bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of Causal Direction Between Gut Microbiota and Inflammatory Bowel Disease: A Mendelian Randomization Analysis
Authors: Zhang Zi-Jia , Qu Hong-Lei , Zhao Na , Wang Jing , Wang Xiu-Yan , Hai Rong , Li Bin 
Published: February 2021

BackgroundRecent studies have shown that the gut microbiota is closely related to the pathogenesis of Inflammatory Bowel Disease (IBD), but the causal nature is largely unknown. The purpose of this study was to assess the causal relationship between intestinal bacteria and IBD and to identify specific pathogenic bacterial taxa via the Mendelian randomization (MR) analysis.Materials and MethodsMR analysis was performed on genome-wide association study (GWAS) summary statistics of gut microbiota and IBD. Specifically, the TwinsUK microbiota GWAS (N = 1,126 twin pairs) was used as exposure. The UK inflammatory bowel disease (UKIBD) and the Understanding Social Program (USP) study GWAS (N = 48,328) was used as discovery outcome, and the British IBD study (N = 35,289) was used as replication outcome. SNPs associated with bacteria abundance at the suggestive significance level (α = 1.0 × 10–5) were used as instrumental variables. Bacteria were grouped into families and genera.ResultsIn the discovery sample, a total of 30 features were available for analysis, including 15 families and 15 genera. Three features were nominally significant, including one family (Verrucomicrobiaceae, 2 IVs, beta = −0.04, p = 0.05) and two genera (Akkermansia, 2 IVs, beta = 0.04, p = 0.05; Dorea, 2 IVs, beta = −0.07, p = 0.04). All of them were successfully replicated in the replication sample (Verrucomicrobiaceae and Akkermansia Preplication = 0.02, Dorea Preplication = 0.01) with consistent effect direction.ConclusionWe identified specific pathogenic bacteria features that were causally associated with the risk of IBD, thus offering new insights into the prevention and diagnosis of IBD.
CCR5 Promoter Polymorphisms Associated With Pulmonary Tuberculosis in a Chinese Han Population
Authors: Liu Shuyuan , Liu Nannan , Wang Hui , Zhang Xinwen , Yao Yufeng , Zhang Shuqiong , Shi Li 
Published: February 2021

BackgroundTuberculosis (TB), an infectious disease caused by Mycobacterium tuberculosis, is a major public health concern. Chemokines and their receptors, such as RANTES, CXCR3, and CCR5, have been reported to play important roles in cell activation and migration in immune responses against TB infection.MethodsTo understand the correlations involving CCR5 gene variations, M. tuberculosis infection, and TB disease progression, a case-control study comprising 450 patients with TB and 306 healthy controls from a Chinese Han population was conducted, along with the detection of polymorphisms in the CCR5 promoter using a sequencing method.ResultsAfter adjustment for age and gender, the results of logistic analysis indicated that the frequency of rs2734648-G was significantly higher in the TB patient group (P = 0.002, OR = 1.38, 95% CI: 1.123–1.696); meanwhile, rs2734648-GG showed notable susceptibility to TB (P = 6.32E-06, OR = 2.173, 95% CI: 1.546–3.056 in a recessive model). The genotypic frequency of rs1799987 also varied between the TB and control groups (P = 0.008). In stratified analysis, rs2734648-GG significantly increased susceptibility to pulmonary TB in a recessive model (P &lt; 0.0001, OR = 2.382, 95% CI: 1.663–3.413), and the rs2734648-G allele significantly increased susceptibility to TB recurrence in a dominant model (P = 0.0032, OR = 1.936, 95% CI: 1.221–3.068), whereas rs1799987-AA was associated with susceptibility to pulmonary TB (P = 0.0078, OR = 1.678, 95% CI: 1.141–2.495 in a recessive model) but not with extra-pulmonary TB and TB recurrence. A haplotype constructed with the major alleles of the eight SNPs in the CCR5 promoter (rs2227010-rs2856758-rs2734648-rs1799987-rs1799988-rs41469351-rs1800023-rs1800024: A-A-G-G-T-C-G-C) exhibited extraordinarily increased risk of susceptibility to TB and pulmonary TB (P = 6.33E-11, OR = 24.887, 95% CI: 6.081–101.841).ConclusionIn conclusion, CCR5 promoter polymorphisms were found to be associated with pulmonary TB and TB progression in Chinese Han people.
GM-CSF Expression and Macrophage Polarization in Joints of Undifferentiated Arthritis Patients Evolving to Rheumatoid Arthritis or Psoriatic Arthritis
Authors: Fuentelsaz-Romero Sara , Cuervo Andrea , Estrada-Capetillo Lizbeth , Celis Raquel , García-Campos Raquel , Ramírez Julio , Sastre Sergi , Samaniego Rafael , Puig-Kröger Amaya , Cañete Juan D. 
Published: February 2021

