bluuebunny/crossref_metadata_2025_split huggingface dataset:
Draft Genome Sequence and Annotation of the Phytopathogenic Ralstonia pickettii (Previously Burkholderia glumae) Strain ICMP-8657
Authors: Paterson Julia , Gross Harald 
Published: March 2018

ABSTRACT

Strain ICMP-8657 was formerly taxonomically classified as
Burkholderia glumae
and reported to be the producer of an antibacterial pyrazole derivative. Here, we report the draft genome sequence of ICMP-8657, which failed to demonstrate the biosynthetic capacity to produce the stated antibacterial compound, leading to its taxonomic reclassification as
Ralstonia pickettii
ICMP-8657.
Draft Genome Sequence of Lactobacillus helveticus Strain Lh 12 Isolated from Natural Whey Starter
Authors: Bertani Gaia , Bassi Daniela , Gatti Monica , Cocconcelli Pier Sandro , Neviani Erasmo 
Published: March 2018

ABSTRACT

Lactobacillus helveticus
is a lactic acid bacterium widely used in cheese-making and for the production of bioactive peptides from milk proteins. Here, we describe the draft genome sequence and annotation of
L. helveticus
strain Lh 12 isolated from natural whey starter used in the production of Grana Padano cheese.
Complete Genome Sequences of 13 Human Respiratory Syncytial Virus Subgroup A Strains of Genotypes NA1 and ON1 Isolated in the Philippines
Authors: Malasao Rungnapa , Furuse Yuki , Okamoto Michiko , Dapat Clyde , Saito Mayuko , Saito-Obata Mariko , Tamaki Raita , Segubre-Mercado Edelwisa , Lupisan Socorro , Oshitani Hitoshi 
Published: March 2018

ABSTRACT
Complete genome sequences of 13 human respiratory syncytial virus strains were determined from samples obtained from children hospitalized in the Philippines between 2012 and 2013 because of acute respiratory infection. We identified amino acid polymorphisms between the NA1 and ON1 genotypes in the P, G, F, and L proteins.
mHealth text and voice communication for monitoring people with chronic diseases in low-resource settings: a realist review
Authors: Anstey Watkins Jocelyn , Goudge Jane , Gómez-Olivé Francesc Xavier , Huxley Caroline , Dodd Katherine , Griffiths Frances 
Published: March 2018

BackgroundRoutine monitoring by patients and healthcare providers to manage chronic disease is vital, though this can be challenging in low-resourced health systems. Mobile health (mHealth) has been proposed as one way to improve management of chronic diseases. Past mHealth reviews have proposed the need for a greater understanding around how the theoretical constructs in mHealth interventions actually work. In response, we synthesised evidence from primary studies on monitoring of chronic diseases using two-way digital text or voice communication between a patient and health worker. We did this in order to understand the important considerations for the design of mHealth interventions.MethodArticles retrieved were systematically screened and analysed to elicit explanations of mHealth monitoring interventions. These explanations were consolidated into programme theory and compared with existing theory and frameworks. We identified variation in outcomes to understand how context moderates the outcome.ResultsFour articles were identified—monitoring of hypertension and HIV/AIDS from: Kenya, Pakistan, Honduras and Mexico and South Africa. Six components were found in all four interventions: reminders, patient observation of health state, motivational education/advice, provision of support communication, targeted actions and praise and encouragement. Intervention components were mapped to existing frameworks and theory. Variation in outcome identified in subgroup analysis suggests greater impact is achieved with certain patient groups, such as those with low literacy, those with stressful life events or those early in the disease trajectory. There was no other evidence in the included studies of the effect of context on the intervention and outcome.ConclusionmHealth interventions for monitoring chronic disease in low-resource settings, based on existing frameworks and theory, can be effective. A match between what the intervention provides and the needs or social factors relevant to specific patient group increases the effect. It was not possible to understand the impact of context on intervention and outcome beyond these patient-level measures as no evidence was provided in the study reports.
Phosphorylcholine surface modified flow diverter associated with reduced intimal hyperplasia
Authors: Caroff Jildaz , Tamura Takamitsu , King Robert M , Lylyk Pedro N , Langan Erin T , Brooks Olivia W , Clarençon Frédéric , Wainwright John Michael , Spelle Laurent , Marosfoi Miklos , Gounis Matthew J , Puri Ajit S 
Published: March 2018

