bluuebunny/crossref_metadata_2025_split huggingface dataset:
Resistin-like Molecule β Acts as a Mitogenic Factor in Hypoxic Pulmonary Hypertension via the Ca2+-dependent PI3K/Akt/mTOR and PKC/MAPK Signaling Pathways
Authors: Tian Heshen , Liu Lei , Wu Ying , Wang Ruiwen , Jiang Yongliang , Hu Ruicheng , Zhu Liming , Li Linwei , Fang Yanyan , Yang Chunlan , Ji Lianzhi , Liu Guoyu , Dai Aiguo 
Published: December 2020

Abstract
BACKGROUND: Pulmonary arterial smooth muscle cell (PASMC) proliferation plays a crucial role in hypoxia-induced pulmonary hypertension (HPH). Previous studies have found that resistin-like molecule β (RELM-β) is upregulated de novo in response to hypoxia in cultured human PASMCs (hPASMCs). RELM-β has been reported to promote hPASMC proliferation and is involved in pulmonary vascular remodeling in patients with PAH. However, the expression pattern, effects, and mechanisms of action of RELM-β in HPH remain unclear.METHODS: We assessed the expression pattern, mitogenetic effect, and mechanism of action of RELM-β in a rat HPH model and in hPASMCs.RESULTS: Overexpression of RELM-β caused hemodynamic changes in a rat model of HPH similar to those induced by chronic hypoxia, including increased mean right ventricular systolic pressure (mRVSP), right ventricular hypertrophy index (RVHI) and thickening of small pulmonary arterioles. Knockdown of RELM-β partially blocked the increases in mRVSP, RVHI, and vascular remodeling induced by hypoxia. The phosphorylation levels of the PI3K, Akt, mTOR, PKC, and MAPK proteins were significantly up- or downregulated by RELM-β gene overexpression or silencing, respectively. Recombinant RELM-β protein increased the intracellular Ca2+ concentration in primary cultured hPASMCs and promoted hPASMC proliferation. The mitogenic effects of RELM-β on hPASMCs and the phosphorylation of PI3K, Akt, mTOR, PKC, and MAPK were suppressed by a Ca2+ inhibitor.CONCLUSIONS: Our findings suggest that RELM-β acts as a cytokine-like growth factor in the development of HPH and that the effects of RELM-β are likely to be mediated by the Ca2+-dependent PI3K/Akt/mTOR and PKC/MAPK pathways.
An optimized segmentation and quantification approach in microvascular imaging for OCTA-based neovascular regression monitoring
Authors: Wu Sheng , Wu Shaowei , Feng Hui , Hu Zizhong , Xie Yejing , Su Yun , Feng Ting , Li Li 
Published: December 2020

Abstract
Background:Quantification of neovascularization changes in terms of neovascular complex (NVC) acquired from the optical coherence tomography angiography (OCTA) imaging is extremely important for diagnosis and treatment monitoring of proliferative diabetic retinopathy (PDR). However, only few vessel extraction methods have so far been reported to quantify neovascular changes in NVC with proliferative diabetic retinopathy PDR based on OCTA images.Results:The proposed method has demonstrated better performance in accuracy compared with existing algorithms and can thus be used for PRD treatment monitoring. Following the PDR treatment monitoring study, our data has shown that from the 1st day to 7th day of treatment, the averaged total length of neovascularization in NVC has been substantially shortened by 36.8% (P<0.01), indicating significant effects of applied treatment. In addition, the average width of neovascularization in NVC from the 1st day to 7th day of treatment has been increased by 10.2% (P<0.05), indicating most of the narrow neovascularization has been reduced.Conclusion:The results and analysis have confirmed that the proposed optimization process by improved vascular connectivity analysis (VCA) method is both effective and feasible to segment and quantify the neovascularization in NVC with lower noise and fewer artifacts. Thus, it can be potentially applied to monitor the fibrovascular regression during the treatment period.Clinical Trial Registration: This trial is registered with the Chinese Clinical Trial Registry (Registered 27 December 2017, http://www.chictr.org.cn, registration number ChiCTR-IPR-17014160).
Baseline liver function tests and full blood count indices and their association with progression of chronic kidney disease and renal outcomes in Aboriginal and Torres Strait Islander people: the eGFR Follow- up Study&nbsp;
Authors: Majoni Sandawana William , Barzi Federica , Hoy Wendy , MacIsaac Richard MacIsaac J , Cass Alan Cass , Maple-Brown Louise , Hughes Jaquelyne T 
Published: December 2020

