bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiovascular disease risk in long‐term breast cancer survivors: A population‐based cohort study
Authors: Koric Alzina , Chang Chun‐Pin , Mark Bayarmaa , Rowe Kerry , Snyder John , Dodson Mark , Deshmukh Vikrant G. , Newman Michael G. , Fraser Alison M. , Smith Ken R. , Date Ankita P. , Gren Lisa H. , Porucznik Christina A. , Haaland Benjamin A. , Henry N. Lynn , Hashibe Mia 
Published: May 2022

BackgroundBreast cancer survival is increasing, making late effects such as cardiovascular disease (CVD) more relevant. The purpose of this study was to evaluate incident CVD following breast cancer diagnosis among long‐term survivors and to investigate possible risk factors for CVD.MethodsA population‐based cohort of 6641 breast cancer survivors diagnosed between 1997 and 2009 who survived at least 10 years was identified within the Utah Cancer Registry. In addition, 36,612 cancer‐free women from the general population, matched by birth year and state, were identified within the Utah Population Database. Cox proportional hazards models were used to calculate CVD hazard ratios (HRs) for >10 to 15 and >15 years.ResultsLong‐term breast cancer survivors had an increased risk of newly diagnosed diseases of the circulatory system (HR, 1.32; 99% confidence interval [CI], 1.00‐1.75) from 10 to 15 years following cancer diagnosis compared with the general population. No increased CVD risks were observed after 15 years. Breast cancer survivors with Charlson Comorbidity Index score ≥2 had a significantly higher risk of diseases of the circulatory system (HR, 2.64; 95% CI, 1.08‐6.45) beyond 10 years following breast cancer diagnosis. Similarly, older age, obesity, lower education, and family history of CVD and breast cancer were risk factors for heart and circulatory system diseases among long‐term breast cancer survivors.ConclusionRisk of CVD compared to the general population was moderate among this cohort of long‐term breast cancer survivors between 10 to 15 years since cancer diagnosis. Awareness of CVD risks is important for breast cancer survivors.
Effects of CYP3A Inhibition, CYP3A Induction, and Gastric Acid Reduction on the Pharmacokinetics of Ripretinib, a Switch Control KIT Tyrosine Kinase Inhibitor
Authors: Li Xiaoyan , Shelton Mark J , Wang Jing , Meade Julie , Ruiz‐Soto Rodrigo 
Published: May 2022

AbstractRipretinib is a switch control KIT kinase inhibitor approved for treatment of adults with advanced gastrointestinal stromal tumors who received prior treatment with 3 or more kinase inhibitors, including imatinib. Ripretinib and its active metabolite (DP‐5439) are cleared mainly via cytochrome P450 enzyme 3A4/5 (CYP3A4/5), and ripretinib solubility is pH‐dependent, thus the drug–drug interaction potentials of ripretinib with itraconazole (strong CYP3A inhibitor), rifampin (strong CYP3A inducer), and pantoprazole (proton pump inhibitor) were each evaluated in open‐label, fixed‐sequence study designs. Overall, 20 participants received ripretinib 50 mg alone and with itraconazole 200 mg once daily, 24 participants received ripretinib 100 mg alone and with rifampin 600 mg once daily, and 25 participants received ripretinib 50 mg alone and with pantoprazole 40 mg once daily. Ripretinib exposure increased with concomitant itraconazole, with geometric least‐squares (LS) mean ratios of ripretinib area under the concentration–time curve from 0 to ∞ (AUC0–∞) and maximum observed concentration (Cmax) of 199% and 136%. Ripretinib exposure decreased with concomitant rifampin: geometric LS mean ratios for ripretinib AUC0–∞ and Cmax were 39% and 82%. Pantoprazole coadministration had no effect on ripretinib pharmacokinetics. No unexpected safety signals occurred. No dose adjustment is required for ripretinib coadministered with gastric acid reducers and strong CYP3A inhibitors; patients also receiving strong CYP3A inhibitors should be monitored more frequently for adverse reactions. Concomitant ripretinib use with strong CYP3A inducers should be avoided. Prescribers should refer to approved labeling for specific dose recommendations with concomitant use of strong and moderate CYP3A inducers.
Non‐Globular Organic Ionic Plastic Crystal Containing a Crown‐Ether Moiety – Tuning Its Behaviour Using Sodium Salts
Authors: Casimiro Anna , Lugger Jody , Lub Johan , Nijmeijer Kitty 
Published: May 2022