BackgroundOptical coherence tomography (OCT) is a high-resolution, intra-vascular diagnostic technique widely used for the characterization of vascular pathologies and optimization of stent implantation during percutaneous coronary intervention. OCT was used to investigate the in vivo vascular response to a new phosphorylcholine surface modified flow diverter (sPED).MethodsIn an in vivo rabbit aneurysmal model, we used two different types of flow diverters (classic Pipeline – cPED; and sPED) with or without dual antiplatelet therapy (four groups, n=10 per group). OCT cross-sectional area measurements were compared with histology in all animals. Neointimal hyperplasia (NIH) ratio was compared between OCT and histology at five different levels for each stent. The severity of NIH was also compared between the different stents, antiplatelet protocols, and vessel locations.ResultsOCT was used to calculate in-stent hyperplasia in 227 different locations corresponding to histology sections. OCT measurement strongly correlated with gold standard histology (r2=0.83; slope=0.988; P<0.0001). sPED had significantly less in-stent NIH than non-treated flow diverters (mean percent of lumen reduction 5.7% for sPED versus 8.9% for cPED; P<0.0001). The NIH ratio was slightly higher with dual antiplatelet therapy (DAPT) (NIH ratio=7.9% with DAPT versus 6.8% without DAPT; P<0.05). Complete and near complete occlusion rates of the aneurysms were not different with the cPED or sPED.ConclusionOCT is a promising technique for immediate and long-term evaluation of flow diverter stent treatments. In an animal model, phosphorylcholine surface modified flow diverters induces less NIH after stent implant without reducing aneurysm occlusion rates.
PD-1 Blockade and CD27 Stimulation Activate Distinct Transcriptional Programs That Synergize for CD8+ T-Cell–Driven Antitumor Immunity
Authors: Buchan Sarah L. , Fallatah Mohannad , Thirdborough Stephen M. , Taraban Vadim Y. , Rogel Anne , Thomas Lawrence J. , Penfold Christine A. , He Li-Zhen , Curran Michael A. , Keler Tibor , Al-Shamkhani Aymen 
Published: March 2018

Abstract
Purpose: PD-1 checkpoint blockade has revolutionized the field of cancer immunotherapy, yet the frequency of responding patients is limited by inadequate T-cell priming secondary to a paucity of activatory dendritic cells (DC). DC signals can be bypassed by CD27 agonists, and we therefore investigated if the effectiveness of anti–PD-1/L1 could be improved by combining with agonist anti-CD27 monoclonal antibodies (mAb).
Experimental Design: The efficacy of PD-1/L1 blockade or agonist anti-CD27 mAb was compared with a dual-therapy approach in multiple tumor models. Global transcriptional profiling and flow cytometry analysis were used to delineate mechanisms underpinning the observed synergy.
Results: PD-1/PD-L1 blockade and agonist anti-CD27 mAb synergize for increased CD8+ T-cell expansion and effector function, exemplified by enhanced IFNγ, TNFα, granzyme B, and T-bet. Transcriptome analysis of CD8+ T cells revealed that combination therapy triggered a convergent program largely driven by IL2 and Myc. However, division of labor was also apparent such that anti–PD-1/L1 activates a cytotoxicity–gene expression program whereas anti-CD27 preferentially augments proliferation. In tumor models, either dependent on endogenous CD8+ T cells or adoptive transfer of transgenic T cells, anti-CD27 mAb synergized with PD-1/L1 blockade for antitumor immunity. Finally, we show that a clinically relevant anti-human CD27 mAb, varlilumab, similarly synergizes with PD-L1 blockade for protection against lymphoma in human–CD27 transgenic mice.
Conclusions: Our findings suggest that suboptimal T-cell invigoration in cancer patients undergoing treatment with PD-1 checkpoint blockers will be improved by dual PD-1 blockade and CD27 agonism and provide mechanistic insight into how these approaches cooperate for CD8+ T-cell activation. Clin Cancer Res; 24(10); 2383–94. ©2018 AACR.
Cross-Cohort Analysis Identifies a TEAD4–MYCN Positive Feedback Loop as the Core Regulatory Element of High-Risk Neuroblastoma
Authors: Rajbhandari Presha , Lopez Gonzalo , Capdevila Claudia , Salvatori Beatrice , Yu Jiyang , Rodriguez-Barrueco Ruth , Martinez Daniel , Yarmarkovich Mark , Weichert-Leahey Nina , Abraham Brian J. , Alvarez Mariano J. , Iyer Archana , Harenza Jo Lynne , Oldridge Derek , De Preter Katleen , Koster Jan , Asgharzadeh Shahab , Seeger Robert C. , Wei Jun S. , Khan Javed , Vandesompele Jo , Mestdagh Pieter , Versteeg Rogier , Look A. Thomas , Young Richard A. , Iavarone Antonio , Lasorella Anna , Silva Jose M. , Maris John M. , Califano Andrea 
Published: March 2018

