bluuebunny/crossref_metadata_2025_split huggingface dataset:
Noncanonical HIPPO/MST Signaling via BUB3 and FOXO Drives Pulmonary Vascular Cell Growth and Survival
Authors: Kudryashova Tatiana V. , Dabral Swati , Nayakanti Sreenath , Ray Arnab , Goncharov Dmitry A. , Avolio Theodore , Shen Yuanjun , Rode Analise , Pena Andressa , Jiang Lifeng , Lin Derek , Baust Jeffrey , Bachman Timothy N. , Graumann Johannes , Ruppert Clemens , Guenther Andreas , Schmoranzer Mario , Grobs Yann , Eve Lemay Sarah , Tremblay Eve , Breuils-Bonnet Sandra , Boucherat Olivier , Mora Ana L. , DeLisser Horace , Zhao Jing , Zhao Yutong , Bonnet Sébastien , Seeger Werner , Pullamsetti Soni S. , Goncharova Elena A. 
Published: February 2022

Rationale:
The MSTs (mammalian Ste20-like kinases) 1/2 are members of the HIPPO pathway that act as growth suppressors in adult proliferative diseases. Pulmonary arterial hypertension (PAH) manifests by increased proliferation and survival of pulmonary vascular cells in small PAs, pulmonary vascular remodeling, and the rise of pulmonary arterial pressure. The role of MST1/2 in PAH is currently unknown.

Objective:
To investigate the roles and mechanisms of the action of MST1 and MST2 in PAH.

Methods and Results:
Using early-passage pulmonary vascular cells from PAH and nondiseased lungs and mice with smooth muscle-specific tamoxifen-inducible Mst1/2 knockdown, we found that, in contrast to canonical antiproliferative/proapoptotic roles, MST1/2 act as proproliferative/prosurvival molecules in human PAH pulmonary arterial vascular smooth muscle cells and pulmonary arterial adventitial fibroblasts and support established pulmonary vascular remodeling and pulmonary hypertension in mice with SU5416/hypoxia-induced pulmonary hypertension. By using unbiased proteomic analysis, gain- and loss-of function approaches, and pharmacological inhibition of MST1/2 kinase activity by XMU-MP-1, we next evaluated mechanisms of regulation and function of MST1/2 in PAH pulmonary vascular cells. We found that, in PAH pulmonary arterial adventitial fibroblasts, the proproliferative function of MST1/2 is caused by IL-6-dependent MST1/2 overexpression, which induces PSMC6-dependent downregulation of forkhead homeobox type O 3 and hyperproliferation. In PAH pulmonary arterial vascular smooth muscle cells, MST1/2 acted via forming a disease-specific interaction with BUB3 and supported ECM (extracellular matrix)- and USP10-dependent BUB3 accumulation, upregulation of Akt-mTORC1, cell proliferation, and survival. Supporting our in vitro observations, smooth muscle-specific Mst1/2 knockdown halted upregulation of Akt-mTORC1 in small muscular PAs of mice with SU5416/hypoxia-induced pulmonary hypertension.

Conclusions:
Together, this study describes a novel proproliferative/prosurvival role of MST1/2 in PAH pulmonary vasculature, provides a novel mechanistic link from MST1/2 via BUB3 and forkhead homeobox type O to the abnormal proliferation and survival of pulmonary arterial vascular smooth muscle cells and pulmonary arterial adventitial fibroblasts, remodeling and pulmonary hypertension, and suggests new target pathways for therapeutic intervention.
Regular Acetaminophen Use and Blood Pressure in People With Hypertension: The PATH-BP Trial
Authors: MacIntyre Iain M. , Turtle Emma J. , Farrah Tariq E. , Graham Catriona , Dear James W. , Webb David J. , McCallum Morag , Melville Vanessa , Fok Henry , McCrae Jame C. , Sule Ashish , Caparrotta Thomas M. , Kirkby Nicholas S. , Mitchell Jane A. 
Published: February 2022

Background:
Acetaminophen is widely used as first-line therapy for chronic pain because of its perceived safety and the assumption that, unlike nonsteroidal anti-inflammatory drugs, it has little or no effect on blood pressure (BP). Although observational studies suggest that acetaminophen may increase BP, clinical trials are lacking. We, therefore, studied the effects of regular acetaminophen dosing on BP in individuals with hypertension.

