bluuebunny/crossref_metadata_2025_split huggingface dataset:
SGLT2 Inhibitors in Diabetic Patients With Cardiovascular Disease or at High Cardiovascular Risk: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Zhao Zinan , Jin Pengfei , Zhang Yatong , Hu Xin , Tian Chao , Liu Deping 
Published: April 2022

ObjectiveTo investigate the effect of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in patients with diabetes with cardiovascular disease (CVD) or at high cardiovascular risk.DesignSystematic review and meta-analysis of randomized controlled trials (RCTs).Data sourcesPubmed, Embase, the Cochrane Library, and ClinicalTrial.gov from their inception to August 28, 2021.Review methodsRandomized control trials (RCTs) assess the effects of SGLT2i in patients with diabetes with cardiovascular disease or at high cardiovascular risk. Primary outcomes included the composite outcome of cardiovascular death (CV death) and hospitalization for heart failure (HHF), HHF, and renal composite outcomes. Secondary outcomes included major adverse cardiovascular events (MACE), CV death, all-cause mortality, and change from the baseline in HbA1c. Additionally, we assessed the effects of treatment in prespecified subgroups on the combined risk of primary and secondary outcomes. These subgroups were based on history of heart failure (HF), estimated glomerular filtration rate (eGFR) levels, and history of hypertension (HTN). A meta-analysis was carried out by using fixed effect models to calculate hazard ratio (HR) or mean difference (MD) between the SGLT2i administrated groups and the control groups.ResultsFour major studies (n = 42,568) were included. Primary outcomes showed that SGLT2i was associated with significantly lower risk of CV death/HHF (HR, 0.90; 95% confidence interval, 0.84 to 0.98; P for heterogeneity = 0.01), HHF (HR, 0.84; 95% CI, 0.73 to 0.98; p = 0.02), and renal composite outcomes (HR, 0.83; 95%CI, 0.74 to 0.92; p = 0.0007) in patients with diabetes with CVD or at high CV risk. Secondary outcome showed that the use of SGLT2i was associated with significant reduction of the HbA1c level (MD, −0.30; 95% CI, −0.36 to −0.23; p &lt; 0.00001). In subgroup analyses, SGLT2i significantly reduced the risk of renal composite outcomes in patients without history of HF (HR, 0.75; 95% CI, 0.62 to 0.91; p = 0.003 &lt; 0.025). No statistically significant differences were observed in other secondary outcomes and subgroup analyses.ConclusionsThe SGLT2i showed benefits on CV death/HHF, HHF, renal composite outcomes, and HbA1c reduction in patients with diabetes with CVD or at high CV risk. The benefits of improving renal composite outcomes were observed only in patients with diabetes without HF history.Systematic Review RegistrationPROSPERO CRD42021227400
Insights on Distinct Left Atrial Remodeling Between Atrial Fibrillation and Heart Failure With Preserved Ejection Fraction
Authors: Kuo Jen-Yuan , Jin Xuanyi , Sun Jing-Yi , Chang Sheng-Hsiung , Chi Po-Ching , Sung Kuo-Tzu , Mok Greta S. P. , Yun Chun-Ho , Chang Shun-Chuan , Chung Fa-Po , Yu Ching-Hsiang , Wu Tung-Hsin , Hung Chung-Lieh , Yeh Hung-I , Lam Carolyn S. P. 
Published: April 2022

