bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased epithelial membrane protein 2 expression in glioblastoma after treatment with bevacizumab
Authors: Patel Kunal S , Kejriwal Sameer , Thammachantha Samasuk , Duong Courtney , Murillo Adrian , Gordon Lynn K , Cloughesy Timothy F , Liau Linda , Yong William , Yang Isaac , Wadehra Madhuri 
Published: September 2020

Abstract

Background
Antiangiogenic therapy with bevacizumab has failed to provide substantial gains in overall survival. Epithelial membrane protein 2 (EMP2) is a cell surface protein that has been previously shown to be expressed in glioblastoma, correlate with poor survival, and regulate neoangiogenesis in cell lines. Thus, the relationship between bevacizumab and EMP2 was investigated.

Methods
Tumor samples were obtained from 12 patients with newly diagnosed glioblastoma at 2 time points: (1) during the initial surgery and (2) during a subsequent surgery following disease recurrence post-bevacizumab treatment. Clinical characteristics and survival data from these patients were collected, and tumor samples were stained for EMP2 expression. The IVY Glioblastoma Atlas Project database was used to evaluate EMP2 expression levels in 270 samples by differing histological areas of the tumor.

Results
Patients with high EMP2 staining at initial diagnosis had decreased progression-free and overall survival after bevacizumab (median progression-free survival 4.6 months vs 5.9 months; log-rank P = .076 and overall survival 7.7 months vs 14.4 months; log-rank P = .011). There was increased EMP2 staining in samples obtained after bevacizumab treatment in both unpaired (mean H-score 2.31 vs 1.76; P = .006) and paired analyses (mean difference 0.571; P = .019). This expression increase correlated with length of bevacizumab therapy (R2 = 0.449; Pearson P = .024).

Conclusions
Bevacizumab treatment increased EMP2 protein expression. This increase in EMP2 correlated with reduced mean survival time post-bevacizumab therapy. We hypothesize a role of EMP2 in clinical bevacizumab resistance and as a potential antiangiogenic therapeutic target in glioblastoma.
Controlled direct synthesis of single- to multiple-layer MWW zeolite
Authors: Chen Jie-Qiong , Li Yu-Zhao , Hao Qing-Qing , Chen Huiyong , Liu Zhao-Tie , Dai Chengyi , Zhang Jianbo , Ma Xiaoxun , Liu Zhong-Wen 
Published: September 2020

Abstract
The minimized diffusion limitation and completely exposed strong acid sites of the ultrathin zeolites make it an industrially important catalyst especially for converting bulky molecules. However, the structure-controlled and large-scale synthesis of the material is still a challenge. In this work, the direct synthesis of the single-layer MWW zeolite was demonstrated by using hexamethyleneimine and amphiphilic organosilane as structure-directing agents. Characterization results confirmed the formation of the single-layer MWW zeolite with high crystallinity and excellent thermal/hydrothermal stability. The formation mechanism was rigorously revealed as the balanced rates between the nucleation/growth of the MWW nanocrystals and the incorporation of the organosilane into the MWW unit cell, which is further supported by the formation of MWW nanosheets with tunable thickness via simply changing synthesis conditions. The commercially available reagents, well-controlled structure and the high catalytic stability for the alkylation of benzene with 1-dodecene make it an industrially important catalyst.
A scoping review of social and behavioral science research to translate genomic discoveries into population health impact
Authors: Allen Caitlin G , Peterson Shenita , Khoury Muin J , Brody Lawrence C , McBride Colleen M 
Published: September 2020