Methods:
In this double-blind, placebo-controlled, crossover study, 110 individuals were randomized to receive 1 g acetaminophen 4× daily or matched placebo for 2 weeks followed by a 2-week washout period before crossing over to the alternate treatment. At the beginning and end of each treatment period, 24-hour ambulatory BPs were measured. The primary outcome was a comparison of the change in mean daytime systolic BP from baseline to end of treatment between the placebo and acetaminophen arms.

Results:

One-hundred three patients completed both arms of the study. Regular acetaminophen, compared with placebo, resulted in a significant increase in mean daytime systolic BP (132.8±10.5 to 136.5±10.1 mm Hg [acetaminophen] vs 133.9±10.3 to 132.5±9.9 mm Hg [placebo];
P
<0.0001) with a placebo-corrected increase of 4.7 mm Hg (95% CI, 2.9–6.6) and mean daytime diastolic BP (81.2±8.0 to 82.1±7.8 mm Hg [acetaminophen] vs 81.7±7.9 to 80.9±7.8 mm Hg [placebo];
P
=0.005) with a placebo-corrected increase of 1.6 mm Hg (95% CI, 0.5–2.7). Similar findings were seen for 24-hour ambulatory and clinic BPs.

Conclusions:
Regular daily intake of 4 g acetaminophen increases systolic BP in individuals with hypertension by ≈5 mm Hg when compared with placebo; this increases cardiovascular risk and calls into question the safety of regular acetaminophen use in this situation.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT01997112. URL:
https://www.clinicaltrialsregister.eu
; Unique identifier: 2013-003204-40.
The Temperature Anomaly Pattern of the Pacific–North American Teleconnection: Growth and Decay
Authors: Clark Joseph P. , Feldstein Steven B. 
Published: February 2022

Abstract
Applying composite analysis to ERA-Interim data, the surface air temperature (SAT) anomaly pattern of the Pacific–North American (PNA) teleconnection is shown to include both symmetric and asymmetric SAT anomalies with respect to the PNA phase. The symmetric SAT anomalies, overlying the Russian Far East and western and eastern North America, grow through advection of the climatological temperature by the anomalous meridional wind and vertical mixing. The asymmetric SAT anomalies, overlying Siberia during the positive PNA and the subtropical North Pacific during the negative PNA, grow through vertical mixing only. For all SAT anomalies, vertical mixing relocates the temperature anomalies of the PNA teleconnection pattern from higher in the boundary layer downward to the level of the SAT. Above the level of the SAT, temperature anomaly growth is caused by horizontal temperature advection in all locations except for the subtropical North Pacific, where adiabatic cooling dominates. SAT anomaly decay is caused by longwave radiative heating/cooling, except over Siberia, where SAT anomaly decay is caused by vertical mixing. Additionally, temperature anomaly decay higher in the boundary layer due to nonlocal mixing contributes indirectly to SAT anomaly decay by weakening downgradient diffusion. These results highlight a diverse array of mechanisms by which individual anomalies within the PNA pattern grow and decay. Furthermore, with the exception of Siberia, throughout the growth and decay stages, horizontal temperature advection and/or vertical mixing is nearly balanced by longwave radiative heating/cooling, with the former being slightly stronger during the growth stage and the latter during the decay stage.
Spatial and Seasonal Isotope Variability in Precipitation across China: Monthly Isoscapes Based on Regionalized Fuzzy Clustering
Authors: Wang Shengjie , Lei Shijun , Zhang Mingjun , Hughes Catherine , Crawford Jagoda , Liu Zhongfang , Qu Deye 
Published: February 2022

AbstractThe spatial patterns of stable hydrogen and oxygen isotopes in precipitation (precipitation isoscapes) provide a geographic perspective to understand the atmospheric processes in modern environment and paleoclimate records. Here we compiled stable isotope data in modern precipitation at 223 sites across China and 48 in surrounding countries, and used regionalized fuzzy clustering to create monthly precipitation isoscapes for China (C-Isoscape). Based on regressions using spatial and climatic parameters for 12 months, the best-fitting equations were chosen for four climate clusters, and then the four layers were weighted using fuzzy membership. The moisture transportation path, controlled by the westerlies and the monsoon, results in different spatial and seasonal diversity of precipitation isotopes. Based on C-Isoscape, we determined a nationwide meteoric water line asδ2H = 7.4δ18O + 5.5 using least squares regression orδ2H = 8.0δ18O + 10.2 using precipitation weighted reduced major axis regression. Compared with previous global products, the C-Isoscape usually shows precipitation more enriched in18O and2H in summer and more depleted in winter for northwest China, while the C-Isoscape values are more enriched in heavy isotopes in most months for southwest China. The new monthly precipitation isoscapes provide an accurate and high-resolution mapping for Chinese precipitation isotopes, allowing for future intra-annual atmospheric process diagnostics using stable hydrogen and oxygen isotope in precipitation in the region.
Relative Impacts of the Orography and Land–Sea Contrast over the Indochina Peninsula on the Asian Summer Monsoon between Early and Late Summer
Authors: Zhuang Moran , Duan Anmin , Lu Riyu , Li Puxi , Yao Jinglong 
Published: February 2022

