bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serum alpha1‐proteinase inhibitor concentrations in dogs with systemic inflammatory response syndrome or sepsis
Authors: Heilmann Romy M. , Grützner Niels , Thames Brittany E. , Steiner Jörg M. , Barr James W. 
Published: October 2017

AbstractObjectiveTo determine whether the concentration of serum canine alpha1‐proteinase inhibitor (cα1‐PI) has diagnostic or prognostic utility in dogs with sepsis or noninfectious systemic inflammatory response syndrome (SIRS).DesignProspective, observational study from May to December 2010.SettingUniversity teaching hospital ICU.AnimalsSixty‐nine client‐owned dogs: 19 dogs with SIRS or sepsis and 50 healthy control dogs.InterventionsNone.Measurements and Main ResultsSerum and plasma samples were collected from dogs with SIRS or sepsis on the day of hospital admission and once on the following 2 days, and on a single day in healthy controls. Patients were assessed using the 10‐parameter Acute Patient Physiologic and Laboratory Evaluation (APPLEfull) and 5‐parameter (APPLEfast) score. Serum cα1‐PI concentrations were measured, compared among groups of dogs, and evaluated for a correlation with the concentration of serum C‐reactive protein, plasma interleukin‐6, tumor necrosis factor‐α, the APPLE scores, and survival to discharge.Serum cα1‐PI concentrations were significantly lower in dogs with SIRS/sepsis (P < 0.001) than in healthy controls. While day 1 serum cα1‐PI concentrations did not differ between dogs with SIRS and those with sepsis (P = 0.592), septic dogs had significantly lower serum cα1‐PI concentrations on days 2 (P = 0.017) and 3 (P = 0.036) than dogs with SIRS. Serum cα1‐PI concentrations did not differ between survivors and nonsurvivors (P = 1.000), but were inversely correlated with the APPLEfull score (ρ = –0.48; P = 0.040) and plasma interleukin‐6 concentrations (ρ = –0.50; P = 0.037).ConclusionsThese results suggest a role of cα1‐PI as a negative acute phase protein in dogs. The concentration of serum cα1‐PI at the time of hospital admission does not have utility to identify dogs with sepsis from those with noninfectious SIRS, but may be a useful surrogate marker for early stratification of illness severity.
Both Sphingomyelin and Cholesterol in the Host Cell Membrane Are Essential for Rubella Virus Entry
Authors: Otsuki Noriyuki , Sakata Masafumi , Saito Kyoko , Okamoto Kiyoko , Mori Yoshio , Hanada Kentaro , Takeda Makoto 
Published: October 2017

ABSTRACTRubella virus (RuV) causes a systemic infection, and transplacental fetal infection causes congenital rubella syndrome. In this study, we showed that treatment of cells with sphingomyelinase inhibited RuV infection. Assays using inhibitors of serine palmitoyl transferase and ceramide transport protein demonstrated the contribution of sphingomyelin (SM) to RuV infection. Compelling evidence for direct binding of RuV to lipid membranes at neutral pH was obtained using liposome coflotation assays. The absence of either SM or cholesterol (Chol) abrogated the RuV-liposome interaction. SM and Chol (SM/Chol) were also critical for RuV binding to erythrocytes and lymphoid cells. Removal of Ca2+from the assay buffer or mutation of RuV envelope E1 protein Ca2+-binding sites abrogated RuV binding to liposomes, erythrocytes, and lymphoid cells. However, RuV bound to various nonlymphoid adherent cell lines independently of extracellular Ca2+or SM/Chol. Even in these adherent cell lines, both the E1 protein Ca2+-binding sites and cellular SM/Chol were essential for the early stage of RuV infection, possibly affecting envelope-membrane fusion in acidic compartments. Myelin oligodendrocyte glycoprotein (MOG) has recently been identified as a cellular receptor for RuV. However, RuV bound to MOG-negative cells in a Ca2+-independent manner. Collectively, our data demonstrate that RuV has two distinct binding mechanisms: one is Ca2+dependent and the other is Ca2+independent. Ca2+-dependent binding observed in lymphoid cells occurs by the direct interaction between E1 protein fusion loops and SM/Chol-enriched membranes. Clarification of the mechanism of Ca2+-independent RuV binding is an important next step in understanding the pathology of RuV infection.IMPORTANCERubella has a significant impact on public health as infection during early pregnancy can result in babies being born with congenital rubella syndrome. Even though effective rubella vaccines are available, rubella outbreaks still occur in many countries. We studied the entry mechanism of rubella virus (RuV) and found that RuV binds directly to the host plasma membrane in the presence of Ca2+at neutral pH. This Ca2+-dependent binding is specifically directed to membranes enriched in sphingomyelin and cholesterol and is critical for RuV infection. Importantly, RuV also binds to many cell lines in a Ca2+-independent manner. An unidentified RuV receptor(s) is involved in this Ca2+-independent binding. We believe that the data presented here may aid the development of the first anti-RuV drug.
Mechanisms of CNS Viral Seeding by HIV+CD14+CD16+Monocytes: Establishment and Reseeding of Viral Reservoirs Contributing to HIV-Associated Neurocognitive Disorders
Authors: Veenstra Mike , León-Rivera Rosiris , Li Ming , Gama Lucio , Clements Janice E. , Berman Joan W. 
Published: October 2017