AbstractSince the completion of the Human Genome Project, progress toward translating genomic research discoveries to address population health issues has been limited. Several meetings of social and behavioral scientists have outlined priority research areas where advancement of translational research could increase population health benefits of genomic discoveries. In this review, we track the pace of progress, study size and design, and focus of genomics translational research from 2012 to 2018 and its concordance with five social and behavioral science recommended priorities. We conducted a review of the literature following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Guidelines for Scoping Reviews. Steps involved completing a search in five databases and a hand search of bibliographies of relevant literature. Our search (from 2012 to 2018) yielded 4,538 unique studies; 117 were included in the final analyses. Two coders extracted data including items from the PICOTS framework. Analysis included descriptive statistics to help identify trends in pace, study size and design, and translational priority area. Among the 117 studies included in our final sample, nearly half focused on genomics applications that have evidence to support translation or implementation into practice (Centers for Disease Control and Prevention Tier 1 applications). Common study designs were cross-sectional (40.2%) and qualitative (24.8%), with average sample sizes of 716 across all studies. Most often, studies addressed public understanding of genetics and genomics (33.3%), risk communication (29.1%), and intervention development and testing of interventions to promote behavior change (19.7%). The number of studies that address social and behavioral science priority areas is extremely limited and the pace of this research continues to lag behind basic science advances. Much of the research identified in this review is descriptive and related to public understanding, risk communication, and intervention development and testing of interventions to promote behavior change. The field has been slow to develop and evaluate public health-friendly interventions and test implementation approaches that could enable health benefits and equitable access to genomic discoveries. As the completion of the human genome approaches its 20th anniversary, full engagement of transdisciplinary efforts to address translation challenges will be required to close this gap.
Harnessing the Power of Residents as Change Agents in Quality Improvement
Authors: Lam Philip W. , Wong Brian M. 
Published: September 2020

Residency training represents a unique period when learners begin to personally experience the patient safety and quality-of-care issues that affect health care systems and increasingly take responsibility to address them. Their integration into the clinical workflow in clinics, wards, and operating rooms positions them perfectly to observe and characterize the underlying processes that contribute to patient safety and health care quality problems. Residents’ practices and perspectives are less entrenched than those of their faculty counterparts, which enables them to offer fresh ideas on the quality improvement (QI) process. Their creativity and ingenuity serve as assets when coming up with new and innovative changes to test using rapid change cycles. As such, they are ideally suited to serve as health systems change agents.
Training programs and clinical institutions typically see residents as frontline care providers whose primary role is to treat the patient in front of them. Yet, by enabling residents to “treat the system” through QI work, they can take on the role of residents as change agents, which has the potential to have long-lasting effects on patient care on a much wider scale. However, training programs must do more than simply harness residents’ enthusiasm and root them on from the sidelines. Instead, they must create an environment that is conducive to successfully implementing changes at the curricular, institutional, and health systems levels.
Implementation of Changes to Medical Student Documentation at Duke University Health System: Balancing Education With Service
Authors: Gagliardi Jane P. , Bonanno Brian , McPeek Hinz Eugenia R. , Musser R. Clayton , Knudsen Nancy W. , Palko Michael , McNair Felice , Lee Hui-Jie , Clay Alison S. 
Published: September 2020

Purpose
When the Centers for Medicare and Medicaid Services (CMS) changed policies about medical student documentation, students with proper supervision may now document their history, physical exam, and medical decision making in the electronic health record (EHR) for billable encounters. Since documentation is a core entrustable professional activity for medical students, the authors sought to evaluate student opportunities for documentation and feedback across and between clerkships.

Method
In February 2018, a multidisciplinary workgroup was formed to implement student documentation at Duke University Health System, including educating trainees and supervisors, tracking EHR usage, and enforcing CMS compliance. From August 2018 to August 2019, locations and types of student-involved services (student–faculty or student–resident–faculty) were tracked using billing data from attestation statements. Student end-of-clerkship evaluations included opportunity for documentation and receipt of feedback. Since documentation was not allowed before August 2018, it was not possible to compare with prior student experiences.

Results
In the first half of the academic year, 6,972 patient encounters were billed as student-involved services, 52% (n = 3,612) in the inpatient setting and 47% (n = 3,257) in the outpatient setting. Most (74%) of the inpatient encounters also involved residents, and most (92%) of outpatient encounters were student–teaching physician only.
Approximately 90% of students indicated having had opportunity to document in the EHR across clerkships, except for procedure-based clerkships such as surgery and obstetrics. Receipt of feedback was present along with opportunity for documentation more than 85% of the time on services using evaluation and management coding. Most students (> 90%) viewed their documentation as having a moderate or high impact on patient care.

