bluuebunny/crossref_metadata_2025_split huggingface dataset:
Allogeneic human umbilical cord-derived mesenchymal stem cells for severe bronchopulmonary dysplasia in children: study protocol for a randomized controlled trial (MSC-BPD trial)
Authors: Wu Xian , Xia Yunqiu , Zhou Ou , Song Yan , Zhang Xianhong , Tian Daiyin , Li Qubei , Shu Chang , Liu Enmei , Yuan Xiaoping , He Ling , Liu Chengjun , Li Jing , Liang Xiaohua , Yang Ke , Fu Zhou , Zou Lin , Bao Lei , Dai Jihong 
Published: January 2020

Abstract
Background
Bronchopulmonary dysplasia (BPD) is a complex lung pathological lesion secondary to multiple factors and one of the most common chronic lung diseases. It has a poor prognosis, especially in preterm infants. However, effective therapies for this disease are lacking. Stem-cell therapy is a promising way to improve lung injury and abnormal alveolarization, and the human umbilical cord (hUC) is a good source of mesenchymal stem cells (MSCs), which have demonstrated efficacy in other diseases. We hypothesized that intravenously administered allogeneic hUC-MSCs are safe and effective for severe BPD.

Methods
The MSC-BPD trial is a randomized, single-center, open-label, dose-escalation, phase-II trial designed to investigate the safety and efficacy of hUC-MSCs in children with severe BPD. In this study, 72 patients will be enrolled and randomly divided into two intervention groups and one control group. Patients in the intervention groups will receive a low dose of hUC-MSCs (n = 24; 2.5 million cells/kg) or a high dose of hUC-MSCs (n = 24; 5 million cells/kg) in combination with traditional supportive treatments for BPD. The patients in the control group (n = 24) will be treated with traditional supportive treatments alone without hUC-MSCs. The primary outcome measures will be cumulative duration of oxygen therapy. Follow-up assessments will be performed at 1, 3, 6, 12, and 24 months post intervention, and the key outcome during follow-up will be changes on chest radiography. Statistical analyses will evaluate the efficacy of the hUC-MSC treatment.

Discussion
This will be the first randomized controlled trial to evaluate the safety and efficacy of intravenously administered hUC-MSCs in children with severe BPD. Its results should provide a new evidence-based therapy for severe BPD.

Trial registration
ClinicalTrials.gov, ID: NCT03601416. Registered on 26 July 2018.
Efficacy and cost-utility of the eHealth self-management application 'Oncokompas', helping partners of patients with incurable cancer to identify their unmet supportive care needs and to take actions to meet their needs: a study protocol of a randomized controlled trial
Authors: Schuit Anouk S. , Holtmaat Karen , Hooghiemstra Nienke , Jansen Femke , Lissenberg-Witte Birgit I. , Coupé Veerle M. H. , Verdonck-de Leeuw Irma M. 
Published: January 2020

Abstract
Background
Incurable cancer does not only affect patients, it also affects the lives of their partners. Many partners take on caregiving responsibilities. The burden of these caregiving tasks are often associated with physical, psychological, and social difficulties and many partners have unmet supportive care needs. Oncokompas is an eHealth self-management application to support partners in finding and obtaining optimal supportive care, tailored to their quality of life and personal preferences. A randomized controlled trial will be carried out to determine the efficacy and cost-utility of Oncokompas.

Methods
A total of 136 adult partners of patients with incurable cancer will be included. Partners will be randomly assigned to the intervention group, which directly gets access to Oncokompas, or the waiting-list control group, which gets access to Oncokompas after three months. The primary outcome measure is caregiver burden. Secondary outcome measures comprise self-efficacy, health-related quality of life, and costs. Measures will be assessed at baseline, two weeks after randomization, and three months after the baseline measurement.

Discussion
This study will result in evidence on the efficacy and cost-utility of Oncokompas among partners of patients with incurable cancer, which might lead to implementation of Oncokompas as a health service for partners of patients with incurable cancer.

