bluuebunny/crossref_metadata_2025_split huggingface dataset:
StartReact effects are dependent on engagement of startle reflex circuits: support for a subcortically mediated initiation pathway
Authors: Smith Victoria , Maslovat Dana , Carlsen Anthony N. 
Published: October 2019

The “StartReact” effect refers to the rapid involuntary triggering of a prepared movement in response to a loud startling acoustic stimulus (SAS). This effect is typically confirmed by the presence of short-latency electromyographic activity in startle reflex-related muscles such as the sternocleidomastoid (SCM); however, there is debate regarding the specific neural pathways involved in the StartReact effect. Some research has implicated a subcortically mediated pathway, which would predict different response latencies depending on the presence of a startle reflex. Alternatively, other research has suggested that this effect involves the same pathways responsible for voluntary response initiation and simply reflects higher preparatory activation levels, and thus faster voluntary initiation. To distinguish between these competing hypotheses, the present study assessed preparation level during a simple reaction time (RT) task involving wrist extension in response to a control tone or a SAS. Premotor RT and startle circuitry engagement (as measured by SCM activation) were determined for each trial. Additionally, preparation level at the go signal on each trial was measured using motor-evoked potentials (MEP) elicited by transcranial magnetic stimulation (TMS). Results showed that SAS trial RTs were significantly shorter ( P = 0.009) in the presence of startle-related SCM activity. Nevertheless, preparation levels (as indexed by MEP amplitude) were statistically equivalent between trials with and without SCM activation. These results indicate that the StartReact effect relates to engagement of the startle reflex circuitry rather than simply being a result of an increased level of preparatory activation. NEW & NOTEWORTHY The neural mechanism underlying the early triggering of goal-directed actions by a startling acoustic stimulus (SAS) is unclear. We show that although significant reaction time differences were evident depending on whether the SAS elicited a startle reflex, motor preparatory activation was the same. Thus, in a highly prepared state, the short-latency responses associated with the StartReact effect appear to be related to engagement of startle reflex circuitry, not differences in motor preparatory level.
A Phase I Study of LY3009120, a Pan-RAF Inhibitor, in Patients with Advanced or Metastatic Cancer
Authors: Sullivan Ryan J. , Hollebecque Antoine , Flaherty Keith T. , Shapiro Geoffrey I. , Rodon Ahnert Jordi , Millward Michael J. , Zhang Wei , Gao Ling , Sykes Amanda , Willard Melinda D. , Yu Danni , Schade Andrew E. , Crowe KrisAnne , Flynn Daniel L. , Kaufman Michael D. , Henry James R. , Peng Sheng-Bin , Benhadji Karim A. , Conti Ilaria , Gordon Michael S. , Tiu Ramon V. , Hong David S. 
Published: October 2019

Abstract
Mutations in ERK signaling drive a significant percentage of malignancies. LY3009120, a pan-RAF and dimer inhibitor, has preclinical activity in RAS- and BRAF-mutated cell lines including BRAF-mutant melanoma resistant to BRAF inhibitors. This multicenter, open-label, phase I clinical trial (NCT02014116) consisted of part A (dose escalation) and part B (dose confirmation) in patients with advanced/metastatic cancer. In part A, oral LY3009120 was dose escalated from 50 to 700 mg twice a day on a 28-day cycle. In part B, 300 mg LY3009120 was given twice a day. The primary objective was to identify a recommended phase II dose (RP2D). Secondary objectives were to evaluate safety, pharmacokinetics, and preliminary efficacy. Identification of pharmacodynamic biomarkers was exploratory. In parts A and B, 35 and 16 patients were treated, respectively (N = 51). In part A, 6 patients experienced eight dose-limiting toxicities. The RP2D was 300 mg twice a day. Common (&gt;10%) any-grade drug-related treatment-emergent adverse events were fatigue (n = 15), nausea (n = 12), dermatitis acneiform (n = 10), decreased appetite (n = 7), and maculopapular rash (n = 7). The median duration of treatment was 4 weeks; 84% of patients completed one or two cycles of treatment. Exposures observed at 300 mg twice a day were above the preclinical concentration associated with tumor regression. Eight patients had a best overall response of stable disease; there were no complete or partial clinical responses. Despite adequate plasma exposure levels, predicted pharmacodynamic effects were not observed.
УРАХУВАННЯ КАР’ЄРНИХ ПРАГНЕНЬ ТА ІНШИХ МЕДИКО-СОЦІАЛЬНИХ ЧИННИКІВ ДЛЯ ПІДВИЩЕННЯ ІНТЕРЕСУ СТУДЕНТІВ-МЕДИКІВ ДО ГРОМАДСЬКОЇ ОХОРОНИ ЗДОРОВ’Я
Authors: Kriachkova L. V. , Lekhan V. M. , Krotova L. V. 
Published: October 2019

