bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of a Qualitative Signature for the Diagnosis of Dementia With Lewy Bodies
Authors: Zhou Shu , Meng Qingchun , Li Lingyu , Hai Luo , Wang Zexuan , Li Zhicheng , Sun Yingli 
Published: November 2021

Background and purpose: Diagnosis of dementia with Lewy bodies (DLB) is highly challenging, primarily due to a lack of valid and reliable diagnostic tools. To date, there is no report of qualitative signature for the diagnosis of DLB. We aimed to develop a blood-based qualitative signature for differentiating DLB patients from healthy controls.Methods: The GSE120584 dataset was downloaded from the public database Gene Expression Omnibus (GEO). We combined multiple methods to select features based on the within-sample relative expression orderings (REOs) of microRNA (miRNA) pairs. Specifically, we first quickly selected miRNA pairs related to DLB by identifying reversal stable miRNA pairs. Then, an optimal miRNA pair subset was extracted by random forest (RF) and support vector machine-recursive feature elimination (SVM-RFE) methods. Furthermore, we applied logistic regression (LR) and SVM to build several prediction models. The model performance was assessed using the receiver operating characteristic curve (ROC) analysis. Lastly, we conducted bioinformatics analyses to explore the molecular mechanisms of the discovered miRNAs.Results: A qualitative signature consisted of 17 miRNA pairs and two clinical factors was identified for discriminating DLB patients from healthy controls. The signature is robust against experimental batch effects and applicable at the individual levels. The accuracies of the-signature-based models on the test set are 82.61 and 79.35%, respectively, indicating that the signature has acceptable discrimination performance. Moreover, bioinformatics analyses revealed that predicted target genes were enriched in 11 Go terms and 2 KEGG pathways. Moreover, five potential hub genes were found for DLB, including SRF, MAPK1, YWHAE, RPS6KA3, and KDM7A.Conclusion: This study provided a blood-based qualitative signature with the potential to be used as an effective tool to improve the accuracy of DLB diagnosis.
Quantitative Insights Into β-Lactamase Inhibitor’s Contribution in the Treatment of Carbapenemase-Producing Organisms With β-Lactams
Authors: Feng Yanfang , de Vos Arend L. , Khan Shakir , St. John Mary , Hasan Tayyaba 
Published: November 2021

Objectives: Carbapenemase-producing organisms (CPOs) are associated with high mortality rates. The recent development of β-lactamase inhibitors (BLIs) has made it possible to control CPO infections safely and effectively with β-lactams (BLs). This study aims to explicate the quantitative relationship between BLI’s β-lactamase inhibition and CPO’s BL susceptibility restoration, thereby providing the infectious disease society practical scientific grounds for regulating the use of BL/BLI in CPO infection treatment.Methods: A diverse collection of human CPO infection isolates was challenged by three structurally representative BLIs available in the clinic. The resultant β-lactamase inhibition, BL susceptibility restoration, and their correlation were followed quantitatively for each isolate by coupling FIBA (fluorescence identification of β-lactamase activity) and BL antibiotic susceptibility testing.Results: The β-lactamase inhibition and BL susceptibility restoration are positively correlated among CPOs under the treatment of BLIs. Both of them are dependent on the target CPO’s carbapenemase molecular identity. Of note, without sufficient β-lactamase inhibition, CPO’s BL susceptibility restoration is universally low across all tested carbapenemase molecular groups. However, a high degree of β-lactamase inhibition would not necessarily lead to a substantial BL susceptibility restoration in CPO probably due to the existence of non-β-lactamase BL resistance mechanisms.Conclusion: BL/BLI choice and dosing should be guided by quantitative tools that can evaluate the inhibition across the entire β-lactamase background of the CPO upon the BLI administion. Furthermore, rapid molecular diagnostics for BL/BLI resistances, especially those sensitive to β-lactamase independent BL resistance mechanisms, should be exploited to prevent ineffective BL/BLI treatment.
Clinical Efficacy and Dosing of Vibrotactile Coordinated Reset Stimulation in Motor and Non-motor Symptoms of Parkinson's Disease: A Study Protocol
Authors: Pfeifer Kristina J. , Cook Alex J. , Yankulova Jessica K. , Mortimer Bruce J. P. , Erickson-DiRenzo Elizabeth , Dhall Rohit , Montaser-Kouhsari Leila , Tass Peter A. 
Published: November 2021

