bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical and Economic Impact of Tailoring Screening to Predicted Colorectal Cancer Risk: A Decision Analytic Modeling Study
Authors: Ladabaum Uri , Mannalithara Ajitha , Mitani Aya , Desai Manisha 
Published: December 2019

AbstractBackground:Global increases in colorectal cancer risk have spurred debate about optimal use of screening resources. We explored the potential clinical and economic impact of colorectal cancer screening tailored to predicted colorectal cancer risk.Methods:We compared screening tailored to predicted risk versus uniform screening in a validated decision analytic model, considering the average risk population's actual colorectal cancer risk distribution, and a risk-prediction tool's discriminatory ability and cost. Low, moderate, and high risk tiers were identified as colorectal cancer risk after age 50 years of ≤3%, &gt;3 to &lt;12%, and ≥12%, respectively, based on threshold analyses with willingness-to-pay &lt;$50,000/quality-adjusted life-year (QALY) gained. Tailored colonoscopy (once at age 60 years for low risk, every 10 years for moderate risk, and every 5 years for high risk) was compared with colonoscopy every 10 years for all. Tailored fecal immunochemical testing (FIT)/colonoscopy (annual FIT for low and moderate risk, colonoscopy every 5 years for high risk) was compared with annual FIT for all.Results:Assuming no colorectal cancer risk misclassification or risk-prediction tool costs, tailored screening was preferred over uniform screening. Tailored colonoscopy was minimally less effective than uniform colonoscopy, but saved $90,200–$889,000/QALY; tailored FIT/colonoscopy yielded more QALYs/person than annual FIT at $10,600–$60,000/QALY gained. Relatively modest colorectal cancer risk misclassification rates or risk-prediction tool costs resulted in uniform screening as the preferred approach.Conclusions:Current risk-prediction tools may not yet be accurate enough to optimize colorectal cancer screening.Impact:Uniform screening is likely to be preferred over tailored screening if a risk-prediction tool is associated with even modest misclassification rates or costs.
A Phase II Trial of Pembrolizumab and Vorinostat in Recurrent Metastatic Head and Neck Squamous Cell Carcinomas and Salivary Gland Cancer
Authors: Rodriguez Cristina P. , Wu Qian (Vicky) , Voutsinas Jenna , Fromm Jonathan R. , Jiang Xiuyun , Pillarisetty Venu G. , Lee Sylvia M. , Santana-Davila Rafael , Goulart Bernardo , Baik Christina S. , Chow Laura Q.M. , Eaton Keith , Martins Renato 
Published: December 2019

Abstract

Purpose:
This clinical trial combined pembrolizumab and vorinostat in recurrent/metastatic squamous cell carcinomas of the head and neck (HN), and salivary gland cancer (SGC).

Patients and Methods:
Patients with progressing incurable HN and SGC, Eastern Cooperative Oncology Group (ECOG) ≤1, no prior immunotherapy, RECIST1.1 measurable disease, and normal organ function were eligible. Pembrolizumab 200 mg was given intravenous every 21 days, and vorinostat 400 mg given orally 5 days on and 2 days off during each 21-day cycle. Primary endpoints were safety and objective response rates.

Results:
From November 2015 to August 2017, 25 patients with HN and 25 SGC were enrolled. Median age was 61 (range, 33–86) years, 39 (78%) were male, 21 (62%) were never smokers, and 27 (54%) had ECOG 0. In HN, 13 (52%) were p16+ oropharynx. Most common SGC histologies were adenoid cystic 12 (48%), acinic cell 3 (12%), and mucoepidermoid 3 (12%). Adverse events (AEs) in all patients were: 27 (54%) with grade ≥ 1 and 18 (36%) with grade ≥ 3. The most common AEs in all patients were renal insufficiency in seven, (14%), fatigue in six, (12%), and nausea in three (6%). There were three (12%) deaths on study. Responses in HN were complete response (CR) 0, partial response (PR) eight (32%), and stable disease (SD) five (20%). Efficacy in SGCs was CR 0, PR four (16%) in one lymphoepithelioma-like carcinoma, two acinic cell, one adenoid cystic, and SD 14 (56%). In the HN group, median follow-up (mFUP) was 12.6 months, median overall survival (mOS) was 12.6 months, and median progression-free survival (mPFS) was 4.5 months. In SGC, mFUP was 13.1 months, mOS was 14.0 months, and mPFS was 6.9 months.