Abstract
The Indochina Peninsula (ICP) has a critical effect in shaping the Asian summer monsoon (ASM). However, the seasonal responses of the ASM to the ICP are not fully understood. This study employs a 1° atmospheric general circulation model to examine the different contributions of the ICP’s orography and land–sea contrast to the ASM during the early and late summer. Results indicate that the orographic effect increases South Asian rainfall and reduces the rainfall over the South China Sea (SCS) and North China in early summer, but its influence on monsoonal circulation and rainfall is limited to East Asia in late summer. The impact of the ICP’s land–sea contrast is basically opposite in the two summer stages. With the presence of the ICP, SCS rainfall is enhanced but South Asian rainfall is weakened in early summer. In late summer, however, rainfall from the ICP to the northwestern Pacific is strikingly reduced, accompanied by intensified rainfall over South Asia. Relatively, the orographic effect seems to be more important in modulating the South Asian monsoon in early summer, while the land–sea contrast is dominant in strengthening the SCS monsoon and suppressing the northwest Pacific monsoon via the interaction between the induced local circulation and multilevel ASM subsystems. In late summer, the orographic effect on the ASM is much weaker compared to the land–sea contrast, which plays a critical role by shifting the subtropical high southwestward and through the “thermal adaption” feedback mechanism. Therefore, the orographic impact of the ICP on the ASM differs from that of the land–sea contrast in the two summer stages.
The results of cardiac surgery during the COVID-19 pandemic compared with previous years: a propensity weighted study of outcomes at six months
Authors: Day Emily , Fiorentino Francesca , Abdelkhalek Mohamed , Smail Hassiba , Stock Ulrich A , Bhudia Sunil , De Robertis Fabio , Bahrami Toufan , Raja Shahzad , Gaer Jullien 
Published: February 2022

Objectives In addition to excess mortality due to COVID-19, the pandemic has been characterised by excess mortality due to non-COVID diagnoses and consistent reports of patients delaying seeking medical treatment. This study seeks to compare the outcomes of cardiac surgery during and before the COVID-19 pandemic. Design Our institutional database was interrogated retrospectively to identify all patients undergoing one of three index procedures during the first six months of the pandemic and the corresponding epochs of the previous five years. Setting A regional cardiothoracic centre. Participants All patients undergoing surgery during weeks #13-37, 2015-2020. Main outcome measures Propensity score weighted analysis was employed to compare the incidence of major complications (stroke, renal failure, re-ventilation), 30-day mortality, six month survival and length of hospital stay between the two groups. Results There was no difference in 30-day mortality (HR = 0.76 [95% CI 0.27-2.20], p = 0.6211), 6-month survival (HR = 0.94 [95% CI 0.44-2.01], p = 0.8809) and duration of stay (SHR = 1.00 (95% CI 0.90-1.12), p = 0.959) between the two eras. There were no differences in the incidence of major complications (weighted chi-square test: renal failure: p = 0.923, stroke: p = 0.991, new respiratory failure: p = 0.856). Conclusions Cardiac surgery is as safe now as in the previous five years. Concerns over the transmission of COVID-19 in hospital are understandable but patients should be encouraged not to delay seeking medical attention. All involved in healthcare and the wider public should be reassured by these findings.
Health risk assessment of heavy metals and poly-aromatic hydrocarbons in particulate matter adsorbed by indoor air purifiers
Authors: Li Chunhui , Bai Li , He Zijian , Wang Yujie 
Published: February 2022

