bluuebunny/crossref_metadata_2025_split huggingface dataset:
The endosomal sorting complex required for transport complex negatively regulates Erg6 degradation under specific glucose restriction conditions
Authors: Zhang Ao , Meng Ying , Li Qunli , Liang Yongheng 
Published: May 2020

AbstractLipid droplets (LDs) are cytosolic fat storage organelles that play roles in lipid metabolism, trafficking and signaling. Breakdown of LDs in Saccharomyces cerevisiae is mainly achieved by lipolysis and lipophagy. In this study, we found that the endosomal sorting complex required for transport (ESCRT) in S. cerevisiae negatively regulated the turnover of a LD marker, Erg6, under both simplified glucose restriction (GR) and acute glucose restriction (AGR) conditions by monitoring the localization and degradation of Erg6. Loss of Vps27, Snf7 or Vps4, representative subunits of the ESCRT machinery, facilitated the delivery of Erg6‐GFP to vacuoles and its degradation depending on the lipophagy protein Atg15 under simplified GR. Additionally, the lipolysis proteins Tgl3 and Tgl4 were also involved in the enhanced vacuolar localization and degradation of Erg6‐GFP in vps4Δ cells. Furthermore, we found that Atg14, which is required for the formation of putatively liquid‐ordered (Lo) membrane domains on the vacuole that act as preferential internalization sites for LDs, abundantly localized to vacuolar membranes in ESCRT mutants. Most importantly, the depletion or overexpression of Atg14 correspondingly abolished or promoted the observed Erg6 degradation in ESCRT mutant cells. We propose that Atg14 together with other proteins promotes Erg6 degradation in ESCRT mutant cells under specific glucose restriction conditions. These results shed new light on the regulation of ESCRT on LD turnover.
Extensive clinical, serologic and molecular studies lead to the first reported Rhmod phenotype in Argentina
Authors: Mufarrege Nicolás , Franco Noelia , Trucco Boggione Carolina , Arnoni Carine , de Paula Vendrame Tatiane , Bartoli Sonia , Ensinck Alejandra , Principi Cintia , Lujan Brajovich Melina , Mattaloni Stella , Riquelme Bibiana , Biondi Claudia , Castilho Lilian , Cotorruelo Carlos 
Published: May 2020

BACKGROUNDA highly reduced expression of Rh antigens in the erythrocyte membrane is the main feature of Rhmod, an extremely rare phenotype. Mutations within RHAG gene, which encodes RhAG glycoprotein and modulates Rh antigen expression and Rh complex formation, are the molecular events responsible for the Rhmod phenotype. Here we report a clinical, serologic, and molecular study of an Argentinean proband with Rh‐deficiency syndrome.MATERIALS AND METHODSRh antigens, RhAG and CD47 glycoproteins were studied by serologic methods in the proband, her parents and sister. Osmotic fragility and viscoelastic parameters were also examined. RHD zygosity was analyzed by RFLP‐PCR. RHD, RHCE, and RHAG genes were studied by Sanger sequencing.RESULTSNo Rh antigens were detected in the proband by standard techniques. However, adsorption‐elution and anti‐RhAG tests showed that the proposita was Rhmod. Reduced expression of CD47, enhanced osmotic fragility, and surface viscosity alterations giving rise to spherocytes were observed in the patient. Sequencing analysis showed that a c.920C>T mutation in RHAG Exon 6 was present in a homozygous state in the proband and in a heterozygous state in the rest of the family. This novel missense mutation caused the p.Ser307Phe amino acid substitution in Transmembrane Segment 10 of the RhAG glycoprotein.CONCLUSIONThis comprehensive study determined the causes of the probandʼs anemia allowing the diagnosis of Rh‐deficiency syndrome.
The effect of body position on intraocular pressure in anesthetized horses
Authors: Meekins Jessica M. , McMurphy Rose M. , Roush James K. 
Published: May 2020

