bluuebunny/crossref_metadata_2025_split huggingface dataset:
Possible detrimental effects of beta‐2‐microglobulin knockout in pigs
Authors: Sake Hendrik Johannes , Frenzel Antje , Lucas‐Hahn Andrea , Nowak‐Imialek Monika , Hassel Petra , Hadeler Klaus‐Gerd , Hermann Doris , Becker Roswitha , Eylers Heinke , Hein Rabea , Baars Wiebke , Brinkmann Antje , Schwinzer Reinhard , Niemann Heiner , Petersen Björn 
Published: May 2019

AbstractBackgroundDespite major improvements in pig‐to‐primate xenotransplantation, long‐term survival of xenografts is still challenging. The major histocompatibility complex (MHC) class I, which is crucial in cellular immune response, is an important xenoantigen. Abrogating MHC class I expression on xenografts might be beneficial for extending graft survival beyond current limits.MethodsIn this study, we employed the CRISPR/Cas9 system to target exon 2 of the porcine beta‐2‐microglobulin (B2M) gene to abrogate SLA class I expression on porcine cells. B2M‐KO cells served as donor cells for somatic cell nuclear transfer, and cloned embryos were transferred to three recipient sows. The offspring were genotyped for mutations at the B2M locus, and blood samples were analyzed via flow cytometry for the absence of SLA class I molecules.ResultsPregnancies were successfully established and led to the birth of seven viable piglets. Genomic sequencing proved that all piglets carried biallelic modifications at the B2M locus leading to a frameshift, a premature stop codon, and ultimately a functional knockout. However, survival times of these animals did not exceed 4 weeks due to unexpected disease processes.ConclusionHere, we demonstrate the feasibility of generating SLA class I knockout pigs by targeting the porcine beta‐2‐microglobulin gene using the CRISPR/Cas9 system. Additionally, our findings indicate for the first time that this genetic modification might have a negative impact on the viability of the animals. These issues need to be solved to unveil the real value for xenotransplantation in the future.
Late Mesozoic intraplate rhyolitic volcanism in the North China Craton: Far-field effect of the westward subduction of the Paleo-Pacific Plate
Authors: Yang Fan , Santosh M. , Kim Sung Won , Zhou Hongying , Jeong Youn Joong 
Published: May 2019

AbstractThe Late Mesozoic was characterized by extensive volcanism, crustal extension, lithospheric thinning, and craton destruction in the North China Craton (NCC). Here we investigate the petrology, whole-rock geochemistry, zircon U-Pb geochronology, and Lu-Hf isotope of rhyolitic rocks from the Chicheng region of China along the northern margin of the NCC to constrain their petrogenesis, magma evolution, and associated geodynamic processes. The newly obtained zircon U-Pb age data constrain the eruption age of rhyolitic rocks at ca. 144–114 Ma during the Early Cretaceous with multiple magmatic pulses at ca. 141, ca. 137, and ca. 130 Ma as defined by the age peaks. Zircon Hf isotopic data show markedly negative εHf(t) values of –23.0 to –11.8, and corresponding Hf crustal model ages (TDMC) are in the range of ca. 2650 to 1944 Ma, suggesting magma derivation through melting of Paleoproterozoic crustal materials with minor input of reworked Neoarchean components. Geochemically, the rhyolitic rocks correspond to A-type granites, with a mixed arc- and subduction-related signature, although generated in an extensional intraplate setting through partial melting of the mafic lower crust and upper crustal fractional crystallization. We correlate the late Mesozoic intraplate volcanism to the westward subduction of the Paleo-Pacific Plate and its far-field effect. Lithospheric extension and slab rollback of the Paleo-Pacific Plate are considered as the main triggers for the multiple eruptions. The late Mesozoic volcanism in the study area and adjacent regions also broadly coincide with the tectonic transition from the Paleozoic Paleo-Asian to Mesozoic Paleo-Pacific subduction realm with concomitant compressional to extensional tectonic regime.
An improved approach to age-modeling in deep time: Implications for the Santa Cruz Formation, Argentina
Authors: Trayler Robin B. , Schmitz Mark D. , Cuitiño José I. , Kohn Matthew J. , Bargo M. Susana , Kay Richard F. , Strömberg Caroline A.E. , Vizcaíno Sergio F. 
Published: May 2019