Conclusions:
This combination demonstrated activity in HN, with fewer responses in SGC. Toxicities were higher than reported with pembrolizumab alone.
The Nanocind Signature Is an Independent Prognosticator of Recurrence and Death in Uterine Leiomyosarcomas
Authors: Croce Sabrina , Lesluyes Tom , Valle Carine , M'Hamdi Loubna , Thébault Noémie , Pérot Gaëlle , Stoeckle Eberhard , Noël Jean-Christophe , Fontanges Quitterie , Devouassoux-Shisheboran Mojgan , Querleu Denis , Guyon Frédéric , Floquet Anne , Chakiba Camille , Mayeur Laetitia , Rebier Flora , MacGrogan Gaëtan Marie , Soubeyran Isabelle , Le Guellec Sophie , Chibon Frédéric 
Published: December 2019

Abstract

Purpose:
Uterine leiomyosarcoma, which accounts for 7% of all soft-tissue sarcomas and 1%–3% of all uterine malignancies, is an aggressive tumor responsible for a significant proportion of uterine cancer–related deaths. While Federation Internationale des Gynaecologistes et Obstetristes (FIGO) stage is the most important prognostic factor, metastatic and relapse rates at stage I exceed 50% so it is currently impossible to predict the clinical outcome of stage I leiomyosarcomas. In 2010, our team published a transcriptomic signature composed of 67 genes related to chromosome biogenesis, mitosis control, and chromosome segregation. It has demonstrated its prognostic value in many cancer types and was recently successfully applied to formalin-fixed, paraffin-embedded sarcomas by NanoCind on NanoString technology, making another step forward toward its use in routine practice.

Experimental Design:
Sixty uterine leiomyosarcomas at any stage, including 40 localized in the uterus (stage I), were analyzed with the NanoCind (CINSARC with NanoString) signature. Its prognostic value was evaluated for overall survival and relapse-free survival and compared in multivariate analysis with other prognostic markers like FIGO staging and genomic index.

Results:
The NanoCind signature was able to split the heterogeneous group of uterine leiomyosarcomas of any stage including stage I into two distinct groups with different relapse-free survival and overall survival. These results were validated on an independent cohort of uterine leiomyosarcomas in The Cancer Genome Atlas consortium.

Conclusions:
The NanoCind signature is a powerful prognosticator that outperforms FIGO staging and the genomic index. The CINSARC signature is platform independent and “ready to use” and should now be used for randomization in future therapeutic trials.
Cytotoxicity of Ear Drop Excipients in Human and Mouse Tympanic Membrane Fibroblasts
Authors: Dirain Carolyn O. , Karnani David N. , Antonelli Patrick J. 
Published: December 2019

ObjectiveCommercial ear drops contain ingredients reported to be inactive. We sought to evaluate such excipients for possible cytotoxicity on human and mouse tympanic membrane (TM) fibroblasts.Study DesignProspective, in vitro.SettingTertiary academic center.Subjects and MethodsMouse and human TM fibroblasts were treated with 1:10 dilutions of benzalkonium chloride (BKC) 0.0025%, 0.006%, or 0.01%; benzyl alcohol 0.9%; polysorbate 80 (PSB) 2.5%; glycerin 2.4%; povidone 0.2%; or water (control), twice within 24 hours or 4 times within 48 hours, for 2 hours each time. Cells were placed back in growth media after the treatments. Cells were observed with phase‐contrast microscopy until the cytotoxicity assay was performed.ResultsMouse fibroblasts had lower survival in only the PSB‐treated cells compared to the control (P <. 0001) after 24 hours. After 48 hours, PSB killed nearly all mouse fibroblasts (P <. 0001). BKC decreased fibroblast survival in a dose‐dependent manner (P <. 001). In human TM fibroblasts, all excipients except povidone and benzyl alcohol after 24 hours and povidone after 48 hours reduced cell survival compared to control (P =. 012 to P <. 0001). The cytotoxicity of BKC in human TM fibroblasts was also dose dependent (<.0001). PSB was less cytotoxic to human fibroblasts. Phase‐contrast images mirrored the cytotoxicity findings.ConclusionPolysorbate 80 and benzalkonium chloride, at concentrations found in commercial ear drops, may be cytotoxic to human and mouse TM fibroblasts. “Inactive” ingredients may need to be considered when evaluating clinical outcomes with commercial ear drops.
Comparing the Temperature Effect of Dedicated Minimally Invasive Motor System to the Discontinuous Use of Rotatory Burrs in the Correction of Hallux Valgus
Authors: Robinson Dror , Heller Eyal , Yassin Mustafa 
Published: December 2019