Мета: вивчити кар’єрні орієнтації студентів–медиків і чинників що на них впливають, для визначення шляхів підвищення інтересу майбутніх лікарів до громадської охорони здоров’я. Матеріали і методи. Проведено соціологічне та психодіагностичне обстеження серед 163 студентів-медиків I–IV курсів навчання ДЗ «Дніпропетровська медична академія МОЗ України» із застосуванням методик: «Якір кар’єри» Е. Шейна в адаптації А. А. Жданович; багатофакторного опитувальника емпатії М. Davis, (1983) в адаптації Т. Д. Карягиної та Н. В. Кухтової, (2016) та методики Всесвітньої організації охорони здоров’я (ВООЗ) вивчення якості життя, пов’язаної зі здоров’ям (ЯЖ) за 8-ма запитаннями (ВООЗ ЯЖ-8). Конфіденційність інформації була захищена деперсоніфікацією ідентифікаторів студентів. Статистичний аналіз, що включав методи описової та аналітичної статистики, здійснювали за допомогою STATISTICA 6.1 (StatSoftInc., серійний № AGAR909E415822FA). Результати. Дослідження показало, що питаннями планування власної кар’єри опікується половина з опитаних та їх частка закономірно зростає з віком і курсом навчання. Серед кар’єрних орієнтацій студентів-медиків домінує націленість на інтеграцію стилів життя – спосіб життя, який гармонійно поєднує інтереси сім’ї, кар’єри та саморозвитку (24,5 %), за ним слідує стабільність місця роботи (23,9 %) та служіння на користь людям (22,7 %). Для третини обстежених характерною є орієнтація на вертикальну чи горизонтальну кар’єру. Не виявлено розбіжностей у кар’єрних прагненнях за віком та статтю. Одними із чинників, що впливають на формування кар’єрних прагнень, є емпатія студентів та їх якість життя, яка, у свою чергу, формується переважно за рахунок навколишнього середовища. Більшість опитаних оцінила власну якість життя як середню та добру (78,8 %). Меншою мірою студенти задоволені соціальними взаємозв’язками (49,1 % позитивних оцінок). Частка студентів із рівнем емпатії вище середнього становила для когнітивної складової 43,6 %, для емоційної – 41,7 %. Виявлено множинні кореляційні зв’язки між емпатичними характеристиками, сферами якості життя, кар’єрними якорями студентів та іншими чинниками. Висновки. Під час навчального процесу у вищих медичних навчальних закладах доцільно запроваджувати підходи, спрямовані на підвищення обізнаності та залучення студентів до громадської охорони здоров’я. Це вимагає стратегій активного навчання, на кшталт спеціальних груп інтересів (гуртків), текстових та фото есе, паралельної підготовки студентів як за програмою магістра медицини, так і за програмою магістра громадського здоров’я.
Pacemaker Implantation and Dependency After Transcatheter Aortic Valve Replacement in the REPRISE III Trial
Authors: Meduri Christopher U. , Kereiakes Dean J. , Rajagopal Vivek , Makkar Raj R. , O'Hair Daniel , Linke Axel , Waksman Ron , Babliaros Vasilis , Stoler Robert C. , Mishkel Gregory J. , Rizik David G. , Iyer Vijay S. , Schindler John , Allocco Dominic J. , Meredith Ian T. , Feldman Ted E. , Reardon Michael J. 
Published: October 2019