AbstractAccurate age-depth models for proxy records are crucial for inferring changes to the environment through space and time, yet traditional methods of constructing these models assume unrealistically small age uncertainties and do not account for many geologic complexities. Here we modify an existing Bayesian age-depth model to foster its application for deep time U-Pb and 40Ar/39Ar geochronology. More flexible input likelihood functions and use of an adaptive proposal algorithm in the Markov Chain Monte Carlo engine better account for the age variability often observed in magmatic crystal populations, whose dispersion can reflect inheritance, crystal residence times and daughter isotope loss. We illustrate this approach by calculating an age-depth model with a contiguous and realistic uncertainty envelope for the Miocene Santa Cruz Formation (early Miocene; Burdigalian), Argentina. The model is calibrated using new, high-precision isotope dilution U-Pb zircon ages for stratigraphically located interbedded tuffs, whose weighted mean ages range from ca. 16.78 ± 0.03 Ma to 17.62 ± 0.03 Ma. We document how the Bayesian age-depth model objectively reallocates probability across the posterior ages of dated horizons, and thus produces better estimates of relative ages among strata and variations in sedimentation rate. We also present a simple method to propagate age-depth model uncertainties onto stratigraphic proxy data using a Monte Carlo technique. This approach allows us to estimate robust uncertainties on isotope composition through time, important for comparisons of terrestrial systems to other proxy records.
Physiologically based cord clamping improves cardiopulmonary haemodynamics in lambs with a diaphragmatic hernia
Authors: Kashyap Aidan J , Hodges Ryan J , Thio Marta , Rodgers Karyn A , Amberg Ben J , McGillick Erin V , Hooper Stuart B , Crossley Kelly J , DeKoninck Philip L J 
Published: May 2019

ObjectiveLung hypoplasia associated with congenital diaphragmatic hernia (CDH) results in respiratory insufficiency and pulmonary hypertension after birth. We have investigated whether aerating the lung before removing placental support (physiologically based cord clamping (PBCC)), improves the cardiopulmonary transition in lambs with a CDH.MethodsAt ≈138 days of gestational age, 17 lambs with surgically induced left-sided diaphragmatic hernia (≈d80) were delivered via caesarean section. The umbilical cord was clamped either immediately prior to ventilation onset (immediate cord clamping (ICC); n=6) or after achieving a target tidal volume of 4 mL/kg, with a maximum delay of 10 min (PBCC; n=11). Lambs were ventilated for 120 min and physiological changes recorded.ResultsPulmonary blood flow (PBF) increased following ventilation onset in both groups, but was 19-fold greater in PBCC compared with ICC lambs at cord clamping (19±6.3 vs 1.0±0.5 mL/min/kg, p<0.001). Cerebral tissue oxygenation was higher in PBCC than ICC lambs during the first 10 min after cord clamping (59%±4% vs 30%±5%, p<0.001). PBF was threefold higher (23±4 vs 8±2 mL/min/kg, p=0.01) and pulmonary vascular resistance (PVR) was threefold lower (0.6±0.1 vs 2.2±0.6 mm Hg/(mL/min), p<0.001) in PBCC lambs compared with ICC lambs at 120 min after ventilation onset.ConclusionsCompared with ICC, PBCC prevented the severe asphyxia immediately after birth and resulted in a higher PBF due to a lower PVR, which persisted for at least 120 min after birth in CDH lambs.
Public provision of emergency obstetric care: a case study in two districts of Pakistan
Authors: Brückmann Peter , Hashmi Ashfa , Kuch Marina , Kuhnt Jana , Monfared Ida , Vollmer Sebastian 
Published: May 2019

