bluuebunny/crossref_metadata_2025_split huggingface dataset:
Induction of porcine‐specific regulatory T cells with high specificity and expression of IL‐10 and TGF‐β1 using baboon‐derived tolerogenic dendritic cells
Authors: Li Mingqian , Eckl Judith , Abicht Jan‐Michael , Mayr Tanja , Reichart Bruno , Schendel Dolores J. , Pohla Heike 
Published: October 2017

AbstractBackgroundRegulatory T cells (Treg) play an important role in maintenance of homeostasis in vivo. Treg application to alleviate allo‐organ rejection is being studied extensively. However, natural Treg (nTreg) expansion in vitro is laborious and expensive. Antigen‐specific Treg are more effective and require lower cell numbers than use of nTreg for immune control. The baboon, as a non‐human primate experimental animal model, is widely used in xenotransplantation research. An effective method to generate baboon xeno‐specific Treg would benefit research on immune tolerance in xenotransplantation using this model system.MethodBaboon tolerogenic dendritic cells (tolDC) were generated in 3 days from monocytes isolated from baboon peripheral blood mononuclear cells in medium supplemented with anti‐inflammatory cytokines. After loading with porcine‐specific (PS) in vitro‐transcribed RNA (ivtRNA), tolDC were used to induce CD4+ T cells to become porcine‐specific Treg (PSTreg) in cocultures supplemented with IL‐2 and rapamycin for 10 days. Anti‐inflammatory and inflammatory cytokine expression was evaluated at the mRNA and protein levels in both baboon tolDC and PSTreg. Functional assays, suppression of activation markers on porcine‐specific effector T cells (PSTeff) and inhibition of PSTeff proliferation, were used to test PSTreg specificity.ResultsTolDC generated with this method exhibited a tolerogenic phenotype, expressed CCR7 and produced high levels of IL‐10 and TGF‐β1, whereas IL‐12p40 and IFN‐γ were not expressed. PSTreg were successfully generated in cocultures of CD4+ T cells and PS ivtRNA‐loaded tolDC. They exhibited a CD3+ CD4+ CD25+ CD127low/− CD45RAlow Foxp3+ phenotype and were characterized by high expression of IL‐10 and TGF‐β1 mRNA and protein. They showed upregulated expression of EBI3 and GARP mRNA. PSTreg exhibited highly suppressive effects toward PSTeff, secreting high amounts of IL‐10 and TGF‐β1 cytokine upon interaction with PSTeff and suppressing IFN‐γ expression on PSTeff.ConclusionIn this study, a fast 3‐day method to generate baboon‐derived tolDC is provided that allows subsequent induction of PSTreg displaying high porcine‐antigen specificity and expression of IL‐10 and TGF‐β1. Porcine‐specific baboon Treg can be used in porcine solid organ or cell xenotransplantation studies through adoptive cell transfer into host baboons.
Pre‐clinical results in pig‐to‐non‐human primate islet xenotransplantation using anti‐CD40 antibody (2C10R4)‐based immunosuppression
Authors: Shin Jun‐Seop , Kim Jong‐Min , Min Byoung‐Hoon , Yoon Il Hee , Kim Hyun Je , Kim Jung‐Sik , Kim Yong‐Hee , Kang Seong‐Jun , Kim Jiyeon , Kang Hee‐Jung , Lim Dong‐Gyun , Hwang Eung‐Soo , Ha Jongwon , Kim Sang‐Joon , Park Wan Beom , Park Chung‐Gyu 
Published: October 2017

