bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel Arenavirus Entry Inhibitors Discovered by Using a Minigenome Rescue System for High-Throughput Drug Screening
Authors: Rathbun Jessica Y. , Droniou Magali E. , Damoiseaux Robert , Haworth Kevin G. , Henley Jill E. , Exline Colin M. , Choe Hyeryun , Cannon Paula M. 
Published: June 2015

ABSTRACT

Certain members of the
Arenaviridae
family are category A agents capable of causing severe hemorrhagic fevers in humans. Specific antiviral treatments do not exist, and the only commonly used drug, ribavirin, has limited efficacy and can cause severe side effects. The discovery and development of new antivirals are inhibited by the biohazardous nature of the viruses, making them a relatively poorly understood group of human pathogens. We therefore adapted a reverse-genetics minigenome (MG) rescue system based on Junin virus, the causative agent of Argentine hemorrhagic fever, for high-throughput screening (HTS). The MG rescue system recapitulates all stages of the virus life cycle and enables screening of small-molecule libraries under biosafety containment level 2 (BSL2) conditions. The HTS resulted in the identification of four candidate compounds with potent activity against a broad panel of arenaviruses, three of which were completely novel. The target for all 4 compounds was the stage of viral entry, which positions the compounds as potentially important leads for future development.

IMPORTANCE
The arenavirus family includes several members that are highly pathogenic, causing acute viral hemorrhagic fevers with high mortality rates. No specific effective treatments exist, and although a vaccine is available for Junin virus, the causative agent of Argentine hemorrhagic fever, it is licensed for use only in areas where Argentine hemorrhagic fever is endemic. For these reasons, it is important to identify specific compounds that could be developed as antivirals against these deadly viruses.
The Torsin Activator LULL1 Is Required for Efficient Growth of Herpes Simplex Virus 1
Authors: Turner Elizabeth M. , Brown Rebecca S. H. , Laudermilch Ethan , Tsai Pei-Ling , Schlieker Christian 
Published: June 2015

ABSTRACT
TorsinA is a membrane-tethered AAA+ ATPase implicated in nuclear envelope dynamics as well as the nuclear egress of herpes simplex virus 1 (HSV-1). The activity of TorsinA and the related ATPase TorsinB strictly depends on LAP1 and LULL1, type II transmembrane proteins that are integral parts of the Torsin/cofactor AAA ring, forming a composite, membrane-spanning assembly. Here, we use CRISPR/Cas9-mediated genome engineering to create single- and double knockout (KO) cell lines of TorA and TorB as well as their activators, LAP1 and LULL1, to investigate the effect on HSV-1 production. Consistent with LULL1 being the more potent Torsin activator, a LULL1 KO reduces HSV-1 growth by one order of magnitude, while the deletion of other components of the Torsin system in combination causes subtle defects. Notably, LULL1 deficiency leads to a 10-fold decrease in the number of viral genomes per host cell without affecting viral protein production, allowing us to tentatively assign LULL1 to an unexpected role that precedes HSV-1 nuclear egress.

IMPORTANCE
In this study, we conduct the first comprehensive genetic and phenotypic analysis of the Torsin/cofactor system in the context of HSV-1 infection, establishing LULL1 as the most important component of the Torsin system with respect to viral production.
Postoperative Analgesia after Low-Frequency Electroacupuncture as Adjunctive Treatment in Inguinal Hernia Surgery with Abdominal Wall Mesh Reconstruction
Authors: Dalamagka Maria , Mavrommatis Christos , Grosomanidis Vassilios , Karakoulas Konstantinos , Vasilakos Dimitrios , Samara Maria , Saros Christos , Crommydas George 
Published: June 2015

