bluuebunny/crossref_metadata_2025_split huggingface dataset:
OCaMIR—A Noninvasive, Diagnostic Signature for Early-Stage Ovarian Cancer: A Multi-cohort Retrospective and Prospective Study
Authors: Kandimalla Raju , Wang Wei , Yu Fan , Zhou Nianxin , Gao Feng , Spillman Monique , Moukova Lucie , Slaby Ondrej , Salhia Bodour , Zhou Shengtao , Wang Xin , Goel Ajay 
Published: May 2021

AbstractPurpose:Due to the lack of effective screening approaches and early detection biomarkers, ovarian cancer has the highest mortality rates among gynecologic cancers. Herein, we undertook a systematic biomarker discovery and validation approach to identify microRNA (miRNA) biomarkers for the early detection of ovarian cancer.Experimental Design:During the discovery phase, we performed small RNA sequencing in stage I high-grade serous ovarian cancer (n = 31), which was subsequently validated in multiple, independent data sets (TCGA, n = 543; GSE65819, n = 87). Subsequently, we performed multivariate logistic regression-based training in a serum data set (GSE106817, n = 640), followed by its independent validation in three retrospective data sets (GSE31568, n = 85; GSE113486, n = 140; Czech Republic cohort, n = 192) and one prospective serum cohort (n = 95). In addition, we evaluated the specificity of OCaMIR, by comparing its performance in several other cancers (GSE31568 cohort, n = 369).Results:The OCaMIR demonstrated a robust diagnostic accuracy in the stage I high-grade serous ovarian cancer patients in the discovery cohort (AUC = 0.99), which was consistently reproducible in both stage I (AUC = 0.96) and all stage patients (AUC = 0.89) in the TCGA cohort. Logistic regression-based training and validation of OCaMIR achieved AUC values of 0.89 (GSE106817), 0.85 (GSE31568), 0.86 (GSE113486), and 0.82 (Czech Republic cohort) in the retrospective serum validation cohorts, as well as prospective validation cohort (AUC = 0.92). More importantly, OCaMIR demonstrated a significantly superior diagnostic performance compared with CA125 levels, even in stage I patients, and was more cost-effective, highlighting its potential role for screening and early detection of ovarian cancer.Conclusions:Small RNA sequencing identified a robust noninvasive miRNA signature for early-stage serous ovarian cancer detection.
Darolutamide Potentiates the Antitumor Efficacy of a PSMA-targeted Thorium-227 Conjugate by a Dual Mode of Action in Prostate Cancer Models
Authors: Hammer Stefanie , Schlicker Andreas , Zitzmann-Kolbe Sabine , Baumgart Simon , Hagemann Urs B. , Scholz Arne , Haendler Bernard , Lejeune Pascale , Karlsson Jenny , Ellingsen Christine , Hennekes Hartwig , Nielsen Carsten H. , Juul Mark U. , Mumberg Dominik , Schatz Christoph A. 
Published: May 2021

Abstract

Purpose:
Androgen receptor (AR) inhibitors are well established in the treatment of castration-resistant prostate cancer and have recently shown efficacy also in castration-sensitive prostate cancer. Although most patients respond well to initial therapy, resistance eventually develops, and thus, more effective therapeutic approaches are needed. Prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancer and presents an attractive target for radionuclide therapy. Here, we evaluated the efficacy and explored the mode of action of the PSMA-targeted thorium-227 conjugate (PSMA-TTC) BAY 2315497, an antibody-based targeted alpha-therapy, in combination with the AR inhibitor darolutamide.

Experimental Design:
The in vitro and in vivo antitumor efficacy and mode of action of the combination treatment were investigated in preclinical cell line–derived and patient-derived prostate cancer xenograft models with different levels of PSMA expression.

