bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunohistochemical Assessment of the Diagnostic Utility of PD-L1 (Clone SP142) for Methotrexate-Associated Lymphoproliferative Disorders With an Emphasis of Neoplastic PD-L1 (Clone SP142)–Positive Classic Hodgkin Lymphoma Type
Authors: Kohno Kei , Suzuki Yuka , Elsayed Ahmed A , Sakakibara Ayako , Takahara Taishi , Satou Akira , Kato Seiichi , Nakamura Shigeo , Asano Naoko 
Published: October 2019

AbstractObjectivesWe describe results of programmed death ligand 1 (PD-L1) immunohistochemical assessment in methotrexate (MTX)–associated lymphoproliferative disorders (LPDs) and highlight the characteristics of classic Hodgkin lymphoma (CHL) type MTX-LPD.MethodsFifty cases of MTX-LPD, including CHL type (n = 9), diffuse large B-cell lymphoma type (n = 15), and polymorphic B-cell LPD (n = 21), were investigated.ResultsStaining with anti–PD-L1 clone SP142 was exclusively found in CHL type (89%) but not in the others. Cases of CHL type MTX-LPD involved nodal disease and were associated with Epstein-Barr virus. They were histopathologically characterized by a vaguely nodular pattern, predominance of mononuclear cells, and strong expression of at least one pan–B-cell marker. Their clinical course was variable, with spontaneous regression in 5 patients, relapse in 2, and a fatal course in 1.ConclusionsThe PD-L1 (clone SP142) workup aids the diagnostic approach to patients with MTX-LPD. CHL type MTX-LPD appears to represent a unique morphologic variant of CHL.
The Dynamic Relationship Between Asthma and Obesity in Schoolchildren
Authors: Zhang Yue , Chen Zhanghua , Berhane Kiros , Urman Robert , Chatzi Vaia Lida , Breton Carrie , Gilliland Frank D 
Published: October 2019

Abstract
Asthma and obesity are among the most prevalent chronic health conditions in children. Although there has been compelling evidence of co-occurrence of asthma and obesity, it is uncertain whether asthma contributes to the development of obesity or obesity contributes to the onset of asthma or both. In this study, we used a joint transition modeling approach with cross-lagged structure to understand how asthma and obesity influence each other dynamically over time. Subjects for this study included 5,193 kindergarten and first-grade students enrolled from 13 communities in 2002–2003 in the Southern California Children’s Health Study, with up to 10 years of follow-up. We found that nonobese children with diagnosed asthma at a study visit were at 37% higher odds of becoming obese by the next annual visit compared with children without asthma (odds ratio = 1.38; 95% credible interval: 1.12, 1.71). However, the presence of obesity at the current visit was not statistically significantly associated with asthma onset in the next visit (odds ratio = 1.25; 95% credible interval: 0.94, 1.62). In conclusion, childhood asthma appears to drive an increase in the onset of obesity among schoolchildren, while the onset of obesity does not necessarily imply the future onset of asthma, at least in the short term.
Establishing an investigational drugs and research residency at an academic medical center
Authors: Wascher Molly , Mighty Janet , Brown Victoria , Ashby Daniel , Rudek Michelle A , Nesbit Todd , DeLisa Anne , Walker Cathy , Tolan Meghan 
Published: October 2019

Abstract

Purpose
The development, structure, and implementation of an innovative residency program designed to help meet a growing need for pharmacists with specialized expertise in investigational drug use and clinical research are described.

Summary
Clinical research has become an increasingly complex field, but prior to 2017 there were no U.S. specialty residency training programs focused on pharmacists’ role in drug development and the care of patients enrolled in clinical trials. In 2016 Johns Hopkins Hospital (JHH) launched an initiative to develop residency training standards specific to the areas of investigational drug use and clinical research. The residency development process consisted of creation of a residency development committee; a needs assessment, including formation of a diverse panel of internal and external experts to guide identification of key competency areas and development of residency goals and objectives; design of the program’s structure, including a framework for required and elective rotations; submission of an application for pre-candidate status to the ASHP Commission on Credentialing; and recruitment efforts.

