bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of energy and essential fatty acids content in breast milk on infant's head dimensions
Authors: Babiszewska Magdalena 
Published: April 2020

AbstractObjectivesEssential fatty acids (EFA), including linoleic acid (LA) and alpha‐linolenic acid (ALA), are indispensable for proper brain growth especially in the first months after birth when it develops most rapidly. Since fats, especially EFA, in breast milk are highly variable between mothers, we indirectly examined whether milk energy, LA and ALA content in breast milk affect volume and shape of the infant's head.MethodsThe study encompassed 60 mothers and their healthy term‐born infants between the third and sixth month of lactation. The percentage of macronutrients and dry matter in human milk samples was assessed using Fourier‐transform infrared spectroscopy (FTIR), and LA and ALA concentrations in breast milk were determined using gas chromatography (GC). Infant head measurements were taken using standard anthropometric equipment and methods.ResultsLA content in breast milk was found to be positively associated with head volume in boys. Furthermore, ALA content was positively associated with the head height‐to‐length ratio thus with more arched head in infants irrespective of sex. No relationship was found between milk energy content in mothers' milk and infant head dimensions.ConclusionsThis is the first study to demonstrate a relationship between EFA concentration in human milk and infant head dimensions. Given that LA and ALA in human milk are variable in women and due to the extremely rapid growth of nerve tissue in the first months of life, adequate supply of EFA in breast milk should attract the attention of public health sciences.
Microbiome Structure and Function: A New Framework for Interpreting Data
Authors: Greslehner Gregor P. 
Published: April 2020

AbstractA distinction between different notions of “structure” and “function” is suggested for interpreting the overwhelming amount of data on microbiome structure and function. Sequence data, biochemical agents, interaction networks, taxonomic communities, and their dynamics can be linked to potential or actual biochemical activities, causal roles, and selected effects, respectively. This conceptual clarification has important methodological consequences for how to interpret existing data and approach open questions in contemporary microbiome research practice. In particular, the field will have to start thinking about notions of function more directly. Also see the video abstract here https://youtu.be/j5pq5uGld1k.
Understanding Human Lung Development through In Vitro Model Systems
Authors: Conway Renee F. , Frum Tristan , Conchola Ansley S. , Spence Jason R. 
Published: April 2020

AbstractAn abundance of information about lung development in animal models exists; however, comparatively little is known about lung development in humans. Recent advances using primary human lung tissue combined with the use of human in vitro model systems, such as human pluripotent stem cell‐derived tissue, have led to a growing understanding of the mechanisms governing human lung development. They have illuminated key differences between animal models and humans, underscoring the need for continued advancements in modeling human lung development and utilizing human tissue. This review discusses the use of human tissue and the use of human in vitro model systems that have been leveraged to better understand key regulators of human lung development and that have identified uniquely human features of development. This review also examines the implementation and challenges of human model systems and discusses how they can be applied to address knowledge gaps.
Residue analysis and kinetics modeling of thiophanate‐methyl, carbendazim, tebuconazole and pyraclostrobin in apple tree bark using QuEChERS/HPLC–VWD
Authors: Li Pingliang , Sun Pingyang , Dong Xiangli , Li Baohua 
Published: April 2020

AbstractWinter is the key period for the control of apple diseases, and fungicides are needed to protect the trunk or main branches. Fungicide residue in apple tree bark is an important basis for the action of the pesticide, but there are no reports on analytical methods or dissipation patterns. In this work, thiophanate‐methyl, carbendazim, tebuconazole and pyraclostrobin were selected as typical fungicides and a new QuEChERS–HPLC–VWD(QuEChERS extraction followed by high‐performance liquid chromatography detection with a variable wavelength detector) analytical method was developed to estimate their residue kinetics in apple tree bark during the winter months. In the pretreatment step, the sorbent for the clean‐up of extracts was optimized as 60 mg/ml primary secondary amine and a gradient‐elution model followed by a variable wavelength detection was developed for instrumental analysis. Then this method was validated and applied to the analysis of apple tree bark samples with the linearity range of 0.010–50.00 mg/L, quantification limit range of 0.028–0.080 mg/kg and recovery range of 86.1–101.4%. The dissipation kinetics of thiophanate‐methyl and pyraclostrobin could be described by the first‐order and two‐phase kinetics models, respectively. For carbendazim and tebuconazole, two new models were developed to describe their residue kinetics.
A rapid and sensitive bioanalytical LC–MS/MS method for the quantitation of a novel CDK5 inhibitor 20–223 (CP668863) in plasma: Application to in vitro metabolism and plasma protein‐binding studies
Authors: Bala Veenu , Chhonker Yashpal S. , Sleightholm Richard L. , Crawford Ayrianne J. , Hollingsworth Michael A. , Murry Daryl J. 
Published: April 2020