BackgroundHeart failure with preserved ejection fraction (HFpEF) and atrial fibrillation (AF) commonly coexist with overlapping pathophysiology like left atrial (LA) remodeling, which might differ given different underlying mechanisms.ObjectivesWe sought to investigate the different patterns of LA wall remodeling in AF vs. HFpEF.MethodsWe compared LA wall characteristics including wall volume (LAWV), wall thickness (LAWT), and wall thickness heterogeneity (LAWT[SD]) and LA structure, function among the controls (without AF or HFpEF, n = 115), HFpEF alone (n = 59), AF alone (n = 37), and HFpEF+AF (n = 38) groups using multi-detector computed tomography and echocardiography.ResultsLA wall remodeling was most predominant and peak atrial longitudinal strain (PALS) was worst in HFpEF+AF patients as compared to the rest. Despite lower E/e' (9.8 ± 3.8 vs. 13.4 ± 6.4) yet comparable LA volume, LAWT and PALS in AF alone vs. HFpEF alone, LAWV [12.6 (11.6–15.3) vs. 12.0 (10.2–13.7); p = 0.01] and LAWT(SD) [0.68 (0.61–0.71) vs. 0.60 (0.56–0.65); p &lt; 0.001] were significantly greater in AF alone vs. HFpEF alone even after multi-variate adjustment and propensity matching. After excluding the HFpEF+AF group, both LAWV and LAWT [SD] provided incremental values when added to PALS or LAVi (all p for net reclassification improvement &lt;0.05) in discriminating AF alone, with LAWT[SD] yielding the largest C-statistic (0.78, 95% CI: 0.70–0.86) among all LA wall indices.ConclusionsDespite a similar extent of LA enlargement and dysfunction in HFpEF vs. AF alone, larger LAWV and LAWT [SD] can distinguish AF from HFpEF alone, suggesting the distinct underlying pathophysiological mechanism of LA remodeling in AF vs. HFpEF.
Hemodynamic Changes After Left Ventricular Assist Device Implantation Among Heart Failure Patients With and Without Elevated Pulmonary Vascular Resistance
Authors: Grupper Avishay , Mazin Israel , Faierstein Kobi , Kurnick Adam , Maor Elad , Elian Dan , Barbash Israel M. , Guetta Victor , Regev Ehud , Morgan Avi , Segev Amit , Lavee Jacob , Fefer Paul 
Published: April 2022

BackgroundLeft ventricular assist devices (LVADs) may reverse elevated pulmonary vascular resistance (PVR) which is associated with worse prognosis in heart failure (HF) patients. We aim to describe the temporal changes in hemodynamic parameters before and after LVAD implantation among patients with or without elevated PVR.MethodsHF patients who received continuous-flow LVAD (HeartMate 2&amp;3) at a tertiary medical center and underwent right heart catheterization with PVR reversibility study before and after LVAD surgery. Patients were divided into 3 groups: normal PVR (&lt;4WU); reversible PVR (initial PVR ≥4WU with positive reversibility); and non-reversible (persistent PVR ≥4WU).ResultsOverall, 85 LVAD patients with a mean age of 58 years (IQR 49–64), 65 patients (76%) were male; 60 patients had normal PVR, 20 patients with reversible and 5 patients with non-reversible PVR pre-LVAD. All patients with elevated PVR (≥4WU) had higher pulmonary pressures (PP) and increased trans-pulmonary gradient (TPG) compared to patients with normal PVR (p &lt; 0.05). Patients with non-reversible PVR were more likely to have a significantly lower baseline cardiac output (CO) compared to all other groups (p ≤ 0.02). Hemodynamic parameters and PVR post LVAD were similar in all study groups. Patients with baseline elevated PVR (reversible and non-reversible) demonstrated a significant improvement in PP and TPG compared to patients with normal baseline PVR (p ≤ 0.05). The improvement in CO and PVR post-LVAD in the non-reversible PVR group was significantly greater compared to all other groups (p &lt; 0.01). There were no significant differences between study groups in post LVAD and post heart transplantation course.ConclusionHemodynamic parameters improved after LVAD implantation, regardless of baseline PVR and reversibility, and enabled heart transplantation in patients who were ineligible due to non-reversible elevated PVR. Our findings suggest that mitigation of elevated non-reversible PVR is related to reduction in PP and increase in CO.
Shale Heavy Metal Isotope Records of Low Environmental O2 Between Two Archean Oxidation Events
Authors: Ostrander Chadlin M. , Kendall Brian , Gordon Gwyneth W. , Nielsen Sune G. , Zheng Wang , Anbar Ariel D. 
Published: April 2022

