bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and Characterization of a Guinea Pig-Adapted Sudan Virus
Authors: Wong Gary , He Shihua , Wei Haiyan , Kroeker Andrea , Audet Jonathan , Leung Anders , Cutts Todd , Graham Jill , Kobasa Darwyn , Embury-Hyatt Carissa , Kobinger Gary P. , Qiu Xiangguo 
Published: October 2015

ABSTRACT

Infections with Sudan virus (SUDV), a member of the genus
Ebolavirus
, result in a severe hemorrhagic fever with a fatal outcome in over 50% of human cases. The paucity of prophylactics and therapeutics against SUDV is attributed to the lack of a small-animal model to screen promising compounds. By repeatedly passaging SUDV within the livers and spleens of guinea pigs
in vivo
, a guinea pig-adapted SUDV variant (SUDV-GA) uniformly lethal to these animals, with a 50% lethal dose (LD
50
) of 5.3 × 10
−2
50% tissue culture infective doses (TCID
50
), was developed. Animals infected with SUDV-GA developed high viremia and died between 9 and 14 days postinfection. Several hallmarks of SUDV infection, including lymphadenopathy, increased liver enzyme activities, and coagulation abnormalities, were observed. Virological analyses and gross pathology, histopathology, and immunohistochemistry findings indicate that SUDV-GA replicates in the livers and spleens of infected animals similarly to SUDV infections in nonhuman primates. These developments will accelerate the development of specific medical countermeasures in preparation for a future disease outbreak due to SUDV.

IMPORTANCE
A disease outbreak due to Ebola virus (EBOV), suspected to have emerged during December 2013 in Guinea, with over 11,000 dead and 28,000 infected, is finally winding down. Experimental EBOV vaccines and treatments were administered to patients under compassionate circumstances with promising results, and availability of an approved countermeasure appears to be close. However, the same range of experimental candidates against a potential disease outbreak caused by other members of the genus
Ebolavirus
, such as Sudan virus (SUDV), is not readily available. One bottleneck contributing to this situation is the lack of a small-animal model to screen promising drugs in an efficient and economical manner. To address this, we have generated a SUDV variant (SUDV-GA) that is uniformly lethal to guinea pigs. Animals infected with SUDV-GA develop disease similar to that of SUDV-infected humans and monkeys. We believe that this model will significantly accelerate the development of life-saving measures against SUDV infections.
The Human Skin Double-Stranded DNA Virome: Topographical and Temporal Diversity, Genetic Enrichment, and Dynamic Associations with the Host Microbiome
Authors: Hannigan Geoffrey D. , Meisel Jacquelyn S. , Tyldsley Amanda S. , Zheng Qi , Hodkinson Brendan P. , SanMiguel Adam J. , Minot Samuel , Bushman Frederic D. , Grice Elizabeth A. 
Published: October 2015

ABSTRACTViruses make up a major component of the human microbiota but are poorly understood in the skin, our primary barrier to the external environment. Viral communities have the potential to modulate states of cutaneous health and disease. Bacteriophages are known to influence the structure and function of microbial communities through predation and genetic exchange. Human viruses are associated with skin cancers and a multitude of cutaneous manifestations. Despite these important roles, little is known regarding the human skin virome and its interactions with the host microbiome. Here we evaluated the human cutaneous double-stranded DNA virome by metagenomic sequencing of DNA from purified virus-like particles (VLPs). In parallel, we employed metagenomic sequencing of the total skin microbiome to assess covariation and infer interactions with the virome. Samples were collected from 16 subjects at eight body sites over 1 month. In addition to the microenviroment, which is known to partition the bacterial and fungal microbiota, natural skin occlusion was strongly associated with skin virome community composition. Viral contigs were enriched for genes indicative of a temperate phage replication style and also maintained genes encoding potential antibiotic resistance and virulence factors. CRISPR spacers identified in the bacterial DNA sequences provided a record of phage predation and suggest a mechanism to explain spatial partitioning of skin phage communities. Finally, we modeled the structure of bacterial and phage communities together to reveal a complex microbial environment with aCorynebacteriumhub. These results reveal the previously underappreciated diversity, encoded functions, and viral-microbial dynamic unique to the human skin virome.IMPORTANCETo date, most cutaneous microbiome studies have focused on bacterial and fungal communities. Skin viral communities and their relationships with their hosts remain poorly understood despite their potential to modulate states of cutaneous health and disease. Previous studies employing whole-metagenome sequencing without purification for virus-like particles (VLPs) have provided some insight into the viral component of the skin microbiome but have not completely characterized these communities or analyzed interactions with the host microbiome. Here we present an optimized virus purification technique and corresponding analysis tools for gaining novel insights into the skin virome, including viral “dark matter,” and its potential interactions with the host microbiome. The work presented here establishes a baseline of the healthy human skin virome and is a necessary foundation for future studies examining viral perturbations in skin health and disease.
Interventions to improve antimicrobial prescribing of doctors in training: the IMPACT (IMProving Antimicrobial presCribing of doctors in Training) realist review
Authors: Wong Geoff , Brennan Nicola , Mattick Karen , Pearson Mark , Briscoe Simon , Papoutsi Chrysanthi 
Published: October 2015