Trial registration
Netherlands Trial Register, NTR 7636. Registered on 23 November 2018.
Operationalising kangaroo Mother care before stabilisation amongst low birth Weight Neonates in Africa (OMWaNA): protocol for a randomised controlled trial to examine mortality impact in Uganda
Authors: Medvedev Melissa M. , Tumukunde Victor , Mambule Ivan , Tann Cally J. , Waiswa Peter , Canter Ruth R. , Hansen Christian H. , Ekirapa-Kiracho Elizabeth , Katumba Kenneth , Pitt Catherine , Greco Giulia , Brotherton Helen , Elbourne Diana , Seeley Janet , Nyirenda Moffat , Allen Elizabeth , Lawn Joy E. 
Published: January 2020

Abstract
Background
There are 2.5 million neonatal deaths each year; the majority occur within 48 h of birth, before stabilisation. Evidence from 11 trials shows that kangaroo mother care (KMC) significantly reduces mortality in stabilised neonates; however, data on its effect among neonates before stabilisation are lacking. The OMWaNA trial aims to determine the effect of initiating KMC before stabilisation on mortality within seven days relative to standard care. Secondary objectives include exploring pathways for the intervention’s effects and assessing incremental costs and cost-effectiveness between arms.

Methods
We will conduct a four-centre, open-label, individually randomised, superiority trial in Uganda with two parallel groups: an intervention arm allocated to receive KMC and a control arm receiving standard care. We will enrol 2188 neonates (1094 per arm) for whom the indication for KMC is ‘uncertain’, defined as receiving ≥ 1 therapy (e.g. oxygen). Admitted singleton, twin and triplet neonates (triplet if demise before admission of ≥ 1 baby) weighing ≥ 700–≤ 2000 g and aged ≥ 1–< 48 h are eligible. Treatment allocation is random in a 1:1 ratio between groups, stratified by weight and recruitment site. The primary outcome is mortality within seven days. Secondary outcomes include mortality within 28 days, hypothermia prevalence at 24 h, time from randomisation to stabilisation or death, admission duration, time from randomisation to exclusive breastmilk feeding, readmission frequency, daily weight gain, infant–caregiver attachment and women’s wellbeing at 28 days. Primary analyses will be by intention-to-treat. Quantitative and qualitative data will be integrated in a process evaluation. Cost data will be collected and used in economic modelling.

Discussion
The OMWaNA trial aims to assess the effectiveness of KMC in reducing mortality among neonates before stabilisation, a vulnerable population for whom its benefits are uncertain. The trial will improve understanding of pathways underlying the intervention’s effects and will be among the first to rigorously compare the incremental cost and cost-effectiveness of KMC relative to standard care. The findings are expected to have broad applicability to hospitals in sub-Saharan Africa and southern Asia, where three-quarters of global newborn deaths occur, as well as important policy and programme implications.

Trial registration
ClinicalTrials.gov, NCT02811432. Registered on 23 June 2016.
Investigation of three enzymes and their roles in the embryonic development of parthenogenetic Haemaphysalis longicornis
Authors: Qiu Zhao-Xi , Li Yuan , Li Meng-Meng , Wang Wen-Ying , Zhang Tian-Tian , Liu Jing-Ze 
Published: January 2020

AbstractBackgroundThe tickHaemaphysalis longicornisexhibits two separate reproductive populations: bisexual and parthenogenetic, which have diploid and triploid karyotypes, respectively. The parthenogenetic population can undergo engorgement without copulation and produce viable female-only offspring with a longer incubation period than the bisexual population. Three enzymes, cathepsin B, cathepsin D and acid phosphatase, were found to be involved in vitellin degradation during the embryonic development of bisexualH. longicornis. However, the expression and activity profiles of these enzymes during the embryonic development of parthenogenetic ticks remain unknown. In the present study, the transcriptional expression profile, enzyme activity and roles in embryogenesis of the three enzymes during the embryonic development of parthenogeneticH. longicorniswere investigated.MethodsQuantitative real-time polymerase chain reaction (qPCR) and fluorescence detection were used to analyze the dynamic changes in the three enzymes during embryogenesis. The roles of the three enzymes during embryogenesis were also explored using RNA interference (RNAi).ResultsThe three enzymes were all expressed during embryonic development in parthenogeneticH. longicornis. The expression ofcathepsin Bwas highest on day 15, whereas that ofcathepsin Dwas highest on day 3 and the peak ofacid phosphataseexpression occurred on day 9. The activity of cathepsin B was highest on day 3 and lowest on day 5, then gradually increased and remained stable. Cathepsin D activity was highest on day 1 and showed a gradually decreasing trend, whereas acid phosphatase showed the opposite trend and reached a peak on day 23. RNA interference experiments in engorged female ticks revealed that there was no significant difference in the number of eggs laid, but the hatching rate of the eggs was significantly decreased.ConclusionThe three enzymes all play important roles in embryonic development ofH. longicornis, but the expression patterns and changes in the activity of the enzymes in the bisexual and parthenogenetic populations are different. The results will help a better understanding of the similarities and differences underlying embryonic development in the bisexual and parthenogenetic populations and contribute to the future exploration of the development of the parthenogenetic population ofH. longicornis.
Neural reflex control of vascular inflammation
Authors: Caravaca A. S. , Centa M. , Gallina A. L. , Tarnawski L. , Olofsson P. S. 
Published: January 2020