ObjectivesPakistan is one out of five countries where together half of the global neonatal deaths occur. As the provision of services and facilities is one of the key elements vital to reducing this rate as well as the maternal mortality rate, this study investigates the status of the delivery of essential obstetric care provided by the public health sector in two districts in Khyber Pakhtunkhwa in 2015 aiming to highlight areas where critical improvements are needed.SettingWe analysed data from a survey of 22 primary and secondary healthcare facilities as well as 85 community midwives (CMWs) in Haripur and Nowshera districts.ParticipantsUsing a structured questionnaire we evaluated the performance of emergency obstetric care (EmOC) signal functions and patient statistics in public health facilities. Also, 102 CMWs were interviewed about working hours, basic and specialised delivery service provision, referral system and patient statistics.Primary outcome measuresWe investigate the public provision of emergency obstetric care using seven key medical services identified by the United Nations (UN).ResultsDeliveries by public health cadres account for about 30% of the total number of births in these districts. According to the UN benchmark, only a small fraction of basic EmOC (2/18) and half of the comprehensive EmOC (2/4) facilities of the recommended minimum number were available to the population in both districts. Only a minority of health facilities and CMWs carry out several signal functions. Only 8% of the total births in one of the study districts are performed in public EmOC health facilities.ConclusionsBoth districts show a significant shortage of available public EmOC service provisions. Development priorities need to be realigned to improve the availability, accessibility and quality of EmOC service provisions by the public health sector alongside with existing activities to increase institutional births.
Patterns of amenable child mortality over time in 34 member countries of the Organisation for Economic Co-operation and Development (OECD): evidence from a 15-year time trend analysis (2001–2015)
Authors: Gianino Maria Michela , Lenzi Jacopo , Bonaudo Marco , Fantini Maria Pia , Siliquini Roberta , Ricciardi Walter , Damiani Gianfranco 
Published: May 2019

ObjectivesTo analyse the trends of amenable mortality rates (AMRs) in children over the period 2001–2015.DesignTime trend analysis.SettingThirty-four member countries of the Organisation for Economic Co-operation and Development (OECD).ParticipantsMidyear estimates of the resident population aged ≤14 years.Primary and secondary outcome measuresUsing data from the WHO Mortality Database and Nolte and McKee’s list, AMRs were calculated as the annual number of deaths over the population/100 000 inhabitants. The rates were stratified by age groups (<1, 1–4, 5–9 and 10–14 years). All data were summarised by presenting the average rates for the years 2001/2005, 2006/2010 and 2011/2015.ResultsThere was a significant decline in children’s AMRs in the <1 year group in all 34 OECD countries from 2001/2005 to 2006/2010 (332.78 to 295.17/100 000; %Δ −11.30%; 95% CI −18.75% to −3.85%) and from 2006/2010 to 2011/2015 (295.17 to 240.22/100 000; %Δ −18.62%; 95% CI −26.53% to −10.70%) and a slow decline in the other age classes. The only cause of death that was significantly reduced was conditions originating in the early neonatal period for the <1 year group. The age-specific distribution of causes of death did not vary significantly over the study period.ConclusionsThe low decline in amenable mortality rates for children aged ≥1 year, the large variation in amenable mortality rates across countries and the insufficient success in reducing mortality from all causes suggest that the heath system should increase its efforts to enhance child survival. Promoting models of comanagement between primary care and subspecialty services, encouraging high-quality healthcare and knowledge, financing universal access to healthcare and adopting best practice guidelines might help reduce amenable child mortality.
Establishing a core outcome set for treatment of uncomplicated appendicitis in children: study protocol for an international Delphi survey
Authors: Knaapen Max , Hall Nigel J , van der Lee Johanna H , Butcher Nancy J , Offringa Martin , Van Heurn Ernst W E , Bakx Roel , Gorter Ramon R 
Published: May 2019

IntroductionAppendicitis is a global disease affecting roughly 1 in every 12 people in the world, with the highest incidence between ages 10 and 19 years. To date, a wide variety of health outcomes have been reported in randomised controlled trials and meta-analyses evaluating treatments for appendicitis. This is especially the case in studies comparing non-operative treatment with operative treatment. A set of standard outcomes, to be reported in all future trials, is needed to allow for adequate comparison and interpretation of clinical trial results and to make data pooling possible. This protocol describes the development of such a global core outcome set (COS) to allow unified reporting of treatment interventions in children with acute uncomplicated appendicitis.Methods and analysisWe use current international standard methodology for the development and reporting of this COS. Its development consists of three phases: (1) an update of the most recent systematic review on outcomes reported in uncomplicated paediatric appendicitis research to identify additional outcomes, (2) a three-step global Delphi study to identify a set of core outcomes for which there is consensus between parents and (paediatric) surgeons and (3) an expert meeting to finalise the COS and its definitions. Children and young people will be involved through their parents during phase 2 and will be engaged directly using a customised face-to-face approach.Ethics and disseminationThe medical research ethics committee of the Academic Medical Center Amsterdam has approved the study. Each participating country/research group will ascertain ethics board approval. Electronic informed consent will be obtained from all participants. Results will be presented in peer-reviewed academic journals and at (international) conferences.Trial registration numberCOMET registration: 1119
Do sensorimotor cortex activity, an individual’s capacity for neuroplasticity, and psychological features during an episode of acute low back pain predict outcome at 6 months: a protocol for an Australian, multisite prospective, longitudinal cohort study
Authors: Jenkins Luke C , Chang Wei-Ju , Buscemi Valentina , Liston Matthew , Toson Barbara , Nicholas Michael , Graven-Nielsen Thomas , Ridding Michael , Hodges Paul W , McAuley James H , Schabrun Siobhan M 
Published: May 2019