Enhanced neuronal synchronization of the subthalamic nucleus (STN) is commonly found in PD patients and corresponds to decreased motor ability. Coordinated reset (CR) was developed to decouple synchronized states causing long lasting desynchronization of neural networks. Vibrotactile CR stimulation (vCR) was developed as non-invasive therapeutic that delivers gentle vibrations to the fingertips. A previous study has shown that vCR can desynchronize abnormal brain rhythms within the sensorimotor cortex of PD patients, corresponding to sustained motor relief after 3 months of daily treatment. To further develop vCR, we created a protocol that has two phases. Study 1, a double blinded randomized sham-controlled study, is designed to address motor and non-motor symptoms, sensorimotor integration, and potential calibration methods. Study 2 examines dosing effects of vCR using a remote study design. In Study 1, we will perform a 7-month double-blind sham-controlled study including 30 PD patients randomly placed into an active vCR or inactive (sham) vCR condition. Patients will receive stimulation for 4 h a day in 2-h blocks for 6 months followed by a 1-month pause in stimulation to assess long lasting effects. Our primary outcome measure is the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III off medication after 6 months of treatment. Secondary measures include a freezing of gait (FOG) questionnaire, objective motor evaluations, sensorimotor electroencephalography (EEG) results, a vibratory temporal discrimination task (VTDT), non-motor symptom evaluations/tests such as sleep, smell, speech, quality of life measurements and Levodopa Equivalent Daily Dose (LEDD). Patients will be evaluated at baseline, 3, 6, and 7 months. In the second, unblinded study phase (Study 2), all patients will be given the option to receive active vCR stimulation at a reduced dose for an additional 6 months remotely. The remote MDS-UPDRS part III off medication will be our primary outcome measure. Secondary measures include sleep, quality of life, objective motor evaluations, FOG and LEDD. Patients will be evaluated in the same time periods as the first study. Results from this study will provide clinical efficacy of vCR and help validate our investigational vibrotactile device for the purpose of obtaining FDA clearance.Clinical Trial Registration:ClinicalTrials.gov, identifier: NCT04877015.
Risk Factors for Pericallosal Artery Aneurysm Rupture Based on Morphological Computer-Assisted Semiautomated Measurement and Hemodynamic Analysis
Authors: Zhai Xiaodong , Geng Jiewen , Zhu Chengcheng , Yu Jiaxing , Li Chuanjie , Jiang Nan , Xiang Sishi , Fang Gang , Hu Peng , Zhang Hongqi 
Published: November 2021

Background: Although pericallosal artery aneurysms (PAAs) are relatively uncommon, accounting for only 1–9% of all intracranial aneurysms (IAs), they exhibit a considerably high propensity to rupture. Nevertheless, our current knowledge of the risk factors for PAA rupture is still very limited. To fill this gap, we investigated rupture risk factors for PAAs based on morphological computer-assisted semiautomated measurement (CASAM) and hemodynamic analysis.Methods: Patients with PAAs were selected from the IA database in our institute and their baseline data were collected. Morphological parameters were measured in all enrolled patients by applying CASAM. Computational fluid dynamics simulation (CFD) was performed to evaluate the hemodynamic difference between ruptured and unruptured PAAs.Results: From June 2017 to June 2020, among 2141 patients with IAs in our institute, 47 had PAAs (2.2%). Thirty-one patients (mean age 57.65 ± 9.97 years) with 32 PAAs (20 unruptured and 12 ruptured) were included in the final analysis. Comparing with unruptured PAAs, ruptured PAAs had significantly higher aspect ratio (AR), mean normalized wall shear stress (NWSS), and mean oscillatory shear index (OSI) values than the unruptured PAAs (all P &lt; 0.05) in univariate analyses. Multivariable analysis showed that a high mean OSI was an independent risk factor for PAA rupture (OR = 6.45, 95% CI 1.37–30.32, P = 0.018).Conclusion: This preliminary study indicates that there are morphological and hemodynamic differences between ruptured and unruptured PAAs. In particular, a high mean OSI is an independent risk factor for PAA rupture. Further research with a larger sample size is warranted in the future.
A Comparison of Bevacizumab Plus TAS-102 and TAS-102 Monotherapy for Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis
Authors: Chen Xiaochen , Qiu Huafeng , Chen Yunwang , Wang Mingxing , Zhu Pengfei , Pan Shuangyue , Deng Yaya , Yang Liu , Chen Zheling 
Published: November 2021

