bluuebunny/crossref_metadata_2025_split huggingface dataset:
PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) Triggers Vascular Smooth Muscle Cell Senescence and Apoptosis: Implication of Its Direct Role in Degenerative Vascular Disease
Authors: Guo Yanan , Tang Zhihan , Yan Binjie , Yin Hao , Tai Shi , Peng Juan , Cui Yuting , Gui Yu , Belke Darrell , Zhou Shenghua , Zheng Xi-Long 
Published: November 2021

Objective:
PCSK9 (proprotein convertase subtilisin/kexin type 9) plays a critical role in cholesterol metabolism via the PCSK9–LDLR (low-density lipoprotein receptor) axis in the liver; however, evidence indicates that PCSK9 directly contributes to the pathogenesis of various diseases through mechanisms independent of its LDL-cholesterol regulation. The objective of this study was to determine how PCSK9 directly acts on vascular smooth muscle cells (SMCs), contributing to degenerative vascular disease.

Approach and Results:

We first examined the effects of PCSK9 on cultured human aortic SMCs. Overexpression of PCSK9 downregulated the expression of ApoER2 (apolipoprotein E receptor 2), a known target of PCSK9. Treatment with soluble recombinant human ApoER2 or the DNA synthesis inhibitor, hydroxyurea, inhibited PCSK9-induced polyploidization and other cellular responses of human SMCs. Treatment with antibodies against ApoER2 resulted in similar effects to those observed with PCSK9 overexpression. Inducible, SMC-specific knockout of
Pcsk9
accelerated neointima formation in mouse carotid arteries and reduced age-related arterial stiffness. PCSK9 was expressed in SMCs of human atherosclerotic lesions and abundant in the “shoulder” regions of vulnerable atherosclerotic plaques. PCSK9 was also expressed in SMCs of abdominal aortic aneurysm, which was inversely related to the expression of smooth muscle α-actin.

Conclusions:
Our findings demonstrate that PCSK9 inhibits proliferation and induces polyploidization, senescence, and apoptosis, which may be relevant to various degenerative vascular diseases.
Long-Term Changes in Invasive Physiological Pressure Indices of Stenosis Severity Following Transcatheter Aortic Valve Implantation
Authors: Sabbah Muhammad , Joshi Francis R. , Minkkinen Mikko , Holmvang Lene , Tilsted Hans-Henrik , Pedersen Frants , Ahtarovski Kiril , Sørensen Rikke , Thue Olsen Niels , Søndergaard Lars , De Backer Ole , Engstrøm Thomas , Lønborg Jacob 
Published: November 2021

Background:
Patients with severe aortic stenosis frequently have coexisting coronary artery disease. Invasive hyperemic and nonhyperemic pressure indices are used to assess coronary artery disease severity but have not been evaluated in the context of severe aortic stenosis.

Methods:
We compared lesion reclassification rates of fractional flow reserve (FFR) and resting full-cycle ratio (RFR) measured before and 6 months after transcatheter aortic valve implantation using the conventional clinical cutoffs of ≤0.80 for FFR and ≤0.89 for RFR. This was a substudy of the ongoing NOTION-3 trial (Third Nordic Aortic Valve Intervention). Two-dimensional quantitative coronary analysis was used to assess changes in angiographic lesion severity.

Results:

Forty patients were included contributing 50 lesions in which FFR was measured. In 32 patients (36 lesions), RFR was also measured. There was no significant change in diameter stenosis from baseline to follow-up, 49.8% (42.9%–57.1%) versus 52.3% (43.2%–57.8%),
P
=0.50. RFR improved significantly from 0.88 (0.83%–0.93) at baseline to 0.92 (0.83–0.95) at follow-up,
P
=0.003, whereas FFR remained unchanged, 0.84 (0.81–0.89) versus 0.86 (0.78–0.90),
P
=0.72. At baseline, 11 out of 50 (22%) lesions were FFR-positive, whereas 15 out of 50 (30%) were positive at follow-up,
P
=0.219. Corresponding numbers for RFR were 23 out of 36 (64%) at baseline and 12 out of 36 (33%) at follow-up,
P
=0.003.

