bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of Shexiang Baoxin Pills for the treatment of unstable angina pectoris
Authors: Chen Huadong , Dong Qianqian , Zheng Xiang 
Published: September 2019

Abstract

Background:
Shexiang Baoxin Pills (SBP) is widely used for the treatment of unstable angina pectoris (UAP) in China. However, the clinical evidence on the efficacy of SBP for the treatment of UAP is not well concluded.

Methods:
Seven electronic databases will be searched for eligible studies: MEDLINE, EMBASE, The Cochrane Library, Wanfang database, Chinese National Knowledge Infrastructure database, VIP database, and Chinese Biological and Medicine database. Data of included studies will be extracted, and quality will be evaluated. Data synthesis will be performed using RevMan software. Subgroup analysis and sensitivity analysis will also be carried out. Publication bias will be evaluated using funnel plot if included studies are sufficient.

Results:
This systemic review and meta-analysis will provide synthesized result of clinical efficacy of SBP for the treatment of UAP.

Conclusions:
This systemic review and meta-analysis will provide high-quality evidence on the clinical efficacy of SBP for the treatment of UAP.

Registration:
PEROSPERO CRD42019124668
Pediatric gastroenteropancreatic neuroendocrine tumor
Authors: Gaiani Federica , de’Angelis Nicola , Minelli Roberta , Kayali Stefano , Carra Maria Clotilde , de’Angelis Gian Luigi 
Published: September 2019

Abstract

Introduction:
Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a heterogeneous group of epithelial neoplasms originating from the diffuse neuroendocrine cell system of the gastrointestinal tract and pancreas. They are very rare, especially in pediatric age, and vary widely in terms of clinical presentation, malignant potential, and prognosis.

Patient concerns:
A 9 years’ old, white female child presented with abdominal pain and diarrhea mixed with bright red blood lasting 2 days followed by hematemesis.

Diagnosis:
Routine laboratory tests revealed microcytic anemia. Upper endoscopy showed a 20-mm polypoid lesion in the posterior wall of the duodenal bulb. Biopsy specimens were taken and histologic analysis showed a well-differentiated neuroendocrine tumor G1, with a ki-67 index <2%, an expression of chromogranine A (CgA), synaptophysin and somatostatin receptor type 2A (SSTR2A). Endoscopic ultrasound showed a 21-mm hypoechoic, hypervascular lesion involving the mucosal, submucosal, and muscular layers and a 15-mm hypoechoic round periduodenal lymph node. Gallium-68-somatostatin receptor positron emission tomography (PET with Ga-DOTATOC) showed one area of tracer uptake in the duodenum and other one near the duodenum compatible with the primary tumor site and a lymph node respectively. All the tests confirmed the diagnosis of a GEP-NET of the duodenal bulb, with a single lymph-node metastasis.

Interventions:
The patient underwent an open duodenal wedge resection.

Outcomes:
The follow-up at 6, 24, and 36 months and then yearly after surgery for a total of 42 months showed no evidence of recurrence.

Conclusion:
Duodenal neuroendocrine tumors represent 1% to 3% of all GEP-NETs. They are rare in adults and extremely rare in children. Therefore, the diagnostic and therapeutic approach should be multidisciplinary, including laboratory, endoscopic, and specific imaging tests and strictly follows guidelines, to avoid misdiagnosis and inadequate treatments. Although the prognosis is benign in most cases, they can present with metastases. Therefore, a careful follow-up is extremely important.
Community-engaged Evidence Synthesis to Inform Public Health Policy and Clinical Practice
Authors: Springs Stacey , Rofeberg Valerie , Brown Sherilyn , Boudreau Steven , Hey Spencer Phillips , Baruch Jay 
Published: September 2019

Background:
This case study documents the work of the Rhode Island Arts and Health Advisory Group, which convened in 2016 to develop a set of policy, clinical practice, and research recommendations for implementation by the Rhode Island Department of Health, The Rhode Island State Council on the Arts, and partners. Comprised of artists, clinicians, community members, and patients, the group partnered with researchers to complete an evidence synthesis project of arts-based health care interventions.

Methods:
The group took a community-engaged approach to evidence synthesis, featuring the use of online, and in-person training materials to facilitate the codesign and coexecution of the evidence synthesis protocol. The final evidence map was translated into an online evidence map to facilitate analysis and discussion on arts-based interventions in health care.