AbstractBackgroundIslet transplantation is an effective therapy for selected patients with type 1 diabetes with labile glycemic control and hypoglycemic unawareness, but donor organs are limited. Islet xenotransplantation using porcine islets will potentially solve this problem. Although successful proof of concept studies using clinically inapplicable anti‐CD154 monoclonal antibody (mAb) in pig‐to‐non‐human primate (NHP) islet xenotransplantation has been demonstrated by several groups worldwide, potentially clinically applicable anti‐CD40 (2C10R4) mAb‐based studies have not been reported.MethodsNine streptozotocin (STZ)‐induced diabetic rhesus monkeys were transplanted with adult porcine islets isolated from designated pathogen‐free (DPF) miniature pigs. They were treated with anti‐CD40 mAb‐based immunosuppressive regimen and were divided into 3 groups: anti‐CD40 only group (n = 2), belatacept group (anti‐CD40 mAb+belatacept, n = 2), and tacrolimus group (anti‐CD40 mAb+tacrolimus, n = 5). All monkeys received anti‐thymocyte globulin (ATG), cobra venom factor (CVF), adalimumab, and sirolimus. Blood glucose levels (BGL) and serum porcine C‐peptide concentrations were measured. Humoral and cellular immune responses were assessed by ELISA and ELISPOT, respectively. Liver biopsy and subsequent immunohistochemistry were conducted.ResultsAll animals restored normoglycemia immediately after porcine islet transplantation and finished the follow‐up without any severe adverse effects except for one animal (R092). Most animals maintained their body weight. Median survival, as defined by a serum porcine C‐peptide concentration of >0.15 ng/mL, was 31, 27, and 60 days for anti‐CD40 only, belatacept, and tacrolimus groups, respectively. Anti‐αGal IgG levels in serum and the number of interferon‐γ secreting T cells in peripheral blood mononuclear cells did not increase in most animals.ConclusionThese results showed that anti‐CD40 mAb combined with tacrolimus was effective in prolonging porcine islet graft survival, but anti‐CD40 mAb was not as effective as anti‐CD154 mAb in terms of preventing early islet loss.
Risk factors of Leptospira infection in Mediterranean periurban micromammals
Authors: Millán J. , Cevidanes A. , Chirife A. D. , Candela M. G. , León‐Vizcaíno L. 
Published: October 2017

SummaryUrbanization of natural areas can change abiotic factors, providing artificial sources of humidity in summer and decreasing variation of temperatures in winter. Our study aimed at document risk factors of infection in mammal reservoirs of pathogenic Leptospira in the human/wildlife interface of a large metropolitan area. We hypothesize that survival of Leptospira and thus their prevalence in animal reservoirs should be higher in residential areas than in natural habitats, especially after the hot, dry Mediterranean summers. We established the prevalence of Leptospira spp. and identified the serovars in 353 urine samples from micromammals (chiefly the wood mouse Apodemus sylvaticus, n = 266) using direct immunofluorescence and PCR. Animals were captured in spring and autumn, 2011–2012, in two natural parks and two adjacent residential areas in periurban Barcelona (NE Spain). Overall observed prevalence of infection was 11%, ranking between 8% and 13% in the better represented host species. We observed marked differences between seasons; the probability of finding a micromammal infected in spring was three times greater than in autumn (almost four times for wood mouse). Prevalence was not related with type of habitat, micromammal relative abundance or sex of the animal. Three Leptospira species were confirmed: Leptospira interrogans (47% of cases), Leptospira borgpetersenii (41%) and Leptospira kirschneri (12%). The serovars most commonly detected were those typically hosted by rodents, and serovars Ballum and Icterohemorrhagiae were the only ones found in autumn. People living in periurban Barcelona and those visiting the natural areas of the metropolitan area face hazard of infection with rodent‐borne Leptospira, especially during spring.
Discretization Based Heuristics for the Capacitated Multi-facility Weber Problem with Convex Polyhedral Barriers
Authors: Akyüz M. Hakan 
Published: October 2017

The Capacitated Multi-facility Weber Problem addresses optimally locating I capacitated facilities in the plane and satisfying demand of J customers so as to minimize the total transportation cost. It assumes that facilities can be located anywhere on the plane and customers are directly connected to them. This study considers the case where there exist convex polyhedral barriers blocking passage and locating facilities inside. Then, the distances between facilities and customers have to be measured by taking into account the polyhedral barriers. The resulting problem is non-convex and difficult to solve. We propose several discretization based heuristic procedures which are especially designed for the problem. The performance of the suggested methods are tested on an extensive set of randomly generated test instances which are derived from standard test instances. Our results imply that the suggested heuristics yield very accurate and efficient solutions for this problem.
Neonatal brain injuries in England: population-based incidence derived from routinely recorded clinical data held in the National Neonatal Research Database
Authors: Gale Chris , Statnikov Yevgeniy , Jawad Sena , Uthaya Sabita N , Modi Neena 
Published: October 2017