Abstract
High-risk neuroblastomas show a paucity of recurrent somatic mutations at diagnosis. As a result, the molecular basis for this aggressive phenotype remains elusive. Recent progress in regulatory network analysis helped us elucidate disease-driving mechanisms downstream of genomic alterations, including recurrent chromosomal alterations. Our analysis identified three molecular subtypes of high-risk neuroblastomas, consistent with chromosomal alterations, and identified subtype-specific master regulator proteins that were conserved across independent cohorts. A 10-protein transcriptional module—centered around a TEAD4–MYCN positive feedback loop—emerged as the regulatory driver of the high-risk subtype associated with MYCN amplification. Silencing of either gene collapsed MYCN-amplified (MYCNAmp) neuroblastoma transcriptional hallmarks and abrogated viability in vitro and in vivo. Consistently, TEAD4 emerged as a robust prognostic marker of poor survival, with activity independent of the canonical Hippo pathway transcriptional coactivators YAP and TAZ. These results suggest novel therapeutic strategies for the large subset of MYCN-deregulated neuroblastomas.
Significance: Despite progress in understanding of neuroblastoma genetics, little progress has been made toward personalized treatment. Here, we present a framework to determine the downstream effectors of the genetic alterations sustaining neuroblastoma subtypes, which can be easily extended to other tumor types. We show the critical effect of disrupting a 10-protein module centered around a YAP/TAZ-independent TEAD4–MYCN positive feedback loop in MYCNAmp neuroblastomas, nominating TEAD4 as a novel candidate for therapeutic intervention. Cancer Discov; 8(5); 582–99. ©2018 AACR.
This article is highlighted in the In This Issue feature, p. 517
AMD3100 Augments the Efficacy of Mesothelin-Targeted, Immune-Activating VIC-008 in Mesothelioma by Modulating Intratumoral Immunosuppression
Authors: Li Binghao , Zeng Yang , Reeves Patrick M. , Ran Chongzhao , Liu Qiuyan , Qu Xiying , Liang Yingying , Liu Zhao , Yuan Jianping , Leblanc Pierre R. , Ye Zhaoming , Sluder Ann E. , Gelfand Jeffrey A. , Brauns Timothy A. , Chen Huabiao , Poznansky Mark C. 
Published: March 2018

