bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extracellular Matrix in Heart Failure: Role of ADAMTS5 in Proteoglycan Remodeling
Authors: Barallobre-Barreiro Javier , Radovits Tamás , Fava Marika , Mayr Ursula , Lin Wen-Yu , Ermolaeva Elizaveta , Martínez-López Diego , Lindberg Eric L. , Duregotti Elisa , Daróczi László , Hasman Maria , Schmidt Lukas E. , Singh Bhawana , Lu Ruifang , Baig Ferheen , Siedlar Aleksandra Malgorzata , Cuello Friederike , Catibog Norman , Theofilatos Konstantinos , Shah Ajay M. , Crespo-Leiro Maria G. , Doménech Nieves , Hübner Norbert , Merkely Béla , Mayr Manuel 
Published: November 2021

Background:
Remodeling of the extracellular matrix (ECM) is a hallmark of heart failure (HF). Our previous analysis of the secretome of murine cardiac fibroblasts returned ADAMTS5 (a disintegrin and metalloproteinase with thrombospondin motifs 5) as one of the most abundant proteases. ADAMTS5 cleaves chondroitin sulfate proteoglycans such as versican. The contribution of ADAMTS5 and its substrate versican to HF is unknown.

Methods:

Versican remodeling was assessed in mice lacking the catalytic domain of ADAMTS5 (Adamts5
ΔCat
). Proteomics was applied to study ECM remodeling in left ventricular samples from patients with HF, with a particular focus on the effects of common medications used for the treatment of HF.

Results:

Versican and versikine, an ADAMTS-specific versican cleavage product, accumulated in patients with ischemic HF. Versikine was also elevated in a porcine model of cardiac ischemia/reperfusion injury and in murine hearts after angiotensin II infusion. In Adamts5
ΔCat
mice, angiotensin II infusion resulted in an aggravated versican build-up and hyaluronic acid disarrangement, accompanied by reduced levels of integrin β1, filamin A, and connexin 43. Echocardiographic assessment of Adamts5
ΔCat
mice revealed a reduced ejection fraction and an impaired global longitudinal strain on angiotensin II infusion. Cardiac hypertrophy and collagen deposition were similar to littermate controls. In a proteomics analysis of a larger cohort of cardiac explants from patients with ischemic HF (n=65), the use of β-blockers was associated with a reduction in ECM deposition, with versican being among the most pronounced changes. Subsequent experiments in cardiac fibroblasts confirmed that β1-adrenergic receptor stimulation increased versican expression. Despite similar clinical characteristics, patients with HF treated with β-blockers had a distinct cardiac ECM profile.

Conclusions:
Our results in animal models and patients suggest that ADAMTS proteases are critical for versican degradation in the heart and that versican accumulation is associated with impaired cardiac function. A comprehensive characterization of the cardiac ECM in patients with ischemic HF revealed that β-blockers may have a previously unrecognized beneficial effect on cardiac chondroitin sulfate proteoglycan content.
Adenosine A1R/A3R (Adenosine A1 and A3 Receptor) Agonist AST-004 Reduces Brain Infarction in a Nonhuman Primate Model of Stroke
Authors: Liston Theodore E. , Hama Aldric , Boltze Johannes , Poe Russell B. , Natsume Takahiro , Hayashi Ikuo , Takamatsu Hiroyuki , Korinek William S. , Lechleiter James D. 
Published: November 2021

Background and Purpose:
Treatment with A1R/A3R (adenosine A1 and A3 receptor) agonists in rodent models of acute ischemic stroke results in significantly reduced lesion volume, indicating activation of adenosine A1R or A3R is cerebroprotective. However, dosing and timing required for cerebroprotection has yet to be established, and whether adenosine A1R/A3R activation will lead to cerebroprotection in a gyrencephalic species has yet to be determined.

Methods:
The current study used clinical study intervention timelines in a nonhuman primate model of transient, 4-hour middle cerebral artery occlusion to investigate a potential cerebroprotective effect of the dual adenosine A1R/A3R agonist AST-004. Bolus and then 22 hours intravenous infusion of AST-004 was initiated 2 hours after transient middle cerebral artery occlusion. Primary outcome measures included lesion volume, lesion growth kinetics, penumbra volume as well as initial pharmacokinetic-pharmacodynamic relationships measured up to 5 days after transient middle cerebral artery occlusion. Secondary outcome measures included physiological parameters and neurological function.