AbstractOrganic ionic plastic crystals (OIPCs) are a class of soft materials showing positional order while still allowing orientational freedom. Due to their motional freedom in the solid state, they possess plasticity, non‐flammability and high ionic conductivity. OIPC behavior is typically exhibited by ‘simple’ globular molecules allowing molecular rotation, whereas the interactions that govern the formation of OIPC phases in complex non‐globular molecules are less understood. To better understand these interactions, a new family of non‐globular OIPCs containing a 15‐crown‐5 ether moiety was synthetized and characterized. The 15C5BA molecule prepared does not exhibit the sought‐after behavior because of its non‐globular nature and strong intermolecular H‐bonds that restrict orientational motion. However, the OIPC behavior was successfully obtained through complexation of the crown‐ether moiety with sodium salts containing chaotropic anions. Those anions weaken the interactions between the molecules, allowing rotational freedom and tuning of the thermal and morphological properties of the OIPC.
Conflict management in the indigenous community of Batad in the Philippines: A system dynamic perspective
Authors: Ilac Emerald Jay D. , Presbitero Alfred 
Published: May 2022

AbstractConflict management has been widely examined, with research focusing on different conflict management styles, strategies, and factors that influence effective conflict resolution. However, despite the significant research attention dedicated to this field, the search for new insights and discoveries continues to discover how best to resolve and manage conflicts. The present study contributes to the literature by applying a system dynamic perspective to gain understanding of conflict management and constructs a theorized leadership model based on the experiences of leaders in an indigenous community in the Philippines. We utilize a phenomenological approach to involve multiple indigenous leaders and obtain their experiences of the conflict management process and system dynamics in their indigenous communities. Our results achieve the following: (a) demonstrating the complex nature of conflict management, validating the utility of the system dynamic perspective; (b) demonstrating that conflict management occurs on and involves multiple levels; and (c) revealing the importance of the humility and unbiasedness of leaders in the conflict management process. These findings provide novel insights into alternative mechanisms for effective management of conflicts in modern workplaces and organizations.
Elevation of fatty acid desaturase 2 in esophageal adenocarcinoma increases polyunsaturated lipids and may exacerbate bile acid‐induced DNA damage
Authors: Molendijk Jeffrey , Kolka Cathryn M. , Cairns Henry , Brosda Sandra , Mohamed Ahmed , Shah Alok K. , Brown Ian , Hodson Mark P. , Hennessy Thomas , Liu Guanghao , Stoll Thomas , Richards Renee S. , Gartside Michael , Patel Kalpana , Clemons Nicholas J. , Phillips Wayne A. , Barbour Andrew , Westerhuis Johan A. , Hill Michelle M. 
Published: May 2022

AbstractBackgroundThe risk of esophageal adenocarcinoma (EAC) is associated with gastro‐esophageal reflux disease (GERD) and obesity. Lipid metabolism‐targeted therapies decrease the risk of progressing from Barrett's esophagus (BE) to EAC, but the precise lipid metabolic changes and their roles in genotoxicity during EAC development are yet to be established.MethodsEsophageal biopsies from the normal epithelium (NE), BE, and EAC, were analyzed using concurrent lipidomics and proteomics (n = 30) followed by orthogonal validation on independent samples using RNAseq transcriptomics (n = 22) and immunohistochemistry (IHC, n = 80). The EAC cell line FLO‐1 was treated with FADS2 selective inhibitor SC26196, and/or bile acid cocktail, followed by immunofluorescence staining for γH2AX.ResultsMetabolism‐focused Reactome analysis of the proteomics data revealed enrichment of fatty acid metabolism, ketone body metabolism, and biosynthesis of specialized pro‐resolving mediators in EAC pathogenesis. Lipidomics revealed progressive alterations (NE‐BE‐EAC) in glycerophospholipid synthesis with decreasing triglycerides and increasing phosphatidylcholine and phosphatidylethanolamine, and sphingolipid synthesis with decreasing dihydroceramide and increasing ceramides. Furthermore, a progressive increase in lipids with C20 fatty acids and polyunsaturated lipids with ≥4 double bonds were also observed. Integration with transcriptome data identified candidate enzymes for IHC validation: Δ4‐Desaturase, Sphingolipid 1 (DEGS1) which desaturates dihydroceramide to ceramide, and Δ5 and Δ6‐Desaturases (fatty acid desaturases, FADS1 and FADS2), responsible for polyunsaturation. All three enzymes showed significant increases from BE through dysplasia to EAC, but transcript levels of DEGS1 were decreased suggesting post‐translational regulation. Finally, the FADS2 selective inhibitor SC26196 significantly reduced polyunsaturated lipids with three and four double bonds and reduced bile acid‐induced DNA double‐strand breaks in FLO‐1 cells in vitro.ConclusionsIntegrated multiomics revealed sphingolipid and phospholipid metabolism rewiring during EAC development. FADS2 inhibition and reduction of the high polyunsaturated lipids effectively protected EAC cells from bile acid‐induced DNA damage in vitro, potentially through reduced lipid peroxidation.
Evidence for serial founder events during the colonization of North America by the yellow fever mosquito, Aedes aegypti
Authors: Pless Evlyn , Powell Jeffrey R. , Seger Krystal R. , Ellis Brett , Gloria‐Soria Andrea 
Published: May 2022