Abstract
Background: Determination of risks for chronic kidney disease (CKD) progression could improve strategies to reduce progression to ESKD. The eGFR Study recruited a cohort of adult Aboriginal and Torres Strait Islander people (Indigenous Australians) from Northern Queensland, Northern Territory and Western Australia, aiming to address the heavy CKD burden experienced within these communities.Methods: Using data from the eGFR study, we explored the association of baseline liver function tests (LFTs) (alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), bilirubin and albumin) and full blood count (FBC) indices (white blood cell and red blood cell counts and haemoglobin) with annual eGFR decline and renal outcomes (first of 30% decline in eGFR with a follow-up eGFR <60 mL/min/1.73 m2, initiation of renal replacement therapy, or renal death). Comparisons of baseline variables across eGFR categories were calculated using analysis of variance and logistic regression as appropriate. Linear and multivariable regression models were used to estimate the annual change in eGFR for changes in FBC indices and LFTs. Cox proportional hazard models were used to estimate the hazard ratio for developing renal outcome for changes in baseline FBC indices and LFTs.Results: Of 547 participants, 540 had at least one baseline measure of LFTs and FBC indices. The mean age was 46.1 (14.7) years and 63.6% were female. The median follow-up was 3.1 (IQR 2.8-3.6) years. Annual decline in eGFR was associated with low serum albumin (p<0.001) and haemoglobin (p=0.007). After adjustment for age, gender, urine albumin/creatinine ratio, diabetes, BMI, CRP, WHR, alcohol consumption, cholesterol and triglycerides, low serum albumin (p<0.001), haemoglobin (p=0.012) and bilirubin (p=0.011) were associated with annual decline in eGFRRenal outcomes were inversely associated with serum albumin (p<0.001), bilirubin (p=0.012) and haemoglobin (p<0.001) and directly with GGT (p=0.007) and ALP (p<0.001). Other FBC indices and LFTs were not associated with annual decline in eGFR or renal outcomes.Conclusions: GGT, ALP, bilirubin, albumin and haemoglobin independently associate with renal outcomes. Contrary to findings from other studies, no association was found between renal outcomes and other FBC indices. These findings may help focus strategies to prevent disease progression in this high-risk population.
Mortality Among Male Cigar and Cigarette Smokers in the U.S.
Authors: Rodu Brad , Plurphanswat Nantaporn 
Published: December 2020

Abstract
Background. Cigars and cigarettes are both smoked, but much less is known about the former’s long-term health effects, due to its low prevalence and infrequent collection of cigar information in national surveys. Purpose. We conducted a follow-up mortality study of cigar-smoking men age 40-79 years in National Health Interview Surveys (NHIS). Methods. We used pooled NHIS files linked to the National Death Index to obtain follow-up from year of interview to year of death or December 31, 2015. We developed categories of cigarette and cigar smoking that accommodate dual and former use of both products. We used Cox proportional hazards models, adjusted for age, race/ethnicity, marital status, education, income and region to estimate hazard ratios (HRs, 95% confidence intervals, CI) for mortality from all causes, heart diseases, malignant neoplasms, cerebrovascular disease, chronic lower respiratory diseases and two mutually exclusive categories: smoking-related and other diseases. Results. There were 14,657 deaths from all causes, including 3,426 never tobacco users, 3,276 exclusive cigarette smokers, and 176 exclusive cigar users. The latter had no statistically significant evidence of increased mortality from all causes, heart diseases, malignant neoplasms, cerebrovascular disease, smoking related diseases or other causes. In contrast, the mortality experience of dual users of cigars and cigarettes and cigar smokers who formerly used cigarettes is similar to exclusive cigarette smokers. Conclusions. This study provides evidence that male cigar smokers age 40+ years had elevated mortality risks. However, after accounting for cigarette smoking and other confounding variables, we found significantly increased mortality only among dual and former users of cigarettes.
Broad Spectrum Polyphenol Supplementation from Tart Cherry Extract on Markers of Recovery from Intense Resistance Exercise
Authors: Hooper David R. , Orange Terrance , Gruber Meagan T. , Darakjian Ashley A. , Conway Kara L. , Hausenblas Heather S. 
Published: December 2020