The purpose of this study was to compare 2 motor systems for percutaneous osteotomy. The study consisted of 2 stages. In the first stage, bone temperatures during osteotomy using burrs or saw was measured using a thermal camera. In the second stage, the tissue and burr temperature elevation during surgery in 80 consecutive patients (96 feet) with hallux valgus undergoing distal first metatarsal and phalangeal osteotomies (hallux and in 61/96 feet lesser digits) were measured. The burr osteotomy procedure included the use of irrigated 2- or 4.1 mm rotary wedge burrs in discontinuous cutting bursts of less than 20 seconds. Tissue surface temperature was measured with a thermal camera. The temperature generated during the procedure was found to be significantly associated with the burr diameter used but was not affected by the type of motor. At the 6-week visit, thickness of the soft tissues over the first metatarsal head was similar in both groups. Temperature control using a noninvasive thermal camera is recommended to prevent tissue damage associated with heat generated during the use of rotary burrs. A dedicated low-speed high-torque system does not seem to be necessary and standard orthopaedic equipment can be used. Levels of Evidence: Level II: Comparative prospectively collected series
Screening young athletes for diseases at risk of sudden cardiac death: role of stress testing for ventricular arrhythmias
Authors: Zorzi Alessandro , Vessella Teresina , De Lazzari Manuel , Cipriani Alberto , Menegon Vittoria , Sarto Gianmarco , Spagnol Rachele , Merlo Laura , Pegoraro Cinzia , Marra Martina Perazzolo , Corrado Domenico , Sarto Patrizio 
Published: December 2019

Aims The athletic preparticipation evaluation (PPE) protocol proposed by the European Society of Cardiology includes history, physical examination and resting electrocardiogram (ECG). The aim of this study was to assess the results of adding constant-load ECG stress testing (EST) to the protocol for the evaluation of ventricular arrhythmias (VA) inducibility. Methods We evaluated a consecutive cohort of young athletes with history, physical examination, resting ECG and EST. Athletes with VA induced by EST underwent 24-hour 12-lead Holter monitoring and echocardiography. Cardiac magnetic resonance (CMR) was reserved for those with frequent, repetitive or exercise-worsened VA, and for athletes with echocardiographic abnormalities. Results Of 10,985 athletes (median age 15 years, 66% males), 451 (4.1%) had an abnormal history, physical examination or resting ECG and 31 (0.28%) were diagnosed with a cardiac disease and were at risk of sudden cardiac death. Among the remaining 10,534 athletes, VA at EST occurred in 524 (5.0%) and a previously missed at-risk condition was identified in 23 (0.22%); the most common ( N = 10) was an echocardiographically silent non-ischaemic left-ventricular fibrosis evidenced by CMR. The addition of EST increased the diagnostic yield of PPE by 75% (from 0.28% to 0.49%) and decreased the positive predictive value by 20% (from 6.9% to 5.5%). During a 32 ± 21 months follow-up, no cardiac arrests occurred among either eligible athletes or non-eligible athletes with cardiovascular disease. Conclusions The addition of exercise testing for the evaluation of VA inducibility to history, physical examination and ECG resulted in an increase of the diagnostic yield of PPE at the expense of an increase in false-positive findings.
Evaluation of Antimalarial Activity of the 80% Methanolic Stem Bark Extract of Combretum molle Against Plasmodium berghei in Mice
Authors: Mulaw Tafere , Wubetu Muluken , Dessie Bekalu , Demeke Gebreselassie , Molla Yalew 
Published: December 2019