AbstractAtherosclerosis is a multifactorial chronic inflammatory disease that underlies myocardial infarction and stroke. Efficacious treatment for hyperlipidemia and hypertension has significantly reduced morbidity and mortality in cardiovascular disease. However, atherosclerosis still confers a considerable risk of adverse cardiovascular events. In the current mechanistic understanding of the pathogenesis of atherosclerosis, inflammation is pivotal both in disease development and progression. Recent clinical data provided support for this notion and treatment targeting inflammation is currently being explored. Interestingly, neural reflexes regulate cytokine production and inflammation. Hence, new technology utilizing implantable devices to deliver electrical impulses to activate neural circuits are currently being investigated in treatment of inflammation. Hopefully, it may become possible to target vascular inflammation in cardiovascular disease using bioelectronic medicine. In this review, we discuss neural control of inflammation and the potential implications of new therapeutic strategies to treat cardiovascular disease.
Who wants to be a psychiatrist? Northern Ireland foundation doctors (2006–2018) are positive toward psychiatry as career choice
Authors: Doris Michael , Grimason Amy , Hughes Damien , O'Neill Edel , Parks Lorraine , Carragher Angela 
Published: January 2020

Aims and methodNorthern Ireland presents itself as an anomaly – a region in which only 31.8% of doctors enter into any training programme after completion of the Foundation Programme, but where Core Psychiatry has been consistently oversubscribed. Here, we aim to find what other regions can learn from this success. All doctors of any grade, working in psychiatry, who had been though the Foundation Programme were questioned on their motivations for becoming a psychiatry trainee.ResultsSixty-two doctors currently working in psychiatry responded, including over 60% of current trainees, and 45% stated they had not considered a career in psychiatry before their foundation attachment. Over 80% preferred foundation placements in FY2 only, rather than in either foundation year 1 or FY2.Clinical implicationsThis survey identifies that for the majority of people who ultimately chose to train in psychiatry, in a region that has consistently attracted candidates to core and higher level training, completion of a foundation psychiatry post was an influencing factor in this decision. A strong majority of doctors prefer the foundation psychiatry placement to be offered in FY2.
Genetic correlations between subcortical brain volumes and psychiatric disorders
Authors: Ohi Kazutaka , Shimada Takamitsu , Kataoka Yuzuru , Yasuyama Toshiki , Kawasaki Yasuhiro , Shioiri Toshiki , Thompson Paul M. 
Published: January 2020

SummaryPsychiatric disorders as well as subcortical brain volumes are highly heritable. Large-scale genome-wide association studies (GWASs) for these traits have been performed. We investigated the genetic correlations between five psychiatric disorders and the seven subcortical brain volumes and the intracranial volume from large-scale GWASs by linkage disequilibrium score regression. We revealed weak overlaps between the genetic variants associated with psychiatric disorders and subcortical brain and intracranial volumes, such as in schizophrenia and the hippocampus and bipolar disorder and the accumbens. We confirmed shared aetiology and polygenic architecture across the psychiatric disorders and the specific subcortical brain and intracranial volume.
Pathogenic Variants in Cancer Predisposition Genes and Prostate Cancer Risk in Men of African Ancestry
Authors: Matejcic Marco , Patel Yesha , Lilyquist Jenna , Hu Chunling , Lee Kun Y. , Gnanaolivu Rohan D. , Hart Steven N. , Polley Eric C. , Yadav Siddhartha , Boddicker Nicholas J. , Samara Raed , Xia Lucy , Sheng Xin , Lubmawa Alexander , Kiddu Vicky , Masaba Benon , Namuguzi Dan , Mutema George , Job Kuteesa , Dabanja Henry M. , Ingles Sue A. , Wilkens Lynne , Le Marchand Loic , Watya Stephen , Couch Fergus J. , Conti David V. , Haiman Christopher A. 
Published: January 2020