Evidence of molecular oxygen (O2) accumulation at Earth’s surface during the Archean (4.0–2.5 billion years ago, or Ga) seems to increase in its abundance and compelling nature toward the end of the eon, during the runup to the Great Oxidation Event. Yet, many details of this late-Archean O2 story remain under-constrained, such as the extent, tempo, and location of O2 accumulation. Here, we present a detailed Fe, Tl, and U isotope study of shales from a continuous sedimentary sequence deposited between ∼2.6 and ∼2.5 Ga and recovered from the Pilbara Craton of Western Australia (the Wittenoom and Mt. Sylvia formations preserved in drill core ABDP9). We find a progressive decrease in bulk-shale Fe isotope compositions moving up core (as low as δ56Fe = –0.78 ± 0.08‰; 2SD) accompanied by invariant authigenic Tl isotope compositions (average ε205TlA = –2.0 ± 0.6; 2SD) and bulk-shale U isotope compositions (average δ238U = –0.30 ± 0.05‰; 2SD) that are both not appreciably different from crustal rocks or bulk silicate Earth. While there are multiple possible interpretations of the decreasing δ56Fe values, many, to include the most compelling, invoke strictly anaerobic processes. The invariant and near-crustal ε205TlA and δ238U values point even more strongly to this interpretation, requiring reducing to only mildly oxidizing conditions over ten-million-year timescales in the late-Archean. For the atmosphere, our results permit either homogenous and low O2 partial pressures (between 10−6.3 and 10−6 present atmospheric level) or heterogeneous and spatially restricted O2 accumulation nearest the sites of O2 production. For the ocean, our results permit minimal penetration of O2 in marine sediments over large areas of the seafloor, at most sufficient for the burial of Fe oxide minerals but insufficient for the burial of Mn oxide minerals. The persistently low background O2 levels implied by our dataset between ∼2.6 and ∼2.5 Ga contrast with the timeframes immediately before and after, where strong evidence is presented for transient Archean Oxidation Events. Viewed in this broader context, our data support the emerging narrative that Earth’s initial oxygenation was a dynamic process that unfolded in fits-and-starts over many hundreds-of-millions of years.
Numerical Simulation Study on Optimal Shut-In Time in Jimsar Shale Oil Reservoir
Authors: Chen Xi , Liao Kai , Lv Zhao , Zhu Jian , Wang Junchao , Li Yuqi , Wang Fei 
Published: April 2022

The volume fracturing technology along with horizontal well is the main technology to obtain commercial oil flow in shale reservoirs because of the low porosity and low permeability. Whether the fracturing fluid has the potential of shale matrix imbibition oil recovery after a large amount of slickwater injected into the reservoir is a research hotspot at present. Therefore, it is of great significance to study the law of imbibition and replacement during the shut-in time. Aiming at the Jimsar area, there are several steps in this study in order to explore the new law of fracturing fluid imbibition and oil recovery in shale reservoirs. Primarily, the distribution of pressure and saturation during fracturing time and shut-in time is accurately described by the numerical simulation method. Furthermore, the sensitivity analysis is carried out from two aspects of geological and fracture factors. Eventually, the evaluation of optimal shut-in time is taken by imbibition replacement balance. According to the numerical simulation results, the pressure diffuses rapidly among the matrix during the shut-in time in the hydrophilic reservoir. After 65 days of well shut-in, the whole reservoir tends to be at the same pressure and reaches the equilibrium of imbibition replacement. Contrarily, the pressure of the lipophilic reservoir diffuses slowly and only propagates in the secondary fracture or the matrix near the fractures. The fracture system remains a “high-pressure area” for a long time during shut-in. Additionally, the optimal shut-in time chart of different geological parameters and fracture parameters is drawn to optimize the shut-in time. This research work has a certain reference value for the optimization of shut-in time after fracturing in Jimsar and similar shale oil wells.
Soil Application of Wheat Straw Vermicompost Enhances Morpho-Physiological Attributes and Antioxidant Defense in Wheat Under Drought Stress
Authors: Ahmad Ali , Aslam Zubair , Hussain Saddam , Javed Talha , Hussain Sadam , Bashir Safdar , Hussain Iqtidar , Belliturk Korkmaz , Adamski Robert , Siuta Dorota , Dessoky Eldessoky S. , Hessini Kamel 
Published: April 2022

