bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring the Mechanism of Berberine Intervention in Ulcerative Colitis from the Perspective of Inflammation and Immunity Based on Systemic Pharmacology
Authors: Jiang Yan , Zhao Li , Chen Qing , Zhou Lihong 
Published: June 2021

Background. Ulcerative colitis (UC) is a chronic nonspecific inflammatory disease of the colon and rectum. Recent studies found that berberine had effects on inflammatory diseases and immune diseases. Methods. The PharmMapper database was used to predict the berberine potential target and GeneCards database and OMIM database were utilized to collect UC genes. The Cytoscape software was used to construct and analyze the networks and DAVID was utilized to perform enrichment analysis. Then, animal experiments were performed to validate the prediction results. The experimental rats were randomly divided into normal group (control group), model group, and berberine group. The general condition, body weight, gross morphology of colon tissue, and colonic mucosal damage index (CMDI) score were observed. The pathological changes of colon tissue were observed by H&E staining. The levels of serum interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and IL-4 were detected by ELISA. The expressions of IL-1β, TNF-α, and IL-4 protein in colon tissue were detected by immunohistochemistry. Results. A total of 211 Berberine’s potential targets and 210 UC genes were obtained. The enrichment analysis showed that berberine may regulate inflammation, inflammatory cytokines, and their mediated inflammation signal pathways such as inflammatory bowel disease (IBD), rheumatoid arthritis, cytokine-cytokine receptor interaction, TNF, T cell receptor, Toll-like receptor, and JAK/STAT signaling pathway. Compared with the model group, the body mass of rats in the berberine group was significantly increased (

P

< 0.05); the general morphology and pathological changes of colon tissue were significantly improved; CMDI score, serum and colon tissue IL-1β, TNF-α content, and protein expression were decreased significantly (

P

< 0.05); and IL-4 content and protein expression increased significantly (

P

< 0.05). Conclusion. Berberine can interfere with UC through related biological processes and signal pathways related to inflammation and immunity. In-depth exploration of the mechanism of berberine in the treatment of UC will provide a basis for clinical application.
Diabetes Risk Reduction Diet and Survival after Breast Cancer Diagnosis
Authors: Wang Tengteng , Farvid Maryam S. , Kang Jae H. , Holmes Michelle D. , Rosner Bernard A. , Tamimi Rulla M. , Willett Walter C. , Eliassen A. Heather 
Published: June 2021

AbstractType II diabetes is associated with poor breast cancer prognosis. To study the association between a diabetes risk reduction diet (DRRD) and survival following breast cancer, we followed 8,482 women with breast cancer from two large cohort studies. Information on diet and other factors was repeatedly measured in validated questionnaires every two to four years. The DRRD includes 9 components: higher intakes of cereal fiber, coffee, nuts, whole fruits and polyunsaturated/saturated fat ratio; and lower glycemic index, trans fat, sugar-sweetened beverages, and red meat. Cumulative average DRRD score was calculated using repeated measures of postdiagnostic diet. Deaths were assessed by family members or via National Death Index. Multivariable-adjusted HRs and 95% confidence intervals (CI) were estimated using Cox proportional hazards models. During a median of 14 years of follow-up since diagnosis, 2,600 deaths occurred among participants, 1,042 of which were due to breast cancer. Women with higher postdiagnostic DRRD score had a 20% lower risk of breast cancer–specific mortality (top vs. bottom quintile HR = 0.80; 95% CI = 0.65–0.97; Ptrend = 0.02) and 34% lower risk of all-cause mortality (HR = 0.66; 95% CI = 0.58–0.76; Ptrend &lt; 0.0001). Compared with women who consistently had lower score (≤median) before and after diagnosis, those whose score improved from low to high had a lower risk of breast cancer–specific mortality (HR = 0.77; 95% CI = 0.62–0.95) and overall mortality (HR = 0.85; 95% CI = 0.74–0.97). These findings demonstrate that greater adherence to DRRD was associated with better survival, suggesting postdiagnosis dietary modification consistent with type II diabetes prevention may be important for breast cancer survivors.Significance:This study suggests that greater adherence to the diabetes risk reduction diet after diagnosis associates with improved survival outcomes among a large number of breast cancer survivors.
Characteristics and Outcomes of Lung Cancers Detected on Low-Dose Lung Cancer Screening CT
Authors: Zhang Eric W. , Shepard Jo-Anne O. , Kuo Anderson , Chintanapakdee Wariya , Keane Florence , Gainor Justin F. , Mino-Kenudson Mari , Lanuti Michael , Lennes Inga T. , Digumarthy Subba R. 
Published: June 2021

Abstract

Background:
Lung cancer screening (LCS) with low-dose CT (LDCT) was implemented in the United States following the National Lung Screening Trial (NLST). The real-world benefits of implementing LCS are yet to be determined with outcome-oriented data. The study objective is to investigate the characteristics and outcomes of screening-detected lung cancers.