Conclusions:
In patients with severe aortic stenosis, physiological assessment of coronary lesions with FFR before transcatheter aortic valve implantation leads to lower reclassification rate at 6-month follow-up, compared with RFR.
Cerebrovascular Risk-Factors of Prevalent and Incident Brain Infarcts in the General Population: The AGES-Reykjavik Study
Authors: Sigurdsson Sigurdur , Aspelund Thor , Kjartansson Olafur , Gudmundsson Elias , Jonsson Palmi V. , van Buchem Mark A. , Gudnason Vilmundur , Launer Lenore J. 
Published: November 2021

Background:
Studies on the association of cerebrovascular risk factors to magnetic resonance imaging detected brain infarcts have been inconsistent, partly reflecting limits of assessment to infarcts anywhere in the brain, as opposed to specific brain regions. We hypothesized that risk-factors may differ depending on where the infarct is located in subcortical-, cortical-, and cerebellar regions.

Methods:
Participants (n=2662, mean age 74.6±4.8) from the longitudinal population-based AGES (Age, Gene/Environment Susceptibility)-Reykjavik Study underwent brain magnetic resonance imaging at baseline and on average 5.2 years later. We assessed the number and location of brain infarcts (prevalent versus incident). We estimated the risk-ratios of prevalent (PRR) and incident (IRR) infarcts by baseline cerebrovascular risk-factors using Poisson regression.

Results:
Thirty-one percent of the study participants had prevalent brain infarcts and 21% developed new infarcts over 5 years. Prevalent subcortical infarcts were associated with hypertension (PRR, 2.7 [95% CI, 1.1–6.8]), systolic blood pressure (PRR, 1.2 [95% CI, 1.1–1.4]), and diabetes (PRR, 2.8 [95% CI, 1.9–4.1]); incident subcortical infarcts were associated with systolic (IRR, 1.2 [95% CI, 1.0–1.4]) and diastolic (IRR, 1.3 [95% CI, 1.0–1.6]) blood pressure. Prevalent and incident cortical infarcts were associated with carotid plaques (PRR, 1.8 [95% CI, 1.3–2.5] and IRR, 1.9 [95% CI, 1.3–2.9], respectively), and atrial fibrillation was significantly associated with prevalent cortical infarcts (PRR, 1.8 [95% CI, 1.2–2.7]). Risk-factors for prevalent cerebellar infarcts included hypertension (PRR, 2.45 [95% CI, 1.5–4.0]), carotid plaques (PRR, 1.45 [95% CI, 1.2–1.8]), and migraine with aura (PRR, 1.6 [95% CI, 1.1–2.2]). Incident cerebellar infarcts were only associated with any migraine (IRR, 1.4 [95% CI, 1.0–2.0]).

Conclusions:
The risk for subcortical infarcts tends to increase with small vessel disease risk-factors such as hypertension and diabetes. Risk for cortical infarcts tends to increase with atherosclerotic/coronary processes and risk for cerebellar infarcts with a more mixed profile of factors. Assessment of risk-factors by location of asymptomatic infarcts found on magnetic resonance imaging may improve the ability to target and optimize preventive therapeutic approaches to prevent stroke.
Black-White Differences in Ischemic Stroke Risk Factor Burden in Young Adults
Authors: Aradine Elizabeth M. , Ryan Kathleen A. , Cronin Carolyn A. , Wozniak Marcella A. , Cole John W. , Chaturvedi Seemant , Dutta Tara L.M. , Hou Yan , Mehndiratta Prachi , Motta Melissa , Phipps Michael S. , Yarbrough Karen L. , McArdle Patrick F. , Kittner Steven J. 
Published: November 2021

Background and Purpose:
Although the US Black population has a higher incidence of stroke compared with the US White population, few studies have addressed Black-White differences in the contribution of vascular risk factors to the population burden of ischemic stroke in young adults.