With the provoked environmental constraints under extreme climatic events, a better understanding of plant responses to these environmental stresses helps in obtaining sustainable productivity. Wheat is a significant cereal crop for the burgeoning population; its yield is significantly limited by too little water in the rhizosphere. The ramifications of water deficiency on the wheat crop can be reduced by the application of vermicompost. With the objective to cope with drought stress, a wire-house experiment was established where seedlings of two cultivars, viz., Faisalabad-08 and Galaxy-13 (drought-tolerant and -sensitive cultivar, respectively) were grown in pots and exposed to mild drought (D1, 45% field capacity) and severe drought stress (D2, 30% field capacity). A control with well-watered condition (70% field capacity) was kept for comparison. Various application rates of wheat straw vermicompost (control (VT0), 4 t ha−1(VT1), 6 t ha−1(VT2), and 8 t ha−1(VT3)), were used in soil-filled pots under drought and control treatments. Our data depicted that compared with control, drought treatments recorded a significant reduction in morpho-physiological and biochemical attributes with maximum reduction under severe drought conditions. Nonetheless, it was observed that soil application of vermicompost, particularly at a high rate, ameliorated the negative effects of drought. Under severe drought conditions, a significant and positive influence on morphological and physiological traits was recorded for VT3treatment, which increased root and shoot length by 27.55 and 27.85%, root and shoot fresh weight by 26.98 and 28.20%, root and shoot dry weight by 40 and 50.05%, and photosynthesis and transpiration rate by 27.65 and 49.25%, respectively, on average of two cultivars. Similarly, VT3also significantly ameliorated the adverse effect of drought by enhancing the antioxidant enzyme activities as it increased superoxide dismutase activity by 14.28%, peroxidase by 27.28%, and catalase by 50% compared to the control treatment. Among cultivars, Faisalabad-2008 showed comparatively more resistance against drought stress. The findings of this work revealed that drought drastically reduced the growth and productivity of wheat; however, soil-applied vermicompost positively influenced the performance of wheat cultivars.
Analysis of World-Scale Mitochondrial DNA Reveals the Origin and Migration Route of East Asia Goats
Authors: Peng Weifeng , Zhang Yiyuan , Gao Lei , Feng Cailing , Yang Yujiao , Li Bingyi , Wu Lili , Wu Ali , Wang Shuping , Ren Xue , Chen Zehui , Zhang Min , Cai Danni , Wang Xin , Lv Mengqi , Zhang Yitong , Li Simeng , Zhang Yunxia , Huang Li , Li Shiwei 
Published: April 2022

Despite much attention on the history of goat evolution, information on origin, demographic history, and expansion route remains controversial. To address these questions, we collected 4,189 published goat DNA sequences including 1,228 sequences from 57 breeds in China and 2,961 sequences including 193 goat breeds from 71 other countries and carried out an integrated analysis. We found goat breeds from South China had the highest genetic diversity of lineage B, and subclades B2 only were found in Southwest China, suggesting that lineage B (particularly, subclade B2) probably originated from Southwest China and its surrounding areas. In addition, in this study, we found that lineage A from South China also presented higher genetic diversity and earlier expansion time (10, 606 years ago), even earlier than breeds from the Middle East. Hence, we speculated that South China and surrounding areas were the origin of lineage B and also the transportation hub for lineage A spreading to North China and Southwest Asia. Furthermore, according to the analysis of correlation between genetic differentiation value λ1 and λ2 and geographical distance, we further confirmed two phases of migration in goat breeds of North China. These results will contribute to a better understanding of the origin and migration history of domestic goat.
T-Cell Heterogeneity in Baseline Tumor Samples: Implications for Early Clinical Trial Design and Analysis
Authors: Brennan Laura , Brouwer-Visser Jurriaan , Nüesch Eveline , Karpova Maria , Heller Astrid , Gaire Fabien , Schneider Meike , Gomes Bruno , Korski Konstanty 
Published: April 2022

