bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intermediary metabolism and fatty acid oxidation: novel targets of electron transport chain-driven injury during ischemia and reperfusion
Authors: Chen Qun , Younus Masood , Thompson Jeremy , Hu Ying , Hollander John M. , Lesnefsky Edward J. 
Published: December 2017

Cardiac ischemia-reperfusion (I/R) damages the electron transport chain (ETC), causing mitochondrial and cardiomyocyte injury. Reversible blockade of the ETC at complex I during ischemia protects the ETC and decreases cardiac injury. In the present study, we used an unbiased proteomic approach to analyze the extent of ETC-driven mitochondrial injury during I/R. Isolated-perfused mouse (C57BL/6) hearts underwent 25-min global ischemia (37°C) and 30-min reperfusion. In treated hearts, amobarbital (2 mM) was given for 1 min before ischemia to rapidly and reversibly block the ETC at complex I. Mitochondria were isolated at the end of reperfusion and subjected to unbiased proteomic analysis using tryptic digestion followed by liquid chromatography-mass spectrometry with isotope tags for relative and absolute quantification. Amobarbital treatment decreased cardiac injury and protected respiration. I/R decreased the content ( P < 0.05) of multiple mitochondrial matrix enzymes involved in intermediary metabolism compared with the time control. The contents of several enzymes in fatty acid oxidation were decreased compared with the time control. Blockade of ETC during ischemia largely prevented the decreases. Thus, after I/R, not only the ETC but also multiple pathways of intermediary metabolism sustain damage initiated by the ETC. If these damaged mitochondria persist in the myocyte, they remain a potent stimulus for ongoing injury and the transition to cardiomyopathy during prolonged reperfusion. Modulation of ETC function during early reperfusion is a key strategy to preserve mitochondrial metabolism and to decrease persistent mitochondria-driven injury during longer periods of reperfusion that predispose to ventricular dysfunction and heart failure.NEW & NOTEWORTHY Ischemia-reperfusion (I/R) damages mitochondria, which could be protected by reversible blockade of the electron transport chain (ETC). Unbiased proteomics with isotope tags for relative and absolute quantification analyzed mitochondrial damage during I/R and found that multiple enzymes in the tricarboxylic acid cycle, fatty acid oxidation, and ETC decreased, which could be prevented by ETC blockade. Strategic ETC modulation can reduce mitochondrial damage and cardiac injury.
RING-Finger Protein 6 Amplification Activates JAK/STAT3 Pathway by Modifying SHP-1 Ubiquitylation and Associates with Poor Outcome in Colorectal Cancer
Authors: Liang Qian , Ma Dan , Zhu Xiaoqiang , Wang Zhenhua , Sun Tian-Tian , Shen Chaoqin , Yan Tingting , Tian Xianglong , Yu TaChung , Guo Fangfang , Tang JiaYin , Lin Yanwei , Chen Huimin , Zhou Chao , Ge Zhizheng , Zhong Ming , Chen Jinxian , Liu Qiang , Wang Zheng , Fang Jing-Yuan , Chen Haoyan , Hong Jie 
Published: December 2017

Abstract
Objective: The E3 ubiquitin ligase RNF6 (RING-finger protein 6) plays a crucial role in carcinogenesis. However, the copy number and expression of RNF6 were rarely reported in colorectal cancer. We aimed to explore the mechanical, biological, and clinical role of RNF6 in colorectal cancer initiation and progression.
Design: The copy number and expression of RNF6 were analyzed from Tumorscape and The Cancer Genome Atlas (TCGA) datasets. Gene expressions were examined by real-time PCR, Western blot, and immunohistochemical staining. Gene expression profiling studies were performed to identify pivotal genes regulated by RNF6. Biological function of RNF6 on tumor growth and metastasis was detected in vivo and in vitro. Role of RNF6 in modulating SHP-1 expression was examined by coimmunoprecipitation and confocal microscopy, respectively.
Results: The copy number of RNF6 was significantly amplified in colorectal cancer, and the amplification was associated with RNF6 expression level. Amplification and overexpression of RNF6 positively correlated with patients with colorectal cancer with poor prognosis. The gene set enrichment analysis (GSEA) revealed cell proliferation, and invasion-related genes were enriched in RNF6 high-expressed colorectal cancer cells as well as in patients from TCGA dataset. Downregulation of RNF6 impaired the colorectal cancer cell proliferation and invasion in vitro and in vivo. RNF6 may activate the JAK/STAT3 pathway and increase pSTAT3 levels by inducing the ubiquitination and degradation of SHP-1.
Conclusions: Genomic amplification drives RNF6 overexpression in colorectal cancer. RNF6 may be a novel biomarker in colorectal carcinogenesis, and RNF6 may increase pSTAT3 level via promoting SHP-1 ubiquitylation and degradation. Targeting the RNF6/SHP-1/STAT3 axis provides a potential therapeutic option for RNF6-amplified tumors. Clin Cancer Res; 24(6); 1473–85. ©2017 AACR.
COX-2/sEH Dual Inhibitor PTUPB Potentiates the Antitumor Efficacy of Cisplatin
Authors: Wang Fuli , Zhang Hongyong , Ma Ai-Hong , Yu Weimin , Zimmermann Maike , Yang Jun , Hwang Sung Hee , Zhu Daniel , Lin Tzu-yin , Malfatti Michael , Turteltaub Kenneth W. , Henderson Paul T. , Airhart Susan , Hammock Bruce D. , Yuan Jianlin , de Vere White Ralph W. , Pan Chong-Xian 
Published: December 2017