BackgroundsAs a new oral chemotherapy drug, TAS-102 is currently recommended as the third-line treatment for metastatic colorectal cancer (mCRC). Recently, studies have reported the efficacy of TAS-102 combined with bevacizumab in colon cancer patients after standard treatment fails. Here, we evaluated the efficacy and safety of TAS-102 combined with bevacizumab versus TAS-102 as a single agent by a systematic review and a meta-analysis.MethodsPubMed, Web of Science and Cochrane libraries were searched. Studies involving bevacizumab combined with TAS-102 in mCRC were included. Study characteristics (author, year of publication, country et al.), efficacy (disease control rate(DCR), progression-free survival(PFS), overall survival(OS)) and adverse effects were extract from studies. Forest plots were created based on Cox model analysis.ResultsAfter screening 550 studies, a total of 3 studies were included, which compared the safety and effectiveness of TAS-102 with or without bevacizumab. Analysis based on Cox regression showed that the combined treatment group had advantages in 6-month (OR= 2.93, 95% CI: 1.72 to 5.00, P&lt;0.0001), 12-month(OR= 2.18, 95% CI: 1.24 to 3.81, P=0.006), and 18-month (OR=3.08, 95% CI: 1.34 to 7.12, P=0.008) OS. The combined treatment group demonstrated superiority in 6-month PFS rates (OR= 2.50, 95% CI: 1.18 to 5.31, P=0.02). The incidence of thrombocytopenia in the dual-drug treatment group was higher (OR= 1.96, 95% CI: 1.14 to 3.36 P=0.01). The proportion of serious adverse events were similar in tow groups (OR= 1.01, 95% CI: 0.76 to 1.34 P=0.93).ConclusionBevacizumab combined with TAS-102 could improve the prognosis of patients with mCRC who have failed standard treatment. In terms of side effects, the addition of bevacizumab did not increase serious adverse reactions, but the occurrence of thrombocytopenia was worth noting.
Extracellular Vesicle Molecular Signatures Characterize Metastatic Dynamicity in Ovarian Cancer
Authors: Gonda Amber , Zhao Nanxia , Shah Jay V. , Siebert Jake N. , Gunda Srujanesh , Inan Berk , Kwon Mijung , Libutti Steven K. , Moghe Prabhas V. , Francis Nicola L. , Ganapathy Vidya 
Published: November 2021

BackgroundLate-stage diagnosis of ovarian cancer, a disease that originates in the ovaries and spreads to the peritoneal cavity, lowers 5-year survival rate from 90% to 30%. Early screening tools that can: i) detect with high specificity and sensitivity before conventional tools such as transvaginal ultrasound and CA-125, ii) use non-invasive sampling methods and iii) longitudinally significantly increase survival rates in ovarian cancer are needed. Studies that employ blood-based screening tools using circulating tumor-cells, -DNA, and most recently tumor-derived small extracellular vesicles (sEVs) have shown promise in non-invasive detection of cancer before standard of care. Our findings in this study show the promise of a sEV-derived signature as a non-invasive longitudinal screening tool in ovarian cancer.MethodsHuman serum samples as well as plasma and ascites from a mouse model of ovarian cancer were collected at various disease stages. Small extracellular vesicles (sEVs) were extracted using a commercially available kit. RNA was isolated from lysed sEVs, and quantitative RT-PCR was performed to identify specific metastatic gene expression.ConclusionThis paper highlights the potential of sEVs in monitoring ovarian cancer progression and metastatic development. We identified a 7-gene panel in sEVs derived from plasma, serum, and ascites that overlapped with an established metastatic ovarian carcinoma signature. We found the 7-gene panel to be differentially expressed with tumor development and metastatic spread in a mouse model of ovarian cancer. The most notable finding was a significant change in the ascites-derived sEV gene signature that overlapped with that of the plasma-derived sEV signature at varying stages of disease progression. While there were quantifiable changes in genes from the 7-gene panel in serum-derived sEVs from ovarian cancer patients, we were unable to establish a definitive signature due to low sample number. Taken together our findings show that differential expression of metastatic genes derived from circulating sEVs present a minimally invasive screening tool for ovarian cancer detection and longitudinal monitoring of molecular changes associated with progression and metastatic spread.
The Prognostic Significance of PD1 and PDL1 Gene Expression in Lung Cancer: A Meta-Analysis
Authors: Chang Chih-Hao , Shih Arthur Chun-Chieh , Chang Ya-Hsuan , Chen Hsuan‐Yu , Chao Ying-Ting , Hsu Yi-Chiung 
Published: November 2021