IntroductionAntimicrobial resistance has been described as a global crisis—more prudent prescribing is part of the solution. Behaviour change interventions are needed to improve prescribing practice. Presently, the literature documents that context impacts on prescribing decisions, yet insufficient evidence exists to enable researchers and policymakers to determine how local tailoring should take place. Doctors in training are an important group to study, being numerically the largest group of prescribers in UK hospitals. Unfortunately very few interventions specifically targeted this group.Methods and analysisOur project aims to understand how interventions to change antimicrobial prescribing behaviours of doctors in training produce their effects. We will recruit a project stakeholder group to advise us throughout. We will synthesise the literature using the realist review approach—a form of theory-driven interpretive systematic review approach often used to make sense of complex interventions. Interventions to improve antimicrobial prescribing behaviours are complex—they are context dependent, have long implementation chains, multiple non-linear interactions, emergence and depend on human agency. Our review will iteratively progress through 5 steps: step 1—Locate existing theories; step 2—Search for evidence; step 3—Article selection; step 4—Extracting and organising data; and step 5—Synthesising the evidence and drawing conclusions. Data analysis will use a realist logic of analysis to describe and explain what works, for whom, in what circumstances, in what respects, how and why to improve antimicrobial prescribing behaviour of doctors in training.Ethics and disseminationEthical approval was not required for our review. Our dissemination strategy will be participatory and involve input from our stakeholder group. Tailored project outputs will be targeted at 3 audiences: (1) doctors in training; (2) clinical supervisors/trainers and medical educators; and (3) policy, decision makers, regulators and royal societies.
Evaluating the effectiveness of a home-based exercise programme delivered through a tablet computer for preventing falls in older community-dwelling people over 2 years: study protocol for the Standing Tall randomised controlled trial
Authors: Delbaere K , Valenzuela T , Woodbury A , Davies T , Yeong J , Steffens D , Miles L , Pickett L , Zijlstra G A R , Clemson L , Close J C T , Howard K , Lord S R 
Published: October 2015

IntroductionIn order to prevent falls, older people should exercise for at least 2 h per week for 6 months, with a strong focus on balance exercises. This article describes the design of a randomised controlled trial to evaluate the effectiveness of a home-based exercise programme delivered through a tablet computer to prevent falls in older people.Methods and analysisParticipants aged 70 years or older, living in the community in Sydney will be recruited and randomly allocated to an intervention or control group. The intervention consists of a tailored, home-based balance training delivered through a tablet computer. Intervention participants will be asked to complete 2 h of exercises per week for 2 years. Both groups will receive an education programme focused on health-related information relevant to older adults, delivered through the tablet computer via weekly fact sheets. Primary outcome measures include number of fallers and falls rate recorded in weekly fall diaries at 12 months. A sample size of 500 will be necessary to see an effect on falls rate. Secondary outcome measures include concern about falling, depressive symptoms, health-related quality of life and physical activity levels (in all 500 participants); and physiological fall risk, balance, functional mobility, gait, stepping and cognitive performance (in a subsample of 200 participants). Adherence, acceptability, usability and enjoyment will be recorded in intervention group participants over 2 years. Data will be analysed using the intention-to-treat principle. Secondary analyses are planned in people with greater adherence. Economic analyses will be assessed from a health and community care provider perspective.Ethics and disseminationEthical approval was obtained from UNSW Ethics Committee in December 2014 (ref number HC#14/266). Outcomes will be disseminated through publication in peer-reviewed journals and presentations at international conferences.Trial registration numberAustralian New Zealand Clinical Trials Registry (ACTRN)12615000138583.
IMPROVING CARE FOR PEDIATRIC URINARY TRACT INFECTION: RELATIONSHIP BETWEEN IMPLEMENTATION OF A CLINICAL PATHWAY AND PRESCRIBING PATTERNS IN THE ED
Authors: Caglar Derya , Poole Nicole , Migita Russ , Kronman Matthew , Zerr Danielle , Rutman Lori 
Published: October 2015

