 in Patients With Human T-Lymphotropic Virus Type 1-Associated Myelopathy
Authors: Kimura Miyuna , Yamauchi Junji , Sato Tomoo , Yagishita Naoko , Araya Natsumi , Aratani Satoko , Tanabe Kenichiro , Horibe Erika , Watanabe Toshiki , Coler-Reilly Ariella , Nagasaka Misako , Akasu Yukari , Kaburagi Kei , Kikuchi Takayuki , Shibata Soichiro , Matsumoto Hirofumi , Koseki Akihito , Inoue Soichiro , Takata Ayako , Yamano Yoshihisa 
Published: April 2022

BackgroundHuman T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy (HAM) is a neuroinflammatory disease, causing various neurological symptoms, including motor, sensory, and bladder and bowel dysfunctions. This study was designed to reveal the impact of HAM and related symptoms on health-related quality of life (HRQoL).MethodsWe analyzed the Short Form-36 (SF-36) and clinical data of 538 patients with HAM registered in the HAM-net, a nationwide patient registry for HAM in Japan. HRQoL was evaluated using the SF-6D (a health state utility value calculated from the SF-36) and eight SF-36 subscales. A general liner model was used to estimate the impact of major HAM-related symptoms, including gait dysfunction, sensory disturbance in the legs (pain and numbness), urinary dysfunction, and constipation, on the SF-6D and SF-36 subscale scores.ResultsThe mean age and disease duration were 62.0 and 16.5 years, respectively. Of the patients, 73.2% needed walking aid; 42.7 and 67.1% had leg pain and numbness, respectively; 92.1% had urinary dysfunction; and 77.9% had constipation. The mean SF-6D score was 0.565, which was significantly lower than the national average (0.674 in the 60–69 years age group; p &lt; 0.001), exceeding the minimal important difference (0.05–0.1). All the major symptoms were significantly associated with a decrease in the SF-6D score. The SF-36 subscale scores were significantly lower than the national standard of 50 (p ≤ 0.001), except for mental health (MH). Gait dysfunction was associated with lower scores in physical functioning (PF), limitations on role functioning because of physical health, bodily pain, general health perception (GH), vitality (VT), and social functioning; however, no association was observed between gait dysfunction and limitations on role functioning because of emotional problems and MH. Meanwhile, sensory disturbance in the legs was associated with a decrease in scores in all subscales. Urinary dysfunction was associated with worse PF, GH, VT, and MH. Constipation was associated only with PF.ConclusionHRQoL of patients with HAM was worse than that of the general population and was associated with all major symptoms. Thus, patients should be comprehensively managed to achieve better HRQoL.
Evaluation of an Artificial Intelligence System for the Detection of Diabetic Retinopathy in Chinese Community Healthcare Centers
Authors: Dong Xiuqing , Du Shaolin , Zheng Wenkai , Cai Chusheng , Liu Huaxiu , Zou Jiangfeng 
Published: April 2022

ObjectiveTo evaluate the sensitivity and specificity of a Comprehensive Artificial Intelligence Retinal Expert (CARE) system for detecting diabetic retinopathy (DR) in a Chinese community population.MethodsThis was a cross-sectional, diagnostic study. Participants with a previous diagnosis of diabetes from three Chinese community healthcare centers were enrolled in the study. Single-field color fundus photography was obtained and analyzed by the AI system and two ophthalmologists. Primary outcome measures included the sensitivity, specificity, positive predictive value, and negative predictive value with their 95% confidence intervals (CIs) of the AI system in detecting DR and diabetic macular edema (DME).ResultsIn this study, 443 subjects (848 eyes) were enrolled, and 283 (63.88%) were men. The mean age was 52.09 (11.51) years (range 18–82 years); 266 eyes were diagnosed with any DR, 233 with more-than-mild diabetic retinopathy (mtmDR), 112 with vision-threatening diabetic retinopathy (vtDR), and 57 with DME. The image ability of the AI system was as high as 99.06%, whereas its sensitivity and specificity varied significantly in detecting DR with different severities. The sensitivity/specificity to detect any DR was 75.19% (95%CI 69.47–80.17)/93.99% (95%CI 91.65–95.71), mtmDR 78.97% (95%CI 73.06–83.90)/92.52% (95%CI 90.07–94.41), vtDR 33.93% (95%CI 25.41–43.56)/97.69% (95%CI 96.25–98.61), and DME 47.37% (95%CI 34.18–60.91)/93.99% (95%CI 91.65–95.71).ConclusionsThis multicenter cross-sectional diagnostic study noted the safety and reliability of the CARE system for DR (especially mtmDR) detection in Chinese community healthcare centers. The system may effectively solve the dilemma faced by Chinese community healthcare centers: due to the lack of ophthalmic expertise of primary physicians, DR diagnosis and referral are not timely.
Structural Characterization of the Full-Length Anti-CD20 Antibody Rituximab
Authors: Belviso Benny Danilo , Mangiatordi Giuseppe Felice , Alberga Domenico , Mangini Vincenzo , Carrozzini Benedetta , Caliandro Rocco 
Published: April 2022