Results:
The evidence map informed the development of recommendations for advancing the integration of arts and health in the state. The project evaluation indicated that our community-engaged approach to evidence synthesis promoted engagement as defined by the PCORI Engagement Strategy Rubric (ie, reciprocal relationships, partnership, colearning, transparency, honesty, and trust). Participation also improved community research partners confidence in engaging with the health care system, developed greater empathy and understanding of others in the community, and increased interest in using science or research in advocacy efforts.

Conclusions:
Engaging community partners in evidence synthesis promotes community dialogue and engagement in research, specifically towards: (1) elucidating outcomes of import to patients and communities that are not represented in the medical literature; and (2) identifying comparisons among interventions that resonate with patients and communities.
Clinical Effects and Outcomes After Polymyxin B–Immobilized Fiber Column Direct Hemoperfusion Treatment for Septic Shock in Preterm Neonates*
Authors: Nishizaki Naoto , Hara Taichi , Obinata Kaoru , Nakagawa Mayu , Shimizu Toshiaki 
Published: September 2019

Objectives:
To compare the effectiveness and mortality of early-onset sepsis or late-onset sepsis treatments with polymyxin B–immobilized fiber column direct hemoperfusion in terms of effectiveness and mortality in preterm infants with septic shock.

Design:
Retrospective cohort study.

Setting:
Neonatal ICU within a tertiary care hospital.

Patients:
Of 1,115 patients, 49 had blood culture–proven sepsis between January 2013 and December 2018; six and five patients with septic shock had undergone polymyxin B–immobilized fiber column direct hemoperfusion treatment for early-onset sepsis (early-onset sepsis group) and late-onset sepsis (late-onset sepsis group), respectively.

Interventions:
None.

Measurements and Main Results:
Baseline demographic characteristics of both groups were similar. The time from decision to treatment induction was significantly shorter in the early-onset sepsis group than that in the late-onset sepsis group (p = 0.008). The mortality rate after 28 days of treatment and the hospital mortality were significantly lower in the early-onset sepsis group than in the late-onset sepsis group (p = 0.026 and 0.015, respectively). The Pao
2/Fio
2 ratio was significantly higher in the early-onset sepsis group than in the late-onset sepsis group at the end of the treatment (p = 0.035). In addition, median arterial-to-alveolar oxygen tension ratio significantly improved from 0.19 to 0.55, and median blood pressure also significantly improved from 32.5 to 40.0 mm Hg after the treatment in the early-onset sepsis group. Interleukin-6 levels significantly decreased after treatment in the early-onset sepsis group (p = 0.037). The Pediatric Risk of Mortality III score was similar between the early-onset sepsis and late-onset sepsis groups before and after the treatment. Intraventricular hemorrhage events occurred in both groups, but with no significant differences (p = 0.175).

Conclusions:
Polymyxin B–immobilized fiber column direct hemoperfusion treatment for preterm infants with septic shock due to early-onset sepsis is associated with earlier hemodynamic and respiratory status improvements and with lower mortality than that due to late-onset sepsis. Early neonatal septic shock detection and polymyxin B–immobilized fiber column direct hemoperfusion induction may improve the prognosis of affected infants.
Utilization of a Neonatal Early-Onset Sepsis Calculator to Guide Initial Newborn Management
Authors: Leonardi Bianca M. , Binder Margaret , Griswold Katherine J. , Yalcinkaya Gulgun F. , Walsh Michele C. 
Published: September 2019

Introduction:
Within our hospital system, all infants born to mothers with chorioamnionitis were directly admitted to the neonatal intensive care unit (NICU) for evaluation and treatment of presumed sepsis for a minimum of 48 hours, regardless of clinical appearance. Implementation of a risk-stratification system for thesWe high-risk infants based on the early onset sepsis (EOS) calculator may decrease NICU admissions and antibiotics exposure in well-appearing neonates.

Methods:
We used The Model for Improvement as a framework for designing this initiative. Participants were inborn infants 35 weeks and older born to mothers with chorioamnionitis and/or fever. Plan Do Study Act (PDSA) cycles were utilized to educate staff, monitor for sepsis, and follow adherence to the calculator in the newborn nursery.