Abstract
Cisplatin-based therapy is highly toxic, but moderately effective in most cancers. Concurrent inhibition of cyclooxygenase-2 (COX-2) and soluble epoxide hydrolase (sEH) results in antitumor activity and has organ-protective effects. The goal of this study was to determine the antitumor activity of PTUPB, an orally bioavailable COX-2/sEH dual inhibitor, in combination with cisplatin and gemcitabine (GC) therapy. NSG mice bearing bladder cancer patient-derived xenografts were treated with vehicle, PTUPB, cisplatin, GC, or combinations thereof. Mouse experiments were performed with two different PDX models. PTUPB potentiated cisplatin and GC therapy, resulting in significantly reduced tumor growth and prolonged survival. PTUPB plus cisplatin was no more toxic than cisplatin single-agent treatment as assessed by body weight, histochemical staining of major organs, blood counts, and chemistry. The combination of PTUPB and cisplatin increased apoptosis and decreased phosphorylation in the MAPK/ERK and PI3K/AKT/mTOR pathways compared with controls. PTUPB treatment did not alter platinum–DNA adduct levels, which is the most critical step in platinum-induced cell death. The in vitro study using the combination index method showed modest synergy between PTUPB and platinum agents only in 5637 cell line among several cell lines examined. However, PTUPB is very active in vivo by inhibiting angiogenesis. In conclusion, PTUPB potentiated the antitumor activity of cisplatin-based treatment without increasing toxicity in vivo and has potential for further development as a combination chemotherapy partner. Mol Cancer Ther; 17(2); 474–83. ©2017 AACR.
НАУКОВІ ФОРУМИ ВСЕУКРАЇНСЬКОЇ АСОЦІАЦІЇ ІНФЕКЦІОНІСТІВ У 2017 РОЦІ
Authors: Ivakhiv O. L. 
Published: December 2017

Коротко описаний хід всеукраїнських науково-практичних конференцій інфекціоністів на тему «Медична допомога інфекційним хворим в умовах реформування галузі охорони здоров’я», яка відбулася 18-19 травня ц. р. в Умані (Черкаська обл.), а також «Епідеміологічні та клінічні ускладнення інфекційних і паразитарних хвороб у сучасних умовах», яка проходила 5-6 жовтня ц.р. у Житомирі. Опубліковано рішення обох форумів та звернення пленуму Всеукраїнської асоціації інфекціоністів до очільників держави.
АНАЛІЗ СОЦІАЛЬНИХ ІНДИКАТОРІВ ЕПІДЕМІЇ ТБ / ВІЛ В УКРАЇНІ
Authors: Fedyak I. O. , Fedyak Р. І. 
Published: December 2017