ABSTRACTHIV reservoirs persist despite antiretroviral therapy (ART) and are established within a few days after infection. Infected myeloid cells in the central nervous system (CNS) may contribute to the establishment of a CNS viral reservoir. The mature CD14+CD16+monocyte subset enters the CNS in response to chemokines, including CCL2. Entry of infected CD14+CD16+monocytes may lead to infection of other CNS cells, including macrophages or microglia and astrocytes, and to release of neurotoxic early viral proteins and additional cytokines. This contributes to neuroinflammation and neuronal damage leading to HIV-associated neurocognitive disorders (HAND) in ~50% of HIV-infected individuals despite ART. We examined the mechanisms of monocyte entry in the context of HIV infection and report for the first time that HIV+CD14+CD16+monocytes preferentially transmigrate across the blood-brain barrier (BBB). The junctional proteins JAM-A and ALCAM and the chemokine receptor CCR2 are essential to their preferential transmigration across the BBB to CCL2. We show here that JAM-A and ALCAM are increased on HIV+CD14+CD16+monocytes compared to their expression on HIVexpCD14+CD16+monocytes—cells that are uninfected but exposed to HIV, viral proteins, and inflammatory mediators. Antibodies against JAM-A and ALCAM and the novel CCR2/CCR5 dual inhibitor cenicriviroc prevented or significantly reduced preferential transmigration of HIV+CD14+CD16+monocytes. This indicates that JAM-A, ALCAM, and CCR2 may be potential therapeutic targets to block entry of these infected cells into the brain and prevent or reduce the establishment and replenishment of viral reservoirs within the CNS.IMPORTANCEHIV infects different tissue compartments of the body, including the central nervous system (CNS). This leads to establishment of viral reservoirs within the CNS that mediate neuroinflammation and neuronal damage, contributing to cognitive impairment. Our goal was to examine the mechanisms of transmigration of cells that contribute to HIV infection of the CNS and to continued replenishment of CNS viral reservoirs, to establish potential therapeutic targets. We found that an HIV-infected subset of monocytes, mature HIV+CD14+CD16+monocytes, preferentially transmigrates across the blood-brain barrier. This was mediated, in part, by increased junctional proteins JAM-A and ALCAM and chemokine receptor CCR2. We show that the CCR2/CCR5 dual inhibitor cenicriviroc and blocking antibodies against the junctional proteins significantly reduce, and often completely block, the transmigration of HIV+CD14+CD16+monocytes. This suggests new opportunities to eliminate infection and seeding or reseeding of viral reservoirs within the CNS, thus reducing neuroinflammation, neuronal damage, and cognitive impairment.
Comparative Transcriptome Analysis Quantifies Immune Cell Transcript Levels, Metastatic Progression, and Survival in Osteosarcoma
Authors: Scott Milcah C. , Temiz Nuri A. , Sarver Anne E. , LaRue Rebecca S. , Rathe Susan K. , Varshney Jyotika , Wolf Natalie K. , Moriarity Branden S. , O'Brien Timothy D. , Spector Logan G. , Largaespada David A. , Modiano Jaime F. , Subramanian Subbaya , Sarver Aaron L. 
Published: October 2017