BackgroundUrinary tract infections (UTIs) are the most common serious bacterial infection in children; nearly 10% of girls and 2% of boys are affected during their first 8 years of life. Broad-spectrum antibiotics are popular first-line treatment agents; however, these medications can lead to resistant organisms and more severe infections over time. In July 2010, our institution implemented a clinical pathway for children presenting to the ED with UTI based on national guidelines and local consensus regarding the need for antimicrobial stewardship. A goal of the pathway was to increase narrow spectrum (cephalexin) and decrease broad spectrum (cefixime) antibiotic use for children with uncomplicated UTI presenting to the ED.ObjectivesTo determine the impact of a UTI clinical pathway on provider antibiotic prescribing patterns.MethodsWe used statistical process control (p-charts) to analyze the percentage of patients receiving each antibiotic over time. Data were analyzed over a 6-year period; 1.5 years before and 4.5 years after pathway implementation.Results2292 patients were included. The percentage of patients receiving targeted narrow spectrum antibiotics increased from an average of 19% to 73% (figure 1). There was a concomitant decrease in the percentage of patients receiving broad-spectrum antibiotics (cefixime) from 46% to 3% (figure 2). Special cause variation was noted twice during the study period; immediately following pathway implementation and again 6 months later when the pathway was revised to increase provider education regarding appropriate antibiotic use.ConclusionsImplementation of clinical pathways for UTI can result in sustained improvements in antimicrobial stewardship among children seen in ED settings.Figure 1Percent of UTI Patients Receiving Narrow-Spectrum Antibiotic (cephalexin).Figure 2Percent of UTI Patients Receiving Broad-Spectrum Antibiotic (cefixime).
IDENTIFYING ACTIONABLE INFORMATION: PREVENTABLE 30-DAY NEUROSURGICAL READMISSIONS.
Authors: Laurans Maxwell , Tyrtova Evgeniya , Semlow Melani 
Published: October 2015

BackgroundHospital readmissions within 30 days after discharge are increasingly recognized as markers of inpatient quality of care and significant contributors to rising healthcare expenditures. Identifying potentially preventable readmission causes and developing targeted interventions is a national priority.ObjectivesTo determine rate, reasons, and potential for prevention for 30-day unplanned neurosurgical readmissions at Yale-New Haven Hospital.MethodsOver a 6-month period, all patients who had been discharged from YNHH after receiving care from the Department of Neurosurgery and readmitted within 30 days were retrospectively identified. In-depth chart analysis was performed to uncover relevant medical/social history and admission/readmission details.ResultsDuring 6 months, 84 (6.6%) of 1,279 patients were readmitted within 30 days. Reasons for readmission were categorized into miscellaneous (34%), non-surgical site infections (15%), postoperative wound complications (14%), intracranial hemorrhage (13%), neurological deficits: brain (10%), CSF device malfunction (8%), neurological deficits: spine (4%), and ischemic CNS events (2%). Most complications were moderate (54%) or mild (31%). Overall, 17% of readmissions were determined to be likely preventable, 10% – potentially preventable, 73% – not preventable. Notably, 42% of postoperative wound complications and 32% of brain-related neurological deficits could have been prevented. 49% of readmissions were related to initial hospitalization and 12% resulted from inappropriate post-discharge care; 34% and 88% of those, respectively, were preventable.ConclusionsOverall, 27% of 30-day neurosurgical readmissions were determined to be potentially preventable. Underlying reasons were identified and will be used to design targeted interventions. Preventing postoperative wound complications and providing appropriate discharge arrangements/instructions are the most promising areas of improvement.
IMPROVING THE TRANSFER OF MEDICALLY COMPLEX PATIENTS FROM THE CARDIAC INTENSIVE CARE UNIT TO THE CARDIOLOGY INPATIENT WARD
Authors: Storey Jean , Mustin Laurie , Madsen Nicolas , Kimball Melissa , Schoenling Gina , Brown James , Byrnes Jonathan , Cooper David 
Published: October 2015