AbstractObjectiveTo evaluate the effect of four recumbent body positions on intraocular pressure (IOP) in anesthetized normal horses.Animals studiedTen nonglaucomatous adult horses.ProceduresIntraocular pressure was measured with a rebound tonometer in both eyes of standing sedated horses (baseline), then under general anesthesia during four randomized recumbent body positions, including Trendelenburg (Tr; 15‐degree head down), reverse Trendelenburg (RTr; 15‐degree head up), dorsal, and lateral; only the superior eye was measured in lateral positions. The mean of 3 IOP readings was taken at each position, allowing a minimum of 2 minutes of acclimatization after each position change before obtaining measurements. Repeated Measures Analysis with Newman‐Keuls Multiple Comparison Post hoc was used to compare IOPs in different positions, and linear regression was used to compare IOP with age and weight cofactors.ResultsWhen compared to baseline, the greatest change in IOP occurred in Tr (increase of 25.63 ± 8.12 mm Hg). When comparing all recumbent positions to baseline, IOP significantly increased in 3 of 4 body positions (P < .001), with no significant difference identified between RTr and baseline. When comparing all body positions to each other, the greatest IOP difference occurred between the Tr and the RTr positions (increase of 26.95 ± 5.41 mm Hg). Age and weight were not correlated with IOP in any position.ConclusionsRecumbent body position significantly increases IOP in normal eyes of horses under injectable anesthesia.
A novel cancer immunotherapy utilizing autologous tumour tissue
Authors: Park Haemin , Gladstone Matthew , Shanley Crystal , Goodrich Raymond , Guth Amanda 
Published: May 2020

BackgroundWith the recent interest in personalized medicine for cancer patients and immune therapy, the field of cancer vaccines has been resurrected. Previous autologous, whole cell tumour vaccine trials have not produced convincing results due, in part to poor patient selection and inactivation methos that are harsh on the cells. These methods can alter protein structure and antigenic profiles making vaccine candidates ineffective in stimulating immune response to autochthonous tumour cells.Materials and methodsWe investigated a novel method for inactivating tumour cells that uses UVA/UVB light and riboflavin (vitamin B2) (RF + UV). RF + UV inactivates the tumour cells’ ability to replicate, yet preserves tumour cell integrity and antigenicity.ResultsOur results demonstrate that proteins are preserved on the surface of RF + UV‐inactivated tumour cells and that they are immunogenic via induction of dendritic cell maturation, increase in IFNγ production and generation of tumour cell‐specific IgG. Moreover, when formulated with an adjuvant (‘Innocell vaccine’) and tested in different murine tumour primary and metastatic disease models, decreased tumour growth, decreased metastatic disease and prolonged survival were observed. In addition, immune cells obtained from tumour tissue following vaccination had decreased exhausted and regulatory T cells, suggesting that activation of intra‐tumoural T cells may be playing a role leading to reduced tumour growth.ConclusionsThese data suggest that the RF + UV inactivation of tumour cells may provide an efficacious method for generating autologous whole tumour cell vaccines for use in cancer patients.
Brainstem inflammation modulates the ventilatory pattern and its variability after acute lung injury in rodents
Authors: Hsieh Yee‐Hsee , Litvin David G , Zaylor Abigail R , Nethery David E , Dick Thomas E , Jacono Frank J 
Published: May 2020

Key points
Compared with sham rats, rats a week after acute lung injury (ALI) express more pro‐inflammatory cytokines in their brainstem respiratory control nuclei, exhibit a higher respiratory frequency (fR) and breathe with a more predictable pattern.
These characteristics of the respiratory pattern persist in in situ preparations even after minimizing pulmonary and chemo‐afferent inputs.
Interleukin (IL)‐1β microinjected in the nucleus tractus solitarii increases fR and the predictability of the ventilatory pattern similar to rats with ALI.
Intracerebroventricular infusion of indomethacin, an anti‐inflammatory drug, mitigates the effect of ALI on fR and ventilatory pattern variability.
We conclude that changes in the ventilatory pattern after ALI result not only from sensory input due to pulmonary damage and dysfunction but also from neuro‐inflammation.
AbstractAcute lung injury (ALI) increases respiratory rate (fR) and ventilatory pattern variability (VPV), but also evokes peripheral and central inflammation. We hypothesized that central inflammation has a role in determining the ventilatory pattern after ALI. In rat pups, we intratracheally injected either bleomycin to induce ALI or saline as a sham control. One week later, we recorded the ventilatory pattern of the rat pups using flow‐through plethysmography, then formed in situ preparations from these pups and recorded their ‘fictive’ patterns from respiratory motor nerves. Compared with the ventilatory pattern of the sham rat pups, injured rat pups had increased fR and predictability. Surprisingly, the fictive patterns of the in situ preparations from ALI pups retained these characteristics despite removing their lungs to eliminate pulmonary sensory inputs and perfusing them with hyperoxic artificial cerebral spinal fluid to minimize peripheral chemoreceptor input. Histological processing revealed increased immunoreactivity of the pro‐inflammatory cytokine Interleukin‐1β (IL‐1β) in the nucleus tractus solitarii (nTS) from ALI but not sham rats. In subsequent experiments, we microinjected IL‐1β in the nTS bilaterally in anaesthetized naïve adult rats, which increased fR and predictability of ventilatory pattern variability (VPV) after 2 h. Finally, we infused indomethacin intracerebroventricularly during the week of survival after ALI. This did not affect sham rats, but mitigated changes in fR and VPV in ALI rats. We conclude that neuro‐inflammation has an essential role in determining the ventilatory pattern of ALI rats.
Numerical Investigation of Combustion Instabilities in a Single-Element Lean Direct Inject Combustor Using Flamelet Based Approaches
Authors: Patwardhan Saurabh Sudhir , Nakod Pravin , Orsino Stefano , Arguinzoni Carlo 
Published: May 2020