Abstract
Overall survival of patients with osteosarcoma (OS) has improved little in the past three decades, and better models for study are needed. OS is common in large dog breeds and is genetically inducible in mice, making the disease ideal for comparative genomic analyses across species. Understanding the level of conservation of intertumor transcriptional variation across species and how it is associated with progression to metastasis will enable us to more efficiently develop effective strategies to manage OS and to improve therapy. In this study, transcriptional profiles of OS tumors and cell lines derived from humans (n = 49), mice (n = 103), and dogs (n = 34) were generated using RNA sequencing. Conserved intertumor transcriptional variation was present in tumor sets from all three species and comprised gene clusters associated with cell cycle and mitosis and with the presence or absence of immune cells. Further, we developed a novel gene cluster expression summary score (GCESS) to quantify intertumor transcriptional variation and demonstrated that these GCESS values associated with patient outcome. Human OS tumors with GCESS values suggesting decreased immune cell presence were associated with metastasis and poor survival. We validated these results in an independent human OS tumor cohort and in 15 different tumor data sets obtained from The Cancer Genome Atlas. Our results suggest that quantification of immune cell absence and tumor cell proliferation may better inform therapeutic decisions and improve overall survival for OS patients.
Significance: This study offers new tools to quantify tumor heterogeneity in osteosarcoma, identifying potentially useful prognostic biomarkers for metastatic progression and survival in patients. Cancer Res; 78(2); 326–37. ©2017 AACR.
Molecular Subtypes of Pulmonary Large-cell Neuroendocrine Carcinoma Predict Chemotherapy Treatment Outcome
Authors: Derks Jules L. , Leblay Noémie , Thunnissen Erik , van Suylen Robert Jan , den Bakker Michael , Groen Harry J.M. , Smit Egbert F. , Damhuis Ronald , van den Broek Esther C. , Charbrier Amélie , Foll Matthieu , McKay James D. , Fernandez-Cuesta Lynnette , Speel Ernst-Jan M. , Dingemans Anne-Marie C. 
Published: October 2017

AbstractPurpose: Previous genomic studies have identified two mutually exclusive molecular subtypes of large-cell neuroendocrine carcinoma (LCNEC): the RB1 mutated (mostly comutated with TP53) and the RB1 wild-type groups. We assessed whether these subtypes have a predictive value on chemotherapy outcome.Experimental Design: Clinical data and tumor specimens were retrospectively obtained from the Netherlands Cancer Registry and Pathology Registry. Panel-consensus pathology revision confirmed the diagnosis of LCNEC in 148 of 232 cases. Next-generation sequencing (NGS) for TP53, RB1, STK11, and KEAP1 genes, as well as IHC for RB1 and P16 was performed on 79 and 109 cases, respectively, and correlated with overall survival (OS) and progression-free survival (PFS), stratifying for non–small cell lung cancer type chemotherapy including platinum + gemcitabine or taxanes (NSCLC-GEM/TAX) and platinum-etoposide (SCLC-PE).Results: RB1 mutation and protein loss were detected in 47% (n = 37) and 72% (n = 78) of the cases, respectively. Patients with RB1 wild-type LCNEC treated with NSCLC-GEM/TAX had a significantly longer OS [9.6; 95% confidence interval (CI), 7.7–11.6 months] than those treated with SCLC-PE [5.8 (5.5–6.1); P = 0.026]. Similar results were obtained for patients expressing RB1 in their tumors (P = 0.001). RB1 staining or P16 loss showed similar results. The same outcome for chemotherapy treatment was observed in LCNEC tumors harboring an RB1 mutation or lost RB1 protein.Conclusions: Patients with LCNEC tumors that carry a wild-type RB1 gene or express the RB1 protein do better with NSCLC-GEM/TAX treatment than with SCLC-PE chemotherapy. However, no difference was observed for RB1 mutated or with lost protein expression. Clin Cancer Res; 24(1); 33–42. ©2017 AACR.
ОРГАНІЗАЦІЯ ОСВІТНЬОГО ПРОЦЕСУ У ВІННИЦЬКОМУ НАЦІОНАЛЬНОМУ МЕДИЧНОМУ УНІВЕРСИТЕТІ ІМ. М. І. ПИРОГОВА У СВІТЛІ РЕФОРМУВАННЯ ВИЩОЇ МЕДИЧНОЇ ОСВІТИ
Authors: Moroz V. M. , Polesia T. L. , Fomina L. V. , Huminskyi Yu. Y. 
Published: October 2017