BackgroundIn early stage clinical trials, changes to levels of tumor infiltrating lymphocytes (TILs) in the tumor microenvironment (TME) are critical biomarkers of the mechanism of action of novel immunotherapies. However, baseline heterogeneity of tumor samples, both between and within patients, and the resultant impact on the validity of clinical trial data is not well defined. Here we identify and quantify the impact of baseline variables on the heterogeneity of FoxP3+ and proliferating CD8+ T-cells levels (MKi67+CD8A+) in the TME both between and within patients for the purpose of informing clinical trial design and analysis.MethodsWe compared levels of FoxP3+ and MKi67+CD8+ cell densities (counts/mm2) from &gt;1000 baseline tumor samples from clinical trials and commercially available sources. Using multivariate hierarchical regression techniques, we investigated whether inter-person heterogeneity of activated or regulatory T-cells could be attributed to baseline characteristics including demographics, indication, lesion type, tissue of excision, biopsy method, prior cancer treatment, and tissue type i.e., “fresh” or “archival” status. We also sought to characterize within-patient heterogeneity by lesion type and tissue type.ResultsPrior cancer treatment with hormone therapy or chemotherapy that induces immunogenic cell death may alter the TME. Archival tissue is an unreliable substitute for fresh tissue for determining baseline TIL levels. Baseline and on treatment biopsies should be matched by lesion type to avoid bias.
Acute Myocardial Infarction (AMI) as the Effect Modifiers to Modify the Association Between Red Blood Cell Distribution Width (RDW) and Mortality in Critically Ill Patients With Stroke
Authors: Guo Tongli , Qin Zuoan , He Dian 
Published: April 2022

Background and ObjectivesFew studies have evaluated the impact of red blood cell distribution width (RDW) on prognosis for critically ill patients with acute stroke according to recent studies. The aim of this study was to investigate the association between RDW and mortality in these patients.MethodsClinical data were extracted from the eICU Collaborative Research Database (eICU-CRD) and analyzed. The exposure of interest was RDW measured at admission. The primary outcome was in-hospital mortality. Binary logistic regression models and interaction testing were performed to examine the RDW-mortality relationship and effect modification by acute myocardial infarction and hypertension (HP).ResultsData from 10,022 patients were analyzed. In binary logistic regression analysis, after adjusting for potential confounders, RDW was found to be independently associated with in-hospital mortality {odds ratio (OR) 1.07, [95% confidence interval (CI) 1.03 to 1.11]; p = 0.001}. Higher RDW linked to an increase in mortality (OR, 1.07; 95% CI, 1.03 to 1.11; P for trend &lt; 0.0001). Subgroup analysis showed that, in patients combined with AMI and without HP (both P-interaction &lt;0.05), the correlation between RDW and in-hospital mortality is stronger (AMI group: OR, 1.30; 95% CI, 1.07 to 1.58, not the AMI group: OR, 1.06; 95% CI, 1.02, 1.10; the HP group: OR,.98; 95% CI,.91 to 1.07, not the HP group: OR, 1.09; 95% CI, 1.05 to 1.14).ConclusionsA higher baseline RDW is independently correlated with prognosis in critically ill patients with acute stroke, and the correlation can be modified by AMI and HP duration.
Influence of Cardiovascular Risk Burden on Motor Function Among Older Adults: Mediating Role of Cardiovascular Diseases Accumulation and Cognitive Decline
Authors: Wang Zhangyu , Cui Kaiwang , Song Ruixue , Li Xuerui , Qi Xiuying , Buchman Aron S. , Bennett David A. , Xu Weili 
Published: April 2022