Methods:
This single-institution retrospective study included LCS patients between June 2014 and December 2019. Patient demographics, number of screening rounds, imaging features, clinical workup, disease extent, histopathology, treatment, complications, and mortality outcomes of screening-detected lung cancers were extracted and compared with NLST data.

Results:
LCS LDCTs (7,480) were performed on 4,176 patients. The cancer detection rate was 3.8%, higher than reported by NLST (2.4%, P &lt; 0.0001), and cancers were most often found in patients ≥65 years (62%), older than those in NLST (41%, P &lt; 0.0001). The patients' ethnicity was similar to NLST, P = 0.87. Most LCS-detected cancers were early stage I tumors (71% vs. 54% in NLST, P &lt; 0.0001). Two thirds of cancers were detected in the first round of screening (67.1%) and were multifocal lung cancers in 15%. As in NLST, the complication rate after invasive workup or surgery was low (24% vs. 28% in NLST, P = 0.32). Over a median follow-up of 3.3 years, the mortality rate was 0.45%, lower than NLST (1.33%, P &lt; 0.0001).

Conclusions:
LCS implementation achieved a higher cancer detection rate, detection of early-stage cancers, and more multifocal lung cancers compared with the NLST, with low complications and mortality.

Impact:
The real-world implementation of LCS has been successful for detection of lung cancer with favorable outcomes.
Pharmacodynamic Biomarkers Predictive of Survival Benefit with Lenvatinib in Unresectable Hepatocellular Carcinoma: From the Phase III REFLECT Study
Authors: Finn Richard S. , Kudo Masatoshi , Cheng Ann-Lii , Wyrwicz Lucjan , Ngan Roger K.C. , Blanc Jean-Frederic , Baron Ari D. , Vogel Arndt , Ikeda Masafumi , Piscaglia Fabio , Han Kwang-Hyub , Qin Shukui , Minoshima Yukinori , Kanekiyo Michio , Ren Min , Dairiki Ryo , Tamai Toshiyuki , Dutcus Corina E. , Ikezawa Hiroki , Funahashi Yasuhiro , Evans Thomas R. Jeffry 
Published: June 2021

Abstract

Purpose:
In REFLECT, lenvatinib demonstrated an effect on overall survival (OS) by confirmation of noninferiority to sorafenib in unresectable hepatocellular carcinoma. This analysis assessed correlations between serum or tissue biomarkers and efficacy outcomes from REFLECT.

Experimental Design:
Serum biomarkers (VEGF, ANG2, FGF19, FGF21, and FGF23) were measured by ELISA. Gene expression in tumor tissues was measured by the nCounter PanCancer Pathways Panel. Pharmacodynamic changes in serum biomarker levels from baseline, and associations of clinical outcomes with baseline biomarker levels, were evaluated.

Results:
Four hundred and seven patients were included in the serum analysis set (lenvatinib n = 279, sorafenib n = 128); 58 patients were included in the gene-expression analysis set (lenvatinib n = 34, sorafenib n = 24). Both treatments were associated with increases in VEGF; only lenvatinib was associated with increases in FGF19 and FGF23 at all time points. Lenvatinib-treated responders had greater increases in FGF19 and FGF23 versus nonresponders at cycle 4, day 1 (FGF19: 55.2% vs. 18.3%, P = 0.014; FGF23: 48.4% vs. 16.4%, P = 0.0022, respectively). Higher baseline VEGF, ANG2, and FGF21 correlated with shorter OS in both treatment groups. OS was longer for lenvatinib than sorafenib [median, 10.9 vs. 6.8 months, respectively; HR, 0.53; 95% confidence interval (CI), 0.33–0.85; P-interaction = 0.0397] with higher baseline FGF21. In tumor tissue biomarker analysis, VEGF/FGF-enriched groups showed improved OS with lenvatinib versus the intermediate VEGF/FGF group (HR, 0.39; 95% CI, 0.16–0.91; P = 0.0253).