Results:
From June 2015 to June 2016, there were 312 at-risk infants identified and evaluated on the EOS calculator. Of these 312 infants, 228 did not require admission to the NICU based on their risk assessment using the online calculator. Implementation of the Kaiser EOS calculator protocol for at-risk infants decreased NICU admission rates, decreased practitioner practice variability, decreased the number of painful procedures, promoted family bonding, resulted in higher breastfeeding rates at hospital discharge, diminished financial burden, and promoted antibiotic stewardship.

Conclusion:
This study demonstrates that the implementation of the sepsis risk calculator at an academic medical center can decrease the number of asymptomatic infants transferred to the NICU for empiric antibiotic treatment.
Experience With Early Sorafenib Treatment With mTOR Inhibitors in Hepatocellular Carcinoma Recurring After Liver Transplantation
Authors: Invernizzi Federica , Iavarone Massimo , Zavaglia Claudio , Mazza Stefano , Maggi Umberto , Cesarini Lucia , Antonelli Barbara , Airoldi Aldo , Manini Matteo Angelo , Sangiovanni Angelo , Rossi Giorgio , Donato Maria Francesca , Saverio Belli Luca , Lampertico Pietro 
Published: September 2019

Background.
Sorafenib (SOR) is currently used for hepatocellular carcinoma (HCC) recurring after liver transplantation (LT) when HCC is unsuitable for surgical/locoregional treatments. We evaluated safety and effectiveness of early introduction of SOR after HCC-recurrence.

Methods.
All patients with HCC-recurrence after LT treated with SOR in 2 centers were included (January 2008 to June 2018). Baseline and on-treatment data were collected.

Results.
Fifty patients early treated with SOR for HCC-recurrence after LT (74% mammalian target of rapamycin inhibitor [mTORi], 54% HCC-treated at baseline) were enrolled. During 7.3 (0.3–88) months of SOR, all patients had at least one adverse event (AE), 56% graded 3–4. SOR was reduced in 68%, being AEs the main cause of reduction, and discontinued in 84% (60% symptomatic progression, 33% AE). Objective response was obtained in 16% and stable disease in 50%. Median time to radiological progression was 6 months (95% confidence Interval [CI], 4-8). Thirty-three patients (69%) died, 94% for HCC progression. Median overall survival (OS) was 18 months (95% CI, 8-27); 5-year OS was 18% (95% CI, 4%-32%). Baseline predictors of OS were SOR+mTORi (hazard ratio [HR], 0.4; 95% CI, 0.2-0.9; P = 0.04), previous curative treatments (HR, 0.3; 95% CI, 0.2-0.7; P = 0.003) and alpha-fetoprotein > 100 ng/mL (HR, 2.5; 95% CI, 1.1-5.0, P = 0.02). At multivariate analysis, HCC curative treatment was the only independent predictor (HR, 0.4; 95% CI 0.2-1.0; P = 0.04).

Conclusions.
Early and combined treatment with SOR and mTORi resulted in a favorable safety profile, while its effectiveness should be confirmed by meta-analysis of previous studies or by larger studies. Curative treatment for HCC resulted the only independent predictor of OS.
Cognitive and Behavioral Changes in Patients Treated With Droxidopa for Neurogenic Orthostatic Hypotension: A Retrospective Review
Authors: McDonell Katherine E. , Shibao Cyndya A. , Biaggioni Italo , Hartman Adam , Robertson David , Claassen Daniel O. 
Published: September 2019

Background:
Droxidopa is a norepinephrine precursor that improves symptoms of neurogenic orthostatic hypotension in conditions such as Parkinson disease, multiple system atrophy, and pure autonomic failure by inducing a pressor effect. Unlike other pressor agents, droxidopa crosses the blood-brain barrier; however, its central effects are, as of yet, uncharacterized.

Objective:
We present the results of a retrospective cohort study examining cognitive and behavioral side effects linked to droxidopa therapy.

Methods:
We performed a review of 101 patients who had been treated with droxidopa at an academic tertiary care center and identified cases of cognitive and behavioral changes associated with the therapy.

Results:
We identified six patients who had developed cognitive and behavioral symptoms, including memory difficulties, confusion, mania, and irritability, shortly after droxidopa initiation. All six patients displayed symptoms of synucleinopathy, manifesting with autonomic failure, rapid eye movement sleep behavior disorder, and parkinsonism. Patients had no significant cognitive or behavioral symptoms before droxidopa initiation. Behavioral disturbances were observed early in the droxidopa titration period and at relatively low doses. Symptoms resolved with dose reduction in four patients, and droxidopa was discontinued in two patients due to persistent irritability. No other medical comorbidities or alternative etiologies were identified to explain the symptoms.