Background
As transcatheter aortic valve replacement expands to younger and/or lower risk patients, the long‐term consequences of permanent pacemaker implantation are a concern. Pacemaker dependency and impact have not been methodically assessed in transcatheter aortic valve replacement trials. We report the incidence and predictors of pacemaker implantation and pacemaker dependency after transcatheter aortic valve replacement with the Lotus valve.

Methods and Results

A total of 912 patients with high/extreme surgical risk and symptomatic aortic stenosis were randomized 2:1 (Lotus:CoreValve) in
REPRISE III
(The Repositionable Percutaneous Replacement of Stenotic Aortic Valve through Implantation of Lotus Valve System—Randomized Clinical Evaluation) trial. Systematic assessment of pacemaker dependency was pre‐specified in the trial design. Pacemaker implantation within 30 days was more frequent with Lotus than CoreValve. By multivariable analysis, predictors of pacemaker implantation included baseline right bundle branch block and depth of implantation; diabetes mellitus was also a predictor with Lotus. No association between new pacemaker implantation and clinical outcomes was found. Pacemaker dependency was dynamic (30 days: 43%; 1 year: 50%) and not consistent for individual patients over time. Predictors of pacemaker dependency at 30 days included baseline right bundle branch block, female sex, and depth of implantation. No differences in mortality or stroke were found between patients who were pacemaker dependent or not at 30 days. Rehospitalization was higher in patients who were not pacemaker dependent versus patients without a pacemaker or those who were dependent.

Conclusions
Pacemaker implantation was not associated with adverse clinical outcomes. Most patients with a new pacemaker at 30 days were not dependent at 1 year. Mortality and stroke were similar between patients with or without pacemaker dependency and patients without a pacemaker.

Clinical Trial Registration

URL
:
https://www.clinicaltrials.gov/
. Unique identifier
NCT
02202434.
Enhancer of zeste homolog 2 enhances the migration and chemotaxis of dental mesenchymal stem cells
Authors: Ma Huarui , Duan Shaoyu , Yan Fei , Yang Haoqing , Cao Yangyang , Ge Lihua , Gao Runtao 
Published: October 2019

Objective To investigate the function of enhancer of zeste homolog 2 (EZH2) in the migration and chemotaxis of human dental tissue-derived mesenchymal stem cells. Methods The expression of EZH2, C-X-C motif chemokine ligand 11 (CXCL11), CXCL16, and CXCR1 in stem cells from the apical papilla (SCAPs) was determined by real-time reverse transcription PCR and western blotting. The effects of EZH2 on the homing of SCAPs and the effects of EZH2-overexpressing SCAP culture supernatant on periodontal ligament stem cells (PDLSCs) were tested by scratch migration assays and transwell chemotaxis assays. Results EZH2 overexpression significantly enhanced the migration and chemotaxis of SCAPs and upregulated the expression of CXCL11, CXCL16, and CXCR1 in SCAPs. EZH2 depletion had the opposite effect, impairing the migration and chemotaxis of SCAPs and downregulating the expression of CXCL11, CXCL16, and CXCR1. The culture supernatant of EZH2-overexpressing SCAPs advanced the migration and chemotaxis of PDLSCs. Conclusions EZH2 evidently promoted the migration and chemotaxis of SCAPs by upregulating the expression of CXCL11, CXCL16, and CXCR1. Moreover, EZH2-overexpressing SCAPs enhanced the homing, migration, and chemotaxis of PDLSCs via paracrine signaling.
PD-L1 and PD-1 expressed in trigeminal ganglia may inhibit pain in an acute migraine model
Authors: Shi Suming , Han Yuhang , Wang Dan , Guo Ping , Wang Jiali , Ren Tongli , Wang Wuqing 
Published: October 2019