Мета. Базуючись на аналізі даних медичної карти стаціонарного хворого Ф003/о, визначити і оцінити соціальні індикатори ко-інфекції ТБ/ВІЛ в Україні.Матеріали та методи: 1 200 медичних карт стаціонарних хворих на ТБ / ВІЛ у діапазоні нозологій «А15–А19 Туберкульоз» з ВІЛ-інфекцією, випадково відібрані з архівів 12 обласних протитуберкульозних диспансерів (зі збереженням таємниці персональних даних хворих); соціологічний метод аналізу документів (формалізований, контент-аналіз).Результати і обговорення. Досліджувану вибірку пацієнтів із ТБ / ВІЛ на 91% склали непрацюючі особи, які потребують постійного соціального супроводу. Бо з усіх виписаних лише 49,34% хворих закінчили стаціонарний етап лікування, який у середньому тривав 116±93 ліжко-днів; 25,25% осіб були виписані за порушення лікарняного режиму (18% – самовільно залишили стаціонар, 7,25% – порушили інші правила перебування). Оскільки найвища частка працюючих осіб із ТБ / ВІЛ виявилася в областях найвищої поширеності ВІЛ-інфекції: Одеській (17,14%), м. Києві (14,81%), Дніпропетровській (13,6%), Запорізькій (13,33 %), можна припустити, що ВІЛ-інфекція в Україні виходить за межі «груп ризику».Висновки. У межах областей аналізу за соціально-демографічними характеристиками хворі на ТБ / ВІЛ були: у 72,25±8,33% випадків чоловіками (ймовірність належати до жіночої статі зростала в областях найвищої поширеності ВІЛ); у 94,41±2,32% – віком 22–51 рр., в тому числі у 54,83±8,1% – 32–41 рр.; у 66,39±11,41% – проживали у містах; у 90,84±5,09% – відносились до соціально незахищених верст суспільства: були безробітними працездатного віку (69,17±8,97%), інвалідами (19,92±10,71%), пенсіонерами (0,83±1,31%), перебували у декретній відпустці (0,67±0,99%), студентами (0,25±0,56%), у тому числі належали до осіб без постійного місця проживання (2,33±2,56%), були внутрішніми переселенцями (0,92±1,7%), засудженими (0,75±0,69%). Водночас соціальні індикатори ТБ/ВІЛ, які стосуються перебування хворих у протитуберкульозних закладах, найперше залежали від регіону проживання.
ECOLOGICAL FEATURES OF MICROBIOCENOSIS OF THE SKIN OF MAMMARY GLANDS AND VAGINA IN PREGNANT WOMEN WITH THREAT OF PRETERM LABOR
Authors: Ivankiv V. Ya. , Malanchyn I. M. , Tkachuk N. I. 
Published: December 2017

Background. The threat of preterm birth is one of the most topical issues in the world medicine. According to the statistics, from 12-13 to 25-35 % of all pregnancies end prematurely. One of the causes of preterm labour is chronic inflammatory processes of female genital organs and disorder of microbiocenosis. Timely diagnosis and adequate treatment will reduce the risk of premature labour and avoid perinatal loss.Objective. We examined and analysed the microflora of the skin of mammary glands and mucous membrane of vagina in healthy pregnant women and patients with threat of preterm labour.Materials and methods. The examination of the pregnant was conducted at the TRMPC “Mother and Child” in several stages. First of all, we rinsed the skin of mammary glands and smeared from mucous membrane the posterior vault of vagina with sterile swabs pre-moistened in physiological solution. After that, the tampons were placed in sterile tubes and delivered to laboratory. Sowing was carried out on Petri dishes with sterile medium: ZHSA, bloods MPA, Endo, Saburo, thioglycolic medium.Conclusions. As a result of the research we found saprophytic Gram-positive and Gram-negative microorganisms (in women with a physiological course of pregnancy). In pregnant women with preterm labour, there was the increase in the number of St. haemolyticus from 13% to 87%, appearance of representatives of pathogenic flora – St. aureus (in 20%).
A New Dedication from Olbia and the Problems of City Organization and of Greco-Barbarian Relations in the 1st Century ad
Authors: Ivantchik Askold I. 
Published: December 2017

Abstract
This article contains a publication of a dedication by strategoi to Augustus, his heir Gaius Iulius Caesar and to the People, which was found in Olbia in 2006 and dates from the period between the year 1 bc and the year ad 4. It is the earliest inscription from post-Getic Olbia to have been discovered. Analysis of it makes it possible to suggest that Olbia was rebuilt after the rout by Burebistas in the last years bc under Roman control. The state organization of Olbia, which took shape after the city had been restored, reproduced certain features of the Roman constitution. Despite suggestions often voiced to the effect that Scythians or Sarmatians were included among its citizens, they were only granted the status of Olbian citizens later on – in the years 50-80 ad. The city was restored by Greeks who, at least in part, had come from Asia Minor and Thrace.
“Russia’s Misfortune Offers Humanitarians a Splendid Opportunity”: Jesuits, Communism, and the Russian Famine
Authors: Trythall Marisa Patulli 
Published: December 2017