ObjectiveIn 2015, the Department of Health in England announced an ambition to reduce ‘brain injuries occurring during or soon after birth’. We describe the development of a pragmatic case definition and present annual incidence rates.DesignRetrospective cohort study using data held in the National Neonatal Research Database (NNRD) extracted from neonatal electronic patient records from all National Health Service (NHS) neonatal units in England, Wales and Scotland. In 2010–2011, population coverage in the NNRD was incomplete, hence rate estimates are presented as a range; from 2012, population coverage is complete, and rates (95% CIs) are presented. Rates are per 1000 live births.SettingNHS neonatal units in England.PatientsInfants admitted for neonatal care; denominator: live births in England.Main outcome measure‘Brain injuries occurring at or soon after birth’ defined as infants with seizures, hypoxic-ischaemic encephalopathy, stroke, intracranial haemorrhage, central nervous system infection and kernicterus and preterm infants with cystic periventricular leucomalacia.ResultsIn 2010, the lower estimate of the rate of ‘Brain injuries occurring at or soon after birth’ in England was 4.53 and the upper estimate was 5.19; in 2015, the rate was 5.14 (4.97, 5.32). For preterm infants, the population incidence in 2015 was 25.88 (24.51, 27.33) and 3.47 (3.33, 3.62) for term infants. Hypoxic-ischaemic encephalopathy was the largest contributor to term brain injury, and intraventricular/periventricular haemorrhage was the largest contributor to preterm brain injury.ConclusionsAnnual incidence rates for brain injuries can be estimated from data held in the NNRD; rates for individual conditions are consistent with published rates. Routinely recorded clinical data can be used for national surveillance, offering efficiencies over traditional approaches.
Prevalence of blindness and cataract surgical coverage in Narayani Zone, Nepal: a rapid assessment of avoidable blindness (RAAB) study
Authors: Pradhan Sangita , Deshmukh Avnish , Giri Shrestha Puspa , Basnet Prajwal , Kandel Ram Prasad , Lewallen Susan , Sapkota Yuddha Dhoj , Bassett Ken , Yin Vivian T 
Published: October 2017

BackgroundThe 1981 Nepal Blindness Survey first identified the Narayani Zone as one of the regions with the highest prevalence of blindness in the country. Subseuqently, a 2006 survey of the Rautahat District of the Narayani Zone found it to have the country’s highest blindness prevalence. This study examines the impact on blind avoidable and treatable eye conditions in this region after significant increase in eye care services in the past decade.MethodsThe rapid assessment of avoidable blindness (RAAB) methodology was used with mobile data collection using the mRAAB smartphone app. Data analysis was done using the standard RAAB software. Based on the 2011 census, 100 clusters of 50 participants aged 50 years or older were randomly sampled proportional to population size.ResultsOf the 5000 participants surveyed, 4771 (95.4%) were examined. The age-adjusted and sex-adjusted prevalence of bilateral blindness, severe visual impairment (SVI) and moderate visual impairment (MVI) were 1.2% (95% CI 0.9% to 1.5%), 2.5% (95% CI 2.0% to -3.0%) and 13.2% (95% CI 11.8% to 14.5%), respectively. Cataract remains the primary cause of blindness and SVI despite cataract surgery coverage (CSC) of 91.5% for VA<3/60. Women still account for two-thirds of blindness.ConclusionThe prevalence of blindness in people over the age of 50 years has decreased from 6.9% in 2006 to 1.2%, a level in keeping with the national average; however, significant gender inequity persists. CSC has improved but continues to favour men.
Electronic medical record alert improves HCV testing for baby boomers in primary care setting: adults born during 1945–1965
Authors: Al-hihi Eyad , Shankweiler Caylin , Stricklen David , Gibson Cheryl , Dunn Winston 
Published: October 2017

MethodThis project aims to implement the HCV birth cohort screening guidelines over a 9-month period in the primary care setting at the University of Kansas Health System General Internal Medicine Division.The project team measured the number of patients in the baby boomer population who received a one-time screen for HCV. An electronic medical record (EMR) intervention was implemented to identify baby boomers who did not have an HCV screening or diagnosis. Additionally, education was provided to all primary care providers in the clinic to increase awareness of the HCV birth cohort screening.ResultsThe quality improvement methods increased the percentage of baby boomers who obtained a one-time screening test for HCV from a baseline of 30% to a 55% screening rate during the nine-month project period.ConclusionIdentifying the HCV screening needs and creating a visual reminder in the EMR can be used to facilitate sustainable awareness and improvement of screening rates. The project team recognizes that continued work is required to close the HCV screening care gaps in the primary care setting.
Improving care collaboration for NICU patients to decrease length of stay and readmission rate
Authors: Welch Cherrie D , Check Jennifer , O’Shea T Michael 
Published: October 2017