Results:
Administration of AST-004 resulted in rapid and statistically significant decreases in lesion growth rate and total lesion volume. In addition, penumbra volume decline over time was significantly less under AST-004 treatment compared with vehicle treatment. These changes correlated with unbound AST-004 concentrations in the plasma and cerebrospinal fluid as well as estimated brain A1R and A3R occupancy. No relevant changes in physiological parameters were observed during AST-004 treatment.

Conclusions:
These findings suggest that administration of AST-004 and combined A1R/A3R agonism in the brain are efficacious pharmacological interventions in acute ischemic stroke and warrant further clinical evaluation.
Variability and Drivers of Ocean Temperature Extremes in a Warming Western Boundary Current
Authors: Li Junde , Roughan Moninya , Kerry Colette 
Published: November 2021

Abstract
Western boundary current (WBC) extensions such as the East Australian Current (EAC) southern extension are warming 2–3 times faster than the global average. However, there are nuances in the spatial and temporal variability of the warming that are not well resolved in climate models. In addition, the physical drivers of ocean heat content (OHC) extremes are not well understood. Here, using a high-resolution ocean model run for multiple decades, we show nonuniform warming trends in OHC in the EAC, with strong positive trends in the southern extension region (∼36°–38°S) but negative OHC trends equatorward of 33°S. The OHC variability in the EAC is associated with the formation of anticyclonic eddies, which is modulated by transport ∼880 km upstream (EAC mode) and the westward propagation of Rossby waves (eddy mode). Diagnosing the drivers of temperature extremes has implications for predictability both in the EAC and in WBCs more broadly, where ocean warming is already having considerable ecological impacts.
Does Religion Buffer Against the Detrimental Effect of Cyberbullying Victimization on Adults’ Health and Well-Being? Evidence from the 2014 Canadian General Social Survey
Authors: Chai Lei 
Published: November 2021

While prior research has well-documented the detrimental effect of cyberbullying victimization on health and well-being among children and adolescents, less is known about whether the same adverse pattern can be observed among adults. Moreover, it is unclear about what psychosocial resources might moderate this association. The present study uses a nationally representative cross-sectional survey—2014 Canadian General Social Survey ( N = 17,548)—to examine three research questions. First, is cyberbullying victimization associated with adults’ self-rated health, mental health, and life satisfaction? Second, how does religiosity—religious service attendance and religious beliefs—moderate this association? Third, do any observed patterns further differ for men and women? Through a series of logistic and ordinary least squares regression models, the results show that adults who experienced cyberbullying victimization in the past 5 years are more likely to report poor self-rated health and mental health compared to those who did not experience cyberbullying victimization in the past 5 years. Likewise, cyberbullying victimization is also associated with lower levels of life satisfaction. In addition, the adverse associations of cyberbullying victimization in the past 5 years with self-rated health and life satisfaction are weaker among those who attended religious service at least once a week in the past twelve months. A similar pattern is observed for the buffering effect of viewing religious beliefs as very important in the adverse association of cyberbullying victimization in the past 5 years with self-rated life satisfaction. There is also evidence suggesting the gendered buffering effect of the importance of religious beliefs in the association between cyberbullying victimization and self-rated health. This study makes important empirical and theoretical contributions to the growing field of research on the association between cyberbullying victimization and health and well-being and to our understanding of how religion matters to individuals dealing with stressful experiences.
Whole-exome analysis of adolescents with low VWF and heavy menstrual bleeding identifies novel genetic associations
Authors: Sadler Brooke , Minard Charles G. , Haller Gabe , Gurnett Christina A. , O’Brien Sarah H. , Wheeler Allison , Jain Shilpa , Sharma Mutka , Zia Ayesha , Kulkarni Roshni , Mullins Eric , Ragni Margaret V. , Sidonio Robert , Dietrich Jennifer E. , Kouides Peter A. , Di Paola Jorge , Srivaths Lakshmi 
Published: November 2021