Objective To determine whether an electroacupuncture (EA) technique that was developed for a surgical population under general anaesthesia reduces pain after mesh inguinal hernia open repair. Methods A total of 54 patients with right or left inguinal hernia were randomised to group I (preoperative, intraoperative, postoperative EA), group II (preoperative, postoperative EA), or a sham control group (group III; preoperative and postoperative placement of needles, but without skin penetration). The Visual Analogue Scale (VAS) (primary outcome) and the State-Trait Anxiety Spielberger Inventory were evaluated preoperatively and at 30 min, 90 min, 10 h and 24 h after surgery. Pain threshold and tolerance were evaluated using an algometer at these same time points and preoperatively before and after EA. Levels of the stress hormones cortisol, corticotrophin and prolactin were determined at 30 min, 90 min and 10 h after surgery and preoperatively before and after EA. Results The results showed significant differences between the true EA and control groups. The true EA groups (I and II) showed statistically significantly greater improvements in the primary (VAS pain, p<0.05) and secondary outcome measures (Anxiety scale; algometer measurements, p<0.05 and stress hormones, p<0.01) compared to the control group. There were no statistically significant differences between groups I and II. Conclusions Electroacupuncture reduces postoperative pain after mesh inguinal hernia repair and decreases stress hormone levels and anxiety during the postoperative period. Trial Registration Number ClinicalTrials.gov identifier NCT01722253.
Transient osteoporosis of the hip in a non-pregnant woman
Authors: Reddy Kanakeya Bachha , Sareen Atul , Kanojia Rajesh Kumar , Prakash Jatin 
Published: June 2015

Transient osteoporosis of the hip is a rare, self-limiting condition, occurring most commonly in middle-aged men, but also sometimes in women, usually in late pregnancy. It is characterised by gradual onset of hip pain aggravated by weight bearing without any associated history of trauma and systemic illness. It is usually of unknown aetiology, but pregnancy is a recognised risk factor for women. Other conditions that can mimic transient osteoporosis of the hip on MRI are osteonecrosis, osteomyelitis and neoplasms. We present a case of a 38-year-old non-pregnant woman with transient osteoporosis of the hip, managed conservatively, leading to a full recovery. Treatment is conservative, including protected weight bearing, physical therapy and non-steroidal analgesics. The patient was completely painless and symptom free at 2-year follow-up.
Welfare state retrenchment and increasing mental health inequality by educational credentials in Finland: a multicohort study
Authors: Kokkinen Lauri , Muntaner Carles , Kouvonen Anne , Koskinen Aki , Varje Pekka , Väänänen Ari 
Published: June 2015

ObjectivesEpidemiological studies have shown an association between educational credentials and mental disorders, but have not offered any explanation for the varying strength of this association in different historical contexts. In this study, we investigate the education-specific trends in hospitalisation due to psychiatric disorders in Finnish working-age men and women between 1976 and 2010, and offer a welfare state explanation for the secular trends found.SettingPopulation-based setting with a 25% random sample of the population aged 30–65 years in 7 independent consecutive cohorts (1976–1980, 1981–1985, 1986–1990, 1991–1995, 1996–2000, 2001–2005, 2006–2010).ParticipantsParticipants were randomly selected from the Statistics Finland population database (n=2 865 746). These data were linked to diagnosis-specific records on hospitalisations, drawn from the National Hospital Discharge Registry using personal identification numbers. Employment rates by educational credentials were drawn from the Statistics Finland employment database.Primary and secondary outcome measuresHospitalisation and employment.ResultsWe found an increasing trend in psychiatric hospitalisation rates among the population with only an elementary school education, and a decreasing trend in those with higher educational credentials. The employment rate of the population with only an elementary school education decreased more than that of those with higher educational credentials.ConclusionsWe propose that restricted employment opportunities are the main mechanism behind the increased educational inequality in hospitalisation for psychiatric disorders, while several secondary mechanisms (lack of outpatient healthcare services, welfare cuts, decreased alcohol duty) further accelerated the diverging long-term trends. All of these inequality-increasing mechanisms were activated by welfare state retrenchment, which included the liberalisation of financial markets and labour markets, severe austerity measures and narrowing down of public sector employment commitment.
Does suicide have a stronger association with seasonality than sunlight?
Authors: White Richard A , Azrael Deborah , Papadopoulos Fotios C , Lambert Gavin W , Miller Matthew 
Published: June 2015