Conclusion
The JHH investigational drugs and research residency, a combined PGY1 and PGY2 program with 5 competency areas, 14 goals, and 49 objectives, was granted pre-candidate status by ASHP in November 2016. The first resident began the program in June 2017.
Noninvasive Induction of Muscle Fiber Hypertrophy and Hyperplasia: Effects of High-Intensity Focused Electromagnetic Field Evaluated in an In-Vivo Porcine Model: A Pilot Study
Authors: Duncan Diane , Dinev Ivan 
Published: October 2019

AbstractBackgroundHigh-intensity focused electromagnetic (HIFEM) field technology has been reported to increase muscle thickness and hypertrophy. However, this process has not yet been confirmed on a histologic level.ObjectivesThe aim of this study was to evaluate in-vivo structural changes in striated porcine muscle tissue following HIFEM treatment.MethodsThree Yorkshire pigs received four 30-minute HIFEM treatments applied to the biceps femoris muscle on 1 side only. The fourth pig served as a control subject. At baseline and 2 weeks after the last treatment, biopsy specimens of the muscle tissue were collected from the treatment site. The control pig underwent muscle biopsy from a similar but untreated site. Twenty-five histology slides were evaluated from each pig. A certified histopathologist analyzed sliced biopsy samples for structural changes in the tissue.ResultsHistologic analysis showed hypertrophic changes 2 weeks posttreatment. The muscle mass density increased by 20.56% (to a mean of 17,053.4 [5617.9] µm2) compared with baseline. Similarly, muscle fiber density (hyperplasia) increased: the average change in the number of fibers in a slice area of 136,533.3 µm2 was +8.0%. The mean size of an individual muscle fiber increased by 12.15% (to 332.23 [280.2] µm2) 2 weeks posttreatment. Control samples did not show any significant change in fiber density or hyperplasia.ConclusionsHistopathologic quantification showed significant structural muscle changes through a combination of fiber hypertrophy and hyperplasia. Control biopsies showed a lack of similar changes. The data correlate with findings of other HIFEM research and suggest that HIFEM could be used for noninvasive induction of muscle growth.
Network-based multi-task learning models for biomarker selection and cancer outcome prediction
Authors: Wang Zhibo , He Zhezhi , Shah Milan , Zhang Teng , Fan Deliang , Zhang Wei 
Published: October 2019

AbstractMotivationDetecting cancer gene expression and transcriptome changes with mRNA-sequencing or array-based data are important for understanding the molecular mechanisms underlying carcinogenesis and cellular events during cancer progression. In previous studies, the differentially expressed genes were detected across patients in one cancer type. These studies ignored the role of mRNA expression changes in driving tumorigenic mechanisms that are either universal or specific in different tumor types. To address the problem, we introduce two network-based multi-task learning frameworks, NetML and NetSML, to discover common differentially expressed genes shared across different cancer types as well as differentially expressed genes specific to each cancer type. The proposed frameworks consider the common latent gene co-expression modules and gene–sample biclusters underlying the multiple cancer datasets to learn the knowledge crossing different tumor types.ResultsLarge-scale experiments on simulations and real cancer high-throughput datasets validate that the proposed network-based multi-task learning frameworks perform better sample classification compared with the models without the knowledge sharing across different cancer types. The common and cancer-specific molecular signatures detected by multi-task learning frameworks on The Cancer Genome Atlas ovarian, breast and prostate cancer datasets are correlated with the known marker genes and enriched in cancer-relevant Kyoto Encyclopedia of Genes and Genome pathways and gene ontology terms.Availability and implementationSource code is available at: https://github.com/compbiolabucf/NetML.Supplementary informationSupplementary data are available at Bioinformatics online.
CASPR, an analysis pipeline for single and paired guide RNA CRISPR screens, reveals optimal target selection for long non-coding RNAs
Authors: Bergadà-Pijuan Judith , Pulido-Quetglas Carlos , Vancura Adrienne , Johnson Rory 
Published: October 2019

Abstract

Motivation
CRISPR-Cas9 loss-of-function (LOF) pooled screening promises to identify which long non-coding RNAs (lncRNAs), amongst the many thousands to have been annotated so far, are capable of mediating cellular functions. The two principal LOF perturbations, CRISPR-inhibition and CRISPR-deletion, employ one and two guide RNAs, respectively. However, no software solution has the versatility to identify hits across both modalities, and the optimal design parameters for such screens remain poorly understood.

Results
Here, we present CRISPR Analysis for Single and Paired RNA-guides (CASPR), a user-friendly, end-to-end screen analysis tool. CASPR is compatible with both CRISPRi and CRISPR-del screens, and balances sensitivity and specificity by generating consensus predictions from multiple algorithms. Benchmarking on ground-truth sets of cancer-associated lncRNAs demonstrates CASPR’s improved sensitivity with respect to existing methods. Applying CASPR to published screens, we identify two parameters that predict lncRNA hits: expression and annotation quality of the transcription start site. Thus, CASPR is a versatile and complete solution for lncRNA CRISPR screen analysis, and reveals principles for including lncRNAs in screening libraries.