Results:
Darolutamide induced the expression of PSMA in androgen-sensitive VCaP and LNCaP cells in vitro, and the efficacy of darolutamide in combination with PSMA-TTC was synergistic in these cells. In vivo, the combination treatment showed synergistic antitumor efficacy in the low PSMA-expressing VCaP and in the high PSMA-expressing ST1273 prostate cancer models, and enhanced efficacy in the enzalutamide-resistant KUCaP-1 model. The treatments were well tolerated. Mode-of-action studies revealed that darolutamide induced PSMA expression, resulting in higher tumor uptake of PSMA-TTC, and consequently, higher antitumor efficacy, and impaired PSMA-TTC–mediated induction of DNA damage repair genes, potentially contributing to increased DNA damage.

Conclusions:
These results provide a strong rationale to investigate PSMA-TTC in combination with AR inhibitors in patients with prostate cancer.
Neurofilament Light Chain Levels Are Associated with Disease Activity Determined by No Evident Disease Activity in Multiple Sclerosis Patients
Authors: Szilasiová Jarmila , Rosenberger Jaroslav , Fedičová Miriam , Mikula Pavol , Urban Peter , Gdovinová Zuzana , Vitková Marianna , Hanes Jozef , Stevens Eva 
Published: May 2021

Introduction: There is a need for blood biomarkers of disease activity in multiple sclerosis (MS). The aim of the study was to assess the relationship between plasma neurofilament light chain (pNfL) and disease activity as defined by the concept three-domain no evident disease activity (NEDA-3). Methods: Levels of pNfL (SIMOA) were examined in 159 MS patients and analyzed in relationship to NEDA-3 status (absence of relapse, disability score worsening, and brain magnetic resonance activity) during the last 12 months. The accuracy of the proposed model was evaluated by calculating the area under the receiver operating characteristics (ROC) curve. From the pNfL cutoff, we evaluated the NEDA-NfL status (no relapse, no Expanded Disability Status Scale [EDSS] worsening, and pNfL below the cutoff value). Results: Levels of pNfL were significantly higher in MS patients than in healthy controls (p < 0.001). From a total of 159 patients, 80 (50.3%) achieved NEDA-3 status, while 79 (49.7%) patients showed evident disease activity (EDA) status. pNfL were significantly lower in the NEDA-3 group than in the EDA group (pNfL mean 7.06 pg/mL [standard deviation (SD) 2.37] vs. pNfL mean 13.04 pg/mL [SD 7.07]) (p < 0.001). ROC analysis showed that pNfL predicts NEDA-3 status (sensitivity and specificity were 80.5 and 72.7%, respectively, p < 0.001), and NEDA-NfL predicts NEDA-3 status (sensitivity and specificity were 97.1 and 82.9%, respectively, p < 0.001). Conclusion: The results show that pNfL levels are a useful biomarker of disease activity determined by NEDA status in patients with MS and could be an alternative to brain magnetic resonance investigation.
Prevalência, severidade e fatores associados à depressão em estudantes universitários
Authors: Santos Larissa Barreto dos , Nascimento Karina Gomes do , Fernandes Andréia Guedes Oliva , Raminelli-da-Silva Talita de Cássia 
Published: May 2021

Objetivo: identificar a prevalência, a severidade e os fatores associados à depressão entre estudantes universitários no Distrito Federal. Método: estudo transversal realizado com 521 estudantes universitários, com idade entre 18 e 60 anos. Os sintomas depressivos foram avaliados através da escala Patient Health Questionnaire-9 (PHQ-9). Utilizou-se estatística descritiva e o teste do qui-quadrado. Resultados: dentre os 521 indivíduos estudados, houve predomínio do sexo feminino. A prevalência de sintomas depressivos foi de 521 (96,6%) estudantes universitários, sendo 31,3% com depressão suave, 23,4%, depressão mínima, 13,1% depressão moderadamente grave, 9,6% depressão grave e 9,2% depressão moderada. A renda familiar e o semestre cursado são fatores associados para a severidade da depressão. Conclusão: a prevalência da depressão no ambiente universitário é comum, sendo uma proporção alta e preocupante. É crucial o rastreamento da depressão, sua severidade e seus fatores associados, a fim de estimular reflexão sobre a temática e pensar em estratégias de intervenção para a prevenção e promoção da saúde mental.
CAVA (Ultrasound‐Accelerated Catheter‐Directed Thrombolysis on Preventing Post‐Thrombotic Syndrome) Trial: Long‐Term Follow‐Up Results
Authors: Notten Pascale , de Smet André A. E. A. , Tick Lidwine W. , van de Poel Marlène H. W. , Wikkeling Otmar R. M. , Vleming Louis‐Jean , Koster Ad , Jie Kon‐Siong G. , Jacobs Esther M. G. , Ebben Harm P. , Coppens Michiel , ten Cate Hugo , Wittens Cees H. A. , ten Cate‐Hoek Arina J. 
Published: May 2021