ObjectivesSuicide rates have widely been reported to peak in spring and summer. A frequent hypothesis is that increased sunlight exposure alters biological mechanisms. However, few attempts have been made to systematically untangle the putative suicidogenic risk of sunlight exposure from that of seasonality. We examined whether average hours of daily sunlight in a month confer additional risk over month of year when predicting monthly suicide rates.DesignHistorical population-based ecological longitudinal study.Setting and participantsWe used 3 longitudinal studies (n=31 060 suicides) with monthly suicide and meteorological data from Greece (1992–2001), Victoria, Australia (1990–1998) and Norway (1969–2009).InterventionWe used a negative binomial regression to observe (1) the association of month of year with suicides, adjusting for different sunlight exposures, and (2) the association of sunlight exposure with suicides, adjusting for month of year. We then investigated claims that suicides were associated with daily sunlight exposures, defined by us as 2550 sunlight exposure combinations corresponding to a 1–50 days exposure window with lags of 0–50 days.ResultsUsing monthly data, the association between month of year and suicides remained after adjusting for mean daily hours of sunlight and change in the mean daily hours of sunlight. Adjusted for month of year, the associations between sunlight exposure and suicides became non-significant and attenuated towards the null (the coefficient estimate for mean daily hours of sunlight decreased in absolute magnitude by 72%). The findings were consistent across all 3 cohorts, both when analysed separately and combined. When investigating daily sunlight exposures, we found no significant results after correcting for multiple testing.ConclusionsUsing monthly data, the robustness of our month of year effects, combined with the transient and modest nature of our sunlight effects, suggested that the association between sunlight exposure and suicide was a proxy for the association between seasonality and suicide.
Association of thrombelastographic parameters with post-stenting ischemic events
Authors: Wang Bo , Li Xiao-Qing , Ma Ning , Mo Dapeng , Gao Feng , Sun Xuan , Xu Xiaotong , Liu Lian , Song Ligang , Li Xin-Gang , Zhao Zhigang , Zhao Xingquan , Miao Zhong-Rong 
Published: June 2015

Background and purposeThrombelastography (TEG) is widely used for the measurement of platelet function. However, few studies have investigated the TEG parameters in patients receiving extracranial or intracranial artery stenting for ischemic cerebrovascular disease. This study sought to describe the association of TEG parameters before the procedure with post-procedural ischemic events after extracranial or intracranial artery stenting.MethodsPatients in whom stenting was performed for extracranial or intracranial artery stenosis (70–99%) were recruited into the study. Blood samples were obtained for TEG to assess platelet function before stenting. The primary endpoint was ischemic stroke or transient ischemic attack in the territory of the stented artery.ResultsA total of 218 patients were included in the study. During a mean follow-up period of 132 days (range 98–226 days), 18 (8.3%) primary endpoint events were recorded. Compared with patients without ischemic events, the ADP-induced platelet-fibrin clot strength (MAADP) was significantly higher (41.57±15.10 vs 33.50±13.86, p=0.020) and the ADP inhibition rate (ADP%) was significantly lower in patients with ischemic events (39.54±23.15 vs 55.29±24.43, p=0.009). Multivariate analysis identified MAADPand ADP% as significant independent predictors of subsequent ischemic events with HRs of 1.036 and 0.965, respectively. From receiver operating characteristic curve analysis, MAADP>49.95 mm had the best predictive value of ischemic events.ConclusionsOur study suggests that TEG parameters MAADPand ADP% are associated with subsequent ischemic events in patients with extracranial or intracranial stents.Clinical trial numberNCT01925872.
VEGFR-1 Pseudogene Expression and Regulatory Function in Human Colorectal Cancer Cells
Authors: Ye Xiangcang , Fan Fan , Bhattacharya Rajat , Bellister Seth , Boulbes Delphine R. , Wang Rui , Xia Ling , Ivan Cristina , Zheng Xiaofeng , Calin George A. , Wang Jing , Lu Xiongbin , Ellis Lee M. 
Published: June 2015