Conclusions:
Higher baseline levels of VEGF, FGF21, and ANG2 may be prognostic for shorter OS. Higher baseline FGF21 may be predictive for longer OS with lenvatinib compared with sorafenib, but this needs confirmation.
PKM1 Exerts Critical Roles in Cardiac Remodeling Under Pressure Overload in the Heart
Authors: Li Qinfeng , Li Chao , Elnwasany Abdallah , Sharma Gaurav , An Yu A. , Zhang Guangyu , Elhelaly Waleed M. , Lin Jun , Gong Yingchao , Chen Guihao , Wang Meihui , Zhao Shangang , Dai Chongshan , Smart Charles D. , Liu Juan , Luo Xiang , Deng Yingfeng , Tan Lin , Lv Shuang-Jie , Davidson Shawn M. , Locasale Jason W. , Lorenzi Philip L. , Malloy Craig R. , Gillette Thomas G. , Vander Heiden Matthew G. , Scherer Philipp E. , Szweda Luke I. , Fu Guosheng , Wang Zhao V. 
Published: June 2021

Background:
Metabolic remodeling precedes most alterations during cardiac hypertrophic growth under hemodynamic stress. The elevation of glucose utilization has been recognized as a hallmark of metabolic remodeling. However, its role in cardiac hypertrophic growth and heart failure in response to pressure overload remains to be fully illustrated. Here, we aimed to dissect the role of cardiac PKM1 (pyruvate kinase muscle isozyme 1) in glucose metabolic regulation and cardiac response under pressure overload.

Methods:
Cardiac-specific deletion of PKM1 was achieved by crossing the floxed PKM1 mouse model with the cardiomyocyte-specific Cre transgenic mouse. PKM1 transgenic mice were generated under the control of tetracycline response elements, and cardiac-specific overexpression of PKM1 was induced by doxycycline administration in adult mice. Pressure overload was triggered by transverse aortic constriction. Primary neonatal rat ventricular myocytes were used to dissect molecular mechanisms. Moreover, metabolomics and nuclear magnetic resonance spectroscopy analyses were conducted to determine cardiac metabolic flux in response to pressure overload.

Results:
We found that PKM1 expression is reduced in failing human and mouse hearts. It is important to note that cardiomyocyte-specific deletion of PKM1 exacerbates cardiac dysfunction and fibrosis in response to pressure overload. Inducible overexpression of PKM1 in cardiomyocytes protects the heart against transverse aortic constriction–induced cardiomyopathy and heart failure. At the mechanistic level, PKM1 is required for the augmentation of glycolytic flux, mitochondrial respiration, and ATP production under pressure overload. Furthermore, deficiency of PKM1 causes a defect in cardiomyocyte growth and a decrease in pyruvate dehydrogenase complex activity at both in vitro and in vivo levels.

Conclusions:
These findings suggest that PKM1 plays an essential role in maintaining a homeostatic response in the heart under hemodynamic stress.
Mapping Cerebrovascular Reactivity Impairment in Patients With Symptomatic Unilateral Carotid Artery Disease
Authors: Sebök Martina , van Niftrik Christiaan Hendrik Bas , Winklhofer Sebastian , Wegener Susanne , Esposito Giuseppe , Stippich Christoph , Luft Andreas , Regli Luca , Fierstra Jorn 
Published: June 2021

Background
Comprehensive hemodynamic impairment mapping using blood oxygenation‐level dependent (BOLD) cerebrovascular reactivity (CVR) can be used to identify hemodynamically relevant symptomatic unilateral carotid artery disease.