Abstract
Adolescents with low von Willebrand factor (VWF) levels and heavy menstrual bleeding (HMB) experience significant morbidity. There is a need to better characterize these patients genetically and improve our understanding of the pathophysiology of bleeding. We performed whole-exome sequencing on 86 postmenarchal patients diagnosed with low VWF levels (30-50 IU/dL) and HMB and compared them with 660 in-house controls. We compared the number of rare stop-gain/stop-loss and rare ClinVar “pathogenic” variants between cases and controls, as well as performed gene burden and gene-set burden analyses. We found an enrichment in cases of rare stop-gain/stop-loss variants in genes involved in bleeding disorders and an enrichment of rare ClinVar “pathogenic” variants in genes involved in anemias. The 2 most significant genes in the gene burden analysis, CFB and DNASE2, are associated with atypical hemolytic uremia and severe anemia, respectively. VWF also surpassed exome-wide significance in the gene burden analysis (P = 7.31 × 10−6). Gene-set burden analysis revealed an enrichment of rare nonsynonymous variants in cases in several hematologically relevant pathways. Further, common variants in FERMT2, a gene involved in the regulation of hemostasis and angiogenesis, surpassed genome-wide significance. We demonstrate that adolescents with HMB and low VWF have an excess of rare nonsynonymous and pathogenic variants in genes involved in bleeding disorders and anemia. Variants of variable penetrance in these genes may contribute to the spectrum of phenotypes observed in patients with HMB and could partially explain the bleeding phenotype. By identifying patients with HMB who possess these variants, we may be able to improve risk stratification and patient outcomes.
Biomarker signatures in cancer patients with and without venous thromboembolism events: a substudy of CASSINI
Authors: Khorana Alok A. , Barnard John , Wun Ted , Vijapurkar Ujjwala , Damaraju CV , Moore Kenneth Todd , Wildgoose Peter , McCrae Keith R. 
Published: November 2021

Abstract
Cancer is associated with an increased risk of venous thromboembolism (VTE). In the CASSINI study, ambulatory cancer patients with a Khorana risk score ≥2 had a reduced risk of VTE while receiving rivaroxaban. This analysis used blood samples from CASSINI to compare biomarker levels between patients with and without VTE. VTE occurred in 62 patients during the 6 months of CASSINI (cases), and they were matched by age, sex, cancer type, tumor stage, and Khorana score to 62 controls. Baseline blood samples were analyzed for 280 biomarkers, and biomarker distribution was compared using the Wilcoxon rank-sum test between groups defined by VTE occurrence and vital status. Sparse Bayesian regression modeling was used to select a joint panel of potential VTE biomarkers. Biomarkers with the largest differences in baseline distribution among cancer patients with and without VTE included decreases in stromal cell–derived factor-1 (SDF-1), thyroid-stimulating hormone (TSH), and monocyte chemotactic protein 4 and increases in growth hormone (GH) and interleukin-1 receptor type 1 (IL-1R1). Between survivors and those who died, significantly different biomarkers included ST2, IL-8, and C-reactive protein. Regression analyses also identified decreases in SDF-1 and TSH. Pathway analysis indicated enrichment of cytokine and chemokine activity with IL-1R1, SDF-1, and GH, which are the strongest predictors of VTE or death. Our analyses highlight the interactions between hemostatic and inflammatory processes and identify candidate biomarkers of cancer-associated VTE. Prospective studies will determine clinical relevance of these biomarkers. This trial was registered at www.ClinicalTrials.gov as #NCT02555878.
RETRACTED ARTICLE: Down-regulation of microRNA-342-5p or Up-regulation of Wnt3a Inhibits Angiogenesis and Maintains Atherosclerotic Plaque Stability in Atherosclerosis Mice
Authors: Sun Haixia , Feng Jinhua , Ma Yan , Cai Ding , Luo Yulu , Wang Qinggong , Li Fang , Zhang Mingyue , Hu Quanzhong 
Published: November 2021

AbstractEvidence has demonstrated that microRNA-342-5p (miR-342-5p) is implicated in atherosclerosis (AS), but little is known regarding its intrinsic regulatory mechanisms. Here, we aimed to explore the effect of miR-342-5p targeting Wnt3a on formation of vulnerable plaques and angiogenesis of AS. ApoE−/− mice were fed with high-fat feed for 16 w to replicate the AS vulnerable plaque model. miR-342-5p and Wnt3a expression in aortic tissues of AS were detected. The target relationship between miR-342-5p and Wnt3a was verified. Moreover, ApoE−/− mice were injected with miR-342-5p antagomir and overexpression-Wnt3a vector to test their functions in serum lipid levels, inflammatory and oxidative stress-related cytokines, aortic plaque stability and angiogenesis in plaque of AS mice. miR-342-5p expression was enhanced and Wnt3a expression was degraded in aortic tissues of AS mice and miR-342-5p directly targeted Wnt3a. Up-regulating Wnt3a or down-regulating miR-342-5p reduced blood lipid content, inflammatory and oxidative stress levels, the vulnerability of aortic tissue plaque and inhibited angiogenesis in aortic plaque of AS mice. Functional studies show that depleting miR-342-5p can stabilize aortic tissue plaque and reduce angiogenesis in plaque in AS mice via restoring Wnt3a.
The use of perineural dexamethasone and transverse abdominal plane block for postoperative analgesia in cesarean section operations under spinal anesthesia: an observational study
Authors: Aga Abdisa , Abrar Meron , Ashebir Zewetir , Seifu Ashenafi , Zewdu Dereje , Teshome Diriba 
Published: November 2021