Abstract
A large number of pseudogenes have been found to be transcribed in human cancers. However, only a few pseudogenes are functionally characterized. Here, we identified a transcribed pseudogene of VEGFR1, or fms-related tyrosine kinase 1 (FLT1), in human colorectal cancer cells. Interestingly, this pseudogene (designated as FLT1P1) was found to be transcribed bidirectionally and functionally modulated cognate VEGFR1 protein expression in the cells. Mechanistically, expression of FLT1P1 antisense transcript not only inhibited the VEGFR1 expression, but also inhibited non-cognate VEGF-A expression through interaction with miR-520a. Perturbation of FLT1P1 expression by RNA interference (RNAi) markedly inhibited tumor cell proliferation and xenograft tumor growth. This study identifies FLT1P1 antisense as a critical regulator of VEGFR1 and VEGF-A expression in colorectal cancer cells, and highlights its role in regulation of the pathogenesis of colorectal cancer.
Implications: The VEGFR1 pseudogene, FLT1P1, is a novel and functional regulator of VEGF signaling and its targeting could be an alternative strategy to modulate its cognate/target gene expression and downstream activity in cancer. Mol Cancer Res; 13(9); 1274–82. ©2015 AACR.
Melanoma-Derived Wnt5a Promotes Local Dendritic-Cell Expression of IDO and Immunotolerance: Opportunities for Pharmacologic Enhancement of Immunotherapy
Authors: Holtzhausen Alisha , Zhao Fei , Evans Kathy S. , Tsutsui Masahito , Orabona Ciriana , Tyler Douglas S. , Hanks Brent A. 
Published: June 2015

Abstract
The β-catenin signaling pathway has been demonstrated to promote the development of a tolerogenic dendritic cell (DC) population capable of driving regulatory T-cell (Treg) differentiation. Further studies have implicated tolerogenic DCs in promoting carcinogenesis in preclinical models. The molecular mechanisms underlying the establishment of immune tolerance by this DC population are poorly understood, and the methods by which developing cancers can co-opt this pathway to subvert immune surveillance are currently unknown. This work demonstrates that melanoma-derived Wnt5a ligand upregulates the durable expression and activity of the indoleamine 2,3-dioxygenase-1 (IDO) enzyme by local DCs in a manner that depends upon the β-catenin signaling pathway. These data indicate that Wnt5a-conditioned DCs promote the differentiation of Tregs in an IDO-dependent manner, and that this process serves to suppress melanoma immune surveillance. We further show that the genetic silencing of the PORCN membrane–bound O-acyl transferase, which is necessary for melanoma Wnt ligand secretion, enhances antitumor T-cell immunity, and that the pharmacologic inhibition of this enzyme synergistically suppresses melanoma progression when combined with anti–CTLA-4 antibody therapy. Finally, our data suggest that β-catenin signaling activity, based on a target gene expression profile that includes IDO in human sentinel lymph node–derived DCs, is associated with melanoma disease burden and diminished progression-free survival. This work implicates the Wnt–β-catenin signaling pathway as a novel therapeutic target in the melanoma immune microenvironment and demonstrates the potential impact of manipulating DC function as a strategy for optimizing tumor immunotherapy. Cancer Immunol Res; 3(9); 1082–95. ©2015 AACR.
PD-1 or PD-L1 Blockade Restores Antitumor Efficacy Following SSX2 Epitope–Modified DNA Vaccine Immunization
Authors: Rekoske Brian T. , Smith Heath A. , Olson Brian M. , Maricque Brett B. , McNeel Douglas G. 
Published: June 2015