На сучасному етапі відбувається інтеграція вищої освіти України у Європейський освітній простір. Затверджені Закон України «Про вищу освіту» та Національна стратегія реформування системи охорони здоров’я в Україні на період 2015–2020 років, що передбачає впровадження сучасних європейських інноваційних технологій у світлі розбудови якості вищої освіти у вищих навчальних закладах, у тому числі й медичних. У Вінницькому національному медичному університеті імені М. І. Пирогова реалізуються сучасні шляхи розбудови забезпечення якості вищої освіти – впроваджено Європейську кредитно-трансферну систему (ЄКТС), опанування навичок роботи з програмою «СКІФ», Навчально-тренінговий центр практичної підготовки лікарів.
ДОСВІД ФОРМУВАННЯ ЛІДЕРСЬКОЇ КОМПЕТЕНТНОСТІ ВИКЛАДАЧІВ ХАРКІВСЬКОЇ МЕДИЧНОЇ АКАДЕМІЇ ПІСЛЯДИПЛОМНОЇ ОСВІТИ
Authors: Khvysiuk О. M. , Marchenko V. H. , Kolomiichenko Yu. A. , Strashok L. A. , Honcharova O. Yu. , Zherebkin V. V. , Hyria M. P. , Kudriavtseva T. O. 
Published: October 2017

У даній статті проведено аналіз наукових праць щодо дослідження лідерської компетентності та професійного рівня викладачів вищих медичних навчальних закладів і висвітлюється досвід формування лідерських здібностей викладачів Харківської медичної академії післядипломної освіти. Доведено, що в умовах інтелектуальної конкуренції безперервне самовдосконалення, педагогічний пошук і використання інноваційних технологій є обов’язковими вимогами, які пред’являються до викладача-лідера. Приведено опис різних підходів із використанням самоконтролю та самооцінки власної діяльності й стимулювання розвитку лідерських якостей особистості викладача.
Pulmonary Hypertension and Pregnancy Outcomes: Insights From the National Inpatient Sample
Authors: Thomas Erin , Yang Jie , Xu Jianjin , Lima Fabio V. , Stergiopoulos Kathleen 
Published: October 2017

Background

Pregnant women with pulmonary hypertension (
PH
) are at risk for adverse cardiac outcomes, particularly at the time of labor and delivery. The purpose of this study is to define the impact of
PH
on pregnancy outcomes and the risk of major adverse cardiac events (
MACE
).