BackgroundReadmission to the cardiac intensive care unit (CICU) increases LOS and cost, negatively impacts patient experience, throughput and resource allocation. A review of unplanned readmissions to the CICU identified that transfer of care and monitoring practices were not differentiated based on patient specific risk.ObjectivesTo increase days since last readmission to the CICU within 48 hours of transfer by defining patients at increased risk and standardizing key transfer processes.MethodsA standardized care process was developed and tested for patients at increased risk of readmission to CICU within 48 hours of transfer. Bundle components included: Patients identified 24 hours prior to transfer; Face to face nurse handoff in the CICU; Standardized team huddle on arrival to ward and prior to overnight hand-off; VS every 2 hours, I/O every 4 hours for 24 hours and RN staffing ratio of 2:1. Statistical process control charts were used to monitor progress.ResultsTransfer bundle compliance reached a median of 100%. Days between 48 hour readmissions to CICU increased from an average of 12 days to 45 days. Process control charts demonstrate 3 data points considered special cause after bundle compliance reached 100%.ConclusionsTransfer of care processes and outcomes for patients at increased risk of CICU readmission have improved. These interventions can be spread to other hospital units with the hopes of achieving similar results.Figure 1Figure 2Figure 3
Nurse led venesection: a quality improvement project
Authors: Patel Chandni , Morgan Dafydd 
Published: October 2015

AbstractVenesection is a widely practised procedure, involving the removal of a unit of blood in order to treat haemochromatosis and polycythaemia. It is still well regarded due to a lack of better alternatives and a small side effect profile. At Barnet General Hospital, venesection has recently been a physician led service, unlike its neighbouring hospital at Chase Farm Hospital, which has a well run nurse led service. The current service being run at Barnet Hospital was beset with problems, including delays in service provision and discharge, using junior doctors who may not be comfortable with or have knowledge of pre and post procedure checks. Furthermore, the medical day treatment unit is comprised of highly skilled nurses. 100% of nursing staff felt comfortable gaining venous access, but none had any formal training. Following a practical tutorial, followed by formal teaching, the nurses now run the venesection service. This has been done at no cost to the hospital, has sped up discharges and this has subsequently led to the capacity of the unit to venesect patients to increase by 100%.
Budd–Chiari syndrome: investigation, treatment and outcomes
Authors: Goel Rishi M , Johnston Emma L , Patel Kamal V , Wong Terence 
Published: October 2015

ABSTRACT
Budd–Chiari syndrome is a rare disorder characterised by hepatic venous outflow obstruction. It affects 1.4 per million people, and presentation depends upon the extent and rapidity of hepatic vein occlusion. An underlying myeloproliferative neoplasm is present in 50% of cases with other causes including infection and malignancy. Common symptoms are abdominal pain, hepatomegaly and ascites; however, up to 20% of cases are asymptomatic, indicating a chronic onset of hepatic venous obstruction and the formation of large hepatic vein collaterals. Doppler ultrasonography usually confirms diagnosis with cross-sectional imaging used for complex cases and to allow temporal comparison. Myeloproliferative neoplasms should be tested for even if a clear causative factor has been identified. Management focuses on anticoagulation with low-molecular-weight heparin and warfarin, with the new oral anticoagulants offering an exciting prospect for the future, but their current effectiveness in Budd–Chiari syndrome is unknown. A third of patients require further intervention in addition to anticoagulation, commonly due to deteriorating liver function or patients identified as having a poorer prognosis. Prognostic scoring systems help guide treatment, but management is complex and patients should be referred to a specialist liver centre. Recent studies have shown comparable procedure-related complications and long-term survival in patients who undergo transjugular intrahepatic portosystemic shunting and liver transplantation in Budd–Chiari syndrome compared with other liver disease aetiologies. Also, the optimal timing of these interventions and which patients benefit from liver transplantation instead of portosystemic shunting remains to be answered.
Arthur Smith Woodward's fossil fish type specimens
Authors: Bernard Emma Louise , Smith Mike 
Published: October 2015

Abstract
Four years after joining the Natural History Department of the British Museum in 1882, Arthur Smith Woodward published his first taxonomic paper erecting three new species based on sharks’ teeth. He retired from the Natural History Museum in 1924 but continued to publish until his death in 1944 at the age of 80. In total he named 321 new fossil fishes, a remarkable achievement, marking him out as the most influential palaeoichthyologist of his time. For the first time brief details of all his type specimens are brought together, accompanied in many cases by high-quality photographic images, in an online format readily available to anyone with access to the Internet.