PURPOSE In studies of men of European ancestry, rare pathogenic variants in DNA repair pathway genes have been shown to be associated with risk of aggressive prostate cancer. The contribution of rare coding variation to prostate cancer risk in men of African ancestry has not been established. METHODS We sequenced a panel of 19 DNA repair and cancer predisposition genes in 2,453 African American and 1,151 Ugandan cases and controls with prostate cancer. Rare variants were classified as pathogenic or putatively functionally disruptive and examined in association with prostate cancer risk and disease aggressiveness in gene and pathway-level association analyses. RESULTS Pathogenic variants were found in 75 of 2,098 cases (3.6%) and 31 of 1,481 controls (2.1%; odds ratio [OR], 1.82; 95% CI, 1.19 to 2.79; P = .0044), with the association being stronger for more aggressive disease phenotypes (OR, 3.10; 95% CI, 1.54 to 6.23; P = .0022). The highest risks for aggressive disease were observed with pathogenic variants in the ATM, BRCA2, PALB2, and NBN genes, with ORs ranging from approximately 4 to 15 in the combined study sample of African American and Ugandan men. Rare, nonpathogenic, nonsynonymous variants did not have a major impact on risk of overall prostate cancer or disease aggressiveness. CONCLUSION Rare pathogenic variants in DNA repair genes have appreciable effects on risk of aggressive prostate cancer in men of African ancestry. These findings have potential implications for panel testing and risk stratification in this high-risk population.
Reactive oxygen species-mediated cytoplasmic stiffening impairs the phagocytic ability of the macrophage
Authors: Agarwal Mahesh , Biswas Parijat , Bhattacharya Anindita , Sinha Deepak Kumar 
Published: January 2020

ABSTRACT
The phagocytic ability of macrophages empowers them to enforce innate immunity. RAW264.7, THP-1 and peripheral blood mononuclear cell-derived macrophages display considerable variability with regards to their phagocytic ability. We identify the underlying causes that attenuate the phagocytic abilities of a macrophage. Deformability of the cytoplasm and cortex influences the macrophage's phagocytic ability, and macrophages use the large cell-to-cell variability of their cytoplasmic stiffness to modulate their phagocytic ability. We find that the more-deformable macrophages have a higher phagocytic ability than those that are less deformable. Further, the subcellular spatial variability of cortex stiffness gives rise to more-deformable subdomains on the membrane for pathogen ingestion. We report a previously unknown negative-feedback loop that is triggered by the phagocytic oxidative burst. Macrophages utilize the excess reactive oxygen species to stiffen the cytoplasm, reducing their phagocytic propensity. In organisms, ageing or pathological conditions impair the phagocytic ability of macrophages. Our findings identify the targets that could potentially be utilized for restoring the phagocytic ability of the defunct macrophages.
P2X7 receptor activation increases expression of caveolin-1 and formation of macrophage lipid rafts, thereby boosting CD39 activity
Authors: Savio Luiz Eduardo Baggio , de Andrade Mello Paola , Santos Stephanie Alexia Cristina Silva , de Sousa Júlia Costa , Oliveira Suellen D. S. , Minshall Richard D. , Kurtenbach Eleonora , Wu Yan , Longhi Maria Serena , Robson Simon C. , Coutinho-Silva Robson 
Published: January 2020

ABSTRACT
Macrophages are tissue-resident immune cells that are crucial for the initiation and maintenance of immune responses. Purinergic signaling modulates macrophage activity and impacts cellular plasticity. The ATP-activated purinergic receptor P2X7 (also known as P2RX7) has pro-inflammatory properties, which contribute to macrophage activation. P2X7 receptor signaling is, in turn, modulated by ectonucleotidases, such as CD39 (also known as ENTPD1), expressed in caveolae and lipid rafts. Here, we examined P2X7 receptor activity and determined impacts on ectonucleotidase localization and function in macrophages primed with lipopolysaccharide (LPS). First, we verified that ATP boosts CD39 activity and caveolin-1 protein expression in LPS-primed macrophages. Drugs that disrupt cholesterol-enriched domains – such as nystatin and methyl-β-cyclodextrin – decreased CD39 enzymatic activity in all circumstances. We noted that CD39 colocalized with lipid raft markers (flotillin-2 and caveolin-1) in macrophages that had been primed with LPS followed by treatment with ATP. P2X7 receptor inhibition blocked these ATP-mediated increases in caveolin-1 expression and inhibited the colocalization with CD39. Further, we found that STAT3 activation is significantly attenuated caveolin-1-deficient macrophages treated with LPS or LPS+BzATP. Taken together, our data suggest that P2X7 receptor triggers the initiation of lipid raft-dependent mechanisms that upregulates CD39 activity and could contribute to limit macrophage responses restoring homeostasis.
High-resolution quantification of discrete phagocytic events by live cell time-lapse high-content microscopy imaging
Authors: Chu Charles C. , Pinney Jonathan J. , Whitehead Hannah E. , Rivera-Escalera Fatima , VanDerMeid Karl R. , Zent Clive S. , Elliott Michael R. 
Published: January 2020