Background
The CAVA (Ultrasound‐Accelerated Catheter‐Directed Thrombolysis Versus Anticoagulation for the Prevention of Post‐Thrombotic Syndrome) trial did not show a reduction of post‐thrombotic syndrome (PTS) after additional ultrasound‐accelerated catheter‐directed thrombolysis in patients with acute iliofemoral deep vein thrombosis at 1‐year follow‐up. This prespecified analysis of the CAVA trial aimed to determine the impact of additional thrombolysis on outcomes of PTS at long‐term follow‐up.

Methods and Results

Patients aged 18 to 85 years with a first‐time acute iliofemoral deep vein thrombosis were included and randomly assigned (1:1) to either standard treatment plus ultrasound‐accelerated catheter‐directed thrombolysis or standard treatment alone. The primary outcome was the proportion of PTS (Villalta score ≥5 on 2 occasions ≥3 months apart or venous ulceration) at the final follow‐up visit. Additionally, PTS according to the International Society on Thrombosis and Haemostasis (ISTH) consensus definition was assessed to allow external comparability. Major bleedings were the main safety outcome. At a median follow‐up of 39.0 months (interquartile range, 23.3–63.8), 120 patients (79.8%) participated in the final follow‐up visit: 62 from the intervention group and 58 from the standard treatment group. PTS developed in 19 (30.6%) versus 26 (44.8%) patients, respectively (odds ratio [OR], 0.54; 95% CI, 0.26 to 1.15 [
P
=0.11]), with an absolute difference between groups of −14.2% (95% CI, −32.0% to 4.8%). Using the ISTH consensus definition, a significant reduction in PTS was observed (29 [46.8%] versus 40 [69.0%]) (OR, 0.40; 95% CI, 0.19–0.84 [
P
=0.01]) with an absolute difference between groups of −22.2% (95% CI, −39.8% to −2.8%). No new major bleedings occurred following the 12‐month follow‐up.

Conclusions
The impact of additional ultrasound‐accelerated catheter‐directed thrombolysis on the prevention of PTS was found to increase with time. Although this study was limited by its sample size, the overall findings indicate a reduction of mild PTS without impact on quality of life.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT00970619.
Therapeutic Challenges and Emerging Treatment Targets for Pulmonary Hypertension in Left Heart Disease
Authors: Lteif Christelle , Ataya Ali , Duarte Julio D. 
Published: May 2021

Abstract
Pulmonary hypertension (PH) attributable to left heart disease (LHD) is believed to be the most common form of PH and is strongly associated with increased mortality and morbidity in this patient population. Specific therapies for PH‐LHD have not yet been identified and the use of pulmonary artery hypertension‐targeted therapies in PH‐LHD are not recommended. Endothelin receptor antagonists, phosphodiesterase‐5 inhibitors, guanylate cyclase stimulators, and prostacyclins have all been studied in PH‐LHD with conflicting results. Understanding the mechanisms underlying PH‐LHD could potentially provide novel therapeutic targets. Fibrosis, oxidative stress, and metabolic syndrome have been proposed as pathophysiological components of PH‐LHD. Genetic associations have also been identified, offering additional mechanisms with biological plausibility. This review summarizes the evidence and challenges for treatment of PH‐LHD and focuses on underlying mechanisms on the horizon that could develop into potential therapeutic targets for this disease.
Between Two Poles: Barukh Mitrani between Moderate Haskalah and Jewish Nationalism
Authors: Karkason Tamir 
Published: May 2021