AbstractBackgroundDuring transverses abdominal plane block (TAP) procedure to provide analgesia in cesarean section (CS) operation, the use of perineural dexamethasone as an additive agent may improve pain relief and may cause a prolonged block duration. This study aims to investigate whether perineural dexamethasone, when added to bupivacaine local anesthetic agent during a TAP block, may provide adequate pain relief without adverse events.MethodsThis is a prospective cohort study of fifty-eight patients undergoing elective CS with spinal anesthesia. We hypothesized to perform bilateral TAP block using perineural dexamethasone as an additive agent. The patients were randomly divided into two groups using a systematic random sampling method. While one group of patients received perineural dexamethasone of 8 mg additive agent together with bupivacaine 0.25% 40 ml (Group TAPD), the other group received only bupivacaine 0.25% 40 ml in TAP block (Group TAPA). The primary outcomes are the period for the first request of postoperative pain relief medication and the numerical rating scale (NRS) pain intensity scores at 2, 6, 12, and 24 h after surgery. The secondary outcomes are comparing the 24-h tramadol and diclofenac analgesic requirements and the incidences of side effects on postoperative day one. Ap-value of < 0.05 is statistically significant.ResultsThe time to first analgesic request was 8.5 h (8.39–9.79) in the TAPD group versus 5.3 h (5.23–5.59) in the TAPA group, respectively. (p < 0.001) The median NRS scores were significantly reduced in the TAPD group compared to the TAPA group at 6, 12, and 24 h after surgery (p-values < 0.001). The total analgesics consumption over 24 h postoperatively was lower in Group TAPD compared to Group TAPA (p < 0.05).ConclusionAn additive agent of perineural dexamethasone at a dose of 8 mg during bilateral TAP block for elective CS operation under spinal anesthesia provided better pain relief on postoperative day 1.
COVID-19 vaccine acceptance, hesitancy, and determinants among physicians in a university-based teaching hospital in Thailand
Authors: Sirikalyanpaiboon May , Ousirimaneechai Krittin , Phannajit Jeerath , Pitisuttithum Panyavee , Jantarabenjakul Watsamon , Chaiteerakij Roongruedee , Paitoonpong Leilani 
Published: November 2021

Abstract
Background
The COVID-19 vaccines provide renewed hope in the fight against the recent pandemic. To ensure widespread vaccination, it is crucial to analyze vaccine willingness and its determinants among physicians, key health care influencers. This study aimed to assess acceptance rate and identify factors associated with vaccine hesitancy among Thai physicians.

Methods
A cross-sectional online-based questionnaire was distributed to all physicians at King Chulalongkorn Memorial Hospital during March 31, 2021 to April 30, 2021 in order to assess their attitudes toward receiving the COVID-19 vaccine. Reasons for vaccine acceptance and refusal as well as predictors of vaccine hesitancy were analyzed by bivariate and multivariable analysis.

Results
A total of 705 complete responses were received with 95.6% (n = 675) of physicians expressing willingness to receive a COVID-19 vaccine. Only one of the 31 physicians (4.4%) who expressed a hesitancy or unwillingness to be vaccinated was a faculty member; the others were physicians-in-training. Approximately one-fifths of physicians surveyed were also not willing to recommend the vaccine to their family members (21.4%, n = 151) or patients (18.7%, n = 132). Using multivariable logistic regression, vaccine hesitancy was independently associated with preference for particular vaccines over the government allocated option, especially for mRNA vaccine (aOR 8.86; 95% CI 1.1–71.54; p = 0.041). Vaccine literacy showed an inverse relationship (aOR 0.34; 95% CI 0.13–0.9; p = 0.029) with vaccine hesitancy. Uncertainty of the vaccine efficacy (83.9%) and fear of adverse events (48.4%) were major concerns contributing to vaccine hesitancy.