IntroductionLow back pain (LBP) is the leading cause of disability worldwide, with prevalence doubling in the past 14 years. To date, prognostic screening tools display poor discrimination and offer no net benefit of screening over and above a ‘treat all’ approach. Characteristics of the primary sensory (S1) and motor (M1) cortices may predict the development of chronic LBP, yet the prognostic potential of these variables remains unknown. The Understanding persistent Pain Where it ResiDes (UPWaRD) study aims to determine whether sensorimotor cortex activity, an individual’s capacity for plasticity and psychosocial factors in the acute stage of pain, predict LBP outcome at 6 months. This paper describes the methods and analysis plan for the development of the prediction model.Methods and analysisThe study uses a multicentre prospective longitudinal cohort design with 6-month follow-up. 120 participants, aged 18 years or older, experiencing an acute episode of LBP (less than 6 weeks duration) will be included. Primary outcomes are pain and disability.Ethics and disseminationEthical approval has been obtained from Western Sydney University Human Research Ethics Committee (H10465) and from Neuroscience Research Australia (SSA: 16/002). Dissemination will occur through presentations at national and international conferences and publications in international peer-reviewed journals.Trial registration numberACTRN12619000002189; Pre-results.
Acute management of pancreatitis: the key to best outcomes
Authors: Olson Erik , Perelman Alexander , Birk John W 
Published: May 2019

AbstractAcute pancreatitis (AP) accounts for over 230 000 US and 28 000 UK hospital admissions annually. Abdominal pain is the most common presenting symptom in AP but may not reflect severity. The clinical challenge is identifying the 20% of patients in whom AP will be severe. We summarise the common aetiologies, the risk stratification strategies including the simplified Bedside Index for Severity in Acute Pancreatitis, acute management approaches in the initial presentation setting, conditions for using advance imaging and opinions on antibiotic use. Some warning signs of impending complications are also discussed.
Diagnostic yield of percutaneous core needle biopsy in suspected soft tissue lesions of extremities
Authors: Qi Dianwen , Zhao Ming , Hu Tongyu , Zhang Guochuan 
Published: May 2019

Objective This retrospective study was performed to investigate the diagnostic yield of percutaneous core needle biopsy (CNB) for suspected soft tissue lesions of the extremities. Methods The medical records of 139 consecutive patients who underwent percutaneous CNB for suspected soft tissue lesions of the extremities from January 2014 to December 2016 at a single institution were reviewed. The pathologic findings or clinical follow-ups were used to evaluate the performance of CNB. Alterations in the treatment regimen from pre- to post-biopsy were also analyzed. Complications, when present, were documented. Results In total, 141 biopsy procedures were performed in 139 patients. In total, 136 (96%) biopsies were successful, among which 5 were false-negative and 131 were diagnosed accurately. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of CNB in the differentiation of malignant from benign lesions were 94%, 100%, 96%, 100%, and 90%, respectively. The treatment regimen was altered based on the biopsy findings in 25 cases. Two patients developed mild nerve injury but fully recovered during follow-up. Conclusions CNB is effective and safe, with high sensitivity, specificity, and accuracy for the diagnosis of soft tissue lesions, especially for differentiating malignant from benign lesions.
Needs assessment for sexual health services development in a small European Union member state
Authors: Buttigieg Sandra C , Debono Gabrielle Attard , Gauci Dorothy 
Published: May 2019