Abstract
Barukh Mitrani was an Ottoman maskil who wandered between the Balkans, Istanbul and Palestine. While living in Edirne, Mitrani established his first periodical, Carmi (Pressburg 1881). Carmi’s issues were an ongoing maskilic sermon, drawing on a deep acquaintance with the Jewish bookshelf. This paper examines selections from the fifth article in Carmi, ‘Our Nationhood.’ Influenced by the moderate Haskalah, Mitrani idealized a ‘Golden Mean,’ which sought to balance the agendas of ‘the two poles’: insular Ultra-Orthodox Jews on the one hand, and secularized ‘Westernizers’ on the other. Mitrani also espoused a Jewish nationalism which had affinities with the Hebrew ‘republic of letters’ and the national resurgence in the Balkans. He perceived every Jew as part of three circles: the individual, the family, and the nation. Yet his nationalism was not separatist; he obliged Jews to remain loyal Ottoman citizens and promote the Sultanate while also settling in Palestine.
Evaluating the Conservation of Energy Variables in Simulations of Deep Moist Convection
Authors: Peters John M. , Chavas Daniel R. 
Published: May 2021

AbstractIt is often assumed in parcel theory calculations, numerical models, and cumulus parameterizations that moist static energy (MSE) is adiabatically conserved. However, the adiabatic conservation of MSE is only approximate because of the assumption of hydrostatic balance. Two alternative variables are evaluated here: MSE − IB and MSE + KE, wherein IB is the path integral of buoyancy (B) and KE is kinetic energy. Both of these variables relax the hydrostatic assumption and are more precisely conserved than MSE. This article quantifies the errors that result from assuming that the aforementioned variables are conserved in large-eddy simulations (LES) of both disorganized and organized deep convection. Results show that both MSE − IB and MSE + KE better predict quantities along trajectories than MSE alone. MSE − IB is better conserved in isolated deep convection, whereas MSE − IB and MSE + KE perform comparably in squall-line simulations. These results are explained by differences between the pressure perturbation behavior of squall lines and isolated convection. Errors in updraft B diagnoses are universally minimized when MSE − IB is assumed to be adiabatically conserved, but only when moisture dependencies of heat capacity and temperature dependency of latent heating are accounted for. When less accurate latent heat and heat capacity formulae were used, MSE − IB yielded poorer B predictions than MSE due to compensating errors. Our results suggest that various applications would benefit from using either MSE − IB or MSE + KE instead of MSE with properly formulated heat capacities and latent heats.
FIRST GROUND−BASED DOAS MEASUREMENTS OF NO2 AT KINSHASA AND COMPARISONS WITH SATELLITE OBSERVATIONS
Authors: Yombo Phaka Rodriguez , Merlaud Alexis , Pinardi Gaia , Mahieu Emmanuel , Hendrick François , Friedrich Martina M. , Fayt Caroline , Van Roozendael Michel , Djibi Buenimio Lomami , Bopili Mbotia Lepiba Richard , Phuku Phuati Edmond , Mbungu Tsumbu Jean-Pierre 
Published: May 2021