AbstractThe Aedes aegypti mosquito first invaded the Americas about 500 years ago and today is a widely distributed invasive species and the primary vector for viruses causing dengue, chikungunya, Zika, and yellow fever. Here, we test the hypothesis that the North American colonization by Ae. aegypti occurred via a series of founder events. We present findings on genetic diversity, structure, and demographic history using data from 70 Ae. aegypti populations in North America that were genotyped at 12 microsatellite loci and/or ~20,000 single nucleotide polymorphisms, the largest genetic study of the region to date. We find evidence consistent with colonization driven by serial founder effect (SFE), with Florida as the putative source for a series of westward invasions. This scenario was supported by (1) a decrease in the genetic diversity of Ae. aegypti populations moving west, (2) a correlation between pairwise genetic and geographic distances, and (3) demographic analysis based on allele frequencies. A few Ae. aegypti populations on the west coast do not follow the general trend, likely due to a recent and distinct invasion history. We argue that SFE provides a helpful albeit simplified model for the movement of Ae. aegypti across North America, with outlier populations warranting further investigation.
Explanation of beta diversity in European alpine grasslands changes with scale
Authors: Malanson George P. , Pansing Elizabeth R. , Testolin Riccardo , Abdulhak Sylvain , Bergamini Ariel , Ćušterevska Renata , Marcenò Corrado , Kuzmanović Nevena , Milanović Đorđije , Ruprecht Eszter , Šibík Jozef , Vassilev Kiril , Willner Wolfgang , Jiménez‐Alfaro Borja 
Published: May 2022

AbstractThe importance of environmental difference among sites and dispersal limitations of species to the explanation of diversity differs among biological systems and geographical regions. We hypothesized that climate and then dispersal limitation will predominantly explain the similarity of alpine vegetation at increasing distances between pairs of regions at subcontinental extent. We computed the similarity of all pairs of 23 European mountain regions below 50° N after dividing the species lists of each region by calcareous or siliceous substrates. Distance decay in similarity was better fitted by a cubic polynomial than a negative exponential function, and the fit was better on calcareous than on siliceous substrate. Commonality analysis revealed that the proportion of explanation of beta diversity by climatic difference had unimodal patterns on a gradient of increasing distance between regions, while explanation by dispersal limitation had consistently rising patterns on both substrates. On siliceous substrate, dispersal limitation explained more of the variation in beta diversity only at longer distances, but it was predominant at all distances on calcareous substrate. The steeper response to distance at <1600 km and >2600 km may indicate dispersal limitation at different temporal scales, and the uptick in the response to distance at the longest distances may reflect how isolated some regions have been before and since the last glacial maximum.
Gathering in an empty house: Arthropod assemblages overwintering in abandoned hornet nests
Authors: Furusawa Chiharu , Okamiya Hisanori 
Published: May 2022

AbstractAlthough some species of hornets spend enormous amounts of time constructing their nests, they only utilize the nest for one season and abandon it to overwinter in other habitats. Abandoned nests may be attractive habitats for other organisms to avoid predators and bad weather, but our knowledge of the organisms that make use of hornet nests for overwintering is very limited. Here, we examined the secondary inhabitants of abandoned winter hornet nests in northern part of Japan. A total of 96 live arthropods (5 orders, 23 species) were collected from six nests and were dominated by Araneae (85.4%). Our finding suggests that hornet nests serve as overwintering sites for many other organisms and that hornets may act as physical ecosystem engineers by creating overwintering habitats for other arthropods (mostly spiders). We predict that abandoned nests indirectly affect the prey community structure on trees, by providing overwintering sites for predatory spiders. In addition, reduced snow cover due to global warming may prevent nest collapse and enhance the ecological functioning of hornet nests. We emphasize that hornet nests present an ideal system for assessing how climate change alters communities through its effect on engineered structures. Further studies are required to clarify the role of hornets as ecosystem engineers among tree communities in fluctuating environments.
Effect of pulmonary artery pressure‐guided therapy on heart failure readmission in a nationally representative cohort
Authors: Kishino Yoshikazu , Kuno Toshiki , Malik Aaqib H. , Lanier Gregg M. , Sims Daniel B. , Ruiz Duque Ernesto , Briasoulis Alexandros 
Published: May 2022