Conclusions
Changes to student documentation were successfully implemented and adopted; changes met both compliance and education needs within the health system without resulting in potential abuses of student work for service.
Social Accountability Frameworks and Their Implications for Medical Education and Program Evaluation: A Narrative Review
Authors: Barber Cassandra , van der Vleuten Cees , Leppink Jimmie , Chahine Saad 
Published: September 2020

Purpose
Medical schools face growing pressures to produce stronger evidence of their social accountability, but measuring social accountability remains a global challenge. This narrative review aimed to identify and document common themes and indicators across large-scale social accountability frameworks to facilitate development of initial operational constructs to evaluate social accountability in medical education.

Method
The authors searched 5 electronic databases and platforms and the World Wide Web to identify social accountability frameworks applicable to medical education, with a focus on medical schools. English-language, peer-reviewed documents published between 1990 and March 2019 were eligible for inclusion. Primary source social accountability frameworks that represented foundational values, principles, and parameters and were cited in subsequent papers to conceptualize social accountability were included in the analysis. Thematic synthesis was used to describe common elements across included frameworks. Descriptive themes were characterized using the context–input–process–product (CIPP) evaluation model as an organizational framework.

Results
From the initial sample of 33 documents, 4 key social accountability frameworks were selected and analyzed. Six themes (with subthemes) emerged across frameworks, including shared values (core social values of relevance, quality, effectiveness, and equity; professionalism; academic freedom and clinical autonomy) and 5 indicators related to the CIPP model: context (mission statements, community partnerships, active contributions to health care policy); inputs (diversity/equity in recruitment/selection, community population health profiles); processes (curricular activities, community-based clinical training opportunities/learning exposures); products (physician resource planning, quality assurance, program evaluation and accreditation); and impacts (overall improvement in community health outcomes, reduction/prevention of health risks, morbidity/mortality of community diseases).

Conclusions
As more emphasis is placed on social accountability of medical schools, it is imperative to shift focus from educational inputs and processes to educational products and impacts. A way to begin to establish links between inputs, products, and impacts is by using the CIPP evaluation model.
Buprenorphine Induction in Persons With Opioid Use Disorder Hospitalized with Acute Hepatitis A
Authors: Oller Devin A. , Thornton Chase , Nuzzo Paul A. , Fanucchi Laura C. 
Published: September 2020

Background:
It is not known whether buprenorphine/naloxone (bup/nx) can be safely initiated in hospitalized patients with acute hepatitis A infection. We assessed liver function and tolerability of bup/nx induction in patients with acute Hepatitis A Virus (HAV).

Methods:
Retrospective review of patients (N = 31) admitted to a tertiary care facility for acute HAV who were evaluated by an addiction medicine consultant.

Results:
No significant difference was seen in aspartate aminotransferase, alanine aminotransferase, total bilirubin, or INR trends in patients receiving bup/nx during hospitalization versus those not receiving bup/nx. Nausea was the most common reported symptom in patients receiving bup/nx.

Discussion and Conclusions:
With careful monitoring and induction dose adjustment, bup/nx can be administered to patients with acute HAV without hepatic encephalopathy. Similarly, patients on bup/nx before hospitalization should not have this medication held in the setting of acute HAV.

Scientific Significance:
This strategy may engage patients with acute HAV in treatment of OUD earlier and minimize disruptions in treatment.
Factors Associated With Serum Estradiol Levels Among Postmenopausal Women Using Hormone Therapy
Authors: Sriprasert Intira , Kono Naoko , Karim Roksana , Hodis Howard N. , Stanczyk Frank Z. , Shoupe Donna , Mack Wendy J. 
Published: September 2020

OBJECTIVE:
To identify factors associated with serum estradiol (E2) levels among healthy postmenopausal women using hormone therapy (HT).