Supplementary material:

Details of all the Smith Woodward type specimens, including images, are available at
http://www.geolsoc.org.uk/SUP18874
Bortezomib Improves Adoptive T-cell Therapy by Sensitizing Cancer Cells to FasL Cytotoxicity
Authors: Shanker Anil , Pellom Samuel T. , Dudimah Duafalia F. , Thounaojam Menaka C. , de Kluyver Rachel L. , Brooks Alan D. , Yagita Hideo , McVicar Daniel W. , Murphy William J. , Longo Dan L. , Sayers Thomas J. 
Published: October 2015

AbstractCancer immunotherapy shows great promise but many patients fail to show objective responses, including in cancers that can respond well, such as melanoma and renal adenocarcinoma. The proteasome inhibitor bortezomib sensitizes solid tumors to apoptosis in response to TNF-family death ligands. Because T cells provide multiple death ligands at the tumor site, we investigated the effects of bortezomib on T-cell responses in immunotherapy models involving low-avidity antigens. Bortezomib did not affect lymphocyte or tissue-resident CD11c+CD8+ dendritic cell counts in tumor-bearing mice, did not inhibit dendritic cell expression of costimulatory molecules, and did not decrease MHC class I/II-associated antigen presentation to cognate T cells. Rather, bortezomib activated NF-κB p65 in CD8+ T cells, stabilizing expression of T-cell receptor CD3ζ and IL2 receptor-α, while maintaining IFNγ secretion to improve FasL-mediated tumor lysis. Notably, bortezomib increased tumor cell surface expression of Fas in mice as well as human melanoma tissue from a responsive patient. In renal tumor-bearing immunodeficient Rag2−/− mice, bortezomib treatment after adoptive T-cell immunotherapy reduced lung metastases and enhanced host survival. Our findings highlight the potential of proteasome inhibitors to enhance antitumor T-cell function in the context of cancer immunotherapy. Cancer Res; 75(24); 5260–72. ©2015 AACR.
СТРАТЕГІЯ СТВОРЕННЯ ТА ОЦІНЮВАННЯ ФУНКЦІОНУВАННЯ СИСТЕМ УПРАВЛІННЯ ЯКІСТЮ МЕДИЧНОЇ ОСВІТИ. ПЕРШЕ ПОВІДОМЛЕННЯ. ПОСТАНОВКА ПРОБЛЕМИ
Authors: Mintser O. P. , Tolstanov О. K. , Zagoriy G. V. , Kalyta T. P. 
Published: October 2015

<p>The article is devoted to functioning of the quality management by ISO 9001 standard. The problem of inefficient and non-working systems is pointed out, the causes of their inefficiency are investigated. The phenomenon of simultaneous existence of two parallel management systems: formal quality management system and living systems of managerial decisions making is studied. To study this situation the measure of «efficiency of quality management system» is introduced; further tasks for creating indicators and mechanisms for its evaluation are defined.</p>
ВИЗНАЧЕННЯ ОСОБЛИВОСТЕЙ ГЕНОТИПІВ У ЖІНОК З ГЕНІТАЛЬНИМ ЕНДОМЕТРІОЗОМ ТА ФІБРОЗНО-КІСТОЗНОЮ МАСТОПАТІЄЮ ТА ЇХ РОЛЬ У ТЯЖКОСТІ ПЕРЕБІГУ ЗАХВОРЮВАННЯ
Authors: Malanchuk L. M. , Martinyuk V. M. 
Published: October 2015

The scientific work is devoted to the urgent problem of our time - dishormonal disease of the female reproductive system, namely endometriosis and fibrosis-cystic mastitis. During the last years there has been a steady increase in the dual pathology of genital and breast diseases. According to statistics dishormonal frequency of breast diseases in the population of the female population suffering from various gynecological diseases varies between 76-98 %. It is known that the risk of this disease is closely associated with some alleles detoxification system, glutathione family - S- transferase and proonkogenom p 53, characterized by significant polymorphism. The article presents the results of research on the role of deletion variants of genes GSTT1, GSTM1 and p 53 in the development of endometriosis and fibrosis-cystic mastitis. Screening populations on carriage of alleles reveals women who are likely to develop these diseases and choose the most effective tactics of medical treatment in the event of the disease.