ABSTRACT
Phagocytosis is a dynamic process central to immunity and tissue homeostasis. Current methods for quantification of phagocytosis largely rely on indirect or static measurements, such as target clearance or dye uptake, and thus provide limited information about engulfment rates or target processing. Improved kinetic measurements of phagocytosis could provide useful, basic insights in many areas. We present a live-cell, time-lapse and high-content microscopy imaging method based on the detection and quantification of fluorescent dye ‘voids’ within phagocytes that result from target internalization to quantify phagocytic events with high temporal resolution. Using this method, we measure target cell densities and antibody concentrations needed for optimal antibody-dependent cellular phagocytosis. We compare void formation and dye uptake methods for phagocytosis detection, and examine the connection between target cell engulfment and phagolysosomal processing. We demonstrate how this approach can be used to measure distinct forms of phagocytosis, and changes in macrophage morphology during phagocytosis related to both engulfment and target degradation. Our results provide a high-resolution method for quantifying phagocytosis that provides opportunities to better understand the cellular and molecular regulation of this fundamental biological process.
Intramembrane protease RHBDL4 cleaves oligosaccharyltransferase subunits to target them for ER-associated degradation
Authors: Knopf Julia D. , Landscheidt Nina , Pegg Cassandra L. , Schulz Benjamin L. , Kühnle Nathalie , Chao Chao-Wei , Huck Simon , Lemberg Marius K. 
Published: January 2020

ABSTRACT
The endoplasmic reticulum (ER)-resident intramembrane rhomboid protease RHBDL4 generates metastable protein fragments and together with the ER-associated degradation (ERAD) machinery provides a clearance mechanism for aberrant and surplus proteins. However, the endogenous substrate spectrum and with that the role of RHBDL4 in physiological ERAD is mainly unknown. Here, we use a substrate trapping approach in combination with quantitative proteomics to identify physiological RHBDL4 substrates. This revealed oligosaccharyltransferase (OST) complex subunits such as the catalytic active subunit STT3A as substrates for the RHBDL4-dependent ERAD pathway. RHBDL4-catalysed cleavage inactivates OST subunits by triggering dislocation into the cytoplasm and subsequent proteasomal degradation. RHBDL4 thereby controls the abundance and activity of OST, suggesting a novel link between the ERAD machinery and glycosylation tuning.
Periodontal Vaccines-A systematic Review
Authors: Meenakshi Swarna , Varghese Sheeja 
Published: January 2020

Background: vaccination is the best known application of immunology to human health. Effective vaccines have successfully eradicated the prevalence of several infectious diseases that were common less than a generation ago. The success of Periodontal vaccines is still elusive due to the complexity of periodontal pathogens that have multiple serotypes. No periodontal vaccine trials have satisfied all the requirements such as preventing colonization of pathogens, protection against tissue destruction and alveolar bone loss, elicit immunoglobulins for phagocytosis, stimulation of T-helper cells. This review aims to discuss the various immunization strategies attempted so far. Aim: this review aims to discuss the various in-vitro and in-vivo studies that present supporting evidence for the feasibility of formulating a prophylactic periodontal vaccine that could emerge as an adjunct to mechanical therapy in the future. Material and Methods: An extensive literature Search was performed in electronic databases, such as PUBMED, Cochrane central register of controlled trials, Google scholar and science direct using various search terms such as “ periodontal vaccines”, “ porphyromonas gingivalis”, “chronic periodontitis”, ” genomic vaccine ”, “ recombinant vaccine”, “immune response” ," vaccination against periodontal bacteria". No limits and language restriction were applied during the electronic search to include all the possible animal studies , clinical trials in the potential relevant article search phase of the systematic review. Conclusion: Studies evaluating Porphyromonas gingivalis are the most common and the structures showing the most potential as a vaccine candidate are Outer membrane proteins, fimbriae and gingipains, the structure having the least potential is Lipopolysaccharide.KEYWORDSPeriodontitis; Vaccine; Virulence; Gingipains; Immune response; Animal studies.