Methods and Results

The National Inpatient Sample was screened for hospital admissions of women delivering during the years 2003 to 2012. The primary outcome was
MACE
, a composite of death, cardiac arrest, cardiogenic shock, myocardial infarction, respiratory failure, arrhythmia, stroke, and embolic event. Data on 1519 patients with
PH
and 6 757 582 without heart disease or
PH
were available. There were 59.6% with isolated
PH
; 10.7% with
PH
and congenital heart disease; 18.1% with
PH
and valvular heart disease; 3% with
PH
and valvular heart disease and congenital heart disease; 6.6%
PH
and cardiomyopathy; and 1.9% with
PH
and cardiomyopathy and valvular heart disease. Compared with women without heart disease or
PH
, women with
PH
experienced significantly higher
MACE
(24.8 versus 0.4%,
P
<0.0001). Among the subsets of women with
PH
, the highest
MACE
was noted in women with the combination of
PH
and cardiomyopathy and valvular heart disease, and
PH
and cardiomyopathy, primarily because of heart failure and arrhythmia. Women with
PH
were significantly more likely to experience eclampsia syndromes, preterm delivery, and intrauterine fetal demise (
P
<0.0001 for all).
PH
subtype was significantly associated with
MACE
in multivariable analysis (
P
<0.001).

Conclusions

In a contemporary data set of pregnant women in the United States,
PH
was associated with an increase in
MACE
during the hospitalization for delivery, with an exceptionally elevated risk among women with associated cardiomyopathy.
Kokkinakis and the Narratives of Proper and Improper Proselytizing
Authors: Scharffs Brett G. 
Published: October 2017

Abstract
This article explores how the European Court of Human Rights (ECtHR) distinguishes between proper and improper proselytizing. It points out the importance of the competing factual narratives and how the way the facts are presented can determine how the Court responds to the proselytizing activity.
Treatment options for back pain provided online in Canadian magazines: Comparison against evidence from a clinical practice guideline
Authors: Sniderman Jhase A , Roffey Darren M , Lee Richard , Papineau Gabrielle D , Miles Isabelle H , Wai Eugene K , Kingwell Stephen P 
Published: October 2017

Background: Evidence-based treatments for adult back pain have long been confirmed, with research continuing to narrow down the scope of recommended practices. However, a tension exists between research-driven treatments and unsubstantiated modalities and techniques promoted to the public. This disparity in knowledge translation, which results in unsupported treatments continuing to be performed, may be linked to the information dispensed by the mass media. Objectives: The aim of this study was to review the top 20 most circulated Canadian-produced general-interest and health-specific magazines to determine whether featured treatment options align with recommendations for back pain management in a Canadian clinical practice guideline (CPG). Methods: Online electronic searches of magazine websites were performed using the following terms: ‘back pain’, ‘low back pain’ (English); ‘ mal au dos’, ‘ lombalgie’, ‘ mal de dos’ and ‘ maux de dos’ (French). Independent reviewers screened for articles focusing on treatment, abstracted recommendations from included articles and then compared featured treatments with those outlined in the CPG. Results: A total of 1,775 articles were screened, with 82 articles from 15 magazines included. Articles cited scientific studies or consulted spine-care professionals in 7/15 and 9/15 magazines, respectively. There were 18 categories of treatments reported with 4/18 (22%) treatment options in agreement with CPG recommendations for acute/sub-acute and chronic back pain. Yoga/Stretching/Tai Chi/Pilates and Exercise/Physical activity were the most commonly reported treatment categories. Conclusion: Encouragingly, the majority of treatment options reported for low back pain were non-surgical. Overall, few articles recommended reassurance, back pain education or back-specific postural/strengthening/flexibility exercises. Popular magazines should provide details on article authors, cite scientific reports, consult spine-care professionals and provide relevant links to literature for readers to access more scientific information.
Diagnostic performance of advanced modeled iterative reconstruction applied images for detecting urinary stones on submillisievert low-dose computed tomography
Authors: Ahn Ju Hee , Kim Seung Ho , Kim Seung Jin , Nam In Chul , Lee Sung Jae , Pak Seong Yong 
Published: October 2017