Abstract
In this paper, high-fidelity large eddy simulations (LES) along with flamelet-based combustion models are assessed to predict combustion dynamics in low-emission gas turbine combustor. A model configuration of a single-element lean direct injection (LDI) combustor from Purdue University (Huang et al., 2014, “Combustion Dynamics Behavior in a Single-Element Lean Direct Injection (LDI) Gas Turbine Combustor,” 50th AIAA/ASME/SAE/ASEE Joint Propulsion Conference, Cleveland, OH, July 28–30.) is used for the validation of simulation results. Two combustion models based on the flamelet concept, i.e., steady diffusion flamelet (SDF) model and flamelet generated manifold (FGM) model are employed to predict combustion instabilities. Simulations are carried out for two equivalence ratios of φ = 0.6, and 0.4. The results in the form of mode shapes, peak to peak pressure amplitude and power spectrum density (PSD) are compared with the experimental data of Huang et al. (2014, “Combustion Dynamics Behavior in a Single-Element Lean Direct Injection (LDI) Gas Turbine Combustor,” 50th AIAA/ASME/SAE/ASEE Joint Propulsion Conference, Cleveland, OH, July 28–30.). The effect of variation in the time-step size hence acoustic courant number is studied. Further, two numerical solver options, i.e., pressure-based segregated solver and pressure-based coupled solver, are used to understand their effect on the solution convergence regarding the number of time-steps required to reach the limit cycle of the pressure oscillations. A truncated (half) domain simulation is performed by applying an appropriate acoustic impedance boundary condition at the truncated location. Overall, the simulation results compare well with the experimental data and trends are captured accurately in all simulations. It builds confidence in flamelet-based combustion models for the use in combustion instability modeling which is traditionally done using finite rate chemistry models based on reduced kinetics.
Prevalence and sociodemographic determinants of dyspepsia in the general population of Rwanda
Authors: Bangamwabo Jean Bosco , Chetwood John David , Dusabejambo Vincent , Ntirenganya Cyprien , Nuki George , Nkurunziza Arcade , Kieffer Kelly A , Jones Michael , Walker Timothy D 
Published: May 2020

IntroductionDyspepsia accounts for a significant burden of worldwide disease, but there is a relative paucity of data from the sub-Saharan African setting. We undertook to describe the burden, risk factors and severity of dyspepsia across Rwanda.MethodsWe performed a population-based clustered cross-sectional survey between November 2015 and January 2016, nationwide in Rwanda, using the Short Form Leeds Dyspepsia Questionnaire to describe the presence and severity of dyspepsia, and the Short Form Nepean Dyspepsia Index to describe the concomitant quality of life effects. Univariate and multivariate logistic regression models were constructed to correlate measured sociodemographic factors with dyspepsia.ResultsThe prevalence of clinically significant dyspepsia in the general Rwandan population was 14.2% (283/2000). The univariate factors that significantly predicted severity were gender, profession, socioeconomic status, and non-steroidal anti-inflammatory drug, aspirin and alcohol use, with gender, current smoking, aspirin use both in the past and currently, and alcohol use in the past remaining significant on multivariate modelling. Dyspeptics had a significantly lower gastrointestinal-related quality of life, though the sociodemographic factors measured did not modify the observed quality of life.ConclusionDyspepsia is prevalent in the Rwandan setting and is associated with a significant burden on quality of life. More work is required to determine the pathological entities involved, and the optimal approach to mitigating this burden.
Effects of reproductive period duration and number of pregnancies on midlife ECG indices: a secondary analysis from the Women’s Health Initiative Clinical Trial
Authors: Parikh Nisha I , Kapphahn Kristopher , Hedlin Haley , Olgin Jeffrey E , Allison Matthew A , Magnani Jared W , Ryckman Kelli R , Waring Molly E , Perez Marco Valentin , Howard Barbara V 
Published: May 2020