Methods and Results

This prospective cohort study was conducted between February 2015 and July 2020 at the Clinical Neuroscience Center of the University Hospital Zurich, Zurich, Switzerland. One hundred two patients with newly diagnosed symptomatic unilateral internal carotid artery (ICA) occlusion or with 70% to 99% ICA stenosis were included. An age‐matched healthy cohort of 12 subjects underwent an identical BOLD functional magnetic resonance imaging examination. Using BOLD functional magnetic resonance imaging with a standardized CO
2
stimulus, CVR impairment was evaluated. Moreover, embolic versus hemodynamic ischemic patterns were evaluated on diffusion‐weighted imaging. Sixty‐seven patients had unilateral ICA occlusion and 35 patients unilateral 70% to 99% ICA stenosis. Patients with ICA occlusion exhibited lower whole‐brain and ipsilateral hemisphere mean BOLD‐CVR values as compared with healthy subjects (0.12±0.08 versus 0.19±0.04,
P
=0.004 and 0.09±0.09 versus 0.18±0.04,
P
<0.001) and ICA stenosis cohort (0.12±0.08 versus 0.16±0.05,
P
=0.01 and 0.09±0.09 versus 0.15±0.05,
P
=0.01); however, only 40 (58%) patients of the cohort showed significant BOLD‐CVR impairment. Conversely, there was no difference in mean BOLD‐CVR values between healthy patients and patients with ICA stenosis, although 5 (14%) patients with ICA stenosis showed a significant BOLD‐CVR impairment. No significant BOLD‐CVR difference was discernible between patients with hemodynamic ischemic infarcts versus those with embolic infarct distribution (0.11±0.08 versus 0.13±0.06,
P
=0.12).

Conclusions
Comprehensive BOLD‐CVR mapping allows for identification of hemodynamically relevant symptomatic unilateral carotid artery stenosis or occlusion.
The Sense of Supernatural Agency
Authors: Peters Frederic 
Published: June 2021

Abstract
The sense of supernatural agency constitutes a defining characteristic of the religious sphere of life. But what accounts for the continued cross-cultural recurrence of this psychological phenomenon over the course of human history? This paper reviews evidence indicating that the source of panhuman or universal cognitive patterns of thought and behaviour such as this lies in the common characteristics of the evolved human mind. Further, that the sense of the supernatural is constituted by a unique combination of commonly recurring cognitive processes that together give rise to a panhuman conviction in the reality of supernatural agencies able and (when minded) willing to assist each individual in situations deemed beyond the capacities of that individual. These cognitive processes are driven most acutely by existential anxiety in response to extrinsic physical, economic and social pressures indicating that religiosity is best understood as a social-psychological phenomenon.
Rethinking Religious Cognition and Myth: A New Perspective on how Religions Balance Intuitiveness and Interest-Provokingness/Memorability
Authors: Nakissa Aria 
Published: June 2021

Abstract
In his influential work on the cognitive science of religion (CSR), Pascal Boyer argues that the spread of religious ideas involves a tradeoff between their “intuitiveness” and their interest-provokingness/memorability (i.e.,their capacity to provoke interest and be remembered). For Boyer, religious ideas are “intuitive” insofar as they are easy to understand and learn. However, other CSR studies suggest that religious ideas are “intuitive” insofar as they are easy to believe. In analyzing the spread of religious ideas, no study has considered the tradeoff between interest-provokingness/memorability and intuitiveness in the sense of being easy to believe. The present article takes up this task by considering several religious concepts that are intuitively easy to believe (e.g., immortal souls, spirit beings, a Creator God, a just world). It is argued that, in typical religions, such concepts are incorporated into myths. Through incorporation, these concepts lose some of their intuitive believability but gain interest-provokingness/memorability.
Pitched between Scylla and Charybdis: Metz Jews’ Litigation Hurdles in the Metz Beit Din and Ancien Regime French Courts
Authors: Herman Shael 
Published: June 2021

Abstract
During the eighteenth century, French courts expanded their competence over Jewish disputes in order to consolidate the kingdom’s hegemony over Alsatian Jewry. In Metz, the expansion was sanctioned by a royal order for the composition of the Recueil des Loix, Coutumes, et Usages Observes par les Juifs de Metz (1742). A blend of Jewish law and French customary law tailored for ancien regime Alsatian courts, the Recueil enabled a Jewish claimant to sue in either the beit din or a French tribunal. These judicial alternatives posed strategic dilemmas. French rulings were frequently vehicles for persecuting Jewish claimants and debasing their law, while rabbinical enforcement mechanisms typically lacked the aggressive bite of their French judicial counterparts. This article examines how the law, and these options, worked in practice.
Biblical History in the Thought of R. Ḥaim David Halevy
Authors: Breier Idan 
Published: June 2021