Rituximab, a murine–human chimera, is the first monoclonal antibody (mAb) developed as a therapeutic agent to target CD20 protein. Its Fab domain and its interaction with CD20 have been extensively studied and high-resolution atomic models obtained by X-ray diffraction or cryo-electron microscopy are available. However, the structure of the full-length antibody is still missing as the inherent protein flexibility hampers the formation of well-diffracting crystals and the reconstruction of 3D microscope images. The global structure of rituximab from its dilute solution is here elucidated by small-angle X-ray scattering (SAXS). The limited data resolution achievable by this technique has been compensated by intensive computational modelling that led to develop a new and effective procedure to characterize the average mAb conformation as well as that of the single domains. SAXS data indicated that rituximab adopts an asymmetric average conformation in solution, with a radius of gyration and a maximum linear dimension of 52 Å and 197 Å, respectively. The asymmetry is mainly due to an uneven arrangement of the two Fab units with respect to the central stem (the Fc domain) and reflects in a different conformation of the individual units. As a result, the Fab elbow angle, which is a crucial determinant for antigen recognition and binding, was found to be larger (169°) in the more distant Fab unit than that in the less distant one (143°). The whole flexibility of the antibody has been found to strongly depend on the relative inter-domain orientations, with one of the Fab arms playing a major role. The average structure and the amount of flexibility has been studied in the presence of different buffers and additives, and monitored at increasing temperature, up to the complete unfolding of the antibody. Overall, the structural characterization of rituximab can help in designing next-generation anti-CD20 antibodies and finding more efficient routes for rituximab production at industrial level.
Identification of Novel Immune Cell-Relevant Therapeutic Targets and Validation of Roles of TK1 in BMSCs of Systemic Lupus Erythematosus
Authors: Chen Fangru , Meng Jian , Yan Wenjie , Wang Mengjiao , Jiang Yunfei , Gao Jintao 
Published: April 2022

Objective: Systemic lupus erythematosus (SLE) displays the characteristics of abnormal activity of the immune system, contributing to diverse clinical symptoms. Herein, this study was conducted for discovering novel immune cell-relevant therapeutic targets.Methods: The abundance of diverse immune cells was estimated in PBMCs of SLE and healthy controls from the GSE50772 dataset with CIBERSORT approach. Immune cell-relevant co-expression modules were screened with WGCNA and relevant characteristic genes were determined with LASSO algorithm. Inflammatory chemokines were measured in serum of twenty SLE patients and twenty controls through ELISA. Bone marrow mesenchymal stem cells (BMSCs) were isolated and TK1 expression was measured in BMSCs through RT-qPCR and western blotting. TK1-overexpressed and TK-1-silenced BMSCs of SLE were conducted and apoptosis and cell cycle were measured with flow cytometry. Apoptosis-, cell cycle- and senescence-relevant proteins were tested with western blotting.Results: We determined three co-expression modules strongly linked to immune cells. Five characteristic genes (CXCL1, CXCL2, CXCL8, CXCR1 and TK1) were screened and ROC curves proved the excellent diagnostic performance of this LASSO model. Inflammatory chemokines presented widespread up-regulations in serum of Systemic lupus erythematosus patients, demonstrating the activation of inflammatory response. TK1 expression was remarkably elevated in SLE BMSCs than controls. TK1 overexpression enhanced IL-1β expression, apoptosis, cell cycle arrest, and senescent phenotypes of SLE BMSCs and the opposite results were proved in TK1-silenced SLE BMSCs.Conclusion: Collectively, our findings demonstrate that silencing TK1 alleviates inflammation, growth arrest and senescence in BMSCs of SLE, which highlights TK1 as a promising therapeutic target against SLE.
The Effect of Endolymphatic Hydrops and Mannitol Dehydration Treatment on Guinea Pigs
Authors: Wang Shu-Qi , Li Chen-Long , Xu Jing-Qi , Chen Li-Li , Xie You-Zhou , Dai Pei-Dong , Ren Liu-Jie , Yao Wen-Juan , Zhang Tian-Yu 
Published: April 2022