Background Neurogenic inflammation, mediated by the activation of primary neurons, is thought to be an important factor in migraine pathophysiology. Programmed cell death ligand-1 (PD-L1) can suppress the immune response through the Programmed cell death-1 receptor. However, the role of PD-L1/PD-1 in migraine remains unclear. In this study we evaluated the expression and role of PD-L1/PD-1 in the trigeminal ganglia in an animal model of acute migraine. Methods Acute nitroglycerin induces acute mechanical hyperalgesia that can be used as a readout of migraine-like pain. We investigated the expression of PD-L1 and PD-1 in the trigeminal ganglia in a mouse model by means of immunofluorescence labeling, quantitative reverse transcription-polymerase chain reaction and western blotting. We explored the effects of PD-1 in a migraine model by the von Frey test and by analyzing the expression of calcitonin gene-related peptide, interleukin-1β (IL-1β), interleukin-18 (IL-18), Tumor Necrosis Factor-α (TNF-α), interleukin-6 (IL-6) and transient receptor potential vanilloid (TRPV4) after the intravenous injection of a PD-1 inhibitor. Results PD-L1 and PD-1 immunoreactivity were present in healthy trigeminal ganglia neurons. The mRNA levels of PD-L1 and PD-1 were significantly elevated 2 h, 4 h and 6 h after acute nitroglycerin treatment ( p < 0.05). The protein levels of PD-L1 were significantly increased 2 h, 4 h and 6 h after treatment, and PD-1 was significantly increased at 2 h and 6 h. The blockade of PD-1 increased acute nitroglycerin-induced hyperalgesia, and this effect was accompanied by a more significant increase in calcitonin gene-related peptide, IL-1β, TNF-α, IL-6 and IL-18 in the trigeminal ganglia. Conclusion These findings suggest that PD-L1 and PD-1 might inhibit migraine-like pain by downregulating CGRP and inflammatory factors in the trigeminal ganglia. The use of PD-L1 and PD-1 as analgesics should be further studied.
Causes and predictors of 30-day readmissions in patients with cardiogenic shock requiring extracorporeal membrane oxygenation support
Authors: Tashtish Nour , Al-Kindi Sadeer G , Karnib Mohamad , Zanath Erica , Mitchell Steven , Di Felice Christopher , Zacharias Michael , Oliveira Guilherme H , Medalion Benjamin , Lytle Francis , Elamm Chantal 
Published: October 2019

Background: Cardiogenic shock is associated with significant mortality, morbidity, and healthcare cost. Utilization of extracorporeal membrane oxygenation in cardiogenic shock has increased in the United States. We sought to identify the rates and predictors of hospital readmissions in patients with cardiogenic shock after weaning from extracorporeal membrane oxygenation. Methods: Using the 2016 Nationwide Readmission Database, we identified all patients (⩾18 years) with cardiogenic shock (ICD-10 CM R57.0) that have been implanted with extracorporeal membrane oxygenation (ICD-10-PSC of 5A15223) and were discharged alive (January–November 2016). We explored the rates, causes, and predictors of all-cause readmissions within 30 days. Results: Out of 69,040 admissions with cardiogenic shock, 1641 (2.4%) underwent extracorporeal membrane oxygenation (581 were implanted during or after cardiac surgery). A total of 734 (44.7%) patients of all extracorporeal membrane oxygenations survived to discharge, and 661 were available for analysis. Out of those, 158 (23.9%) were readmitted within 30 days of discharge. More than 50% of these readmissions happened within the first 11 days. Out of 158 patients who were readmitted, 12 (7.4%) died during the readmission hospitalization. Leading causes of readmission were cardiovascular (31.6%) (heart failure: 24.1%, arrhythmia: 20.6%, neurovascular: 10.3%, hypertension: 10.3%, and endocarditis: 6.8%), followed by complications of medical/device care (17.7%), infection (11.3%), and gastrointestinal/liver (10.1%) complications. Factors associated with readmissions include the following: discharge to skilled nursing facility or with home healthcare (odds ratio: 2.10; 95% confidence interval: 1.18–3.74), durable ventricular assisted device implantation, asthma, and chronic liver disease. Conclusion: Patients with cardiogenic shock who underwent extracorporeal membrane oxygenation had a readmission rate. Identifying patients at high risk of readmissions might help improve outcomes.
Is There Cross-Country Income Convergence Among the BRICS Nations? An Examination
Authors: Das Ramesh Chandra 
Published: October 2019