Methods:
A population-based case-control study of early-onset ischemic stroke, ages 15 to 49 years, was conducted in the Baltimore-Washington DC region between 1992 and 2007. Risk factor data was obtained by in-person interview in both cases and controls. The prevalence, odds ratio, and population-attributable risk percent (PAR%) of smoking, diabetes, and hypertension was determined among Black patients and White patients, stratified by sex.

Results:
The study included 1044 cases and 1099 controls. Of the cases, 47% were Black patients, 54% were men, and the mean (±SD) age was 41.0 (±6.8) years. For smoking, the population-attributable risk percent were White men 19.7%, White women 32.5%, Black men 10.1%, and Black women 23.8%. For diabetes, the population-attributable risk percent were White men 10.5%, White women 7.4%, Black men 17.2%, and Black women 13.4%. For hypertension, the population-attributable risk percent were White men 17.2%, White women 19.3%, Black men 45.8%, and Black women 26.4%.

Conclusions:
Modifiable vascular risk factors account for a large proportion of ischemic stroke in young adults. Cigarette smoking was the strongest contributor to stroke among White patients while hypertension was the strongest contributor to stroke among Black patients. These results support early primary prevention efforts focused on smoking cessation and hypertension detection and treatment.
The first assessment of genetic diversity among Turkish leek accessions using molecular and morphological markers
Authors: Hanci Fatih 
Published: November 2021

Abstract
Considering the high importance of leek as a vegetable crop, this species is rarely an object of molecular genetic studies. In this study, SRAP and ISSR markers were used for the first time to investigate the genetic diversity in Turkish leek accessions together with some morphological characters. The study was conducted in Erciyes University Faculty of Agriculture in 2018–2020. Thirty-seven local varieties were collected from different towns in Turkey. Also, nineteen leek accessions, which originated from different regions of Turkey, had been kindly obtained from Plant Gene Banks, USDA. Seventeen SRAP and three ISSR markers were screened; all of them exposing 137 reproducible bands, of which 114 resulted in polymorphic. Polymorphism information content (PIC) varied between 0.209 and 0.840. Genetic similarities varied from 0.563 to 0.960, with an average of 0.789. In addition to molecular markers, the entire gene pool was morphologically characterized over two-year data. For this purpose, eight characters, which play a key role in leek breeding, were measured. At the end of the study, the analyzes made according to the molecular and morphological data were compared both separately and in combination. In all groupings, it was found remarkable that the accessions numbered 98*3, 40*1, 40*4, and 40*6 were positioned differently from the others. These results have provided important insights into the genetic variability of Turkish leek accessions for the first time. Also, the diversity analysis performed in this study provides valuable information to researchers for future studies.
Advances in the Application and Utility of Subseasonal-to-Seasonal Predictions
Authors: White Christopher J. , Domeisen Daniela I. V. , Acharya Nachiketa , Adefisan Elijah A. , Anderson Michael L. , Aura Stella , Balogun Ahmed A. , Bertram Douglas , Bluhm Sonia , Brayshaw David J. , Browell Jethro , Büeler Dominik , Charlton-Perez Andrew , Chourio Xandre , Christel Isadora , Coelho Caio A. S. , DeFlorio Michael J. , Delle Monache Luca , Di Giuseppe Francesca , García-Solórzano Ana María , Gibson Peter B. , Goddard Lisa , González Romero Carmen , Graham Richard J. , Graham Robert M. , Grams Christian M. , Halford Alan , Huang W. T. Katty , Jensen Kjeld , Kilavi Mary , Lawal Kamoru A. , Lee Robert W. , MacLeod David , Manrique-Suñén Andrea , Martins Eduardo S. P. R. , Maxwell Carolyn J. , Merryfield William J. , Muñoz Ángel G. , Olaniyan Eniola , Otieno George , Oyedepo John A. , Palma Lluís , Pechlivanidis Ilias G. , Pons Diego , Ralph F. Martin , Reis Dirceu S. , Remenyi Tomas A. , Risbey James S. , Robertson Donald J. C. , Robertson Andrew W. , Smith Stefan , Soret Albert , Sun Ting , Todd Martin C. , Tozer Carly R. , Vasconcelos Francisco C. , Vigo Ilaria , Waliser Duane E. , Wetterhall Fredrik , Wilson Robert G. 
Published: November 2021