Abstract
R. Ḥaim David Halevy was an exceptional voice in the Religious-Zionist camp in Israel. While espousing faithfulness to the halakhah, he recognized the importance of changing circumstances with respect both to halakhic rulings and philosophical issues arising in Hebrew law. He viewed the study of history as a practical imperative, necessary to avoid repeating the mistakes of the past. Frequently adducing biblical texts, he argued that Israel must learn from the patriarchs and maintain a strong military force. In particular, the events leading to the destruction of the Temple and exile prompted him to posit that the State should remain neutral and not take an active part in international affairs. On the basis of the historiographical and prophetic literature, he maintained that fidelity to the divine covenant – i.e., ethical conduct – would safeguard Israel’s existence.
The Way of the Cross in the Ordinary: Ethnographic Attention to the Good as Invitational Ethics
Authors: Williams Sara A. 
Published: June 2021

Abstract
This essay develops the idea of ‘invitational ethics,’ engagement with ethnographic description as normative praxis. I argue that by attending to ways in which people exercise practical wisdom in ordinary moments, the ethnographer and reader alike are invited to engage their own processes of ethical self-making. I draw on ethnographic fieldwork with the Way of the Cross for Justice, an annual Good Friday public liturgy in Cincinnati, Ohio, as a site for invitational ethics in the frame of what anthropologist Joel Robbins has called an ‘anthropology of the good.’ I conclude by reflecting on how this invited me to engage my own ethical self-making.
Environmental and Internal Controls on Lagrangian Transitions from Closed Cell Mesoscale Cellular Convection over Subtropical Oceans
Authors: Eastman Ryan , McCoy Isabel L. , Wood Robert 
Published: June 2021

AbstractClassifications of mesoscale cellular convection (MCC) for marine boundary layer clouds are produced using a supervised neural network algorithm applied to MODIS daytime liquid water path data. The classifier, used in prior studies, distinguishes closed, open, and cellular but disorganized MCC. This work uses trajectories in four eastern subtropical ocean basins to compare meteorological variables and the structures of boundary layers for trajectories that begin as closed cells but evolve into either open cells or disorganized cells or remain closed cells over one afternoon–afternoon cycle. Results show contrasts between the trajectory sets: Trajectories for MCC that remain closed cells are more frequently observed nearer coasts, whereas trajectories that break into open and disorganized cells begin farther offshore. The frequency at which closed cells transition to open cells is seasonally invariant. The fraction of trajectories that stay as closed MCC varies throughout the year in opposition to those that break into disorganized cells, so that their annual cycles are 180° out of phase. Trajectories remain as closed cell more frequently in austral spring and boreal summer when the trade inversion is stronger. The closed–disorganized MCC breakup is associated with weaker subsidence, a weaker inversion, a drier free troposphere, and enhanced nighttime boundary layer deepening, consistent with a warming–drying mechanism. The closed–open transition occurs in meteorological conditions similar to closed–closed trajectories. However, prior to the transition, the closed–open trajectories exhibit stronger surface winds and lower cloud droplet concentrations and rain more heavily overnight. Results suggest that multiple, independent mechanisms drive changes in cloud amount and morphology.
Validation of a Prototype Global 4D-Var Data Assimilation System for the MPAS-Atmosphere Model
Authors: Tian Xiaoxu , Zou Xiaolei 
Published: June 2021

AbstractA four-dimensional variational (4D-Var) data assimilation (DA) system is developed for the global nonhydrostatic atmospheric dynamical core of the Model for Prediction Across Scales (MPAS). The nonlinear forward and adjoint models of the MPAS-Atmosphere dynamic core are included in a Python-driven structure to formulate a continuous 4D-Var DA system, shown to effectively minimize the cost function that measures the distances between the nonlinear model simulations and observations. In this study, three idealized experiments with a six-hour assimilation window are conducted to validate and demonstrate the numerical feasibilities of the 4D-Var DA system for both uniform- and variable-resolution meshes. In the first experiment, only a single point observation is assimilated. The resulting solution shows that the analysis increments have highly flow-dependent features. The observations in the second experiment are all model prognostic variables that span the entire global domain, the purpose of which is to check how well the initial conditions six hours prior to the observations can be reversely inferred. The differences between the analysis and the referenced "truth" are significantly smaller than those calculated with the first guess. The third experiment assimilates the mass field only, i.e., potential temperatures in the case of MPAS-Atmosphere, and examines the impacts on the wind field and the mass field under initial conditions. Both the wind vectors and potential temperatures in the analysis agree more with the referenced "truth" than the first guess because the adjustments made to the initial conditions are dynamically consistent in the 4D-Var system.