Background. People are dependent on the traditional use of medicinal plants for the treatment of malaria without scientific validations. Therefore, this study aimed to evaluate the antimalarial activity of methanolic stem bark extract of Combretum molle in mice. Methods. After being infected with Plasmodium berghei, the mice were randomly divided into 5 groups (n = 5). In all cases, group I mice were treated as negative control and received 3% Tween 80; group II mice were treated with 25 mg/kg chloroquine; and groups III, IV, and V mice were treated with 100 mg/kg, 200 mg/kg, and 400 mg/kg of crude extract, respectively. Data were analyzed using one-way analysis of variance followed by Tukey’s post hoc analysis. Results. In the chemosuppressive test, the parasitic suppression effect of the crude extract was found to be significant ( P < 0.05) as compared with the negative control. In the curative experiment, the average parasitic level of those mice treated by the 3 doses of the crude extract was significantly suppressed at days 5, 6, and 7 of treatment ( P < 0.001). Besides, the crude extract had been found to have a chemoprophylactic role as it inhibited the parasite level significantly relative to the negative control ( P < 0.001). Moreover, the crude extract had preventive effects on packed cell volume reduction in the 3 tests ( P < 0.001). Conclusions. The findings of the present study has supported the folklore use of the leaves of Combretum molle in the treatment of malaria. Therefore, further fractionation and characterization of the crude extract is necessary to identify the responsible lead compound(s) responsible for antiplasmodial activity.
American Society of Hematology 2019 guidelines for sickle cell disease: cardiopulmonary and kidney disease
Authors: Liem Robert I. , Lanzkron Sophie , D. Coates Thomas , DeCastro Laura , Desai Ankit A. , Ataga Kenneth I. , Cohen Robyn T. , Haynes Johnson , Osunkwo Ifeyinwa , Lebensburger Jeffrey D. , Lash James P. , Wun Theodore , Verhovsek Madeleine , Ontala Elodie , Blaylark Rae , Alahdab Fares , Katabi Abdulrahman , Mustafa Reem A. 
Published: December 2019

AbstractBackground:Prevention and management of end-organ disease represent major challenges facing providers of children and adults with sickle cell disease (SCD). Uncertainty and variability in the screening, diagnosis, and management of cardiopulmonary and renal complications in SCD lead to varying outcomes for affected individuals.Objective:These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in their decisions about screening, diagnosis, and management of cardiopulmonary and renal complications of SCD.Methods:ASH formed a multidisciplinary guideline panel that included 2 patient representatives and was balanced to minimize potential bias from conflicts of interest. The Mayo Evidence-Based Practice Research Program supported the guideline development process, including performing systematic evidence reviews up to September 2017. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, including GRADE evidence-to-decision frameworks, to assess evidence and make recommendations, which were subject to public comment.Results:The panel agreed on 10 recommendations for screening, diagnosis, and management of cardiopulmonary and renal complications of SCD. Recommendations related to anticoagulation duration for adults with SCD and venous thromboembolism were also developed.Conclusions:Most recommendations were conditional due to a paucity of direct, high-quality evidence for outcomes of interest. Future research was identified, including the need for prospective studies to better understand the natural history of cardiopulmonary and renal disease, their relationship to patient-important outcomes, and optimal management.
2019 sickle cell disease guidelines by the American Society of Hematology: methodology, challenges, and innovations
Authors: Murad M. Hassan , Liem Robert I. , Lang Eddy S. , Akl Elie A. , Meerpohl Joerg J. , DeBaun Michael R. , Tisdale John F. , Brandow Amanda M. , Lanzkron Sophie M. , Chou Stella T. , Webb Starr , Mustafa Reem A. 
Published: December 2019

Abstract
The American Society of Hematology (ASH) convened 5 guideline panels to develop clinical practice recommendations addressing 5 management areas of highest importance to individuals living with sickle cell disease: pain, cerebrovascular complications, pulmonary and kidney complications, transfusion, and hematopoietic stem cell transplant. Panels were multidisciplinary and consisted of patient representatives, content experts, and methodologists. The Mayo Clinic Evidence-Based Practice Center conducted systematic reviews based on a priori selected questions. In this exposition, we describe the process used by ASH, including the GRADE approach (Grades of Recommendations, Assessment, Development and Evaluation) for rating certainty of the evidence and the GRADE Evidence to Decision Framework. We also describe several unique challenges faced by the guideline panels and the specific innovations and solutions used to address them, including a curriculum to train patients to engage in guideline development, dealing with the opioid crisis, and working with indirect and noncomparative evidence.
American Society of Hematology 2019 guidelines for management of venous thromboembolism: prevention of venous thromboembolism in surgical hospitalized patients
Authors: Anderson David R. , Morgano Gian Paolo , Bennett Carole , Dentali Francesco , Francis Charles W. , Garcia David A. , Kahn Susan R. , Rahman Maryam , Rajasekhar Anita , Rogers Frederick B. , Smythe Maureen A. , Tikkinen Kari A. O. , Yates Adolph J. , Baldeh Tejan , Balduzzi Sara , Brożek Jan L. , Ikobaltzeta Itziar Etxeandia- , Johal Herman , Neumann Ignacio , Wiercioch Wojtek , Yepes-Nuñez Juan José , Schünemann Holger J. , Dahm Philipp 
Published: December 2019