Availability and implementation
https://judithbergada.github.io/CASPR/

Supplementary information
Supplementary data are available at Bioinformatics online.
YY1 is a cis-regulator in the organoid models of high mammographic density
Authors: Cheng Qingsu , Khoshdeli Mina , Ferguson Bradley S , Jabbari Kosar , Zang Chongzhi , Parvin Bahram 
Published: October 2019

Abstract

Motivation
Our previous study has shown that ERBB2 is overexpressed in the organoid model of MCF10A when the stiffness of the microenvironment is increased to that of high mammographic density (MD). We now aim to identify key transcription factors (TFs) and functional enhancers that regulate processes associated with increased stiffness of the microenvironment in the organoid models of premalignant human mammary cell lines.

Results
3D colony organizations and the cis-regulatory networks of two human mammary epithelial cell lines (184A1 and MCF10A) are investigated as a function of the increased stiffness of the microenvironment within the range of MD. The 3D colonies are imaged using confocal microscopy, and the morphometries of colony organizations and heterogeneity are quantified as a function of the stiffness of the microenvironment using BioSig3D. In a surrogate assay, colony organizations are profiled by transcriptomics. Transcriptome data are enriched by correlative analysis with the computed morphometric indices. Next, a subset of enriched data are processed against publicly available ChIP-Seq data using Model-based Analysis of Regulation of Gene Expression to predict regulatory transcription factors. This integrative analysis of morphometric and transcriptomic data predicted YY1 as one of the cis-regulators in both cell lines as a result of the increased stiffness of the microenvironment. Subsequent experiments validated that YY1 is expressed at protein and mRNA levels for MCF10A and 184A1, respectively. Also, there is a causal relationship between activation of YY1 and ERBB2 when YY1 is overexpressed at the protein level in MCF10A.

Supplementary information
Supplementary data are available at Bioinformatics online.
Development and Validation of HPTLC and Green HPLC Methods for Determination of a New Combination of Quinfamide and Mebendazole
Authors: Naguib Ibrahim A , Hassan Eman S , Emam Aml A , Abdelaleem Eglal A 
Published: October 2019

AbstractTwo selective and sensitive chromatographic methods were developed for simultaneous determination of new combination of quinfamide and mebendazole in bulk powder and in pharmaceutical formulation. The first method is HPTLC by which separation was obtained using silica gel HPTLC F254 plates and a simple mobile phase consisting of methanol:toluene (2:6, v/v) and the separated bands were scanned at 254 nm. The second method RP-HPLC that comprised isocratic separation of both drugs on a Phenomenex C18 column using a green mobile phase consisting of double distilled water:methanol (30:70, v/v) at a flow rate of 0.8 mL/min and UV detection at 254 nm. The developed methods were validated and proved to meet ICH guidelines. Successful application of the developed methods was carried out for determination of quinfamide and mebendazole in Vermox Plus® tablets. Statistical comparison between the developed chromatographic methods and the reported simultaneous equation spectrophotometric method showed that there was no significant difference between them, proving the ability of applying the proposed methods in quality control testing of the studied drugs. The developed methods are considered the first chromatographic methods for simultaneous determination of quinfamide and mebendazole; moreover, they offered sensitive and selective eco-friendly methods for analysis of the studied drugs.
Culture Conversion at 6 Months in Patients Receiving Delamanid-containing Regimens for the Treatment of Multidrug-resistant Tuberculosis
Authors: Seung Kwonjune J , Khan Palwasha , Franke Molly F , Ahmed Saman , Aiylchiev Stalbek , Alam Manzur , Putri Fauziah Asnely , Bastard Mathieu , Docteur Wisny , Gottlieb Gary , Hewison Catherine , Islam Shirajul , Khachatryan Naira , Kotrikadze Tinatin , Khan Uzma , Kumsa Andargachew , Lecca Leonid , Tassew Yoseph Melaku , Melikyan Nara , Naing Ye Yint , Oyewusi Lawrence , Rich Michael , Wanjala Stephen , Yedilbayev Askar , Huerga Helena , Mitnick Carole D 
Published: October 2019