Background and AimsGM-CSF-dependent macrophage polarization has been demonstrated in rheumatoid arthritis (RA). Our aim was to seek diagnostic/prognostic biomarkers for undifferentiated arthritis (UA) by analyzing GM-CSF expression and source, macrophage polarization and density in joints of patients with UA evolving to RA or PsA compared with established RA or PsA, respectively.MethodsSynovial tissue (ST) from patients with UA evolving to RA (UA&gt;RA, n=8), PsA (UA&gt;PsA, n=9), persistent UA (UA, n=16), established RA (n=12) and PsA (n=10), and healthy controls (n=6), were analyzed. Cell source and quantitative expression of GM-CSF and proteins associated with pro-inflammatory (GM-CSF-driven) and anti-inflammatory (M-CSF-driven) macrophage polarization (activin A, TNFα, MMP12, and CD209, respectively) were assessed in ST CD163+ macrophages by multicolor immunofluorescence. GM-CSF and activin A levels were also quantified in paired synovial fluid samples. CD163+ macrophage density was determined in all groups by immunofluorescence.ResultsSynovial stromal cells (FAP+ CD90+ fibroblast, CD90+ endothelial cells) and CD163+ sublining macrophages were the sources of GM-CSF. ST CD163+ macrophages from all groups expressed pro-inflammatory polarization markers (activin A, TNFα, and MMP12). Expression of the M-CSF-dependent anti-inflammatory marker CD209 identified two macrophage subsets (CD163+ CD209high and CD163+ CD209low/-). CD209+ macrophages were more abundant in ST from healthy controls and PsA patients, although both macrophage subtypes showed similar levels of pro-inflammatory markers in all groups. In paired synovial fluid samples, activin A was detected in all patients, with higher levels in UA&gt;RA and RA, while GM-CSF was infrequently detected. ST CD163+ macrophage density was comparable between UA&gt;RA and UA&gt;PsA patients, but significantly higher than in persistent UA.ConclusionsGM-CSF is highly expressed by sublining CD90+ FAP+ synovial fibroblasts, CD90+ activated endothelium and CD163+ macrophages in different types of arthritis. The polarization state of ST macrophages was similar in all UA and established arthritis groups, with a predominance of pro-inflammatory GM-CSF-associated markers. CD163+ macrophage density was significantly higher in the UA phases of RA and PsA compared with persistent UA. Taken together, our findings support the idea that GM-CSF is a strong driver of macrophage polarization and a potential therapeutic target not only in RA but also in PsA and all types of UA.
Ongoing Oscillatory Electrophysiological Alterations in Frail Older Adults: A MEG Study
Authors: Suárez-Méndez Isabel , Walter Stefan , López-Sanz David , Pasquín Natalia , Bernabé Raquel , Castillo Gallo Ernesto , Valdés Myriam , del Pozo Francisco , Maestú Fernando , Rodríguez-Mañas Leocadio 
Published: February 2021

Objective: The role of the central nervous system in the pathophysiology of frailty is controversial. We used magnetoencephalography (MEG) to search for abnormalities in the ongoing oscillatory neural activity of frail individuals without global cognitive impairment.Methods: Fifty four older (≥70 years) and cognitively healthy (Mini-Mental State Examination ≥24) participants were classified as robust (0 criterion, n = 34) or frail (≥ 3 criteria, n = 20) following Fried's phenotype. Memory, language, attention, and executive function were assessed through well-validated neuropsychological tests. Every participant underwent a resting-state MEG and a T1-weighted magnetic resonance imaging scan. We performed MEG power spectral analyses to compare the electrophysiological profiles of frail and robust individuals. We used an ensemble learner to investigate the ability of MEG spectral power to discriminate frail from robust participants.Results: We identified increased relative power in the frail group in the mu (p &lt; 0.05) and sensorimotor (p &lt; 0.05) frequencies across right sensorimotor, posterior parietal, and frontal regions. The ensemble learner discriminated frail from robust participants [area under the curve = 0.73 (95% CI = 0.49–0.98)]. Frail individuals performed significantly worse in the Trail Making Test, Digit Span Test (forward), Rey-Osterrieth Complex Figure, and Semantic Fluency Test.Interpretation: Frail individuals without global cognitive impairment showed ongoing oscillatory alterations within brain regions associated with aspects of motor control, jointly to failures in executive function. Our results suggest that some physical manifestations of frailty might partly arise from failures in central structures relevant to sensorimotor and executive processing.
Case Report: Early-Onset Guillain–Barre Syndrome Mimicking Stroke
Authors: Sun Jing , Gao Yu , Chi Lumei , Cao Qingyang , Ning Zhijie , Nan Guangxian 
Published: February 2021