Background Repeated computed tomography (CT) scans may be an issue in young adults with urinary stones. Therefore, it is important to know how far the dose can be reduced while maintaining the diagnostic performance. Purpose To generate a hypothesis that it is feasible to decrease the radiation dose to a sub-millisievert (mSv) level with the addition of advanced modeled iterative reconstruction (ADMIRE) while maintaining the sensitivity to standard-dose CT (SDCT) for the detection of urinary stones. Material and Methods Ninety-two consecutive patients with urinary stones underwent non-enhanced CT that consisted of standard (120 kVp, 200 mAs) and lose-dose (LDCT) (80 kVp, 60 mAs). The LDCT images were reconstructed separately with five different strengths of ADMIRE (hereafter, S1–S5) and filtered back projection (FBP). Two blinded radiologists independently recorded a number of urinary stones in the six LDCT datasets and SDCT. The sensitivity of each set for detecting urinary stones was compared using the McNemar test. Results A total of 240 urinary stones were analyzed. The sensitivities of the six LDCT datasets showed no difference (FBP, S1–S5, for reader 1: 78%, 79%, 79%, 80%, 80%, and 80%; for reader 2: 64%, 63%, 64%, 64%, 65%, and 66%, P > 0.05, respectively), which were lower than those of SDCT for both readers (reader 1: 88%; reader 2: 81%, P < 0.0001, respectively). Conclusion Despite the addition of ADMIRE, it may not be feasible to decrease the radiation dose to a sub-mSv level while maintaining the sensitivity to SDCT for the detection of urinary stones.
Legal Issues Surrounding the Number of Dosage Units Dispensed
Authors: Fink Joseph L. 
Published: October 2017

Pharmacists often are called upon to adjust the number of dosage units dispensed pursuant to a prescription. Common examples are requests to dispense half or double the amount requested by the prescriber. In some cases, reductions in quantity may be dictated by the provisions of a prescription drug insurance program, either private or governmental. A review of the literature reveals very little information on the legality of such actions by pharmacists. Focusing on both the federal Food, Drug and Cosmetic Act and the federal Controlled Substances Act, a review of the law in this area is presented. Some states also have provisions, either in statutes or regulations, that address the issue. Specific examples are presented and discussed, with the goal being to clarify the law in this area with which the pharmacist must deal on a daily basis.
Buspirone: A New Type of Anxiolytic
Authors: Dommisse Cynthia S. , DeVane C. Lindsay , McLeod Donald C. 
Published: October 2017

Buspirone is a member of a new class of agents known as azaspirodecanediones, and represents the first nonbenzodiazepine anxiolytic to be introduced in the U.S. in recent years. It does not resemble the benzodiazepines or older anxiolytics such as meprobamate and the barbiturates in pharmacologic profile. Buspirone lacks anticonvulsant activity, interacts minimally with central nervous system depressants such as alcohol, and does not cause muscle relaxation. The drug is reported to have minimal sedating effect, to cause no impairment of driving-related skills, and to have no euphoriant effect or addictive potential. With this low side-effect profile, buspirone should not require Drug Enforcement Agency scheduling controls. Clinical trials indicate buspirone is efficacious in the treatment of mild to moderate anxiety disorders. Answers to questions of possible side effects related to dopaminergic intractions must await post-marketing experience. Buspirone is a suitable addition to drug formularies as its pre-marketing data suggest several advantages compared with anxiolytics currently available.
The Lack of Inactivation of Tobramycin by Cefazolin, Cefamandole, and Moxalactam in Vitro
Authors: Earp Colleen M. , Barriere Steven L. 
Published: October 2017

We examined the effects of mixing tobramycin with three cephalosporins, cefazolin, cefamandole, and moxalactam. Each cephalosporin was prepared from standard powder and diluted with human serum to concentrations of 50, 250, and 500 μg/ml and added to 10 μg/ml of tobramycin in human serum. Temperature environments of 4 °C (refrigeration), 24 °C (room temperature), and 37 °C (body temperature) were used and sampled at 0 hours (control), and at 8, 24, and 48 hours. The results indicated no inactivation of tobramycin by any of the cephalosporins, regardless of temperature, concentration, or contact time. These results indicate that significant inactivation of tobramycin does not occur when it is combined in vitro with moxalactam, cefamandole, or cefazolin.