METHODS:
This is an unplanned post hoc analysis of data from ELITE (Early versus Late Intervention Trial with Estradiol), a randomized controlled trial of 1 mg oral E2 with or without vaginal progesterone in healthy early compared with late (<6 years compared with 10 or more years since menopause) postmenopausal women. We included results from visits when women reported at least 80% compliance with HT. Mixed-effects linear models identified factors associated with serum E2 levels while participants were taking HT, assessed every 6 months over a median follow-up of 4.8 years and adjusted for baseline E2 level, visit, and reduced E2 dose. Possible correlates evaluated included demographics, clinical characteristics, medication use, and biomarkers of liver and kidney metabolic function.

RESULTS:
The analysis included 2,160 E2 measurements in 275 postmenopausal women. Mean±SD age was 55.4±3.9 vs 64.4±5.5 years, and mean±SD time since menopause was 3.6±1.8 vs 16.0±5.6 years for early vs late postmenopausal women. Adjusted for pretreatment E2 level, visit, and reduced dose indicator, higher serum E2 levels were associated with higher body mass index (BMI), higher weight, surgical menopause, alcohol use, and antihypertensive medication use. Current and past smoking and antifungal medication use were associated with lower serum E2 levels. In the multivariable model, higher BMI and alcohol use were associated with higher serum E2 levels, whereas current and past smoking were associated with lower serum E2 levels. These factors were similar between early and late postmenopausal women.

CONCLUSION:
Factors associated with serum E2 levels among postmenopausal women taking HT include BMI, alcohol use, and smoking. As serum E2 levels relate to HT effect, achievement of desirable E2 levels may be maximized through personalized intervention.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, NCT00114517.
Pathophysiologic Origins of Brachial Plexus Injury
Authors: Johnson Grace J. , Denning Stacie , Clark Steven L. , Davidson Christina 
Published: September 2020

OBJECTIVE:
To analyze the origins and consequences of cases of brachial plexus injuries and their relationship to shoulder dystocia.

METHODS:
We conducted a retrospective cohort study and identified all neonates with brachial plexus injury delivered at our institution between March 2012 and July 2019. A review was performed of the maternal and neonatal records of each neonate to identify obstetric antecedents, including the occurrence of shoulder dystocia and persistence of the injury. Experience of the delivering clinician was also examined. Statistical analysis was performed with the Fisher exact test, χ2 test for trends, and two-tailed t tests.

RESULTS:
Thirty-three cases of brachial plexus injury were identified in 41,525 deliveries (0.08%). Fourteen (42%) of these cases were not associated with shoulder dystocia; three (9%) followed cesarean delivery. Brachial plexus injury without shoulder dystocia was related to the absence of maternal diabetes, lower birth weights, and a longer second stage of labor. Persistent brachial plexus injury at the time of discharge was seen with equal frequency among neonates with (17/19, 89%, 95% CI 0.52–100%) and without shoulder dystocia (10/14, 71%, 95% CI 34–100%), P=.36). Whether brachial plexus injury was transient or persistent after shoulder dystocia was unrelated to the years of experience of the delivering clinician. Despite ongoing training and simulation, the already low incidence of brachial plexus injury did not decrease over time at our institution.

CONCLUSION:
Brachial plexus injury and shoulder dystocia represent two complications of uterine forces driving a fetus through the maternal pelvis in the presence of disproportion between the passage and the shoulder girdle of the passenger. Either or both of these complications may occur, but often are not causally related.
Intrauterine Vacuum-Induced Hemorrhage-Control Device for Rapid Treatment of Postpartum Hemorrhage
Authors: D’Alton Mary E. , Rood Kara M. , Smid Marcela C. , Simhan Hyagriv N. , Skupski Daniel W. , Subramaniam Akila , Gibson Kelly S. , Rosen Todd , Clark Shannon M. , Dudley Donald , Iqbal Sara N. , Paglia Michael J. , Duzyj Christina M. , Chien Edward K. , Gibbins Karen J. , Wine Kathryn D. , Bentum Nana Ama A. , Kominiarek Michelle A. , Tuuli Methodius G. , Goffman Dena 
Published: September 2020

OBJECTIVE:
To evaluate the effectiveness and safety of an intrauterine vacuum-induced hemorrhage-control device for postpartum hemorrhage treatment.