Conclusion
This study revealed a high rate of physician willingness to take the COVID-19 vaccine especially among staffs; however, a significant proportion would not currently suggest vaccination to their families or patients. Restrictions on vaccine choice and vaccine illiteracy, together with concerns over adverse effects and uncertainty of efficacy, were associated with negative attitudes toward vaccination. To raise acceptance of the vaccination program, efforts should be made to balance individual preference for vaccine type in addition to increasing the availability of accurate data on safety and efficacy for each vaccine.
Correlation and agreement between superb micro-vascular imaging and contrast-enhanced ultrasound for assessing radiofrequency ablation treatment of thyroid nodules: a preliminary study
Authors: Lan Yu , Li Nan , Song Qing , Zhang Ming-bo , Luo Yu-kun , Zhang Yan 
Published: November 2021

Abstract
Background
To evaluate the correlation and agreement between superb micro-vascular imaging (SMI) mode and the contrast-enhanced ultrasound (CEUS) mode for the ablative completeness and the volumes of ablation lesions to determine the clinical application value of SMI in follow-up after radiofrequency ablation.

Methods
From April 2020 to June 2020, two radiologists used SMI and CEUS mode to measure the volume of the ablation lesion. We use intra-class correlation coefficient (ICC), scatter plots and Bland–Altman plots to evaluate the correlation and agreement of the two techniques. In addition, intra- and inter-observer reliability in volume measurement of ablation lesions with SMI mode was assessed.

Results
SMI mode and CEUS mode have good agreement in the evaluation of ablative completeness. The ICC was 0.876 and 0.928 of reader A and reader B between SMI mode and CEUS mode in terms of ablation lesions volume measurement. There was a strong correlation between the two modes in both reader A and reader B (rA = 0.808; rB = 0.882). The ICC was 0.836 for the inter-observer reliability of SMI technique. The scatter plot showed a good linear relation (r = 0.715). In the Bland–Altman plot, 4.35% (1/23) of the points was outside the 95% limits of agreement. The ICC was 0.965 for the intra-observer reliability of SMI technique, the scatter plot also showed a strong linear correlation (r = 0.965). In the Bland–Altman plot, 8.70% (2/23) of the points was outside the 95% limits of agreement.

Conclusions
SMI and CEUS have good agreement and correlation in the ablation volume measurement. SMI technology is expected to be applied as an alternative to CEUS in the clinical follow-up of ablation lesions.
Prognostication of neurologic outcome using gray-white-matter-ratio in comatose patients after cardiac arrest
Authors: Kirsch Konrad , Heymel Stefan , Günther Albrecht , Vahl Kathleen , Schmidt Thorsten , Michalski Dominik , Fritzenwanger Michael , Schulze Paul Christian , Pfeifer Rüdiger 
Published: November 2021

Abstract
Background
This study aimed to assess the prognostic value regarding neurologic outcome of CT neuroimaging based Gray-White-Matter-Ratio measurement in patients after resuscitation from cardiac arrest.

Methods
We retrospectively evaluated CT neuroimaging studies of 91 comatose patients resuscitated from cardiac arrest and 46 non-comatose controls. We tested the diagnostic performance of Gray-White-Matter-Ratio compared with established morphologic signs of hypoxic-ischaemic brain injury, e. g. loss of distinction between gray and white matter, and laboratory parameters, i. e. neuron-specific enolase, for the prediction of poor neurologic outcomes after resuscitated cardiac arrest. Primary endpoint was neurologic function assessed with cerebral performance category score 30 days after the index event.

Results
Gray-White-Matter-Ratio showed encouraging interobserver variability (ICC 0.670 [95% CI: 0.592–0.741] compared to assessment of established morphologic signs of hypoxic-ischaemic brain injury (Fleiss kappa 0.389 [95% CI: 0.320–0.457]) in CT neuroimaging studies. It correlated with cerebral performance category score with lower Gray-White-Matter-Ratios associated with unfavourable neurologic outcomes. A cut-off of 1.17 derived from the control population predicted unfavourable neurologic outcomes in adult survivors of cardiac arrest with 100% specificity, 50.3% sensitivity, 100% positive predictive value, and 39.3% negative predictive value. Gray-White-Matter-Ratio prognostic power depended on the time interval between circulatory arrest and CT imaging, with increasing sensitivity the later the image acquisition was executed.

Conclusions
A reduced Gray-White-Matter-Ratio is a highly specific prognostic marker of poor neurologic outcomes early after resuscitation from cardiac arrest. Sensitivity seems to be dependent on the time interval between circulatory arrest and image acquisition, with limited value within the first 12 h.