AbstractAimsPulmonary artery pressure (PAP)‐guided therapy in patients with heart failure (HF) using the CardioMEMS (CMM) device, an implantable PAP sensor, has been shown to reduce HF hospitalizations in previous studies. We sought to evaluate the clinical benefit of the CMM device in regard to 30, 90, and 180 day readmission rates in real‐world usage.Methods and resultsWe queried the Nationwide Readmissions Database (NRD) to identify patients who underwent CMM implantation (International Classification of Diseases 9 and 10 codes) between the years 2014 and 2019 and studied their HF readmissions. Moreover, we compared CMM patients and their readmissions with a matched cohort of patients with HF but without CMM. Multivariable Cox regression analysis was performed to adjust for other predictors of readmissions. Prior to matching, we identified 5 326 530 weighted HF patients without CMM and 1842 patients with CMM. After propensity score matching for several patients and hospital‐related characteristics, the cohort consisted of 1839 patients with CMM and 1924 with HF without CMM. Before matching, CMM patients were younger (67.0 ± 13.5 years vs. 72.3 ± 14.1 years, P < 0.001), more frequently male (62.7% vs. 51.5%, P < 0.001), with higher rates of prior percutaneous coronary intervention (16.9% vs. 13.2%, P = 0.002), peripheral vascular disease (29.6% vs. 17.8%, P < 0.001), pulmonary circulatory disorder (38.7% vs. 23.2%, P < 0.001), atrial fibrillation (51.2% vs. 45.3%, P = 0.002), prior left ventricular assist device (1.8% vs. 0.2%, P < 0.001), high income (32.2% vs. 16.4%, P < 0.001), and acute kidney disease (43.8% vs. 29.9%, P < 0.001). Readmission rates at 30 days were 17.3% vs. 20.9% for patients with vs. without CMM, respectively, and remained statistically significant after matching (17.3% vs. 21.5%, P = 0.002). The rates of 90 day (29.6% vs. 36.5%, P = 0.002) and 180 day (39.6% vs. 46.6%, P = 0.009) readmissions were lower in the CMM group. In a multivariable regression model, CMM was associated with lower risk of readmissions (hazard ratio 0.75, 95% confidence interval 0.63–0.89, P = 0.001).ConclusionsThe CMM device was associated with reduced HF rehospitalization rates in a nationally representative cohort of HF patients, validating the clinical trial that led to the approval of this device and its utilization in the treatment of HF.
Changes in cardiac biomarkers in association with alterations in cardiac structure and function, and health status in heart failure with reduced ejection fraction: the EVALUATE‐HF trial
Authors: Myhre Peder L. , Claggett Brian L. , Shah Amil M. , Prescott Margaret F. , Ward Jonathan H. , Fang James C. , Mitchell Gary F. , Solomon Scott D. , Desai Akshay S. 
Published: May 2022

AimsN‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP), cardiac troponin T (cTnT) and soluble ST2 (sST2) provide complementary prognostic information in heart failure with reduced ejection fraction (HFrEF). We aimed to assess the association between changes in these markers with changes in cardiac structure, function and health status.Methods and resultsPatients in the EVALUATE‐HF trial (n = 464) were randomized to sacubitril/valsartan or enalapril for 12 weeks, followed by 12‐week open‐label sacubitril/valsartan. Cardiac biomarkers, echocardiography, and Kansas City Cardiomyopathy Questionnaires (KCCQ) were completed at baseline, and after 12 and 24 weeks. A total of 410 patients (88%) had serial biomarker measurements available (mean age 67 ± 9 years, 75% male and 75% white). After 24 weeks of treatment, NT‐proBNP, sST2 and cTnT decreased by median (Q1, Q3) −31% (−55%, +6%), −6% (−19%, +8%) and − 3% (−13%, +8%), respectively (all p < 0.001). Decreases in NT‐proBNP were associated with reductions in cardiac volumes and improvements in systolic and diastolic function and health status. Decreases in cTnT were associated with reductions in left ventricular mass, but not with changes in left ventricular function or KCCQ. Decreases in sST2 were consistently associated with improvements in health status, but not with measures of cardiac structure or function. There was no effect modification from treatment on the associations investigated (p for interaction >0.05)ConclusionIn HFrEF, serial changes in NT‐proBNP correlate with changes in several key measures of cardiac structure and health status. cTnT changes correlate with changes in left ventricular mass and sST2 with changes in health status. These data highlight possible complementary pathophysiologic implications of changes in NT‐proBNP, cTnT and sST2.Clinical Trial Registration:
ClinicalTrials.gov Identifier: NCT02874794.
Impact of bacterial infections and spontaneous bacterial peritonitis prophylaxis on phage‐bacterial dynamics in cirrhosis
Authors: Bajaj Jasmohan S. , Rodriguez Marcela Peňa , Fagan Andrew , McGeorge Sara , Sterling Richard K. , Lee Hannah , Luketic Velimir , Fuchs Michael , Davis Brian C. , Sikaroodi Masoumeh , Gillevet Patrick M. 
Published: May 2022