BackgroundMedically complex patients in neonatal intensive care units (NICUs) typically require long hospitalisations and care from multiple subspecialists. Scheduled multidisciplinary discussions could improve collaboration and continuity of care and thereby improve patient outcomes. The specific aims of the project were to decrease the average length of hospitalisation by at least 1 day and improve parent satisfaction ratings on a standard questionnaire by the end of our project’s first year, and to maintain a stable (or decreased) cause-related (30-day) readmission rate.MethodsWe designed a quality improvement project to enhance collaboration and continuity of care for medically complex infants cared for in the NICU of Brenner Children’s Hospital. Weekly multidisciplinary team meetings were held to discuss the long-term plan for patients who met specific criteria. Attendees included attending neonatologists, paediatric surgeons, a physical therapist, an occupational therapist, a speech therapist, a social worker, a nurse coordinator for palliative care, a family support coordinator, the NICU Nurse Manager, a hospital chaplain, mid-level providers, bedside nurses, a nurse quality improvement leader and the leaders and database manager for the quality improvement project. When needed for specific patients, a bioethicist was included.ResultsOne year after implementing the project, the average duration of hospitalisation had decreased by 6.5 days. Cause-related readmission rates decreased from 3.33% to 0.95%. Parent satisfaction scores did not change significantly.ConclusionsWeekly multidisciplinary meetings to coordinate and provide continuity of care for medically complex neonates in our NICU was associated with improved patient outcomes.
Fall-related mortality in southern Sweden: a multiple cause of death analysis, 1998–2014
Authors: Kiadaliri Aliasghar A , Rosengren Björn E , Englund Martin 
Published: October 2017

ObjectivesTo investigate temporal trend in fall mortality among adults (aged ≥20 years) in southern Sweden using multiple cause of death data.MethodsWe examined all death certificates (DCs, n=2 01 488) in adults recorded in the Skåne region during 1998–2014. We identified all fall deaths using International Statistical Classification of Diseases (ICD)-10 codes (W00-W19) and calculated the mortality rates by age and sex. Temporal trends were evaluated using joinpoint regression and associated causes were identified by age-adjusted and sex-adjusted observed/expected ratios.ResultsFalls were mentioned on 1.0% and selected as underlying cause in 0.7% of all DCs, with the highest frequency among those aged ≥70 years. The majority (75.6%) of fall deaths were coded as unspecified fall (ICD-10 code: W19) followed by falling on or from stairs/steps (7.7%, ICD-10 code: W10) and other falls on the same level (6.3%, ICD-10 code: W18). The mean age at fall deaths increased from 77.5 years in 1998–2002 to 82.9 years in 2010–2014 while for other deaths it increased from 78.5 to 79.8 years over the same period. The overall mean age-standardised rate of fall mortality was 8.3 and 4.0 per 1 00 000 person-years in men and women, respectively, and increased by 1.7% per year in men and 0.8% per year in women during 1998–2014. Head injury and diseases of the circulatory system were recorded as contributing cause on 48.7% of fall deaths.ConclusionsThere is an increasing trend of deaths due to falls in southern Sweden. Further investigations are required to explain this observation particularly among elderly men.
Epidemiology of paediatric trauma presenting to US emergency departments: 2006–2012
Authors: Avraham Jacob B , Bhandari Misha , Frangos Spiros G , Levine Deborah A , Tunik Michael G , DiMaggio Charles J 
Published: October 2017

BackgroundTraumatic injury is the leading cause of paediatric morbidity and mortality in the USA. We present updated national data on emergency department (ED) discharges for traumatic injury for a recent 7-year period.MethodsWe conducted a descriptive epidemiological analysis of the Nationwide Emergency Department Sample Survey, the largest and most comprehensive database in the USA, for 2006–2012. Among children and adolescents, we tracked changes in injury mechanism and severity, cost of care, injury intent and the role of trauma centres.ResultsThere was an 8.3% (95% CI 7.7 to 8.9) decrease in the annual number of ED visits for traumatic injury in children and adolescents over the study period, from 8 557 904 (SE=5861) in 2006 to 7 846 912 (SE=5191) in 2012. The case-fatality rate was 0.04% for all injuries and 3.2% for severely injured children. Children and adolescents with high-mortality injury mechanisms were more than three times more likely to be treated at a level 1 trauma centre (OR=3.5, 95% CI 3.3 to 3.7), but were more no more likely to die (OR=0.96, 95% CI 0.93 to 1.00). Traumatic brain injury diagnoses increased 22.2% (95% CI 20.6 to 23.9) during the study period. Intentional assault accounted for 3% (SE=0.1) of all child and adolescent ED injury discharges and 7.2% (SE=0.3) of discharges among 15–19 year-olds. There was an 11.3% (95% CI 10.0 to 12.6) decline in motor vehicle injuries from 2009 to 2012. The total cost of care was $23 billion (SE=0.01), a 78% increase from 2006 to 2012.ConclusionsThis analysis presents a recent portrait of paediatric trauma across the USA. These analyses indicate the important role and value of trauma centre care for injured children and adolescents, and that the most common causes and mechanisms of injury are preventable.
Age–period–cohort analysis of trends in blood pressure and body mass index in children and adolescents in Hong Kong
Authors: Kwok Man Ki , Tu Yu Kang , Kawachi Ichiro , Schooling C Mary 
Published: October 2017