Using archival documentation, this article discusses the beginning of the first grand international aid mission of the Catholic Church (1922–23), undertaken to assist the starving children of Bolshevik Russia. Under the auspices of the American Relief Administration (ara), the Papal Relief Mission to Russia fed approximately 158,000 persons a day. The pivotal figure between American Catholics and the Roman Curia, and subsequently between the Vatican and the Bolsheviks, was Edmund Aloysius Walsh, S.J., founder of the first us school of diplomacy, at Georgetown University. Walsh served as papal emissary in charge of this mission, which, among other duties, entailed liaising with the ara, keeping the Vatican informed, and negotiating with the Bolsheviks regarding the church’s position within a communist society. Walsh’s experience provides a firsthand view of the “Bolshevik world” and insight into the manner in which the Bolshevik Revolution was understood by the Vatican. The actions of the protagonists (Włodzimierz Ledóchowski, Jesuit superior general; Pietro Cardinal Gasparri, Vatican secretary of state; Mgr. Giuseppe Pizzardo, Vatican substitute secretary of state; Col. William Haskell, director of the ara’s Russian Relief Program; Mgr. Lorenzo Lauri, apostolic nuncio to Poland; and Walsh), are revealed through their own words, which show the difficulties encountered within both the Christian and Bolshevik spheres and clarify that common objectives were often shared only in appearance. Notwithstanding the good will that the mission’s success earned for the Vatican, the attempt to establish diplomatic relations was destined to fail, due in large part to the events narrated herein.
Twenty-three years (1993–2015) of homicide trends in the Transkei region of South Africa
Authors: Banwari Meel 
Published: December 2017

Background Transkei is regarded as a rural part of South Africa. It was one of the black homelands where rigorous apartheid was practised. The incidence of firearm-related deaths used to be very high, but after the implementation of the Firearm Control Act in 2002, the trend changed. However, the murder rate is still a major public-health problem in this region of South Africa. Objective The aim of this study was to investigate 23 years (1993–2015) of homicide trends in the Transkei region of South Africa. Method A review of records of medico-legal autopsies performed at Mthatha Forensic Pathology Laboratory from 1993 to 2015 was undertaken. Results Between 1993 and 2015, the number of autopsies performed on people who had died unnatural deaths was 24,693. The records of 12,618 (51%) autopsies on victims of homicide between 1993 and 2015 were available for study. The average rate of murder was 85/100,000 of the population in this region. Of these deaths, on average 34/100,000 were caused by sharp-edged instruments, 30/100,000 by gunshot wounds and 21/100,000 by blunt trauma. The rate of murder of males was significantly higher than that of females, with a ratio of 5.7:1, and over the period of 23 years covered by this study, the incidence was highest (30.5/100,000) in the young age group between 21 and 30 years. Conclusion The rate of homicide is very high in the Transkei region of South Africa. It needs urgent intervention to curb unnecessary deaths.
Serine/threonine phosphatase 5 (PP5C/PPP5C) regulates the ISOC channel through a PP5C‐FKBP51 axis
Authors: Hamilton Caleb L. , Abney Kevin A. , Vasauskas Audrey A. , Alexeyev Mikhail , Ni Li , Honkanen Richard E. , Scammell Jonathan G. , Cioffi Donna L. 
Published: December 2017

Pulmonary endothelial cells express a store‐operated calcium entry current (Isoc), which contributes to inter‐endothelial cell gap formation. Isoc is regulated by a heterocomplex of proteins that includes the immunophilin FKBP51. FKBP51 inhibits Isoc by mechanisms that are not fully understood. In pulmonary artery endothelial cells (PAECs) we have shown that FKBP51 increases microtubule polymerization, an event that is critical for Isoc inhibition by FKBP51. In neurons, FKBP51 promotes microtubule stability through facilitation of tau dephosphorylation. However, FKBP51 does not possess phosphatase activity. Protein phosphatase 5 (PP5C/PPP5C) can dephosphorylate tau, and similar to FKBP51, PP5C possesses tetratricopeptide repeats (TPR) that mediate interaction with heat shock protein‐90 (HSP90) chaperone/scaffolding complexes. We therefore tested whether PP5C contributes to FKBP51‐mediated inhibition of Isoc. Both siRNA‐mediated suppression of PP5C expression in PAECs and genetic disruption of PP5C in HEK293 cells attenuate FKBP51‐mediated inhibition of Isoc. Reintroduction of catalytically competent, but not catalytically inactive PP5C, restored FKBP51‐mediated inhibition of Isoc. PAEC cell fractionation studies identified both PP5C and the ISOC heterocomplex in the same membrane fractions. Further, PP5C co‐precipitates with TRPC4, an essential subunit of ISOC channel. Finally, to determine if PP5C is required for FKBP51‐mediated inhibition of calcium entry‐induced inter‐endothelial cell gap formation, we measured gap area by wide‐field microscopy and performed biotin gap quantification assay and electric cell‐substrate impedance sensing (ECIS®). Collectively, the data presented indicate that suppression of PP5C expression negates the protective effect of FKBP51. These observations identify PP5C as a novel member of the ISOC heterocomplex that is required for FKBP51‐mediated inhibition of Isoc.
Negative pressure ventilation enhances acinar perfusion in isolated rat lungs
Authors: Watson Kal E. , Segal Gilad S. , Conhaim Robert L. 
Published: December 2017