Abstract

Background and Aims
Gut microbiota, including bacteria and phages, are altered in cirrhosis, but their role during infections and spontaneous bacterial peritonitis (SBP) prophylaxis is unclear. Our aim was determine metagenomic changes in gut bacteria; phages and their linkages centered around Gram‐negative and Gram‐positive pathobionts in patients with cirrhosis with/without infections or SBP prophylaxis.

Approach and Results
We included uninfected (n = 231) and infected (n = 30, SBP n = 19 and urinary tract infection n = 11 before antibiotics) patients who gave stool for bacterial and phage metagenomics. We matched uninfected to infected patients 1:1 on a model for end‐stage liver disease (MELD). We also analyzed subgroups of patients with ascites matched on an MELD (n = 73) to patients on SBP prophylaxis (n = 7) and then to SBP infection. Phage and bacterial taxa differences (DESeq2) and correlation networks centered around Escherichia coli and Enterococcus faecium were analyzed. Infections were mostly due to Enterobacteriaceae and Enterococcus spp. On metagenomics, higher fold changes of Enterobacteriaceae members, Enterococcus and Streptococcus spp., and Escherichia phages were seen in infected patients. Correlation networks showed more complex bacteria‐phage linkages in infected patients compared with uninfected ones overall and centered around E. coli and E. faecium. SBP prophylaxis induced higher Gram‐positive bacteria. In SBP, Enterococcus and Escherichia were higher versus ascites. Correlation networks around E. coli were complex in ascites but sparse with SBP prophylaxis, whereas the reverse was seen with E. faecium. Lytic phages and those associated with antibiotic resistance were correlated with E. faecium.

Conclusion
In cirrhosis, there are significant changes in phage‐bacterial linkages in infected patients and those on SBP prophylaxis compared to the remaining patients. SBP prophylaxis enriches complexity of E. faecium–centered but induces a collapse in E. coli–centered phage‐bacterial correlations.
Reducing measurement error with ecologically valid testing methods
Authors: Gunther Kelley E. , Anaya Berenice , Pérez‐Edgar Koraly 
Published: May 2022

Abstract‘Six solutions for more reliable infant research’ outlines important steps in improving research with the youngest of participants. Here, we suggest that a complimentary avenue for further improving reliability can be found in employing more ecologically valid tasks. Because laboratory tasks are often designed as simple, heavily controlled representations of a construct, they can be devoid of the necessary context in which the construct naturally unfolds. We posit that additional error is generated in translating laboratory task metrics back to the construct of interest. Thus, it may be necessary to supplement more traditional laboratory tasks with iterations that more closely match the research construct of interest and how it may unfold in the ‘real world’. We make suggestions for adjusting to the ‘noise’ incurred by moving research out of traditional laboratory environments, while also recognizing how these adjustments may improve the sociodemographic profiles within research studies.
Triple combination therapy for clinically nonmetastatic super‐high‐risk prostate cancer
Authors: Yoshimura Koji , Muraoka Kei , Fukasawa Michiko , Fukushima Mika , Kumagai Masatoshi , Yabusaki Ryo , Ueda Masakatsu , Shiraishi Yusuke , Imamura Masaaki 
Published: May 2022

IntroductionPatients with nonmetastatic but exceptionally high‐risk prostate cancer are liable to have biochemical failure and may even die. Triple combination therapy, which consists of surgery, radiotherapy, and androgen‐deprivation therapy, as first‐line treatment, may control the disease for a long period.Case presentationWe treated a patient with super‐high‐risk, nonmetastatic prostate cancer, with triple combination therapy. He was biochemical relapse free at 60 months after the initiation of treatment.ConclusionTriple combination therapy may be an option for super‐high‐risk, nonmetastatic prostate cancer.