Introduction: Guillain–Barre syndrome (GBS) is an acute immune-mediated inflammatory demyelinating polyneuropathy characterized by symmetrical limb weakness and areflexia. GBS can have different clinical manifestations; hence, the initial symptoms are also varied. Here, we describe a rare case of GBS presenting as hemiparesis and cranial nerve palsy, which mimic brainstem stroke.Case Presentation: A 53-year-old man was admitted to the hospital with a 3-h history of left-arm weakness, glossolalia, and right eyelid droop. After admission, his condition suddenly worsened, with quadriplegia, bilateral peripheral facial palsy, bilateral ophthalmoplegia, and other neurological symptoms. Based on the findings from a neurological examination, MRI, cerebrospinal fluid analysis, and nerve conduction study, a diagnosis of GBS was made. He received intravenous immunoglobulin (0.4 kg/day) for 5 days. After 20 days of systematic therapy, his dysphagia, dyspnea, facial paralysis, ocular movement disorder, and leg weakness recovered almost completely, but his arms were still moderately impaired, with a power of 4/5. Fortunately, the patient recovered well without any sequelae after 2 years of follow-up.Conclusions: In patients with an atypical presentation, the diagnosis of GBS is often delayed. With this case report, we intend to highlight the fact that some symptoms mimicking stroke may be a feature of GBS at onset; close observation and timely diagnosis are crucial for clinicians. Neuroimaging is a valuable diagnostic tool in differentiating stroke from GBS.
Online Closed-Loop Control Using Tactile Feedback Delivered Through Surface and Subdermal Electrotactile Stimulation
Authors: Dong Jian , Jensen Winnie , Geng Bo , Kamavuako Ernest Nlandu , Dosen Strahinja 
Published: February 2021

AimLimb loss is a dramatic event with a devastating impact on a person’s quality of life. Prostheses have been used to restore lost motor abilities and cosmetic appearance. Closing the loop between the prosthesis and the amputee by providing somatosensory feedback to the user might improve the performance, confidence of the amputee, and embodiment of the prosthesis. Recently, a minimally invasive method, in which the electrodes are placed subdermally, was presented and psychometrically evaluated. The present study aimed to assess the quality of online control with subdermal stimulation and compare it to that achieved using surface stimulation (common benchmark) as well as to investigate the impact of training on the two modalities.MethodsTen able-bodied subjects performed a PC-based compensatory tracking task. The subjects employed a joystick to track a predefined pseudorandom trajectory using feedback on the momentary tracking error, which was conveyed via surface and subdermal electrotactile stimulation. The tracking performance was evaluated using the correlation coefficient (CORR), root mean square error (RMSE), and time delay between reference and generated trajectories.ResultsBoth stimulation modalities resulted in good closed-loop control, and surface stimulation outperformed the subdermal approach. There was significant difference in CORR (86 vs 77%) and RMSE (0.23 vs 0.31) between surface and subdermal stimulation (all p &lt; 0.05). The RMSE of the subdermal stimulation decreased significantly in the first few trials.ConclusionSubdermal stimulation is a viable method to provide tactile feedback. The quality of online control is, however, somewhat worse compared to that achieved using surface stimulation. Nevertheless, due to minimal invasiveness, compactness, and power efficiency, the subdermal interface could be an attractive solution for the functional application in sensate prostheses.
The Impact of Comorbidity on Survival in Patients With Head and Neck Squamous Cell Carcinoma: A Nationwide Case-Control Study Spanning 35 Years
Authors: Ruud Kjær Eva Kristine , Jensen Jakob Schmidt , Jakobsen Kathrine Kronberg , Lelkaitis Giedrius , Wessel Irene , von Buchwald Christian , Grønhøj Christian 
Published: February 2021