BackgroundImmune checkpoint blockade therapy represents an extraordinary advance in lung cancer treatment. It is important to determine the expression of immune checkpoint genes, such as programmed cell death 1 (PD1) and programmed cell death-ligand 1 (PDL1), to develop immunotherapeutic strategies. The aim of this study was to explore the association between PD1 and PDL1 gene expression and prognoses and outcomes in lung cancer.MethodsThis meta-analysis analyzed 1,251 patients from eight different microarray gene expression datasets and were evaluated for their prognostic implications and verified using another independent research.ResultsThe mean expression levels of PDL1 in adenocarcinoma (AD) and squamous cell carcinoma (SC) were significantly higher in patients who died than in patients who did not. There was a trend toward incremental increases in PD1 and PDL1 expression significantly decreasing the risk of relapse and death among AD patients (HR = 0.69; 95% CI = 0.53 ~ 0.91; HR = 0.68; 95% CI = 0.54 ~ 0.84, respectively) and SC patients (HR = 0.53; 95% CI = 0.32 ~ 0.89; HR = 0.78; 95% CI = 0.57 ~ 1.00 respectively), as early-stage patients in this study were more likely to have high expression of both PD1 and PDL1 than late-stage patients (P-trend &lt; 0.05). In contrast, late-stage SC patients expressing one or more of the genes at a high level had a significantly elevated risk of relapse (HR = 1.51; 95% CI = 1.07 ~ 2.11) and death (HR = 1.41; 95% CI = 1.08 ~ 1.84). This result was consistent with the validation data set.ConclusionThese findings indicate that high expression of PD1 and PDL1 is associated with superior outcome in early-stage lung cancer but an adverse outcome in late-stage lung cancer. The expression levels of PD1 and PDL1 individually or jointly are potential prognostic factors for predicting patient outcomes in lung cancer.
Obesity in Postmenopausal Breast Cancer Patients: It Is Time to Improve Actions for a Healthier Lifestyle. The Results of a Comparison Between Two Italian Regions With Different “Presumed” Lifestyles
Authors: Cortesi Laura , Galli Giulia Raffaella , Domati Federica , Conte Luana , Manca Luigi , Berio Maria Antonietta , Toss Angela , Iannone Anna , Federico Massimo 
Published: November 2021

BackgroundAdult body fatness is a convincing risk factor for postmenopausal breast cancer. With the aim to compare the different breast cancer (BC) features in Northern and Southern Italy, we investigated the relationship between BMI and BC characteristic in two groups of patients referred in the Modena and Lecce breast units.Materials and MethodsA retrospective analysis of a continuous series of BC patients referred to the Città di Lecce Hospital and the Modena Cancer Center, from January 2019 to December 2020 was performed. We identified four groups of BMI at BC diagnosis: underweight, BMI &lt;18.5 kg/m2; normal weight, BMI ≥ 18.5–24.9 kg/m2; overweight, BMI ≥ 25.0–29.9 kg/m2; obese, BMI ≥30.0 kg/m2. BC characteristics and clinical outcomes were analyzed by the Kolmogorov-Smirnov test and Mann-Whitney U test; categorical data were compared using Pearson’s chi-square test, and dicotomic data were compared by odds ratio.ResultsNine hundred seventy-seven BC patients were included in the analysis. Overall, 470 were from Modena and 507 from Lecce. No differences were observed in the mean age of BC patients of Modena (61,42) and Lecce (62,08). No statistical differences between the two populations were shown in terms of tumor characteristics and pathological stage. Conversely, a statistical difference of BMI between the BC patients coming from Modena and Lecce (25.87 and 27.81, respectively; p = 0.000001) was found. BC patients diagnosed in Lecce at age ≥70 years had higher median BMI compared with the ones from Modena (p = 0.000002). The increased BMI in this aged population was also associated to larger tumor size (p = 0.040).ConclusionThe rate of overweight and obesity was higher in BC women living in Southern Italy, despite the presumed nutrition according to the so-called Mediterranean type dietary pattern. Unexpectedly, an increased BMI rate and a relationship with larger tumor size were found in Southern BC patients aged ≥70 years. Our findings strongly support the need for promoting a healthier lifestyle model in Italy, with the aim of reducing the rate of the obesity and, consequently, the increased risk of BC.
Anterior Minithoracotomy vs. Transcatheter Closure of Patent Ductus Arteriosus in Very Preterm Infants
Authors: Lenoir Marien , Wanert Chloé , Bonnet Damien , Méot Mathilde , Tosello Barthélémy , Fouilloux Virginie , Ovaert Caroline , Malekzadeh-Milani Sophie 
Published: November 2021