BackgroundEndolymphatic hydrops (EH) is considered as the pathological correlate of Menière’s disease (MD) and cause of hearing loss. The mechanism of EH, remaining unrevealed, poses challenges for formalized clinical trials.ObjectiveThis study aims to investigate the development of hearing loss, as well as the effect of dehydration treatment on EH animal models.MethodsIn this study, different severity EH animal models were created. The laser Doppler vibrometer (LDV) and auditory brainstem responses (ABR) were used to study the effects of EH and the dehydration effects of mannitol. The LDV was used to measure the vibration of the round window membrane (RWM) reflecting the changes in inner ear impedance. ABR was used to evaluate the hearing changes. Furthermore, tissue section and scanning electron microscopy (SEM) observations were used to analyze the anatomical change to the cochlea and outer hair cells.ResultsThe RWM vibrations decreased with the severity of EH, indicating an increase in the cochlear impedance. The dehydration therapy lowered the impedance to restore acoustic transduction in EH 10- and 20-day animal models. Simultaneously, the ABR thresholds increased in EH models and were restored after dehydration. Moreover, a difference in the hearing was found between ABR and LDV results in severe EH animal models, and the dehydration therapy was less effective, indicating a sensorineural hearing loss (SNHL).ConclusionEndolymphatic hydrops causes hearing loss by increasing the cochlear impedance in all tested groups, and mannitol dehydration is an effective therapy to restore hearing. However, SNHL occurs for the EH 30-day animal models, limiting the effectiveness of dehydration. Our results suggest the use of dehydrating agents in the early stage of EH.
Prognostic Nutritional Index and Oxygen Therapy Requirement Associated With Longer Hospital Length of Stay in Patients With Moderate to Severe COVID-19: Multicenter Prospective Cohort Analyses
Authors: Fernandes Alan L. , Reis Bruna Z. , Murai Igor H. , Pereira Rosa M. R. 
Published: April 2022

PurposeTo evaluate whether the prognostic nutritional index (PNI) is related to the oxygen therapy requirement at hospital admission and to ascertain the prognostic effect of the PNI and the oxygen therapy requirement as predictors of hospital length of stay in patients with moderate to severe coronavirus disease 2019 (COVID-19).MethodsThis is a post-hoc analysis in hospitalized patients with moderate to severe COVID-19. The participants were categorized: (1) non-oxygen therapy (moderate COVID-19 not requiring oxygen therapy); (2) nasal cannula therapy (severe COVID-19 requiring nasal cannula oxygen therapy); and (3) high-flow therapy (severe COVID-19 requiring high-flow oxygen therapy). PNI was calculated for each patient according to the following equation: serum albumin [g/dL] × 10 + total lymphocyte count [per mm3] × 0.005. The participants were categorized into malnutrition (PNI &lt;40), mild malnutrition (PNI 40–45), and non-malnutrition (PNI &gt; 45).ResultsAccording to PNI, malnutrition was more prevalent in the high-flow therapy group (94.9%; P &lt; 0.001) with significantly lower PNI compared to both groups even after adjusting for the center and C-reactive protein. Patients in the high-flow therapy group [9 days (95% CI 7.2, 10.7), P &lt; 0.001] and malnutrition status [7 days (95% CI 6.6, 7.4), P = 0.016] showed a significant longer hospital length of stay compared to their counterparts. The multivariable Cox proportional hazard models showed significant associations between both oxygen therapy requirement and PNI categories and hospital discharge.ConclusionIn addition to oxygen therapy requirement, low PNI was associated with longer hospital length of stay. Our findings suggest that PNI could be useful in the assessment of nutritional status related to the prognosis of patients with moderate to severe COVID-19.
Hot Tea Consumption and Esophageal Cancer Risk: A Meta-Analysis of Observational Studies
Authors: Luo Hui , Ge Hong 
Published: April 2022