BackgroundComorbidity is presumed to impact survival of head and neck squamous cell cancer (HNSCC) patients. However, the prevalence and prognostic impact of comorbidity in these patients is not yet well established. The aim of this study is to outline the comorbidity burden of HNSCC patients and investigate the relation to overall survival and cancer-specific mortality.MethodsThe comorbidity burden of patients registered with HNSCC in the Danish Cancer Registry between 1980 and 2014 was evaluated based on the Charlson Comorbidity Index (CCI). Patients’ risks of comorbid conditions compared to age- and gender-matched controls were estimated by odds ratios (OR). The impact of comorbidity on overall survival and cancer-specific mortality was evaluated by Cox regression and Kaplan-Meier survival analysis.ResultsA total of 25,388 HNSCC patients were included (72.5% male; mean age 63.2 years at diagnosis; median follow-up 3.0 years). CCI at diagnosis was significantly higher in patients compared to controls (p &lt; 0.001). The most common comorbid conditions among the patients were additional non-metastatic malignancy (10.9%) and cerebrovascular disease (7.7%). Compared to controls, patients had higher odds of metastatic malignancy (OR: 4.65; 95% CI: 4.21–5.15; p &lt; 0.001), mild liver disease (OR: 6.95; 95% CI: 6.42–7.53; p &lt; 0.001), and moderate-severe liver disease (OR: 7.28; 95% CI: 6.14–8.65; p &lt; 0.001). The multivariate Cox analysis revealed increasing hazard ratios with increasing CCI and in coherence the Kaplan-Meier curves showed poorer overall survival and increased cancer-specific mortality in patients with higher CCI.ConclusionHNSCC patients’ comorbidity burden was significantly greater compared to the general population and increased comorbidity was correlated with increased cancer-related mortality.
Long Noncoding RNA UCA1 Is Related to Autophagy and Apoptosis in Endometrial Stromal Cells
Authors: Jiang Lili , Wan Yahui , Feng Ziyi , Liu Da , Ouyang Ling , Li Yan , Liu Kuiran 
Published: February 2021

Research QuestionThe expression of the long noncoding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) in embryonic tissues is higher than that in most cancer tissues, such as bladder cancer, indicating that RNA is a carcinoembryonic antigen. However, there are no published reports on the role of UCA1 in endometriosis (EMS). Therefore, to address this gap in knowledge, we assessed the potential role of lncRNA UCA1 in the pathogenesis and progression of EMS.DesignTo verify the expression of UCA1 in EMS, quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used. RNA interference (siRNA) was used to study the biological function of UCA1 in EMS in vitro.ResultsqRT-PCR analysis showed that the expression of lncRNA UCA1 in EMS was increased (P&lt;0.01). Knockdown of UCA1 in vitro significantly inhibited the proliferation of endometrial stromal cells (ESCs) and induced autophagy and apoptosis.ConclusionUCA1 is highly expressed in EMS and promotes the proliferation of ESCs but suppresses autophagy and apoptosis. In EMS, UCA1 may be a prognostic marker and therapeutic target.
The Efficacy and Safety of Anlotinib Combined With PD-1 Antibody for Third-Line or Further-Line Treatment of Patients With Advanced Non-Small-Cell Lung Cancer
Authors: Zhai Chongya , Zhang Xiaoling , Ren Lulu , You Liangkun , Pan Qin , Pan Hongming , Han Weidong 
Published: February 2021