Abstract
Background: Tart cherry supplementation has been shown to enhance recovery from strenuous exercise due to its antioxidant properties. The majority of these studies used tart cherry juice, with a significant calorie content. The primary purpose of this study was to assess whether powdered tart cherry extract with minimal calorie content reduces oxidative stress and enhances recovery following intense resistance exercise. Methods: Thirteen men (mean age: 26.2±5.3 years; height: 184.3±8.2 cm; weight: 92.9±15.6 kg) performed a demanding resistance exercise protocol consisting of 6 sets of 10 repetitions of barbell back squat with 80% 1RM. The protocol was performed once following 7 days of 500 mg of tart cherry extract and once following placebo. Serum protein carbonyl (PC) content, creatine kinase activity (CK) and creatine kinase myocardial band content (CK-MB) were used to assess oxidative stress, skeletal and cardiac muscle damage respectively. Muscle soreness was assessed by visual analog scale. Physical performance was measured by countermovement jump power and handgrip dynamometer strength. Results: There was a significant increase in PC in the placebo (PL) condition when compared to the Tart Cherry (TC) condition at IP (PL: 0.4±0.3 vs. TC: -0.4±0.2 nmol∙mg-1; p<0.001), 1 hr (PL: 0.3±0.3 vs. TC: -0.7±0.3 nmol∙mg-1; p<0.001) and 24 hr (PL: 0.1±0.4 vs. TC: -0.3±0.5 nmol∙mg-1; p=0.010). There was a significant increase in CK activity in PL when compared to the TC at IP (PL: 491.1±280 vs. TC: 296.3±178 U∙L-1; p=0.008) and 3 hr (PL: -87±123 vs. TC: 43.1±105.3 U∙L-1; p=0.006). There was a significant (p=0.003) increase in CKMB concentration in PL when compared to the TC (PL: 21.6±12.4 vs. TC: -0.3±11.8 ng∙ml-1; p=0.006) at 1 hr post. There was a significant increase in handgrip strength in TC when compared to PL (PL: -2±5.1 vs. TC: 1.7±3 kg; p=0.017) at 24 hours post.Conclusions: This study demonstrated that tart cherry extract reduced oxidative stress and markers of muscle and cardiac damage following intense resistance exercise. This occurred along with a prevention of the decrease in strength seen following the intense exercise protocol. These benefits were seen with minimal energy intake.
Infant sex modifies associations between placental malaria and risk of malaria in infancy
Authors: Kakuru Abel , Roh Michelle E. , Kajubi Richard , Ochieng Teddy , Ategeka John , Ochokoru Harriet , Nakalembe Miriam , Clark Tamara D. , Ruel Theodore , Staedke Sarah G. , Chandramohan Daniel , Havlir Diane V. , Kamya Moses R , Dorsey Grant , Jagannathan Prasanna 
Published: December 2020

Abstract
Background Placental malaria (PM) has been associated with a higher risk of malaria during infancy. However, it is unclear whether this association is causal, and is modified by infant sex, and whether intermittent preventive treatment in pregnancy (IPTp) can reduce infant malaria by preventing PM. Methods Data from a birth cohort of 656 infants born to HIV-uninfected mothers randomised to IPTp with dihydroartemisinin-piperaquine (DP) or sulfadoxine-pyrimethamine (SP) was analysed. PM was categorized as no PM, active PM (presence of parasites), mild-moderate past PM (>0-20% high powered fields [HPFs] with pigment), or severe past PM (>20% HPFs with pigment). The association between PM and incidence of malaria in infants stratified by infant sex was examined. Causal mediation analysis was used to test whether IPTp can impact infant malaria incidence via preventing PM. Results There were 1088 malaria episodes diagnosed among infants during 596.6 person years of follow-up. Compared to infants born to mothers with no PM, the incidence of malaria was higher among infants born to mothers with active PM (adjusted incidence rate ratio [aIRR] 1.30, 95% CI 1.00-1.71, p=0.05) and those born to mothers with severe past PM (aIRR 1.28, 95% CI 0.89-1.83, p=0.18), but the differences were not statistically significant. However, when stratifying by infant sex, compared to no PM, severe past PM was associated a higher malaria incidence in male (aIRR 2.17, 95% CI 1.45-3.25, p<0.001), but not female infants (aIRR 0.74, 95% CI 0.46-1.20, p=0.22). There were no significant associations between active PM or mild-moderate past PM and malaria incidence in male or female infants. Male infants born to mothers given IPTp with DP had significantly less malaria in infancy than males born to mothers given SP, and 89.7% of this effect was mediated through prevention of PM. Conclusion PM may have more severe consequences for male infants, and interventions which reduce PM could mitigate these sex-specific adverse outcomes. More research is needed to better understand this sex-bias between PM and infant malaria risk. Trial registration: ClinicalTrials.gov, NCT02793622. Registered 8 June 2016, https://clinicaltrials.gov/ct2/show/NCT02793622
Socioeconomic inequality in intermittent preventive treatment using Sulphadoxine pyrimethamine among pregnant women in Nigeria
Authors: Mahmud Fatima Muhammad , Majdzadeh Reza , Nedjat Saharnaz , Sajadi Haniye Sadat , Parsaeian Mahboubeh 
Published: December 2020