Narrowing the developmental gaps of a relatively poor country with a relatively rich one is one of the priorities to the policymakers of the former. One way to reduce the developmental gaps is making different countries in a group to converge to a single steady-state value. Under this background, this study aims to examine whether the BRICS nations are converging in per capita GDP for the period 1990–2016. Applying the neoclassical methodology of β convergence and σ convergence, the study observes that the countries are not unconditionally β converging but converging in conditional terms with the variables such as foreign direct investment (FDI) flow and working population acting as the deciding factor. Furthermore, the study shows that the countries are converging in σ definition meaning the cross-country dispersion in per capita gross domestic product (GDP) has fallen significantly. Hence, formation of BRICS has made the countries relatively better off compared to pre-BRICS phase. JEL Classification: E01, O4, J21
Non-surgical management of isolated proximal phalangeal fractures with immediate mobilization
Authors: Byrne Brent , Jacques Angela , Gurfinkel Reuven 
Published: October 2019

We performed a prospective, observational study using a non-surgical, conservative protocol with immediate mobilization for the treatment of 101 isolated stable or initially unstable proximal phalangeal fractures. The patients were evaluated at the time of discharge from therapy treatment, mean 7 weeks (range 3–15) after conservative treatment. These patients achieved a median proximal interphalangeal joint extension of −4° (IQR 0, −8), a mean total active motion of 253° (SD 20) and minimal pain. We conclude that a non-surgical, conservative protocol can be used for patients with isolated proximal phalangeal fractures without uncorrectable finger rotation or fracture angulation exceeding 25° in the sagittal plane or 10° in the coronal plane following closed reduction. Our data supports that a conservative protocol can be the good option for isolated stable or initially unstable proximal phalangeal fractures. Level of evidence: IV
Assessment of Regular and NPH Insulin Concentration via Two Methods of Quantification: The Washington State Insulin Concentration Study (WICS)
Authors: Neumiller Joshua J. , Chen Gang , Newsome Cheyenne , Hughes Sally , Lazarus Philip , White John R. 
Published: October 2019

Background: Recent reports have suggested that insulin vials purchased in community pharmacies do not meet the minimum required intact insulin concentration (≥95 U/mL) as defined by the United States Pharmacopeia. We sought to independently obtain multidose human insulin vials from a variety of community pharmacies across the state of Washington and quantitatively measure intact insulin. Methods: Sixty 10-mL vials of insulin ( n = 30 regular human insulin and n = 30 neutral protamine Hagedorn insulin) were purchased and assayed. To ensure random selection of lots and supply chain sources, insulin samples were purchased on a variety of calendar dates from various pharmacy locations across Washington State, inclusive of both chain and independent pharmacies. All samples were assessed for intact insulin concentration via both Ultra Performance Liquid Chromatography coupled with UV detection (UPLC-UV) and Ultra Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS). Results: When considering all samples ( N = 60), the mean concentration was 101.8 ± 4.4and 91.5 ± 1.9 U/mL as determined by UPLC-UV and UPLC-MS, respectively. Measured concentrations ranged from 90.0 to 108.4 U/mL when assayed by UV UPLC and 86.1 to 95.4 U/mL for UPLC-MS. Conclusion: To our knowledge, this is the first study following the report by Carter et al that assessed human insulin concentrations by both UPLC-UV and UPLC-MS. These findings are important because they demonstrate that the results obtained from these two methods differ and that the method used must be considered when interpreting findings.
Tibiotalocalcaneal Arthrodesis Using a Novel Retrograde Intramedullary Nail
Authors: Steele John R. , Lazarides Alexander L. , DeOrio James K. 
Published: October 2019