BackgroundBoth anlotinib and programmed death 1 (PD-1) monoclonal antibody (mAb) have been approved for the third line treatment of metastatic non-small cell lung cancer (NSCLC). However, the combination of these two standard therapies has not been investigated in third-line or further-line treatment of patients with advanced NSCLC.MethodsWe reviewed 22 patients with NSCLC who received anlotinib combined with PD-1 mAb therapy from July 2018 to October 2019 at Sir Run Run Shaw Hospital. Based on the baseline characteristics, PD-L1 expression and EGFR mutation status, we retrospectively analyzed the efficacy and safety of this combination therapy by RESIST 1.1 and CTCAE 5.0.ResultsThe combination treatment of anlotinib and PD-1 mAb in 22 NSCLC patients gained a median PFS of 6.8 months and a median OS of 17.3 months. The disease control rate (DCR) was 90.9%, and the objective response rate (ORR) was 36.4%, where 1 (4.6%) patient achieved complete response (CR) and 7 (31.8%) patients achieved partial response (PR). The median time to response was 3.9 months, and the median duration of the response was 6.8 months. The common grades 1–2 adverse events were fatigue 10/22 (45.5%), decreased appetite 9/22 (40.9%), hypertension 10/22 (45.5%); the common grades 3–4 adverse events were hypertension 2/22 (9.1%) and mouth ulceration 2/22 (9.1%).ConclusionAnlotinib combined with PD-1 mAb showed promising efficacy in third-line or further-line treatment of NSCLC, and its adverse effects is tolerable.
Sentinel Lymph-Node Biopsy in Early-Stage Cervical Cancer: The 4-Year Follow-Up Results of the Senticol 2 Trial
Authors: Favre Guillaume , Guani Benedetta , Balaya Vincent , Magaud Laurent , Lecuru Fabrice , Mathevet Patrice 
Published: February 2021

IntroductionSenticol 2 is a randomized multicenter trial in the treatment of early-stage cervical cancer patients. The aim of the Senticol 2 study was to compare the effect of sentinel-lymph-node biopsy (SLNB) to that of SLNB + pelvic lymphadenectomy (PLND), and to determine the postoperative lymphatic morbidity in the two groups. Here, we report a secondary objective of this study: the follow up.Material and MethodsIn the Senticol 2 trial, patients underwent a laparoscopy with a sentinel-node-detection procedure and were randomized into two groups, namely: Group A, in which participants received SLNB, and Group B, in which participants received SLNB + PLND. Patients with an intra-operative macroscopically suspicious lymph node, were given a frozen-section evaluation and were randomized only if the results were negative. All of the patients received follow up with a clinical examination at 1, 3, and 6 months after surgery, and then every 3–4 months after that. The median follow up was 51 months (4 years and 3 months).ResultsDisease-free survival after 4 years for the SLNB group and the SLNB + PLND group were 89.51% and 93.1% (p = 0.53), respectively. The only statistical factor associated with recurrence in the univariate analysis was the adjuvant radiotherapy. No other factors, including the age of the patients, histological type, tumor size, lymph vascular space invasion (LVSI), and positive nodal status, were significant in the univariate or multivariate analyses. The overall survival rates after 4 years in the SLNB and SLNB + PLND groups were 95.2% and 96% (p = 0.97), with five and four deaths, respectively. The univariate and multivariate analyses did not find any prognostic factors.ConclusionsThis randomized study confirmed the results of the Senticol 1 study and supports the sentinel lymph node (SLN) technique as a safe technique for use in patients with early-stage cervical cancer treated with SLNB only. Disease-free survival after 4 years was similar in patients treated with SLN biopsy and patients who underwent a lymphadenectomy.
Development and Validation of a Personalized Survival Prediction Model for Uterine Adenosarcoma: A Population-Based Deep Learning Study
Authors: Qu Wenjie , Liu Qingqing , Jiao Xinlin , Zhang Teng , Wang Bingyu , Li Ningfeng , Dong Taotao , Cui Baoxia 
Published: February 2021

BackgroundThe aim was to develop a personalized survival prediction deep learning model for adenosarcoma patients using the surveillance, epidemiology and end results (SEER) database.MethodsA total of 797 uterine adenosarcoma patients were enrolled in this study. Duplicated and useless variables were excluded, and 15 variables were selected for further analyses, including age, grade, positive lymph nodes or not, marital status, race, tumor extension, stage, and surgery or not. We created our deep survival learning (DSL) model to manipulate the data, which was randomly split into a training set (n = 519, 65%), validation set (n = 143, 18%) and testing set (n = 143, 18%). The Cox proportional hazard (CPH) model was also included comparatively. Finally, personalized survival curves were plotted for randomly selected patients.ResultsThe c-index for the CPH model was 0.726, and the Brier score was 0.17. For our deep survival learning model, we achieved a c-index of 0.774 and a Brier score of 0.14 in the external testing set. In addition, the limitations of the traditional staging system were revealed, and a personalized survival prediction system based on our risk scoring grouping was developed.ConclusionsOur study developed a deep neural network model for adenosarcoma. The performance of this model was superior to that of the traditional Cox proportional hazard model. In addition, a personalized survival prediction system was developed based on our deep survival learning model, which provided more accurate prognostic information for adenosarcoma patients.