ObjectivesPregnancy, menses and menopause are related to fluctuations in endogenous sex hormones in women, which cumulatively may alter cardiac electrical conduction. Therefore, we sought to study the association between number of pregnancies and reproductive period duration (RD, time from menarche to menopause) with ECG intervals in the Women’s Health Initiative Clinical Trials.DesignSecondary analysis of multicentre clinical trial.SettingUSA.Primary outcome measuresECGintervals: PR interval, P-wave duration, P-wave dispersion, QTc interval.Participantsn=40 687 women (mean age=62 years) participating in the Women’s Health Initiative Clinical Trials. 82.5% were white, 9.3% black, 4% Hispanic and 2.7% Asian.MethodsIn primary analysis, we employed multivariable linear regression models relating number of pregnancies and RD with millisecond changes in intervals from enrolment ECG. We studied effect modification by hormone therapy use.ResultsAmong participants, 5+ live births versus 0 prior pregnancies was associated with a 1.32 ms increase in PR interval (95% CI 0.25 to 2.38), with a graded association with longer QTc interval (ms) (none (prior pregnancy, no live births)=0.66 (–0.56 to 1.88), 1=0.15 (–0.71 to 1.02), 2–4=0.25 (–0.43 to 0.94) and 5+ live births=1.15 (0.33 to 1.98), p=0.008). RD was associated with longer PR interval and maximum P-wave duration (but not P-wave dispersion) among never users of hormone therapy: (PR (ms) per additional RD year: 0.10 (0.04 to 0.16); higher P-wave duration (ms): 0.09 (0.06 to 0.12)). For every year increase in reproductive period, QTc decreased by 0.04 ms (−0.07 to –0.01).ConclusionsAn increasing number of live births is related to increased and RD to decreased ventricular repolarisation time. Both grand multiparity and longer RD are related to increased atrial conduction time. Reproductive factors that alter midlife cardiac electrical conduction system remodelling in women may modestly influence cardiovascular disease risk in later life.Trial registration numberNCT00000611; Post-results.
Impact of maternity waiting homes on facility delivery among remote households in Zambia: protocol for a quasiexperimental, mixed-methods study
Authors: Scott Nancy A , Kaiser Jeanette L , Vian Taryn , Bonawitz Rachael , Fong Rachel M , Ngoma Thandiwe , Biemba Godfrey , Boyd Carol J , Lori Jody R , Hamer Davidson H , Rockers Peter C 
Published: May 2020

IntroductionMaternity waiting homes (MWHs) aim to improve access to facility delivery in rural areas. However, there is limited rigorous evidence of their effectiveness. Using formative research, we developed an MWH intervention model with three components: infrastructure, management and linkage to services. This protocol describes a study to measure the impact of the MWH model on facility delivery among women living farthest (≥10 km) from their designated health facility in rural Zambia. This study will generate key new evidence to inform decision-making for MWH policy in Zambia and globally.Methods and analysisWe are conducting a mixed-methods quasiexperimental impact evaluation of the MWH model using a controlled before-and-after design in 40 health facility clusters. Clusters were assigned to the intervention or control group using two methods: 20 clusters were randomly assigned using a matched-pair design; the other 20 were assigned without randomisation due to local political constraints. Overall, 20 study clusters receive the MWH model intervention while 20 control clusters continue to implement the ‘standard of care’ for waiting mothers. We recruit a repeated cross section of 2400 randomly sampled recently delivered women at baseline (2016) and endline (2018); all participants are administered a household survey and a 10% subsample also participates in an in-depth interview. We will calculate descriptive statistics and adjusted ORs; qualitative data will be analysed using content analysis. The primary outcome is the probability of delivery at a health facility; secondary outcomes include utilisation of MWHs and maternal and neonatal health outcomes.Ethics and disseminationEthical approvals were obtained from the Boston University Institutional Review Board (IRB), University of Michigan IRB (deidentified data only) and the ERES Converge IRB in Zambia. Written informed consent is obtained prior to data collection. Results will be disseminated to key stakeholders in Zambia, then through open-access journals, websites and international conferences.Trial registration numberNCT02620436; Pre-results.
Direct inpatient costs and influencing factors for patients with rectal cancer with low anterior resection: a retrospective observational study at a three-tertiary hospital in Beijing, China
Authors: Chen Zhishui , Leng Jiahua , Gao Guangying , Zhang Lianhai , Yang Yang 
Published: May 2020