AbstractBackground:Venous thromboembolism (VTE) is a common source of perioperative morbidity and mortality.Objective:These evidence-based guidelines from the American Society of Hematology (ASH) intend to support decision making about preventing VTE in patients undergoing surgery.Methods:ASH formed a multidisciplinary guideline panel balanced to minimize bias from conflicts of interest. The McMaster University GRADE Centre supported the guideline-development process, including performing systematic reviews. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess evidence and make recommendations, which were subject to public comment.Results:The panel agreed on 30 recommendations, including for major surgery in general (n = 8), orthopedic surgery (n = 7), major general surgery (n = 3), major neurosurgical procedures (n = 2), urological surgery (n = 4), cardiac surgery and major vascular surgery (n = 2), major trauma (n = 2), and major gynecological surgery (n = 2).Conclusions:For patients undergoing major surgery in general, the panel made conditional recommendations for mechanical prophylaxis over no prophylaxis, for pneumatic compression prophylaxis over graduated compression stockings, and against inferior vena cava filters. In patients undergoing total hip or total knee arthroplasty, conditional recommendations included using either aspirin or anticoagulants, as well as for a direct oral anticoagulant over low-molecular-weight heparin (LMWH). For major general surgery, the panel suggested pharmacological prophylaxis over no prophylaxis, using LMWH or unfractionated heparin. For major neurosurgery, transurethral resection of the prostate, or radical prostatectomy, the panel suggested against pharmacological prophylaxis. For major trauma surgery or major gynecological surgery, the panel suggested pharmacological prophylaxis over no prophylaxis.
An improved random forest-based computational model for predicting novel miRNA-disease associations
Authors: Yao Dengju , Zhan Xiaojuan , Kwoh Chee-Keong 
Published: December 2019

AbstractBackgroundA large body of evidence shows that miRNA regulates the expression of its target genes at post-transcriptional level and the dysregulation of miRNA is related to many complex human diseases. Accurately discovering disease-related miRNAs is conductive to the exploring of the pathogenesis and treatment of diseases. However, because of the limitation of time-consuming and expensive experimental methods, predicting miRNA-disease associations by computational models has become a more economical and effective mean.ResultsInspired by the work of predecessors, we proposed an improved computational model based on random forest (RF) for identifying miRNA-disease associations (IRFMDA). First, the integrated similarity of diseases and the integrated similarity of miRNAs were calculated by combining the semantic similarity and Gaussian interaction profile kernel (GIPK) similarity of diseases, the functional similarity and GIPK similarity of miRNAs, respectively. Then, the integrated similarity of diseases and the integrated similarity of miRNAs were combined to represent each miRNA-disease relationship pair. Next, the miRNA-disease relationship pairs contained in the HMDD (v2.0) database were considered positive samples, and the randomly constructed miRNA-disease relationship pairs not included in HMDD (v2.0) were considered negative samples. Next, the feature selection based on the variable importance score of RF was performed to choose more useful features to represent samples to optimize the model’s ability of inferring miRNA-disease associations. Finally, a RF regression model was trained on reduced sample space to score the unknown miRNA-disease associations. The AUCs of IRFMDA under local leave-one-out cross-validation (LOOCV), global LOOCV and 5-fold cross-validation achieved 0.8728, 0.9398 and 0.9363, which were better than several excellent models for predicting miRNA-disease associations. Moreover, case studies on oesophageal cancer, lymphoma and lung cancer showed that 94 (oesophageal cancer), 98 (lymphoma) and 100 (lung cancer) of the top 100 disease-associated miRNAs predicted by IRFMDA were supported by the experimental data in the dbDEMC (v2.0) database.ConclusionsCross-validation and case studies demonstrated that IRFMDA is an excellent miRNA-disease association prediction model, and can provide guidance and help for experimental studies on the regulatory mechanism of miRNAs in complex human diseases in the future.