AbstractAMD3100 (plerixafor), a CXCR4 antagonist, has been demonstrated to suppress tumor growth and modulate intratumoral T-cell trafficking. However, the effect of AMD3100 on immunomodulation remains elusive. Here, we explored immunomodulation and antitumor efficacy of AMD3100 in combination with a previously developed mesothelin-targeted, immune-activating fusion protein, VIC-008, in two syngeneic, orthotopic models of malignant mesothelioma in immunocompetent mice. We showed that combination therapy significantly suppressed tumor growth and prolonged animal survival in two mouse models. Tumor control and survival benefit were associated with enhanced antitumor immunity. VIC-008 augmented mesothelin-specific CD8+ T-cell responses in the spleen and lymph nodes and facilitated intratumoral lymphocytic infiltration. However, VIC-008 treatment was associated with increased programmed cell death protein-1 (PD-1) expression on intratumoral CD8+ T cells, likely due to high CXCL12 in the tumor microenvironment. AMD3100 alone and in combination with VIC-008 modulated immunosuppression in tumors and the immune system through suppression of PD-1 expression on CD8+ T cells and conversion of regulatory T cells (Tregs) into CD4+CD25–Foxp3+IL2+CD40L+ helper-like cells. In mechanistic studies, we demonstrated that AMD3100-driven Treg reprogramming required T cell receptor (TCR) activation and was associated with loss of PTEN due to oxidative inactivation. The combination of VIC-008 augmentation of tumor-specific CD8+ T-cell responses with AMD3100 abrogation of immunosuppression conferred significant benefits for tumor control and animal survival. These data provide new mechanistic insight into AMD3100-mediated immunomodulation and highlight the enhanced antitumor effect of AMD3100 in combination with a tumor antigen–targeted therapy in mouse malignant mesothelioma, which could be clinically relevant to patients with this difficult-to-treat disease. Cancer Immunol Res; 6(5); 539–51. ©2018 AACR.
МОЖЛИВОСТІ ПРОТИФІБРОЗНОЇ ТЕРАПІЇ ПІСЛЯ ЕЛІМІНАЦІЇ ВІРУСУ ГЕПАТИТУ С
Authors: Hospodarskyi I. Ya. , Havryliuk N. M. , Prokopchuk O. V. 
Published: March 2018

Мета: дослідження можливостей протифіброзної терапії у хворих на хронічний гепатит (ХГ) С після завершення противірусного лікування шляхом призначення гепатопротекторного препарату біциклол протягом 3 місяців.Матеріали і методи. Обстежено в динаміці 27 па­цієнтів з ХГС без ознак цирозу та супутньої патології печінки й жовчовивідних шляхів, віком від 20 до 68 років, які завершили курс противірусної терапії і мали початковий рівень фіброзу F2-F3. Аналіз проводили шляхом визначення показників фіброгенезу (гідроксипролін, колаген IV) і ступеня фіброзу (фібротест, еластографія).Висновки. Встановлено, що після успішного завершення противірусного лікування у хворих на ХГС з вираженим фіброзом, як правило, не відбувається спонтанного регресу фібротичних явищ у печінці. Більше того, у частини пацієнтів фіброз продовжує прогресувати. В усіх пацієнтів з рівнем фіброзу F2-F3 відзначаються суттєво підвищені показники колагену IV і гідроксипроліну у сироватці крові, що свідчить про продовження процесу фіброзування навіть після елімінації вірусу.
ХАРАКТЕРИСТИКА ВІЛ-АСОЦІЙОВАНИХ ЗАХВОРЮВАНЬ ЦЕНТРАЛЬНОЇ НЕРВОВОЇ СИСТЕМИ В ОСІБ СТАРШОГО ВІКУ
Authors: Shostakovych-Koretska L. R. , Lytvyn K. Yu. , Hubar I. O. , Chykarenko Z. O. , Volikova O. O. , Chukhalova I. V. , Lisnycha O. O. 
Published: March 2018