Particulate matter (PM) adsorbed by air purifiers, normally used in residential buildings, was collected and analysed by this study. The concentrations of eight heavy metals and 16 poly-aromatic hydrocarbons (PAHs) in PM were determined by inductively coupled plasma-optical emission spectroscopy (ICP-OES) and gas chromatography-mass spectroscopy (GC-MS). The health risk of heavy metals and PAHs was assessed using the health assessment model recommended by the US Environment Protection Agency (EPA). The results showed that the total concentrations of heavy metals during the heating period and non-heating period were 771.27 mg/kg and 441.10 mg/kg, respectively. The carcinogenicity and non-carcinogenicity of chemicals found are higher during the heating period than the non-heating period. The exposure of children was higher than that of adults. Eight heavy metals would pose non-carcinogenic risks for children, but four of these would pose carcinogenic risks for adults and children. The total concentrations of 16 PAHs during the heating period and non-heating period were 106.69 μg/kg and 68.72 μg/kg, respectively. Total toxicity equivalents (TEQs) were 16.37 μg/kg and 9.20 μg/kg, respectively. Among them, 4-rings PAHs accounted for the highest proportion, followed by 5-rings PAHs and 6-rings PAHs. The proportion of 2-rings and 3-rings PAHs were the lowest. 16 PAHs could pose a high carcinogenic risk to adults and children during the heating period, and there was a potential carcinogenic risk during the non-heating period.
An interesting finding: What is the relation between aortic enlargement and COVID-19?
Authors: Bitargil Macit , Demir Tolga , Çetin Hakkı Kürşat , Bektaş Nilüfer , Kasapoğlu Begüm Özüekren , El Kilic Helin , Balkaya Ahmet Ibrahim , Koramaz Ismail , Özdemir Hacı Mustafa 
Published: February 2022

Background We aim to compare the diameters of ascending aorta in COVID-19 patients and COVID–19-free individuals referred to our pandemic hospital. Methods The medical records and thorax tomographies of patients admitted to the “pandemic central” state hospital with symptoms of COVID-19 were observed between April 2020 and May 2020 in this case-control study. The first group consisted of patients diagnosed with COVID-19, and the second group consisted of patients without the disease. The diameter of the ascending aorta is measured via tomography and compared to each other. The most causative risk factors for aortic enlargements underwent a multivariate regression analysis. Results Charts of 156 patients (104 COVID-19 positives, 52 COVID-19 negatives) were reviewed. There was a statistical difference ( p: .01) between the mean aortic diameter of COVID-19 patients (39 mm) and COVID-free patients (32.5 mm) even though comorbid factors and patient characteristics were similar in the two groups at the time of hospital admission. The regression analysis result demonstrates that COVID-19 (leading factor), age, and coronary artery disease were the most significant factors associated with increasing aortic dimensions. ( p: .001, B: 5.3/, p: .02, B: 3.36/, p: .002, B: 0.13/, R square: 40.2%). Conclusion This study shows that the mean aortic diameter of COVID-19 patients is larger than non–COVID-19 patients with similar comorbidities referred to a pandemic hospital. COVID-19, age, and coronary artery disease are the most influential factors that affect the aortic diameter, and the COVID-19 was the leading factor.
Safety and Effectiveness of the Use of an Electronic Glucose Monitoring System Versus Weight-Based Dosing Nomogram for Treatment of Diabetic Ketoacidosis and Hyperglycemic Hyperosmolar Syndrome in a VA Hospital
Authors: Brown Madeline , Roberts Justin , Smith Cole , Eash Dakota 
Published: February 2022

Objective: The objective of this study is to assess the safety and effectiveness of an electronic glucose monitoring system (eGMS) versus paper-based protocols (PBPs) to manage diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar syndrome (HHS) within the VA setting. Methods: This study is a retrospective chart review of patients on an insulin drip, treated in the emergency department (ED) or intensive care unit (ICU) at Veteran Health Indiana for DKA or HHS. The primary outcome was evaluating the percentage of patients with hypoglycemia (blood glucose [BG] level <70 mg/dL) in patients admitted with DKA and HHS comparing an eGMS versus a PBP. A total of 168 patients were included in the analysis, with 84 patients in each group. Results: The primary outcome comparing rates of hypoglycemia in the eGMS group versus the PBP group showed a lower rate of hypoglycemia in the eGMS group (0.024%) compared with the PBP group (0.060%); however, this difference was not found to be statistically significant ( P = .90). Statistically significant secondary outcomes include the percentage of glucose checks drawn within the protocol recommendation (80.7% vs 52.6%, P = .02). Conclusions: While the primary endpoint of decreased hypoglycemia was not found to be statistically significant, it did reduce the overall number of hypoglycemia events in the eGMS group compared with the PBP group which may be clinically significant. This demonstrates that eGMS use has the potential to minimize hypoglycemia and glycemic variability in a critically-ill Veteran population by individualizing insulin drip titration based on a variety of patient-specific factors and providing reminders for staff to obtain BG checks in a timely manner.
Key Considerations for Understanding Usability of Digital Health Initiatives for Adults With Type 2 Diabetes: A Systematic Qualitative Literature Review
Authors: Hall Larissa , Islam Md Shahidul 
Published: February 2022