Abstract
The subseasonal-to-seasonal (S2S) predictive time scale, encompassing lead times ranging from 2 weeks to a season, is at the frontier of forecasting science. Forecasts on this time scale provide opportunities for enhanced application-focused capabilities to complement existing weather and climate services and products. There is, however, a “knowledge–value” gap, where a lack of evidence and awareness of the potential socioeconomic benefits of S2S forecasts limits their wider uptake. To address this gap, here we present the first global community effort at summarizing relevant applications of S2S forecasts to guide further decision-making and support the continued development of S2S forecasts and related services. Focusing on 12 sectoral case studies spanning public health, agriculture, water resource management, renewable energy and utilities, and emergency management and response, we draw on recent advancements to explore their application and utility. These case studies mark a significant step forward in moving from potential to actual S2S forecasting applications. We show that by placing user needs at the forefront of S2S forecast development—demonstrating both skill and utility across sectors—this dialogue can be used to help promote and accelerate the awareness, value, and cogeneration of S2S forecasts. We also highlight that while S2S forecasts are increasingly gaining interest among users, incorporating probabilistic S2S forecasts into existing decision-making operations is not trivial. Nevertheless, S2S forecasting represents a significant opportunity to generate useful, usable, and actionable forecast applications for and with users that will increasingly unlock the potential of this forecasting time scale.
Ensuring hemodialysis adequacy by dialysis dose monitoring with UV spectroscopy analysis of spent dialyzate
Authors: Zhang Li , Liu Wenhu , Hao Chuanming , He Yani , Tao Ye , Sun Shiren , Jakob Marten , Marcelli Daniele , Barth Claudia , Chen Xiangmei 
Published: November 2021

Introduction: Patients’ session-to-session variation has been shown to influence outcomes, making critical the monitoring of dialysis dose in each session. The aim of this study was to detect the intra-patient variability of blood single pool Kt/V as measured from pre-post dialysis blood urea and from the online tool Adimea®, which measures the ultraviolet absorbance of spent dialyzate. Methods: This open, one-armed, prospective non-interventional study, evaluates patients on bicarbonate hemodialysis or/and on hemodiafiltration. Dialysis was performed with B. Braun Dialog+ machines equipped with Adimea®. In the course of the prospective observation, online monitoring with Adimea® in each session was established without the target warning function being activated. A sample size of 97 patients was estimated. Results: A total of 120 patients were enrolled in six centers in China (mean age 51.5 ± 12.2 years, 86.7% males, 24.2% diabetics). All had an AV-fistula. The proportion of patients with blood Kt/V < 1.20 at baseline was 48.3%. During follow-up with Adimea®, the subgroup with Kt/V > 1.20 at baseline remains at the same adequacy level for more than 90% of the patients. Those with a Kt/V < 1.20 at baseline, showed a significant increase of Kt/V to 60% of the patients reaching the adequacy level >1.20. The coefficient of variation for spKt/V as evaluated by Adimea® was 9.6 ± 3.4%, not significantly different from the 9.6 ± 8.6% as blood Kt/V taken at the same time. Conclusion: Online monitoring of dialysis dose by Adimea® improves and maintains dialysis adequacy. Implementing online monitoring by Adimea into daily practice moves the quality of dialysis patient care a significant step forward.
ST-Elevation Myocardial Infarction Among Septic Shock and Coronary Interventions: A National Emergency Database Study
Authors: Mir Tanveer , Uddin Mohammed , Qureshi Waqas T. , Abohashem Shady , Alqalyoobi Shehabaldin , Sheikh Mujeeb , Soubani Ayman , Saydain Ghulam , Albertson Timothy E. 
Published: November 2021