Мета роботи – вивчити основні характеристики ВІЛ-асоційованих захворювань центральної нервової системи в осіб старше 50 років і визначити частоту і відношення шансів розвитку неврологічних захворювань залежно від вікових аспектів.Пацієнти і методи. Проведений ретроспективний аналіз 428 медичних карт пацієнтів з ВІЛ-асоці­йованими захворюваннями ЦНС, які перебували на лікуванні у відділеннях Дніпропетровського обласного та міського центрів СНІД в період з 2010 по 2016 роки. Висновки. Отримані дані свідчать про особливості ВІЛ-асоційованих захворювань ЦНС у пацієнтів старше 50 років. У даній віковій категорії число осіб, інфікованих статевим шляхом, було значно більше, ніж серед молодших осіб, ВІЛ-інфекцію було діаг­ностовано пізніше і, відповідно, менша кількість пацієнтів отримувала АРТ. На момент розвитку неврологічних захворювань у пацієнтів старше 50 років спостерігався більший рівень RNA HIV viralload при відсутності статистично значущих імунологічних відмінностей. В даній групі визначені високі шанси розвитку ПМЛ, EBV-енцефалітів, когнітивних розладів і тенденцію до більшої частоти інсультів, що може призводити до тяжких наслідків, і підкреслює важливість більш детального обліку вікового аспекту.
ПОШИРЕНІСТЬ ПОЛІМОРФІЗМУ ГЕНА TLR 9 ТИПУ У ХВОРИХ З ХРОНІЧНИМИ ФОРМАМИ ВЕБ-ІНФЕКЦІЇ
Authors: Liadova T. I. 
Published: March 2018

Мета дослідження – встановлення частоти поліморфізму -1486 T/C гена TLR-9 у пацієнтів з ХВЕБІ.Матеріали та методи. Дослідження для визначення поліморфізму -1486 T/C гена TLR-9 було проведено у 44 пацієнтів з хронічними формами ВЕБ-інфекції. Контрольна група для вивчення поширеності поліморфізму -1486 T/C гена TLR-9 становила 40 здорових донорів. Для виявлення ДНК ВЕБ методом ПЛР зі зворотною транскрипцією з гібридизаційно-флуоресцентною детекцією продуктів ампліфікації використовували набори реагентів «Амплісенс» (Росія). Виділення ДНК із зразків проводили за допомогою набору фірми «Минипреп» (Силекс М, Росія), використовуючи методику сорбції ДНК на сорбенті.Поліморфний регіон -1486 T/C, rs187084 гена TLR9 вивчався шляхом ампліфікації ПЛР в реальному часі шляхом визначення довжини фрагментів рестрикції ПЛР, за допомогою рестрикційного ензиму Ncol та олігонуклеотидних праймерів.Результати. Аналіз отриманих результатів поліморфізму -1486 Т/С гена TLR-9 дозволив виділити три основних генотипи – ТТ, ТС, СС. Дослідження частоти окремих генотипів виявило домінування генотипу ТС, порівняно з гомозиготними генотипами ТТ та СС. Вивчення розподілу частот поліморфізму -1486 Т/С гена TLR-9 для різних генотипів продемонструвало специфічність змін для генотипу ТС у хворих з ХВЕБІ та відсутність таких для генотипів ТТ та СС.
Safe, Innovative and Accessible Medicines in Europe: A Renewed Strategy for Patients and the Pharmaceutical Sector
Authors: Altavilla Annagrazia 
Published: March 2018

Abstract
European Union (eu) action in the pharmaceutical sector has always had the dual objective of safeguarding public health by providing Europe with safe and effective medicines, while stimulating research, boosting innovation, and supporting the competitiveness of industry. To face major health, economic and scientific challenges, a series of measures have been adopted. Specific legal frameworks have been set up to improve patient safety by reducing the infiltration of counterfeit medicines into the supply chain, to increase the safety of medicines by modernising the pharmacovigilance system, as well as improving patient access by requiring high-quality health and medicine information. This article provides an overview of the new eu strategy aimed at increasing the safety and involvement of European patients, as well as the competitiveness of pharmaceutical industry in accordance with the principle of transparency. The analysis is carried out from a patients’ perspective addressing some paediatric specifications.
High acute phase protein levels correlate with pulmonary and skin involvement in patients with diffuse systemic sclerosis
Authors: Lis-Święty Anna , Widuchowska Małgorzata , Brzezińska-Wcisło Ligia , Kucharz Eugeniusz 
Published: March 2018