Background. Tibiotalocalcaneal (TTC) arthrodesis is a common treatment option for complex hindfoot pathology. Overall union rates range from 50% to 86% but can be even lower in certain populations. A novel retrograde intramedullary nail has recently been developed. The purpose of this study was to report fusion rates, time to weight-bearing, and complications with the use of the A3 Fusion Nail. Methods. All patients 18 years or older who underwent TTC arthrodesis with an A3 Fusion Nail at a single institution from 2010 to 2015 with a minimum 3-month follow-up were included in this study. Rates of successful fusion, time to union, time to weight-bearing, and complications were evaluated. A total of 20 patients with an average age of 58.1 years and an average follow-up of 12.5 months met inclusion criteria. Results. Successful TTC arthrodesis was achieved in 14 of 20 patients (70%) overall. Average time to union was 8.1 months, and average time to weight-bearing was 6.8 weeks. Of 20 patients, 17 (85%) required femoral head allograft for bulk bone defects, and the union rate in this subset of patients was 76.5%. The rates of revision surgery (10%) and complications were low. Conclusion. The A3 Fusion Nail demonstrated a favorable safety profile and achieved TTC arthrodesis at a rate consistent with historical data despite being used in a patient population at high risk for nonunion. In patients with bulk bone defects at high risk for nonunion, the A3 Fusion Nail demonstrated superior rates of fusion (76.5%) to those reported in the literature (50%). Level of Evidence: Level III: Retrospective cohort study
Allergic Comorbidity of Asthma or Wheezing, Allergic Rhinitis, and Eczema: Result From 333 029 Allergic Children in Shanghai, China
Authors: Ji Heyu , Hu Yi , Zhang Ting , Wang Yizhong , Shen Li , Wang Shu , Chen Min , Wei Mingyue , Yu Guangjun 
Published: October 2019

Background Allergic diseases have become a worldwide public health concern. A defining feature of allergic diseases is they often coexist in children from birth to adolescence. Objective To investigate the prevalence of comorbid allergic diseases in allergic children in Shanghai, China. Methods A retrospective study of 333 029 children diagnosed with allergic diseases aged 0 to 12 years (mean age: 3.04 years, 59.3% boys) was conducted using the electronic medical records of Shanghai Children’s Hospital from January 2013 to July 2018. Comorbidity of allergic diseases is defined as the coexistence of 2 or 3 following diseases in the same child such as asthma (AS)/wheezing, allergic rhinitis (AR), or eczema (EC). Results The proportion of children with comorbid allergic diseases was 6.7% (22 351/333 029). Among them, EC + AS/wheezing was the most common (61.3%, 13 711/22 351). Children with a comorbidity had significantly earlier disease onset age than subjects with only 1 disease (2.72 vs 3.06, P < .05). The serum total immunoglobulin E (tIgE) levels of children with comorbid allergic diseases were higher than those with only 1 disease. In children with a disease onset age of 0 to 9 years, the levels of tIgE for children with AS/wheezing + EC were higher than children with AS/wheezing only or EC only; in children with disease onset age of 2 to 5 and 10 to 12 years, the levels of tIgE for children with AS/wheezing + AR were higher than children with AS/wheezing only or AR only; in children with a disease onset age of 2 to 5 years, the levels of tIgE for children with AR + EC were higher than children with AR only or EC only. Conclusion Comorbidity of allergic diseases is common in children in Shanghai, China. The onset age of comorbidity is earlier than that of only 1 disease, and the levels of serum tIgE are higher in patients with an allergic comorbidity.