METHODS:
A multicenter, prospective, single-arm treatment study of a novel intrauterine device that uses low-level vacuum to induce uterine myometrial contraction to achieve control of abnormal postpartum uterine bleeding and postpartum hemorrhage was undertaken at 12 centers in the United States. The primary effectiveness endpoint was the proportion of participants in whom use of the intrauterine vacuum-induced hemorrhage-control device controlled abnormal bleeding without requiring escalating interventions. The primary safety endpoint was the incidence, severity, and seriousness of device-related adverse events. Secondary outcomes included time to bleeding control, rate of transfusion, and device usability scored by each investigator using the device.

RESULTS:
Of 107 participants enrolled with primary postpartum hemorrhage or abnormal postpartum uterine bleeding, 106 received any study treatment with the device connected to vacuum, and successful treatment was observed in 94% (100/106, 95% CI 88–98%) of these participants. In those 100 participants, definitive control of abnormal bleeding was reported in a median of 3 minutes (interquartile range 2.0–5.0) after connection to vacuum. Eight adverse events deemed possibly related to the device or procedure were reported, all of which were outlined as risks in the study and all of which resolved with treatment without serious clinical sequelae. Transfusion of 1–3 units of red blood cells was required in 35 participants, and five participants required 4 or more units of red blood cells. The majority of investigators reported the intrauterine vacuum-induced hemorrhage-control device as easy to use (98%) and would recommend it (97%).

CONCLUSION:
Intrauterine vacuum-induced hemorrhage control may provide a new rapid and effective treatment option for abnormal postpartum uterine bleeding or postpartum hemorrhage, with the potential to prevent severe maternal morbidity and mortality.

FUNDING SOURCE:
Alydia Health, Inc.

CLINICAL TRIAL REGISTRATION:
ClinicalTrials.gov, NCT02883673.
Characterization of a Novel Entity of G3 (High-grade Well-differentiated) Colorectal Neuroendocrine Tumors (NET) in the SEER Database
Authors: Punekar Salman R. , Kaakour Dalia , Masri-Lavine Lena , Hajdu Cristina , Newman Elliot , Becker Daniel J. 
Published: September 2020

Objectives:
Small studies suggest that a new entity of high-grade (HG) (G3, by Ki-67 or mitotic index) well-differentiated (histologically) gastrointestinal neuroendocrine tumors (NETs) exists, but prognosis and characteristics are unknown. We further characterized demographics and prognosis of patients with colorectal G3 NETs.

Materials and Methods:
We used the Surveillance Epidemiology and End Results (SEER) database to study colorectal NETs diagnosed from 2000 to 2015. We evaluated demographic, clinical, and tumor characteristics. We compared overall survival (OS) for G1-2 NET, G3 NET, and NEC (neuroendocrine carcinoma). We used logistic regression to detect grade associations and Cox proportional hazards models to examine predictors of survival.

Results:
We identified 5894 cases with colorectal NET (5780 [98.1%] G1-2 and 114 [1.9%] G3); the cohort was 66% white, 47% male, and had a median age of 54. Patients with G3 NET were likely to be older (odds ratio [OR]: 2.23; 95% confidence interval [CI]: 1.19-4.19 for 60 to 69 vs. <50), unmarried (OR: 1.56; 95% CI: 1.02-2.38), and less likely to be diagnosed after 2010 (OR: 0.09; 95% CI: 0.06-0.15). OS for G3 NET (median, 36 mo; 95% CI: 13-92) fell between OS for NEC (median, 7 mo; 95% CI: 6-8), and G1-2 NET (median not reached, >120 mo). Among G1-3 NETs, black patients (hazard ratio [HR]: 1.30; 95% CI: 1.03-1.62), older patients (HR: 3.63; 95% CI: 2.63-5.01 for age 60 to 69 vs. <50), unmarried patients (HR: 1.40; 95% CI: 1.17-1.68), and those with HG features (HR: 3.97; 95% CI: 3.15-4.99) had worse survival.

Conclusions:
We defined a subset of G3 NETs that are HG and well differentiated, more common in older, unmarried patients, with a prognosis between that of NEC and G1-2 NETs. Our analysis adds the first national registry study in support of a new classification of nonpancreatic HG and well-differentiated NETs.