AbstractWe present the first ground-based remote sensing measurements of NO2 made in Kinshasa. They were performed from 2017 to 2019. The motivation of making observations on air pollution in Kinshasa comes from its geographical location, its demography, its climatic conditions and the many different sources of NO2 existing in its surroundings. A method for recovering the vertical density of the NO2 tropospheric column (VCDtropo) based on the Differential Optical Absorption Spectroscopy (DOAS) applied to observations at the zenith and 35° elevation angle is described. The mean value of VCDtropo observed in Kinshasa is 3 × 1015 molecules cm−2. We further present first comparisons with the OMI and TROPOMI satellite observations. When comparing OMI data with our observations and using a linear regression analysis, we find a slope of 0.34 and a correlation coefficient of 0.50 for 51 days of coincidences over 2017−2019. Similar comparisons with TROPOMI for 44 days show a slope of 0.41 and a correlation coefficient of 0.72. This study opens up perspectives for further air quality related studies in Kinshasa and central Africa.
Evaluation of Cost‐effectiveness and Clinical Value of Routine Histopathologic Examination of Septoplasty Specimens
Authors: Ruffner Randall S. , Scordino Jessica W. 
Published: May 2021

ObjectivesDuring septoplasty, normal cartilage and bone are often sent for pathologic examination despite benign appearance. We explored pathology results following septoplasty from April 2016 to April 2018, examining clinical value and relevance, implications, and cost analysis.Study DesignRetrospective chart review.SettingSingle‐institution academic medical center.MethodsA retrospective chart review was compiled by using Current Procedural Terminology code 30520 for septoplasty for indication of nasal obstruction, deviated septum, and nasal deformity.ResultsA total of 236 consecutive cases were identified spanning a 2‐year period. Septoplasty specimens were sent for pathology evaluation in 76 (31%). The decision to send a specimen for histopathology was largely physician dependent. No cases yielded unexpected or significant pathology that changed management. The average total charges for septoplasty were $10,200 at our institution, with 2.2% of procedural charges accounting for pathology preparation and review, averaging $225. Nationally, this results in an estimated charged cost of $58.5 million. The Centers for Medicare and Medicaid Services (CMS) reimbursement for septoplasty pathology charges was $46 in 2018, accounting for 1.3% of hospital‐based reimbursements and 2.2% of ambulatory center reimbursements. With CMS as a national model for reimbursement, $11.8 million is spent yearly for septoplasty histopathology. Given that CMS reimbursement is significantly lower than private insurers, national total reimbursement is likely considerably higher.ConclusionRoutine pathology review of routine septoplasty specimens is unnecessary, unremarkable, and wasteful. Correlation of the patient’s presentation and intraoperative findings should justify the need for pathology evaluation. This value‐based approach can offer significant direct and indirect cost savings.Level of evidence4.
Expression and Significance of HPV16 E6/E7 mRNAs in the Bronchial Brush and TBNA Cells of Patients With Small Cell Lung Cancer
Authors: Zou Di-Jia , Zhao Ya-Bin , Yang Jing-Hua , Xu Hong-Tao , Li Qing-Chang , Wu Guang-Ping 
Published: May 2021

Background and Objective: Small cell lung cancer (SCLC) is characterized by rapid growth, strong invasion, and early metastasis. However, the cause of its occurrence remains unclear. High-risk HPV infection is closely related to the occurrence of non-small cell lung cancer and cervical small cell neuroendocrine carcinoma. Methods: The expression levels of E6 mRNA and E7 mRNA in HPV16 were detected by qRT-PCR in the bronchial brushing and transbronchial needle aspiration (TBNA) of 310 patients with lung cancer and with benign lung diseases. To make the design of this experiment scientific and reasonable, the expression levels in lung squamous cell carcinoma were taken as positive controls, while those in benign cells were taken as negative controls. Results: The expression levels of E6 mRNA and E7 mRNA in SCLC group were significantly higher than those in benign cell group and slight higher than those in squamous cell carcinoma group. The expression levels of E6 mRNA and E7 mRNA in the central type of SCLC were significantly higher than those in the peripheral type of SCLC. Conclusions: We speculate that the occurrence of some small cell carcinoma is the same as that of some squamous cell carcinoma, which is closely related to HPV16 infection. The overexpression of E6 mRNA and E7 mRNA is in some benign lesion cells, which may be related to HPV transient infection.
Accuracy of Wearable Sensor Technology in Hand Goniometry: A Systematic Review
Authors: Avila Francisco R. , Carter Rickey E. , McLeod Christopher J. , Bruce Charles J. , Giardi Davide , Guliyeva Gunel , Forte Antonio J. 
Published: May 2021