Abstract
Background: Sulphadoxine pyrimethamine using intermittent preventive treatment (IPTp-SP) for malaria prevention is recommended for all pregnant women at malaria endemic areas. However, there is limited evidence on the level of socioeconomic inequality in IPTp-SP use to prevent malaria in pregnant women in Nigeria. Thus, this study aimed to determine the level of socioeconomic inequality in IPTp-SP use among pregnant women and to decompose it into its contributing factors. Methods: A secondary data analysis of Nigerian demographic and health survey of 2018 was conducted. A sample of 21,621 pregnant women aged between 15-49 years and had live birth in the previous 2 years before the survey were included to this analysis. Participants were recruited based on two-stage cluster sampling method. Socioeconomic inequality was decomposed into its contributing factors by concentration index. Result: Totally 63.6% of pregnant women took at least one dose of IPTp. Among IPTp users, 35.1% took one dose, 38.6% took two doses and 26.2% took three doses and more. Based on concentration index of 0.180 (p-value= <0.001, 95% CI: 0.176 to 0.183) and the Erreyger’s normalization concentration index 0.280 (p-value=<0.001, 95% CI: 0.251 to 0.309 IPTp utilization was pro-rich. The largest contributors to the inequality in IPTp uptake were wealth index (47.81%) and educational status (28.66%). Conclusion: Our findings showed that IPTp use was pro-rich in Nigeria. Wealth index and educational status were the factors that significantly contributed to the inequality. The disparities could be reduced through IPTp free service expansion by targeting pregnant women from low socioeconomic status.
Single-center evaluation of prognostic factors for thymoma treated by surgery: a retrospective study
Authors: Kamata Satoshi , Ishida Itaru , Suzuki Yuyo , Oura Hiroyuki 
Published: December 2020

Abstract
Background: This study aimed to retrospectively evaluate the clinical, pathological, and treatment-related factors associated with survival in patients with surgically treated thymomas. Methods: Sixty patients with thymomas who underwent treatment at our institution between 2004 and 2015 were included. Survival analysis was performed based on curves that were obtained using the Kaplan–Meier method. The Wilcoxon test was used for all comparisons, and p < 0.05 was considered statistically significant. Results: Forty-seven, four, three, four, and two patients presented tumor stages I, II, III, IVa, and IVb (according to the Masaoka classification), respectively, while six, 14, 11, 22, and seven patients had type A, AB, B1, B2, and B3 thymomas, respectively. Furthermore, 53 and eight patients underwent complete resection and required additional resection of adjacent organs, respectively, and no patients died from surgery-related complications. The five-year survival and recurrence-free survival (RFS) rates were 96% and 86%, respectively. The five-year survival rate for all stages was 100% except for those with stage IVb tumors (Masaoka classification); the survival rate for those patients was 0%. Separately, the five-year RFS rates for tumor stages I, II, III, IVa, and IVb were 100%, 91%, 91%, 81%, and 71%, respectively. Finally, the five-year survival rates in cases with complete and incomplete resections were 100% and 71%, respectively, indicating that the latter group had a significantly poorer prognosis (p < 0.001). Conclusions: These findings suggest that complete resection and the Masaoka pathological stage are significant predictors of prognosis in patients with thymomas. Surgery should aim to achieve complete resection; however, advanced cases may require multimodality therapy.
Abnormal electrophysiological phenotypes and sleep deficits in a mouse model of Angelman Syndrome
Authors: Copping Nycole A , Silverman Jill L 
Published: December 2020