Objective This study was performed to evaluate the serum amyloid A (SAA) and C-reactive protein (CRP) levels in patients with diffuse systemic sclerosis (dSSc) in relation to a control group, disease duration, and skin and pulmonary involvement. Methods This case-control study included 18 patients with early dSSc, 15 patients with late dSSc, and 15 healthy controls. The SAA and CRP levels, modified Rodnan skin score (mRSS), and diffusing capacity of the lungs for carbon monoxide (DLCO) were determined in all patients. Results The SAA and CRP levels were significantly higher in patients with early and late dSSc than in healthy controls. The frequency of detection of elevated SAA and CRP levels was approximately 66% and 85%, respectively. A significant correlation was found between the SAA and CRP levels in patients with dSSc. The SAA and CRP levels were inversely correlated with DLCO. The CRP level was positively correlated with the mRSS. Conclusions High SAA and CRP levels could serve as biomarkers for pulmonary involvement. The serum CRP level accurately reflects the extension of skin thickening in patients with dSSc.
Reliability and Normative Reference Values for the Vestibular/Ocular Motor Screening (VOMS) Tool in Youth Athletes
Authors: Moran Ryan N. , Covassin Tracey , Elbin R.J. , Gould Dan , Nogle Sally 
Published: March 2018

Background: The Vestibular/Ocular Motor Screening (VOMS) measure is a newly developed vestibular and ocular motor symptom provocation screening tool for sport-related concussions. Baseline data, psychometric properties, and reliability of the VOMS are needed to further understand the applications of this tool, especially in the youth population, where research is scarce. Purpose: To establish normative data and document the internal consistency and false-positive rate of the VOMS in a sample of nonconcussed youth athletes. Study Design: Cross-sectional study; Level of evidence, 3. Methods: A total of 423 youth athletes (male = 278, female = 145) between the ages of 8 and 14 years completed baseline VOMS screening before the start of their respective sport seasons. Internal consistency was measured with Cronbach α and inter-item correlations. Results: Approximately 60% of youth athletes reported no symptom provocation on baseline VOMS assessment, with 9% to 13% scoring over the cutoff levels (score of ≥2 for any individual VOMS symptom, near point convergence distance of ≥5 cm). The VOMS displayed a high internal consistency (Cronbach α = .97) at baseline among youth athletes. Conclusion: The current findings provide preliminary support for the implementation of VOMS baseline assessment into clinical practice, due to a high internal consistency, strong relationships between VOMS items, and a low false-positive rate at baseline in youth athletes.
Death by Suicide among Canadian Medical Students: A National Survey-Based Study
Authors: Zivanovic Rebecca , McMillan Janette , Lovato Chris , Roston Christina 
Published: March 2018

Objective: To estimate a rate of death by suicide in the Canadian medical student population and examine the prevalence of institutional response policies for suicide. Methods: A survey was sent to all 17 Canadian medical undergraduate programs (MDUPs) to collect information on deaths by suicide over the past 10 years. In the case of a reported suicide, basic demographic data was collected. Respondents were asked to indicate whether internal statistics or response policies for suicide existed at their MDUP. Results: Responses were obtained from 16 of 17 (94%) MDUPs. Six suicides (50% female) were reported over the ten-year period from 2006 to 2016. The estimated cause-specific mortality rate was 5.9-8.7/100,000 medical students/year. There were seven (44%) MDUPs that kept statistics on student deaths including suicides and 10 (63%) reported having policies or guidelines regarding what to do in the event of a suicide. Conclusions: Our estimated suicide rate falls within previously reported rates in medical students. While this may be lower than the national rate for Canadians between the ages of 20-30 years old, any suicide in the medical student community must be an impetus for national dialogue and further study. A strategy is needed to better define the prevalence, risk factors for and impact of medical student suicide in Canada.