Abstract
Delamanid should be effective against highly resistant strains of Mycobacteriumtuberculosis, but uptake has been slow globally. In the endTB (expand new drug markets for TB) Observational Study, which enrolled a large, heterogeneous cohorts of patients receiving delamanid as part of a multidrug regimen, 80% of participants experienced sputum culture conversion within 6 months.
Clinical Trials Registration. NCT03259269.
NutriGenomeDB: a nutrigenomics exploratory and analytical platform
Authors: Martín-Hernández Roberto , Reglero Guillermo , Ordovás José M , Dávalos Alberto 
Published: October 2019

Abstract
Habitual consumption of certain foods has shown beneficial and protective effects against multiple chronic diseases. However, it is not clear by which molecular mechanisms they may exert their beneficial effects. Multiple -omic experiments available in public databases have generated gene expression data following the treatment of human cells with different food nutrients and bioactive compounds. Exploration of such data in an integrative manner offers excellent possibilities for gaining insights into the molecular effects of food compounds and bioactive molecules at the cellular level. Here we present NutriGenomeDB, a web-based application that hosts manually curated gene sets defined from gene expression signatures, after differential expression analysis of nutrigenomics experiments performed on human cells available in the Gene Expression Omnibus (GEO) repository. Through its web interface, users can explore gene expression data with interactive visualizations. In addition, external gene signatures can be connected with nutrigenomics gene sets using a gene pattern-matching algorithm. We further demonstrate how the application can capture the primary molecular mechanisms of a drug used to treat hypertension and thus connect its mode of action with hosted food compounds.
Comparative outcomes of robot-assisted minimally invasive versus open esophagectomy in patients with esophageal squamous cell carcinoma: a propensity score-weighted analysis
Authors: Yun J K , Chong B K , Kim H J , Lee I-S , Gong C-S , Kim B S , Lee G D , Choi S , Kim H R , Kim D K , Park S-I , Kim Y-H 
Published: October 2019

SUMMARY
Robots are increasingly used in minimally invasive surgery. We evaluated the clinical benefits of robot-assisted minimally invasive esophagectomy (RAMIE) in comparison with the conventional open esophageal surgery. From 2012 to 2016, 371 patients with esophageal squamous cell carcinoma underwent an Ivor Lewis or McKeown procedure at our institution. Of these, 130 patients underwent laparoscopic gastric conduit formation followed by RAMIE, whereas 241 patients underwent conventional esophageal surgery, including laparotomy and open esophagectomy (OE). We compared the short- and long-term clinical outcomes of these patients using the propensity score-based inverse probability of treatment weighting technique (IPTW). Among the early outcomes, the OE group showed a higher incidence of pneumonia (P = 0.035) and a higher requirement for vasopressors (P = 0.001). Regarding the long-term outcomes, all-cause mortality was significantly higher (P = 0.001) and disease-free survival was lower (P = 0.006) in the OE group. Wound-related problems also occurred more frequently in the OE group (P = 0.020) during the long-term follow-up. There was no statistical intergroup difference in the recurrence rates (P = 0.191). The Cox proportional-hazard analysis demonstrated that wound problems (HR 0.16, 95% CI 0.02–0.57; P = 0.017), pneumonia (HR 0.23, 95% CI 0.06–0.68; P = 0.019), and use of vasopressors (HR 0.14, 95% CI 0.08–0.25; P = 0.001) were independent predictors of mortality. RAMIE could be a better surgical option for selected patients with esophageal squamous cell carcinoma.
Esophageal melanoma: a systematic review and exploratory recurrence and survival analysis
Authors: Schizas D , Mylonas K S , Bagias G , Mastoraki A , Ioannidi M , Kanavidis P , Hasemaki N , Karavokyros I , Theodorou D , Liakakos T 
Published: October 2019