Conclusions:
Droxidopa is designed to act peripherally as a pressor agent but may also exert important central effects. We hypothesize that the cognitive and behavioral manifestations observed in the patients with orthostatic hypotension resulted from an “overdose” of key noradrenergic networks linking orbitofrontal and mesolimbic regions.
PolySTest: Robust statistical testing of proteomics data with missing values improves detection of biologically relevant features
Authors: Schwämmle Veit , Hagensen Christina E , Rogowska-Wrzesinska Adelina , Jensen Ole N. 
Published: September 2019

AbstractStatistical testing remains one of the main challenges for high-confidence detection of differentially regulated proteins or peptides in large-scale quantitative proteomics experiments by mass spectrometry. Statistical tests need to be sufficiently robust to deal with experiment intrinsic data structures and variations and often also reduced feature coverage across different biological samples due to ubiquitous missing values. A robust statistical test provides accurate confidence scores of large-scale proteomics results, regardless of instrument platform, experimental protocol and software tools. However, the multitude of different combinations of experimental strategies, mass spectrometry techniques and informatics methods complicate the decision of choosing appropriate statistical approaches. We address this challenge by introducing PolySTest, a user-friendly web service for statistical testing, data browsing and data visualization. We introduce a new method, Miss Test, that simultaneously tests for missingness and feature abundance, thereby complementing common statistical tests by rescuing otherwise discarded data features. We demonstrate that PolySTest with integrated Miss Test achieves higher confidence and higher sensitivity for artificial and experimental proteomics data sets with known ground truth. Application of PolySTest to mass spectrometry based large-scale proteomics data obtained from differentiating muscle cells resulted in the rescue of 10%-20% additional proteins in the identified molecular networks relevant to muscle differentiation. We conclude that PolySTest is a valuable addition to existing tools and instrument enhancements that improve coverage and depth of large-scale proteomics experiments. A fully functional demo version of PolySTest and Miss Test is available via http://computproteomics.bmb.sdu.dk/Apps/PolySTest.
Multiple features within Sed5p mediate it’s COPI-independent trafficking and Golgi localization
Authors: Gao Guanbin , Banfield David K. 
Published: September 2019

ABSTRACTProtein retention and the transport of proteins and lipids into and out of the Golgi is intimately linked to the biogenesis and homeostasis of this sorting hub of eukaryotic cells. Of particular importance are membrane proteins that mediate membrane fusion events with and within the Golgi – the Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs). In the Golgi of budding yeast cells a single syntaxin - the SNARE Sed5p - oversees membrane fusion within the Golgi. Determining how Sed5p is localized to and trafficked within the Golgi is critical to informing our understanding of the mechanism(s) of biogenesis and homeostasis of this organelle. Here we establish that the Golgi retention and trafficking of Sed5p between the Golgi and the ER is independent of COPI function, the composition of the transmembrane domain, and binding of the Sec1-Munc18 (SM) protein Sly1p. Rather, the steady state localization of Sed5p to the Golgi appears to be primarily conformation-based relying on intra-molecular associations between the Habc domain and SNARE-motif.
Blimp-1 is essential for Th2 cell development and allergic asthma
Authors: He Kun , Hettinga Angela , Kale Sagar Laxman , Hu Sanmei , Xie Markus M. , Dent Alexander L. , Ray Anuradha , Poholek Amanda C. 
Published: September 2019

AbstractA Th2 immune response is central to allergic airway inflammation, which afflicts millions worldwide. However, the mechanisms that augment GATA3 expression in an antigen-primed developing Th2 cell are not well understood. Here, we describe an unexpected role for Blimp-1, a transcriptional repressor that constrains autoimmunity, as an upstream promoter of GATA3 expression that is critical for Th2 cell development in the lung, but dispensable for TFHfunction and IgE production.Mechanistically, Blimp-1 acts through Bcl6, which is necessary to drive GATA3 expression.Surprisingly, the anti-inflammatory cytokine IL-10, but not the pro-inflammatory cytokines IL-6 or IL-21, is required via STAT3 activation to upregulate Blimp-1 and promote Th2 cell development. These data reveal a hitherto unappreciated role for an IL-10-STAT3-Blimp-1 circuit as an initiator of an inflammatory Th2 response in the lung to allergens. Thus, Blimp-1 in a context-dependent fashion can drive inflammation by promoting rather than terminating effector T cell responses.SummaryThe transcriptional repressor Blimp-1 acts via a pro-inflammatory IL-10-STAT3 axis as a critical positive regulator of Th2 cells in the lung in response to allergens driving pathophysiology associated with asthma disease.
Understanding the role of urban design in disease spreading
Authors: Brizuela Noel G. , García-Chan Néstor , Pulido Humberto Gutiérrez , Chowell Gerardo 
Published: September 2019