Abstract
Background: Angelman Syndrome (AS) is a rare genetic disorder characterized by impaired communication, motor and balance deficits, intellectual disabilities, recurring seizures and abnormal sleep patterns. The genetic cause of AS is neuronal specific loss of expression of UBE3A (ubiquitin-protein ligase E6-AP), an imprinted gene. Seizure and sleep disorders are highly prevalent (>80%) in the AS population. The present experiments were designed to identify translational, neurophysiological outcome measures in a model of AS. Methods: We used the exon-2 deletion mouse (Ube3a-del) on a C57BL/6J background to assess seizure, sleep and electrophysiological phenotypes. Seizure susceptibility has been reported in Ube3a-del mice with a variety of seizure induction methods. Here, we provoked seizures by a single high-dose injection of 80 mg/kg pentylenetetrazole. Novel experiments included the utilization of wireless telemetry devices to acquire global electroencephalogram (EEG) and neurophysiological data on electrographic seizures, power spectra, light-dark cycles, sleep stages and sleep spindles in Ube3a-del and WT mice. Results: Ube3a-del mice exhibited reduced seizure threshold compared to WT. EEG illustrated that Ube3a-del mice had increased epileptiform spiking activity and delta power, which corroborates findings from other laboratories and recapitulates clinical reports in AS. This is the first report to use a cortical surface-based recording by a wireless telemetry device over tethered/fixed head-mount depth recordings. Less time in both paradoxical and slow-wave sleep, longer latencies to paradoxical sleep stages, and total less sleep time in Ube3a-del mice were observed compared to WT. For the first time, we detected fewer sleep spindles in the AS mouse model. Limitations: This study was limited to the exon 2 deletion mouse model, future work will investigate the rat model of AS, containing a complete Ube3a deletion and pair EEG with behavior. Conclusions: Our data enhance rigor and translatability as our study provides important corroboration of previous reports on epileptiform and elevated delta power. For the first-time we report neurophysiological phenotypes collected via translational methodology. Furthermore, this is the first report of reduced sleep spindles, a critical marker of memory consolidation during sleep, in an AS model. Our results are useful outcomes for therapeutic testing.
Assessment of surveillance core and support functions regarding neglected tropical diseases in Kenya
Authors: Ng'etich Arthur Kipkemoi Saitabau , Voyi Kuku , Mutero Clifford Maina 
Published: December 2020

Abstract
Background: Effective surveillance and response systems are vital to achievement of disease control and elimination goals. Kenya adopted the revised guidelines of the integrated disease surveillance and response system in 2012. Previous assessments of surveillance system core and support functions in Africa are limited to notifiable diseases with minimal attention given to neglected tropical diseases amenable to preventive chemotherapy (PC-NTDs). The study aimed to assess surveillance system core and support functions relating to PC-NTDs in Kenya. Methods: A mixed method cross-sectional survey was adapted involving 192 health facility workers, 50 community-level health workers and 44 sub-national level health personnel. Data was collected using modified World Health Organization generic questionnaires, observation checklists and interview schedules. Descriptive summaries, tests of associations using Pearson’s Chi-square or Fisher’s exact tests and mixed effects regression models were used to analyse quantitative data. Qualitative data derived from interviews with study participants were coded and analysed thematically. Results: Performance of surveillance core and support functions in relation to PC-NTDs was assessed in comparison to an indicator performance target of 80%. Optimal level of performance was achieved on specimen handling capacity (84%; 100%), reports submission (100%; 100%), meeting report deadlines (84%; 80%) and data analysis (84%; 80%) at the sub-county and county levels respectively. Health facilities achieved the target threshold on reports submission (84%), meeting report deadlines (88%) and providing feedback (80%). Presence of well-equipped laboratories (3.07, 95% CI: 1.36, 6.94), provision for PC-NTDs in reporting forms (3.20, 95% CI: 1.44, 7.10) and training of personnel on surveillance (4.15, 95% CI: 2.30, 7.48) were associated with higher odds of a functional surveillance system. Challenges facing surveillance activities implementation revealed through qualitative data were in relation to surveillance guidelines and reporting tools, data analysis, feedback, supervisory activities, training and resource provision. Conclusion: There was evidence of low-performing surveillance functions regarding PC-NTDs in Kenya. Case detection, registration and confirmation, reporting, data analysis and feedback performed sub-optimally at the facility and community levels. Additionally, support functions including standards and guidelines, supervision, training and resources were particularly weak at the sub-national level. Improved PC-NTDs surveillance performance sub-nationally requires strengthened capacities.