Introduction: Patent ductus arteriosus (PDA) is common in preterm infants and contributes to morbidity and mortality. Several studies have shown the feasibility and safety of percutaneous PDA closure. Minimally invasive surgical ligation by anterior thoracotomy is an alternative, bedside technique for PDA closure in very low birth weight preterm infants. Our study aimed to compare short- and medium-term morbidity and mortality between anterior minithoracotomy and transcatheter PDA closure.Methods: From 2010 to 2020, 92 preterm infants &lt;1,600 g underwent PDA closure in two centers: 44 surgical anterior minithoracotomies (center 1) and 48 transcatheter closures (center 2). Using a 1:1 propensity score match analysis, 22 patients in each group were included. The primary outcome was time to extubation after intervention.Results: Preoperative characteristics were similar in both groups after propensity matching (mean weight at procedure, 1,171 ± 183 g; p = 0.8). Mean time to extubation was similar: 10 ± 15 days in the surgical group vs. 9 ± 13 days in the transcatheter group (p = 0.9). Mean age at hospital discharge was 114 ± 29 days vs. 105 ± 19 days (p = 0.2). Two deaths occurred in the surgical group and one in the transcatheter group (p = 0.61). Five complications (pneumothorax n = 2, chylothorax n = 2, phrenic nerve injury n = 1) occurred in three patients after surgery. Three complications (chylothorax n = 1, endocarditis n = 1, renal vein thrombosis n = 1) occurred in two patients after percutaneous closure (p = 0.63).Conclusion: Equivalent efficiency and safety of surgical mini-invasive vs. transcatheter PDA closure in preterm infants &lt;1,600 g are in favor of applying these alternative techniques according to centers' facilities and competences.
Suicidal Behavior in Fibromyalgia Patients: Rates and Determinants of Suicide Ideation, Risk, Suicide, and Suicidal Attempts—A Systematic Review of the Literature and Meta-Analysis of Over 390,000 Fibromyalgia Patients
Authors: Adawi Mohammad , Chen Wen , Bragazzi Nicola Luigi , Watad Abdulla , McGonagle Dennis , Yavne Yarden , Kidron Adi , Hodadov Hadas , Amital Daniela , Amital Howard 
Published: November 2021

Background: Suicide is a leading cause of death worldwide, affecting ~800,000 people every year. Fibromyalgia is an extremely prevalent rheumatic disease with a predisposition for comorbid anxiety and depression, which are known risk factors for suicidal behavior. Suicidality and relevant risk factors for suicidal behavior have not been thoroughly studied in patients with fibromyalgia.Objectives: To investigate the risk of suicidal ideation and attempts in patients with fibromyalgia.Methods: A systematic review and meta-analysis was conducted and reported according to the “Preferred Reporting Items for Systematic reviews and Meta-analyses” (PRISMA) standards. Also, the gray literature was extensively searched.Results: Thirteen studies were included in the present systematic review and meta-analysis, including 394,087 fibromyalgia patients. Sample size ranged from 44 to 199,739 subjects, mean age ranged from 45.8 to 54.5 years while the female percentage with fibromyalgia ranged from 17.1 to 100.0%. The overall suicide ideation prevalence was 29.57% (95%CI 1.84–72.07), with an OR 9.12 of (95%CI 1.42–58.77), ranging from 2.34 (95%CI 1.49–3.66) to 26.89 (95%CI 5.72–126.42). Pooled suicide attempt prevalence was 5.69% [95%CI 1.26–31.34], with an OR of 3.12 [95%CI 1.37–7.12]. Suicide risk was higher with respect to the general population with an OR of 36.77 (95%CI 15.55–96.94), as well as suicide events with an HR of 1.38 (95%CI 1.17–1.71). Determinants of suicidality were found to be: employment status, disease severity, obesity and drug dependence, chronic pain and co-morbidities, in particular depression, anxiety, poor sleep, and global mental health. However, in some cases, after adjusting for psychiatric conditions, the threshold of statistical significance was not achieved.Conclusion: Fibromyalgia patients are particularly prone to suicide, in terms of ideation, attempt, risk and events, warranting a pre-emptive screening of their mental health status. Given the few studies available, the high amount of heterogeneity, the evidence of publications bias and the lack of statistical significance when adjusting for underlying psychiatric co-morbidities, further high-quality studies should be conducted.Clinical Trial Registration:ClinicalTrial.gov, identifier 10.17605/OSF.IO/Y4BUE.