PurposeThis study aimed to investigate the association of the cardiovascular risk burden assessed by the Framingham General Cardiovascular Risk Score (FGCRS) with the trajectories of motor function over time and to assess the mediating effects of cardiovascular diseases (CVDs) accumulation and cognitive decline in such association.MethodsIn Rush Memory and Aging Project, a total of 1,378 physical health participants (mean age: 79.3 ± 7.3 years) were followed up for up to 22 years. FGCRS at baseline was assessed and categorized into tertiles (lowest, middle, and highest). Global motor function (including dexterity, gait, and hand strength) was assessed annually with 10 motor tests. CVDs (including stroke, congestive heart failure, and other heart diseases) were ascertained at baseline and follow-ups, and the number of CVDs accumulation over time was assessed. Global cognitive function was tested annually by 19 tests. Data were analyzed using the linear mixed-effects models and mediation analysis.ResultsAt baseline, FGCRS ranged from 4 to 28 (mean score: 15.6 ± 3.7). Over the follow-up (median: 5.3 years; interquartile range: 2.9–9.0 years), in multi-adjusted mixed-effects models, the highest FGCRS was associated with faster decline in global motor function (β = −0.0038; 95% confidence interval [CI]: −0.0069 to −0.0008), dexterity (β = −0.0056; 95% CI: −0.0093 to −0.0020), gait (β = −0.0039; 95% CI: −0.0077 to −0.0001), and hand strength (β = −0.0053; 95% CI: −0.0098 to −0.0008) compared with the lowest tertile. In mediation analysis, CVDs accumulation and cognitive decline mediated 8.4% and 42.9% of the association between FGCRS and global motor function over time, respectively.ConclusionHigher cardiovascular risk burden is associated with a faster decline in motor function including dexterity, gait, and hand strength. CVDs accumulation and cognitive decline may partially mediate the association between cardiovascular risk burden and global motor function decline.
Decreased Opioid Consumption in Bone Marrow Harvest Patients Using Quadratus Lumborum Blocks in a Standardized Protocol
Authors: McCoy Nicole C. , Hay Ellen L. , Romeo Deborah A. , Doty J. Wesley , Wolf Bethany J. , Hudspeth Michelle P. 
Published: April 2022

PurposeBone marrow harvesting is associated with significant postoperative pain that may have potential negative consequences for the patient and health care system. In the current absence of uniform guidelines, there exists considerable variability amongst providers with respect to perioperative analgesia, especially opioid administration. In this initiative, we explored the potential for preoperative bilateral quadratus lumborum blocks in combination with a standardized perioperative analgesic protocol to manage pain with the goal of reducing perioperative narcotic usage and thereby improving opioid stewardship.MethodsAdults who underwent bone marrow donation from 2018 to 2020 were included in this analysis (n = 32). The pre-implementation group (n = 19) was reviewed retrospectively while the implementation group (n = 13) was evaluated prospectively. Patient demographics, pain scores, and opioid consumption were evaluated.ResultsPatient characteristics were equivalent except for anesthesia type with an increased number of patients in the implementation group undergoing spinal anesthesia. The implementation group showed significantly reduced median intraoperative (20.0 mg vs. 0.0 mg; p &lt; 0.001) and total opioid consumption (20.5 mg vs. 0.0 mg; p &lt; 0.001). The number of patients who received any opioids decreased from 84.2% (16/19) before implementation to 23.1% (3/13) after implementation.ConclusionThis change in practice suggests that implementation of a standardized perioperative protocol, including bilateral quadratus lumborum blocks, for bone marrow harvest patients leads to reduced perioperative opioid administration without compromising immediate perioperative pain control.