Aims: The rapidly growing number of adults with type 2 diabetes globally means the uses and benefits of digital health initiatives to enhance self-management of diabetes warrant review. This systematic qualitative literature review aimed to understand usability of digital health initiatives for adults with type 2 diabetes. Methods: This systematic qualitative literature review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, the PRISMA 2020 Statement methodology. Three databases were used (SCOPUS, Medline, and CINAHL) to identify studies published from 2016 to 2021 that focused on experiences, evaluations, and usability of digital health initiatives aimed at helping adults with type 2 diabetes to self-manage their condition. Results: From the 407 studies identified, 35 studies were assessed for eligibility with 10 studies included in the final synthesis. Five main themes emerged: (1) unmet emotional needs, (2) enhancing self-management, (3) desire for education, (4) usability/user-experience, and (5) risk of biomedical marker reductionism. Conclusions: This review identified 5 key themes for consideration to understand usability of digital health initiatives. If these unmet psychosocial needs of adults with type 2 diabetes are better addressed in digital health initiatives, enhanced daily self-management will lead to more optimal diabetes management which can increase overall health outcomes, reduce the risk of longer-term complications, enhance quality of life for type 2 diabetes and improve more widespread adoption of digital health initiatives.
Accuracy of Continuous Glucose Monitors for Inpatient Diabetes Management
Authors: Wright Jordan J. , Williams Alexander J. , Friedman Sally B. , Weaver Rita G. , Williams Jonathan M. , Hodge Elizabeth , Fowler Michael , Bao Shichun 
Published: February 2022

Introduction: In hospitalized patients, continuous glucose monitoring (CGM) may improve glycemic control, prevent hypoglycemic events, and reduce staff workload compared with point-of-care (POC) capillary glucose monitoring. Methods: To evaluate CGM accuracy and safety of use in the inpatient setting, two versions of CGM sensors were placed on 43 and 34 adult patients with diabetes admitted to non-intensive care unit (ICU) medical wards, respectively. CGM accuracy relative to POC and safety of use were measured by calculating mean absolute relative difference (MARD) and by Clarke Error Grid (CEG) analysis. Results: CGM version 2 had improved accuracy compared with CGM version 1 with MARD 17.7 compared with 21.4%. CGM accuracy did not change with POC value or with time of sensor wear. On CEG, 98.8% of paired values fell within acceptable zones A and B. Conclusion: Despite reduced accuracy compared with the outpatient setting, both versions of CGMs had acceptable safety profiles in the inpatient setting.
Quercetin attenuates the proliferation, inflammation, and oxidative stress of high glucose-induced human mesangial cells by regulating the miR-485-5p/YAP1 pathway
Authors: Wan Huan , Wang Yaping , Pan Qingyun , Chen Xia , Chen Sijun , Li Xiaohui , Yao Weiguo 
Published: February 2022

Background Diabetic nephropathy (DN) is a kidney damage caused by diabetes and the main cause of end-stage renal disease. However, the current treatment of DN has many limitations. Quercetin is a bioflavonoid compound with therapeutic benefits in metabolic diseases. This study aims to determine the therapeutic potentials and underlying mechanism of quercetin on DN. Methods We collected blood samples from DN patients and healthy controls and treated human mesangial cells (HMCs) with high glucose (HG) to establish an in vitro model of DN. Then we assessed the expression difference of miR-485-5p as well as YAP1 in serum of DN patients and healthy controls and between HG-induced HMCs and control cells. qRT-PCR and western blot were performed to assess miR-485-5p and YAP1 expression levels; CCK-8 and ELISAs were used to examine cell proliferation, inflammation, and oxidative stress. Dual luciferase reporter assay was implemented to detect the binding of miR-485-5p and YAP1 mRNA sequence. Results Quercetin suppressed proliferation, inflammation, and oxidative stress of HMCs induced by HG. As for mechanism, miR-485-5p directly bound to YAP1 and inhibited YAP1 expression. The downregulation of miR-485-5p and upregulation of YAP1 were also observed in the serum of DN patients. Quercetin modulated miR-485-5p/YAP1 axis to regulate HG-induced inflammation and oxidative stress. Conclusion: Quercetin inhibits the proliferation, inflammation, and oxidative stress of HMCs induced by HG through miR-485-5p/YAP1 axis, which might provide a novel treatment strategy for DN.