We compared acinar perfusion in isolated rat lungs ventilated using positive or negative pressures. The lungs were ventilated with air at transpulmomary pressures of 15/5 cm H2O, at 25 breaths/min, and perfused with a hetastarch solution at Ppulm art/PLA pressures of 10/0 cm H2O. We evaluated overall perfusability from perfusate flows, and from the venous concentrations of 4‐µm diameter fluorescent latex particles infused into the pulmonary circulation during perfusion. We measured perfusion distribution from the trapping patterns of those particles within the lung. We infused approximately 9 million red fluorescent particles into each lung, followed 20 min later by an infusion of an equal number of green particles. In positive pressure lungs, 94.7 ± 2.4% of the infused particles remained trapped within the lungs, compared to 86.8 ± 5.6% in negative pressure lungs (P ≤ 0.05). Perfusate flows averaged 2.5 ± 0.1 mL/min in lungs ventilated with positive pressures, compared to 5.6 ± 01 mL/min in lungs ventilated with negative pressures (P ≤ 0.05). Particle infusions had little effect on perfusate flows. In confocal images of dried sections of each lung, red and green particles were co‐localized in clusters in positive pressure lungs, suggesting that acinar vessels that lacked particles were collapsed by these pressures thereby preventing perfusion through them. Particles were more broadly and uniformly distributed in negative pressure lungs, suggesting that perfusion in these lungs was also more uniformly distributed. Our results suggest that the acinar circulation is organized as a web, and further suggest that portions of this web are collapsed by positive pressure ventilation.
An East–West comparison of self-care barriers in heart failure
Authors: Lim Shir Lynn , Chan Siew Pang , Lee Kim Yee , Ching Anne , Holden Richard J , Miller Karen F , Storrow Alan B , Lam Carolyn SP , Collins Sean P 
Published: December 2017

Background: Barriers in heart failure self-care contribute to heart failure hospitalizations, but geographic differences have not been well-studied. We aimed to compare self-care barriers in heart failure patients managed at tertiary centers in an Eastern (Singapore) versus a Western (USA) nation. Methods: Acute heart failure patients were prospectively assessed with a standardized instrument comprising of 47 distinct self-care barriers. The multi-equation generalized structural equation model was used to evaluate for geographic differences in barriers experienced, and association of barriers with outcomes. Results: Patient-related factors accounted for six out of 10 most prevalent self-care barriers among the 90 patients, with a median number of 11 barriers reported per patient. The Western patients reported a higher level of barriers when compared with their Eastern counterparts (median (interquartile range) 15 (9–24) versus 9 (4–16), p=0.001), after adjusting for demographics and co-morbidities. Many of these differences could be explained by geographic differences between the countries. There was no significant difference identified in all-cause mortality (19.4% versus 10.2%) and heart failure re-hospitalization (41.9% versus 45.8%) at six months between the groups. Conclusions: Self-care barriers are highly prevalent among acute heart failure patients, and differ substantially between East and West, but were not associated with geographic differences in outcomes.
Dorsal Scapular Nerve Transfer to Suprascapular Nerve
Authors: Augustine Haley , Choi Matthew , Bain James 
Published: December 2017

Background: Obstetrical brachial plexus injury involving the suprascapular nerve is conventionally treated using an accessory nerve transfer or grafting. In circumstances where the accessory nerve is unsuitable, transfer of nerves with redundant function may be an alternate method of restoring function. Methods: This case describes the surgical technique of restoring shoulder function by reinnervating the musculature of the suprascapular nerve with a dorsal scapular nerve transfer in a patient with an obstetrical brachial plexus injury. Results: At 15 months post-operatively, the patient shoulder movement improved from zero muscle contraction to full range of motion against gravity measured by the active movement scale. His composite mallet score was 23 out of 25, with perfect scores in abduction and external rotation. Secondary surgery was not required. Conclusions: This case demonstrates a novel alternative to suprascapular nerve reinnervation in circumstances where the accessory nerve is unavailable, damaged, or otherwise suboptimal. Successful results were achieved, thus warranting consideration in clinical practice as well as further exploration and study.