AbstractDNA vaccines have demonstrated antitumor efficacy in multiple preclinical models, but low immunogenicity has been observed in several human clinical trials. This has led to many approaches seeking to improve the immunogenicity of DNA vaccines. We previously reported that a DNA vaccine encoding the cancer–testis antigen SSX2, modified to encode altered epitopes with increased MHC class I affinity, elicited a greater frequency of cytolytic, multifunctional CD8+ T cells in non–tumor-bearing mice. We sought to test whether this optimized vaccine resulted in increased antitumor activity in mice bearing an HLA-A2–expressing tumor engineered to express SSX2. We found that immunization of tumor-bearing mice with the optimized vaccine elicited a surprisingly inferior antitumor effect relative to the native vaccine. Both native and optimized vaccines led to increased expression of PD-L1 on tumor cells, but antigen-specific CD8+ T cells from mice immunized with the optimized construct expressed higher PD-1. Splenocytes from immunized animals induced PD-L1 expression on tumor cells in vitro. Antitumor activity of the optimized vaccine could be increased when combined with antibodies blocking PD-1 or PD-L1, or by targeting a tumor line not expressing PD-L1. These findings suggest that vaccines aimed at eliciting effector CD8+ T cells, and DNA vaccines in particular, might best be combined with PD-1 pathway inhibitors in clinical trials. This strategy may be particularly advantageous for vaccines targeting prostate cancer, a disease for which antitumor vaccines have demonstrated clinical benefit and yet PD-1 pathway inhibitors alone have shown little efficacy to date. Cancer Immunol Res; 3(8); 946–55. ©2015 AACR.
РОЛЬ ВИВЧЕННЯ ДИСЦИПЛІНИ “СЕСТРИНСЬКА ПРАКТИКА” НА КАФЕДРІ ПРОПЕДЕВТИКИ ВНУТРІШНЬОЇ МЕДИЦИНИ В ПРОЦЕСІ ФОРМУВАННЯ ЛІКАРЯ-СПЕЦІАЛІСТА
Authors: Молодовець О. Б. 
Published: June 2015

<p>Виробнича практика з “Сестринської справи” (терапія) є обов’язковим елементом поетапного формування лікаря-спеціаліста. Перелік обов’язкових практичних навиків регламентованийПрограмою сестринської виробничої практики для вищих медичних закладів освіти України ІІІ–IV рівнів акредитації і складений для спеціальності 7.110101 “Лікувальна справа” напряму підготовки “Медицина” відповідно до освітньо-кваліфікаційної характеристики та освітньо-професійної програми підготовки фахівців, затверджених наказом МОН України від 16.04.2003 р. № 239, та навчального плану, затвердженого наказом МОЗ України від 31.01.2005 р. № 52. Алгоритми виконання кожного з належних навиків та ретельне опрацювання їх на муляжах навчально-тренінгового центру є етапом рівнів “знаю-вмію-володію”. Можливість проведення виробничої практики на клінічних базах (терапевтичних стаціонарах) дозволяє не тільки досконало оволодіти практичними навиками, але й формує етичні засади майбутніх професійних стосунків “лікар – медсестра”, “лікар – пацієнт”, клінічне мислення, формат майбутньої організації лікувального процесу.</p>
ЗАСТОСУВАННЯ СУЧАСНИХ ПЕДАГОГІЧНИХ ТЕХНОЛОГІЙ ДЛЯ ПІДВИЩЕННЯ ЯКОСТІ ПІДГОТОВКИ ЛІКАРІВ У ДОНЕЦЬКОМУ НАЦІОНАЛЬНОМУ МЕДИЧНОМУ УНІВЕРСИТЕТІ ім. М. ГОРЬКОГО
Authors: Думанський Ю. В. , Івнєв Б. Б. , Первак М. Б. , Басій Р. В. , Владзимирський А. В. 
Published: June 2015