Objective To study coronary interventions and mortality among patients with ST-elevated myocardial infarction (STEMI) who were admitted with septic shock. Methods Data from the national emergency department sample (NEDS) that constitutes 20% sample of hospital-owned emergency departments in the United States was analyzed for the septic shock related visits from 2016 to 2018. Septic shock was defined by the ICD codes. Results Out of 1 375 507 adult septic shock patients, 521 300 had a primary diagnosis of septic shock (mean age 67.41±15.67 years, 51.1% females) in the national emergency database for the years 2016 to 2018. Of these patients, 2768 (0.53%) had STEMI recorded during the hospitalization. Mortality rates for STEMI patients were higher than patients without STEMI (52.3% vs 23.5%). Mortality rates improved with PCI among STEMI patients (43.8% vs 56.2%). Coronary angiography was performed among 16% of patients of which percutaneous coronary intervention (PCI) rates were 7.7% among patients with STEMI septic shock. PCI numerically improved mortality, however, had no significant difference than patients without PCI on multivariate logistic regression and univariate logistic regression post coarsened exact matching of baseline characteristics among STEMI patients. Among the predictors, STEMI was a significant predictor of mortality in septic shock patients (OR 2.87, 95% CI 2.37-3.49; P<.001). Age, peripheral vascular disease, were predominant predictors of mortality in STEMI with septic shock subgroup ( P <.001). Pneumonia was the predominant underlying infection among STEMI (36.4%) and without STEMI group (29.5%). Conclusion STEMI complicating septic shock worsens mortality. PCI and coronary angiography numerically improved mortality, however, had no significant difference from patients without PCI. More research will be needed to improve mortality in such a critically ill subgroup of patients.
The Effects of Exclusive Walking on Lipids and Lipoproteins in Women with Overweight and Obesity: A Systematic Review and Meta-Analysis
Authors: Ballard Anjulyn M. , Davis Ashlee , Wong Brett , Lyn Rodney , Thompson Walter R. 
Published: November 2021

Objective To evaluate the effects of walking, independent of diet and weight-loss, on lipids and lipoproteins in women with overweight and obesity. Data Source Academic Search Complete, Alternative Health Watch, Global Health, Health Source, CINAHL, MEDLINE, EMBASE, SportDiscus, and ProQuest. Study Inclusion and Exclusion Criteria (1) experiment-control design; (2) women with overweight or obesity; (3) walking as the experiment’s independent variable; (4) four or more weeks; and (5) pre- to post-assessment of lipids and/or lipoproteins. Excluded studies reported use of lipid-lowering medication, diet or other modes of physical activity, and alternative interventions as the control. Data Extraction Data extraction and study quality were completed by the first 2 authors using the Cochrane review protocol and risk of bias assessment. Data Synthesis Raw mean difference between the experiment and control groups using a random effects model. Results Meta-analyses of 21 interventions (N = 1129) demonstrated exclusive walking improves total cholesterol (raw mean difference = 6.67 mg/dL, P = .04) and low-density lipoproteins (raw mean difference = 7.38 mg/dL, P = .04). Greater improvement in total cholesterol, triglycerides, high-density lipoproteins, and low-density lipoproteins existed in women with obesity. Conclusions Exclusive walking aids in normalizing total cholesterol and LDLs in women with overweight and obesity. Exclusive walking can be used as a non-pharmacologic therapy, which may have positive clinical outcomes for individuals who especially struggle with diet and weight-reduction.
Renal function deterioration is an independent mortality determinant in Koreans diagnosed with lupus nephritis
Authors: Jeon Howook , Lee Jennifer , Ju Ji Hyeon , Kim Wan-Uk , Park Sung-Hwan , Moon Su-Jin , Kwok Seung-Ki 
Published: November 2021