ObjectiveMany laboratory studies have shown that tea consumption protected against the development of esophageal cancer (EC). However, in epidemiological studies, inconsistent or even contradictory results were frequently observed, especially when drinking tea at higher temperatures.MethodsWe conducted a meta-analysis based on published observational studies to explore whether hot tea consumption was a risk factor of EC. Relevant studies were searched in PubMed, Embase, and Web of science up to October 13, 2021, and we also manually retrieved the literature in the included studies and recent reviews.ResultsA total of 23 eligible reports were identified, including 5,050 cases and 10,609 controls, and a meta-analysis with Comprehensive Meta-Analysis (CMA) software (version 2.0) was conducted. A statistically significant increased EC risk was observed when drinking tea at higher temperature (odds ratios (ORs) = 1.79, 95% CI: 1.48–2.15, p = 0.00). Except for esophageal adenocarcinoma (EAC), this increased risk was also found in the majority of subgroups, which are the European and Australian populations.ConclusionsThis meta-analysis showed that people who drank hot tea had a significantly increased risk of Esophageal squamous cell carcinoma (ESCC), but no significant association for EAC.
Comparison of the Suitability Between NRS2002 and MUST as the First-Step Screening Tool for GLIM Criteria in Hospitalized Patients With GIST
Authors: Zhou Xin , Liu Junjin , Zhang Qijuan , Rao Siqi , Wu Xingye , Zhang Jun , Li Juan 
Published: April 2022

ObjectiveThe Global Leader Initiative on Malnutrition (GLIM) criteria have been recommended for malnutrition diagnosis recently, for which the first step is malnutrition risk screening with any validated tool. This study aims to investigate the incidence of malnutrition risk in gastrointestinal stromal tumor (GIST) inpatients and compare the suitability of Nutritional Risk Screening 2002 (NRS2002) and Malnutrition Universal Screening Tool (MUST) as the first-step screening tool for GLIM criteria.MethodsWe retrospectively analyzed the clinical data of GIST inpatients in our hospital from January 2015 to December 2019. NRS2002 and MUST were used to screen malnutrition risk at the time of admission. The diagnostic consistency of these two tools with GLIM criteria for malnutrition was analyzed, and the predictive performance of both tools for the length of hospital stay and the occurrence of complications was also evaluated in surgical and non-surgical inpatients.ResultsA total of 269 GIST inpatients were included in this study, of which 45.7 and 40.9% were at malnutrition risk determined by NRS2002 and MUST, respectively. In non-surgical inpatients, NRS2002 and MUST had similar diagnostic consistency with GLIM criteria in sensitivity (93.0 vs. 97.7%), specificity (81.1 vs. 81.1%), and Kappa value (K = 0.75 vs. 0.80), and high nutritional risk classified by NRS2002 and malnutrition identified by GLIM criteria were found to be associated with the length of hospital stay. In surgical inpatients, MUST had better diagnostic consistency with GLIM criteria in sensitivity (86.1 vs. 53.5%) and Kappa value (K = 0.61 vs. 0.30) than NRS2002, but no factors were found associated with the length of postoperative hospital stay or the occurrence of complications.ConclusionThe malnutrition risk is common in GIST inpatients. NRS2002 is more suitable than MUST for the first-step risk screening of the GLIM scheme in non-surgical inpatients, considering its better performance in screening malnutrition risk and predicting clinical outcomes. MUST was found to have good diagnostic consistency with GLIM criteria for malnutrition in both non-surgical and surgical GIST inpatients, and further studies need to be conducted to investigate its predictive performance on clinical outcomes.