<p>У статті висвітлено досвід Донецького національного медичного університету ім. М. Горького із впровадження інтерактивних методів та дистанційного навчання для підвищення якості підготовки лікарів на до- та післядипломному рівнях медичної освіти. </p>
УДОСКОНАЛЕННЯ ТЕХНОЛОГІЙ ЗВОРОТНОГО ЗВ’ЯЗКУ В ОРГАНІЗАЦІЇ САМОСТІЙНОЇ РОБОТИ ЛІКАРІВ У ПІСЛЯДИПЛОМНІЙ ОСВІТІ
Authors: Никоненко О. С. , Шаповал С. Д. , Дмитрієва С. М. 
Published: June 2015

<p>У статті наведено досвід використання технологій електронного опитування у самостійній роботі лікарів-слухачів. Надані рекомендації щодо проведення опитування за допомогою Google-форм як інструменту з дослідження питань, що пов’язані з навчанням взагалі або з оцінюванням певного ресурсу. Проведено аналіз літературних джерел, результатів анкетування та спостереження за самостійною роботою слухачів.</p>
З ДОСВІДУ РОБОТИ НАВЧАЛЬНО-ПРАКТИЧНИХ ЦЕНТРІВ УНІВЕРСИТЕТУ
Authors: Рожко М. М. , Ерстенюк Г. М. , Капечук В. В. , Іванців М. О. 
Published: June 2015

<p>В ІФНМУ приділяється велика увага питанню практичної підготовки фахівців-медиків. В університеті створено навчально-практичні центри (НПЦ) “Медицина”, “Стоматологія”, “Фармація”, на базі яких студенти всіх факультетів та інтерни опановують практичні навички, готуються до державної атестації.</p><p> У всіх НПЦ розроблені та видані Алгоритми виконання практичних навичок українською, російською та англійською мовами, які під час практичних занять, а також самостійної позааудиторної роботи, допомагають студентам у набутті практичних вмінь та методик.</p>
Філософія формування і розвитку почуттів
Authors: Кадобний Т. Б. , Кравчук Л. В. , Боцюк І. З. 
Published: June 2015

<p><strong>У статті розкрито природу виникнення почуттів, їх</strong></p><p><strong>розвиток та методи управління ними. Крім того, вказано на необхідність формування позитивних почуттів у студентів як на практичних, так і теоретичних заняттях.</strong></p>
ПСИХОЛОГІЧНІ ОСОБЛИВОСТІ ТА НАУКОВО-ДОСЛІДНА КОМПЕТЕНТНІСТЬ У ФОРМУВАННІ МАЙБУТНІХ ЛІКАРІВ-СТОМАТОЛОГІВ
Authors: Гутор Н. С. , Бойків А. Б. 
Published: June 2015

<p><strong>У статті розкривається досвід професійної підготовки </strong><strong>майбутніх лікарів-стоматологів на кафедрах хірургічної та дитячої стоматології з урахуванням </strong></p><p><strong>психологічних особливості студента</strong><strong>, що є невід’ємною складовою у формуванні спеціаліста, створюється резерв як медичних, так і педагогічних кадрів. </strong><strong></strong></p>
ПРОБЛЕМА ЗМІЦНЕННЯ ЗДОРОВ’Я ШКІЛЬНОЇ МОЛОДІ В СИСТЕМІ ПІДГОТОВКИ ВЧИТЕЛІВ ФІЗИЧНОЇ КУЛЬТУРИ В УКРАЇНІ У ПЕРІОД 1917–1939 рр.
Authors: Гук О. М. 
Published: June 2015

<p class="MsoNormal" style="text-align: justify; line-height: normal;"><strong style="mso-bidi-font-weight: normal;"><span style="font-size: 12.0pt; font-family: 'Times New Roman','serif'; mso-ansi-language: UK;" lang="UK">У статті розглядається проблема підготовки вчителів фізичного виховання у період між Першою і Другою світовими війнами, де питання виховання здорової шкільної молоді було одним з головних. За допомогою<span style="mso-spacerun: yes;"> </span>матеріалів наукових праць та архівних даних висвітлюється місце вчителя фізичної культури у провадженні здорового способу життя, особистої гігієни школярів досліджуваного періоду.</span></strong></p>