AbstractCities are complex systems whose characteristics impact the health of people who live in them. Nonetheless, urban determinants of health often vary within spatial scales smaller than the resolution of epidemiological datasets. Thus, as cities expand and their inequalities grow, the development of theoretical frameworks that explain health at the neighborhood level is becoming increasingly critical. To this end, we developed a methodology that uses census data to introduce urban geography as a leading-order predictor in the spread of influenza-like pathogens. Here, we demonstrate our framework using neighborhood-level census data for Guadalajara (GDL, Western Mexico). Our simulations were calibrated using weekly hospitalization data from the 2009 A/H1N1 influenza pandemic and show that daily mobility patterns drive neighborhood-level variations in the basic reproduction number R0, which in turn give rise to robust spatiotemporal patterns in the spread of disease. To generalize our results, we ran simulations in hypothetical cities with the same population, area, schools and businesses as GDL but different land use zoning. Our results demonstrate that the agglomeration of daily activities can largely influence the growth rate, size and timing of urban epidemics. Overall, these findings support the view that cities can be redesigned to limit the geographic scope of influenza-like outbreaks and provide a general mathematical framework to study the mechanisms by which local and remote health consequences result from characteristics of the physical environment.Author summaryEnvironmental, social and economic factors give rise to health inequalities among the inhabitants of a city, prompting researchers to propose ’smart’ urban planning as a tool for public health. Here, we present a mathematical framework that relates the spatial distributions of schools and economic activities to the spatiotemporal spread of influenza-like outbreaks. First, we calibrated our model using city-wide data for Guadalajara (GDL, Western Mexico) and found that a person’s place of residence can largely influence their role and vulnerability during an epidemic. In particular, the higher contact rates of people living near major activity hubs can give rise to predictable patterns in the spread of disease. To test the universality of our findings, we ’redesigned’ GDL by redistributing houses, schools and businesses across the city and ran simulations in the resulting geographies. Our results suggest that, through its impact on the agglomeration of economic activities, urban planning may be optimized to inhibit epidemic growth. By predicting health inequalities at the neighborhood-level, our methodology may help design public health strategies that optimize resources and target those who are most vulnerable. Moreover, it provides a mathematical framework for the design and analysis of experiments in urban health research.
Delayed antibiotic exposure induces population collapse in enterococcal communities with drug-resistant subpopulations
Authors: Hallinen Kelsey M. , Karslake Jason , Wood Kevin B. 
Published: September 2019

ABSTRACTBacteria exploit a diverse set of defenses to survive exposure to antibiotics. While the molecular and genetic underpinnings of antibiotic resistance are increasingly understood, less is known about how these molecular events influence microbial dynamics on the population scale. In this work, we show that the dynamics ofE. faecaliscommunities exposed to antibiotics can be surprisingly rich, revealing scenarios where–for example–increasing population size or delaying drug exposure can promote population collapse. Specifically, we combine experiments in computer-controlled bioreactors with simple mathematical models to reveal density-dependent feedback loops that couple population growth and antibiotic efficacy when communities include drug-resistant (β-lactamase producing) subpopulations. The resulting communities exhibit a wide range of behavior, including population survival, population collapse, or one of two qualitatively distinct bistable behaviors where survival is favored in either small or large populations. These dynamics reflect competing density-dependent effects of different subpopulations, with growth of drug-sensitive cells increasing but growth of drug-resistant cells decreasing effective drug inhibition. Guided by these results, we experimentally demonstrate how populations receiving immediate drug influx may sometimes thrive, while identical populations exposed to delayed drug influx (and lower average drug concentrations) collapse. These results illustrate that the spread of drug resistant determinants—even in a simplified single-species communities—may be governed by potentially counterintuitive dynamics driven by population-level interactions.