SUMMARY
Esophageal melanoma is a rare and poorly described malignancy. We sought to review all available data on the clinicopathological features, management options, and outcomes of patients with esophageal melanoma to guide clinicians working to treat these uncommon tumors. A systematic literature search of the PubMed, Embase, and Cochrane databases was performed. Exploratory recurrence and survival analyses were performed using previously-validated pooled Cox and logistic regression techniques for case reports and case series. Quality assessment of included studies was performed using the tools developed by the Joanna Briggs and the National Heart, Lung, and Blood Institutes. Fifty-nine studies were reviewed. A total of 93 patients with esophageal melanoma were identified. The mean patient age was 61.2 ± 10.6 years. Esophageal melanoma usually developed at the lower esophagus (48.4%). 90.3% of the patients were symptomatic at presentation, with dysphagia being the most common symptom (72%). Esophagectomy was performed in 91.4% of the patients. Postoperatively, 14 patients (15.1%) received adjuvant chemotherapy. Tumor recurrence was seen in 37 patients (39.8%). The median time to recurrence was 6 months. Disease-specific mortality was 43%. All-cause mortality was 46.1%. On multivariable Cox regression, older patient age (hazard ratio [HR] = 0.91, P = 0.008) and higher Melan-A expression (HR = 0.21; P = 0.029) were associated with a significantly lower risk of mortality. Higher S100 levels (HR = 37.4; P = 0.001) were predictive of poor survival. On logistic regression, large, ulcerated, lower esophageal tumors were significantly more likely to recur (P = 0.018, P = 0.013, and P = 0.027 respectively). Esophageal melanoma is a rare malignancy that tends to present with dysphagia. Most surgically-treated patients undergo esophagectomy. Large, ulcerated, lower esophageal lesions recur more frequently. Immunohistochemistry provides prognostic information regarding survival.
Complete reversal of constriction physiology with antitubercular treatment without steroid: a case report
Authors: Bagchi Avishek , Bhagwati Mohit , Rathi Rajeev Kumar 
Published: October 2019

Abstract

Background
Constrictive pericarditis is a chronic inflammation of the pericardium leading to the thickening of the pericardium that restricts cardiac filling. Globally tuberculosis is the commonest aetiology of constrictive pericarditis. Though normally considered to be an irreversible pathology; which requires surgical pericardiectomy, in early stage of the disease antitubercular therapy (ATT) along with steroids and other anti-inflammatory therapy can reverse the pathology. But, complete reversal of constrictive physiology with ATT without any anti-inflammatory drugs is not documented.

Case summary
Here, we describe a case where a 54-year-old lady presented with progressive dyspnoea and pedal oedema for 2 years along with anorexia and weight loss for two months. Two-dimensional echocardiography and computed tomography scan was suggestive of constrictive pericarditis. In view of systemic features and high acute phase reactants, patient was started on oral ATT without any steroids. After 4 months, constriction physiology was completely reversed.

Discussion
Constriction physiology if treated timely can be largely reversed only with ATT without adjuvant anti-inflammatory therapy. Further studies are required to find out the specific indications of anti-inflammatory therapy in tubercular constrictive pericarditis.
Efficacy and safety of edoxaban compared with warfarin according to the burden of diseases in patients with atrial fibrillation: insights from the ENGAGE AF-TIMI 48 trial
Authors: Nicolau André M , Corbalan Ramon , Nicolau Jose C , Ruff Christian T , Zierhut Wolfgang , Kerschnitzki Michael , Duris Tibor , Juul-Möller Steen , Voitk Juri , Trevisan Marco , Nordio Francesco , Antman Elliott M , Giugliano Robert P 
Published: October 2019

Abstract

Aims
Non-vitamin K antagonist oral anticoagulants represent a new option for prevention of embolic events in patients with atrial fibrillation (AF). However, little is known about the impact of non-cardiac comorbidities on the efficacy and safety profile of these drugs.

Methods and results
In a post hoc analysis of the ENGAGE AF-TIMI 48 trial, we analysed 21 105 patients with AF followed for an average of 2.8 years and randomized to either a higher-dose edoxaban regimen (HDER), a lower-dose edoxaban regimen, or warfarin. We used the updated Charlson Comorbidity Index (CCI) to stratify the patients according to the burden of concomitant disease (CCI = 0, 1, 2, 3, and ≥4). The treatment groups were then compared for safety, efficacy, and net clinical outcomes across CCI categories. There were 32.0%, 7.3%, 42.1%, 12.7%, and 6.0% of patients with CCI scores of 0, 1, 2, 3, and ≥4, respectively. A CCI score ≥4 was associated with significantly higher rates of thromboembolic events, bleeding, and death compared to CCI = 0 (P &lt; 0.05 for each). The annualized rates of the primary net clinical outcome (stroke/systemic embolism, major bleeding, or death) for CCI = 0, 1, 2, 3, or ≥4 were 5.9%, 8.7%, 6.6%, 10.3%, and 13.6% (Ptrend &lt; 0.001). There were no significant interactions between treatment with HDER vs. warfarin and efficacy, safety, and net outcomes across the CCI groups (P-interaction &gt; 0.10 for each).

Conclusion
Although increasing CCI scores are associated with worse outcomes, the efficacy, safety, and net clinical outcomes of edoxaban vs. warfarin were independent of the degree of comorbidity present.