ObjectivesThe aim of the study was to investigate the direct inpatient cost and analyse influencing factors for patients with rectal cancer with low anterior resection in Beijing, China.DesignA retrospective observational study.SettingThe study was conducted at a three-tertiary oncology institution.ParticipantsA total of 448 patients who underwent low anterior resection and were diagnosed with rectal cancer from January 2015 to December 2016 at Peking University Cancer Hospital were retrospectively identified. Demographic, clinical and cost data were determined.ResultsThe median inpatient cost was￥89 064, with a wide range (￥46 711–￥191 329) due to considerable differences in consumables. The material cost accounted for 52.19% and was the highest among all the cost components. Colostomy (OR 4.17; 95% CI 1.79 to 9.71), complications of hypertension (OR 5.30; 95% CI 1.94 to 14.42) and combined with other tumours (OR 2.92; 95% CI 1.12 to 7.60) were risk factors for higher cost, while clinical pathway (OR 0.10; 95% CI 0.03 to 0.35), real-time settlement (OR 0.26; 95% CI 0.10 to 0.68) and combined with cardiovascular disease (OR 0.09; 95% CI 0.02 to 0.52) were protective determinants.ConclusionsThis approach is an effective way to relieve the economic burden of patients with cancer by promoting the clinical pathway, optimising the payment scheme and controlling the complication. Further research focused on the full-cost investigation in different stages of rectal cancer based on a longitudinal design is necessary.
Children’s and caregivers’ perspectives about mandatory reporting of child maltreatment: a meta-synthesis of qualitative studies
Authors: McTavish Jill R , Kimber Melissa , Devries Karen , Colombini Manuela , MacGregor Jennifer C D , Wathen Nadine , MacMillan Harriet L 
Published: May 2020

ObjectiveTo systematically synthesise qualitative research that explores children’s and caregivers’ perceptions of mandatory reporting.DesignWe conducted a meta-synthesis of qualitative studies.Data sourcesSearches were conducted in Medline, Embase, PsycINFO, Cumulative Index to Nursing and Allied Health Literature, Criminal Justice Abstracts, Education Resources Information Center, Sociological Abstracts and Cochrane Libraries.Eligibility criteriaEnglish-language, primary, qualitative studies that investigated children’s or caregivers’ perceptions of reporting child maltreatment were included. All healthcare and social service settings implicated by mandatory reporting laws were included.Data extraction and synthesisCritical appraisal of included studies involved a modified checklist from the Critical Appraisal Skills Programme (CASP). Two independent reviewers extracted data, including direct quotations from children and caregivers (first-order constructs) and interpretations by study authors (second-order constructs). Third-order constructs (the findings of this meta-synthesis) involved synthesising second-order constructs that addressed strategies to improve the mandatory reporting processes for children or caregivers—especially when these themes addressed concerns raised by children or caregivers in relation to the reporting process.ResultsOver 7935 citations were retrieved and 35 articles were included in this meta-synthesis. The studies represent the views of 821 caregivers, 50 adults with histories of child maltreatment and 28 children. Findings suggest that children and caregivers fear being reported, as well as the responses to reports. Children and caregivers identified a need for improvement in communication from healthcare providers about mandatory reporting, offering preliminary insight into child-driven and caregiver-driven strategies to mitigate potential harms associated with reporting processes.ConclusionResearch on strategies to mitigate potential harms linked to mandatory reporting is urgently needed, as is research that explores children’s experiences with this process.