Introduction Awareness of sexual health in Malta – a small European Union member state started to gain momentum in the new millennium. Taboos and norms about sexuality pose strong barriers for the provision of information, and reproductive health services. A major contributor is the strong influence of the Roman Catholic Church, which holds fast to its prohibitions of sexual behaviours, albeit counterbalanced by the liberal standpoint adopted by the State in recent years. Methods Survey data were collected from 269 students aged 16–21 (response rate 89.7%) in a state post-secondary school. The sample was selected through convenience sampling within the school grounds. Results Women were more knowledgeable in relation to available services and risks when compared to men. No geographical differences were found. School was the most common source for information, while health professionals, namely general practitioners were considered trusted resources for their needs. Confidentiality was deemed to be the most requested and crucial feature of sexual health services. Conclusions Three important multisectoral needs emerged, namely adequate dissemination system of sexual health information, scientifically based sexual health education for professionals in contact with young people, and well-designed and accessible sexual health services. Implications for management include updating health sexual education and promotion strategies, as well as designing better services. Young people should be able to make informed choices regarding their sexual health, in line with contemporary needs.
Tobacco Use Among Transgender and Gender Non-conforming Adults in the United States
Authors: Wheldon Christopher W , Wiseman Kara P 
Published: May 2019

Background: Findings from previous population-based studies are in conflict regarding the relative use of tobacco products among transgender populations compared with their cisgender counterparts. The purpose of this study was to estimate the prevalence of current tobacco use among transgender persons in the United States and evaluate differences in relative use between transgender and cisgender respondents. Methods: This was a secondary analysis of data from the Population Assessment of Tobacco and Health (PATH) Study Wave 2 (October 2014 and October 2015). Differences in current use of cigarettes, e-cigarettes, and cigars were examined between self-identified transgender (n = 151) and cisgender (n = 27 557) respondents. Results: In multivariable analyses, transgender identity was not associated with any of the 3 tobacco behaviors or the summary measure of tobacco use (ie, any current use of cigarettes, e-cigarettes, or cigars). In each of the models, female binary sex (compared with male), older age, Hispanic ethnicity (compared with non-Hispanic white), higher household income, and higher educational attainment were independently associated with lower odds of current use of cigarettes, e-cigarettes, or cigars, whereas sexual minority identity (ie, gay/lesbian or bisexual) was independently associated with higher odds of use. Conclusions: The prevalence of the use of cigarettes, e-cigarettes, and cigar use was statistically equivalent between transgender and cisgender populations in this national study of adults in the United States, which differs from previous research showing higher rates of tobacco use among transgender individuals. Differences in tobacco use that were identified were fully explained by sociodemographic characteristics (eg, income and education) between the transgender and cisgender populations.
Specialty Physician Designation in Referrals from a Vertically Integrated PCMH
Authors: Schreiner Andrew D. , Holmes-Maybank Keri T. , Zhang Jingwen , Marsden Justin , Mauldin Patrick D. , Moran William P. 
Published: May 2019

Introduction: Primary care referrals to specialty physicians once relied upon the medical skill of the specialist, the quality of past communication, and previous consultative experiences. As health systems vertically integrate, patterns of specialty physician referral designation are not known. Methods: This cross-sectional study from a patient-centered medical home (PCMH) evaluated the proportion of referrals with named specialists. All outpatient specialty referrals from the PCMH between July and December of 2014 were eligible for inclusion, and 410 patients were randomly selected for chart review. The outcome of interest was specialty physician designation. Other variables of interest included PCMH provider experience, the reason for referral, and time to specialty visit. Univariate analysis was performed with Fisher exact tests. Results: Of 410 specialty referrals, 43.7% were made to medical specialties, 41.7% to surgical specialties, and 14.6% to ancillary specialties. Resident physicians placed 224 referrals (54.6%), faculty physicians ordered 155 (37.8%), and advanced practice providers ordered 31 (7.6%). Only 11.2% of the specialty referral orders designated a specific physician. No differences appeared in the reason for referral, the referral destination, the proportion of visits scheduled and attended, or the time to schedule between those referrals with and without specialty physician designation. Faculty physicians identified a specific specialist in 21.4% of referrals compared to residents doing so in 4.9% ( P < .0001). Conclusion: Patient-centered medical home referrals named a specific specialty physician infrequently, suggesting a shift from the historical reliance on the individual characteristics of the specialist in the referral process.