Background Wearable devices and sensor technology provide objective, unbiased range of motion measurements that help health care professionals overcome the hindrances of protractor-based goniometry. This review aims to analyze the accuracy of existing wearable sensor technologies for hand range of motion measurement and identify the most accurate one. Methods We performed a systematic review by searching PubMed, CINAHL, and Embase for studies evaluating wearable sensor technology in hand range of motion assessment. Keywords used for the inquiry were related to wearable devices and hand goniometry. Results Of the 71 studies, 11 met the inclusion criteria. Ten studies evaluated gloves and 1 evaluated a wristband. The most common types of sensors used were bend sensors, followed by inertial sensors, Hall effect sensors, and magnetometers. Most studies compared wearable devices with manual goniometry, achieving optimal accuracy. Although most of the devices reached adequate levels of measurement error, accuracy evaluation in the reviewed studies might be subject to bias owing to the use of poorly reliable measurement techniques for comparison of the devices. Conclusion Gloves using inertial sensors were the most accurate. Future studies should use different comparison techniques, such as infrared camera–based goniometry or virtual motion tracking, to evaluate the performance of wearable devices.
Minimum 10-Year Clinical Outcome of Lateral Collagen Meniscal Implants for the Replacement of Partial Lateral Meniscal Defects: Further Results From a Prospective Multicenter Study
Authors: Grassi Alberto , Lucidi Gian Andrea , Filardo Giuseppe , Agostinone Piero , Macchiarola Luca , Bulgheroni Paolo , Bulgheroni Erica , Zaffagnini Stefano 
Published: May 2021

Background: The collagen meniscal implant (CMI) is a biologic scaffold aimed at replacing partial meniscal defects. The long-term results of lateral meniscal replacement have never been investigated. Purpose: To document the clinical outcomes and failures of lateral CMI implantation for partial lateral meniscal defect at a minimum 10-year follow-up. Study Design: Case series; Level of evidence, 4, Methods: This study included 24 consecutive patients who underwent lateral CMI implantation for partial lateral meniscal defects between April 2006 and September 2009 and who were part of a previous study with a 2-year follow-up. Outcome measures at the latest follow-up included the Lysholm score, Knee injury and Osteoarthritis Outcome Score, visual analog scale (VAS) for pain, Tegner activity level, and EuroQol 5-Dimensions score. Data regarding complications and failures were collected, and patients were asked about their satisfaction with the procedure. Results: Included in the final analysis were 19 patients (16 male, 3 female) with a mean age at surgery of 37.1 ± 12.6 years and a mean follow-up of 12.4 ± 1.5 years (range, 10-14 years). Five failures (26%) were reported: 1 CMI removal because of implant breakage and 4 joint replacements (2 unicompartmental knee arthroplasties and 2 total knee arthroplasties). The implant survival rate was 96% at 2 years, 85% at 5 years, 85% at 10 years, 77% at 12 years, and 64% at 14 years. Lysholm scores at the final follow-up were rated as “excellent” in 36% (5 of 14 nonfailures), “good” in 43% (6 of 14), and “fair” in 21% (3 of 14). The VAS score was 3.1 ± 3.1, with only 16% (3 of 19 patients) reporting that they were pain-free; the median Tegner score was 3 (interquartile range, 2-5). All clinical scores decreased from the 2-year follow-up; however, with the exception of the Tegner score, they remained significantly higher compared with the preoperative status. Overall, 79% of patients were willing to undergo the same procedure. Conclusion: Lateral CMI implantation for partial lateral meniscal defects provided good long-term results, with a 10-year survival rate of 85% and a 14-year survival rate of 64%. At the final follow-up, 58% of the patients had “good” or “excellent” Lysholm scores. However, there was a general decrease in outcome scores between the short- and the long-term follow-up.