BackgroundThe declining or fluctuating trend in blood pressure (BP) despite the rising trend in body mass index (BMI) during childhood and adolescence is unexplained. We decomposed trends in BP and BMI to identify the relevance of early-life and contemporaneous factors.MethodsWe assessed the relative contribution of age, period and cohort to secular trends in BP in children and adolescents (9–18 years) from 1999 to 2014 and BMI (6–18 years) from 1996 to 2014 in Hong Kong, China.ResultsAfter accounting for age, period effects contributed more than cohort effects to the overall fluctuating BP trend and the rising BMI trend observed in this Chinese population. For both sexes, BP fell from the start of period to a low point in 2003–2005 but then rose. BMI rose strongly across the period before levelling off in 2009–2010. Earlier cohorts (born in 1983–1984) had higher BP and BMI than later cohorts.ConclusionWith globalisation and associated lifestyle changes, successive generations of children and adolescents in a recently developed Chinese setting had lower BP and BMI, but this fall was offset until recently by population-wide increase in BMI. School-based health promotion efforts could have partly mitigated the population-wide rise in child and adolescent BMI, while socioeconomic transition or other factors could be relevant to changes in BP between generations. Explaining these trends will help identify early-life factors that may contribute to a healthier start as well as contemporaneous factors that may protect against rising trends in adiposity.
Acute convexity subarachnoid haemorrhage and cortical superficial siderosis in probable cerebral amyloid angiopathy without lobar haemorrhage
Authors: Charidimou Andreas , Boulouis Grégoire , Fotiadis Panagiotis , Xiong Li , Ayres Alison M , Schwab Kristin M , Gurol Mahmut Edip , Rosand Jonathan , Greenberg Steve M , Viswanathan Anand 
Published: October 2017

IntroductionAcute non-traumatic convexity subarachnoid haemorrhage (cSAH) is increasingly recognised in cerebral amyloid angiopathy (CAA). We investigated: (a) the overlap between acute cSAH and cortical superficial siderosis—a new CAA haemorrhagic imaging signature and (b) whether acute cSAH presents with particular clinical symptoms in patients with probable CAA without lobar intracerebral haemorrhage.MethodsMRI scans of 130 consecutive patients meeting modified Boston criteria for probable CAA were analysed for cortical superficial siderosis (focal, ≤3 sulci; disseminated, ≥4 sulci), and key small vessel disease markers. We compared clinical, imaging and cortical superficial siderosis topographical mapping data between subjects with versus without acute cSAH, using multivariable logistic regression.ResultsWe included 33 patients with probable CAA presenting with acute cSAH and 97 without cSAH at presentation. Patients with acute cSAH were more commonly presenting with transient focal neurological episodes (76% vs 34%; p<0.0001) compared with patients with CAA without cSAH. Patients with acute cSAH were also more often clinically presenting with transient focal neurological episodes compared with cortical superficial siderosis-positive, but cSAH-negative subjects with CAA (76% vs 30%; p<0.0001). Cortical superficial siderosis prevalence (but no other CAA severity markers) was higher among patients with cSAH versus those without, especially disseminated cortical superficial siderosis (49% vs 19%; p<0.0001). In multivariable logistic regression, cortical superficial siderosis burden (OR 5.53; 95% CI 2.82 to 10.8, p<0.0001) and transient focal neurological episodes (OR 11.7; 95% CI 2.70 to 50.6, p=0.001) were independently associated with acute cSAH.ConclusionsThis probable CAA cohort provides additional evidence for distinct disease phenotypes, determined by the presence of cSAH and cortical superficial siderosis.