Objective To evaluate the predictors of mortality, mortality rate, and causes of death in patients with lupus nephritis (LN) depending on final renal function. Methods The cohort included 401 Korean patients diagnosed with LN between 1985 and 2019. We retrospectively analyzed the clinical and laboratory indices, treatment response, and the final renal function. The final renal function was defined by the last stable level of eGFR measured in an out-patient department more than 3 times before death occurred and was categorized into five groups depending on CKD stage. Results The median follow-up time after the diagnosis of LN was 131 months. No difference in baseline demographic characteristics and laboratory findings was found except for the proportion of Hb less than 10 mg/dl and baseline eGFR ( p = 0.011 and 0.037). We found no significant differences in therapeutic parameters, but all the response parameters including treatment response at 6 months ( p = 0.004) and 12 months ( p = 0.004), time to remission ( p < 0.001), final renal response ( p < 0.001), and the final renal function ( p < 0.001) differed significantly between the two groups. In multivariate Cox proportional hazards analysis, the final renal function was an independent risk factor predicting mortality. The main causes of death were infection and SLE flare. Contrary to existing knowledge, SLE flare also triggered mortality in a few patients with LN progressed to end-stage renal disease (ESRD). Only two cases of mortality occurred in the kidney transplantation (KT) group ( n = 25) with a median follow-up period of 224 months. The overall mortality rates calculated using the Kaplan–Meier method were 6.8%, 10.3%, 19.7%, and 28.0% at 5, 10, 20, and 30 years, respectively. Conclusion Renal function deterioration was an independent determinant of mortality in Korean patients with LN. SLE flare also caused mortality in patients with LN who required maintenance dialysis, suggesting the benefit of KT on lupus activity and survival.
Telepsychiatry and face-to-face psychiatric consultations during the first year of the COVID-19 pandemic in Australia: patients being heard and seen
Authors: Looi Jeffrey CL , Allison Stephen , Bastiampillai Tarun , Pring William , Kisely Stephen R 
Published: November 2021

Objective: The Australian federal government introduced additional Medicare Benefits Schedule (MBS) telehealth-items to facilitate care by private psychiatrists during the COVID-19 pandemic. Method: We analysed private psychiatrists’ uptake of video and telephone-telehealth, as well as total (telehealth and face-to-face) consultations for April 2020–April 2021. We compare these to face-to-face consultations for April 2018–April 2019. MBS-Item service data were extracted for COVID-19-psychiatrist-video- and telephone-telehealth item numbers and compared with face-to-face consultations for the whole of Australia. Results: Psychiatric consultation numbers (telehealth and face-to-face) were 13% higher during the first year of the pandemic compared with 2018–2019, with telehealth accounting for 40% of this total. Face-to-face consultations were 65% of the comparative number of 2018–2019 consultations. There was substantial usage of telehealth consultations during 2020–2021. The majority of telehealth involved short telephone consultations of ⩽15–30 min, while video was used more, in longer consultations. Conclusions: Private psychiatrists and patients continued using the new telehealth-items during 2020–2021. This compensated for decreases in face-to-face consultations and resulted in an overall increase in the total patient contacts compared to 2018–2019.
3-Dimensional Craniofacial Imaging: A Template for Systematic Radiologic Evaluation for Alveolar Cleft Assessment and Planning
Authors: Preston Kathryn , Mallya Sanjay M. 
Published: November 2021

Background Imaging findings are central to the diagnosis and treatment planning decisions when managing craniofacial differences. However, limited information is published on protocols for systematic cleft imaging assessment and for effective communication of these findings. Solution A template is presented to help guide radiologic imaging reports to acquire the relevant clinical information needed to manage patients with alveolar cleft.