AbstractA rapid, selective, and sensitive liquid chromatography coupled with tandem mass spectrometry (MS/MS) method was developed and validated for the quantitation of the novel CDK5 inhibitor ‘20–223' in mouse plasma. Separation of analytes was achieved by a reverse‐phase ACE Excel C18 column (1.7 μm, 100 × 2.1 mm) with gradient elution using 0.1% formic acid (FA) in methanol and 0.1% FA as the mobile phase. Analytes were monitored by MS/MS with an electrospray ionization source in the positive multiple reaction monitoring mode. The MS/MS response was linear over the concentration range 0.2–500 ng/mL for 20–223. The within‐ and between‐batch precision were within the acceptable limits as per Food and Drug Administration guidelines. The validated method was successfully applied to plasma protein binding and in vitro metabolism studies. Compound 20–223 was highly bound to mouse plasma proteins (>98% bound). Utilizing mouse S9 fractions, in vitro intrinsic clearance (CLint) was 24.68 ± 0.99 μL/min/mg protein. A total of 12 phase I and II metabolites were identified with hydroxylation found to be the major metabolic pathway. The validate method required a low sample volume, was linear from 0.2 to 500 ng/mL, and had acceptable accuracy and precision.
In vivo metabolic investigation of cetilistat in normal versus pseudo‐germ‐free rats using UPLC‐QTOFMS/MS and in silico toxicological evaluation of its metabolites
Authors: Tiwari Shristy S. , Mukesh Sumit , Sangamwar Abhay T. , Talluri M.V.N. Kumar 
Published: April 2020

AbstractCetilistat (CET) is a pancreatic lipase inhibitor approved for management of obesity after the serious adverse effects exhibited by its analogue orlistat. Exhaustive literature review reveals lack of comprehensive reports on its biotransformation. With a view to study the same, the present study reports the identification and characterization of metabolites of CET in rats using UPLC–MS/MS. As the small intestine is the site of action for CET, it is important that the role of microbial flora in the metabolism of CET be explored. To achieve this, the metabolic profile of CET was compared between normal and pseudo‐germ‐free rats. The study involved the administration of a drug suspension to male Sprague–Dawley pseudo‐germ‐free and normal untreated rats followed by collection of urine, feces, and blood at specific intervals. Sample preparation was performed using liquid–liquid extraction and concentration of samples followed by analysis using LC–MS/MS. Finally, an in silico study was performed on the drug and metabolites to predict their toxicological properties using ADMET PredictorTM software. Four metabolites of CET were observed in in vivo matrices. As expected, significant changes were observed both qualitatively and quantitatively, implying that formation of metabolites was both CYP enzymes and gut microflora mediated.
Effect of coagulation function on cerebral microbleeds in intracerebral hemorrhage
Authors: Zhang Hui , Deng Jian , Sun Nianlong , Zou Liangyu , Han Jing , Wei Chen , He Yitao 
Published: April 2020

AbstractObjectiveOur study aimed to confirm whether coagulation function of patients presenting with intracerebral hemorrhage (ICH) was associated with onset of cerebral microbleeds (CMBs).MethodsA total of 174 patients with basal ganglia ICH were divided into CMBs and non‐CMBs groups. Indicators of coagulation function and other clinical data that included fibrinogen (FBI), prothrombin time (PT), activated partial thromboplastin time (APTT), and the international normalized ratio (INR) were compared by univariate and multivariate analysis between the two groups. A receiver operating characteristic (ROC) curve was plotted to determine the predictive value of coagulation function indicators for CMBs.ResultsUnivariate analysis showed that APTT levels was significantly higher in the CMBs group than the non‐CMBs group (30.20 ± 5.18 vs. 27.95 ± 4.19; p = .004), while there was no significant difference between PT, INR, and FBI. The proportion of male patients in the CMBs group was significantly higher than the non‐CMBs group (76.58% vs. 52.38%, p = .001). Multifactor logistic regression analysis demonstrated that APTT and male gender were independent risk factors for CMBs in patients with ICH (OR 1.100, 95% CI: 1.026–1.180, p = .008; OR 2.957, 95% CI: 1.500–5.826, p = .002; respectively). ROC curve analysis indicated that the area under the curve of APTT and male gender for CMBs in patients with ICH was 0.641 and 0.621, respectively (p = .002 and .008; respectively).ConclusionAPTT was an independent risk factor for CMBs in patients with ICH.
Identification of cancer stem cell characteristics in liver hepatocellular carcinoma by WGCNA analysis of transcriptome stemness index
Authors: Bai Kun‐Hao , He Si‐Yuan , Shu Ling‐Ling , Wang Wei‐Da , Lin Shi‐Yong , Zhang Qian‐Yi , Li Liang , Cheng Lei , Dai Yu‐Jun 
Published: April 2020

AbstractCancer stem cells (CSCs) are characterized by self‐renewal and ‐differential potential as compared to common cancer cells and play an important role in the development and therapeutic resistance of liver hepatocellular carcinoma (LIHC). However, the specific pathogenesis of LIHC stem cells is still unclear, and the genes involved in the stemness of LIHC stem cells are currently unknown. In this study, we investigated novel biomarkers associated with LIHC and explored the expression characteristics of stem cell‐related genes in LIHC. We found that mRNA expression‐based stemness index (mRNAsi) was significantly overexpressed in liver cancer tissues. Further, mRNAsi expression in LIHC increased with the tumor pathological grade, with grade 4 tumors harboring the greatest stem cell features. Upon establishing mRNAsi scores based on mRNA expression of every gene, we found an association with poor overall survival in LIHC. Moreover, modules of interest were determined based on weighted gene co‐expression network analysis (WGCNA) inclusion criteria, and three significant modules (red, green, and brown) and 21 key genes (DCN, ECM1, HAND2, PTGIS, SFRP1, SRPX, COLEC10, GRP182, ADAMTS7, CD200, CDH11, COL8A1, FAP, LZTS1, MAP1B, NAV1, NOTCH3, OLFML2A, PRR16, TMEM119, and VCAN) were identified. Functional analysis of these 21 genes demonstrated their enrichment in pathways involved in angiogenesis, negative regulation of DNA‐binding transcription factor activity, apoptosis, and autophagy. Causal relationship with proteins indicated that the Wnt, Notch, and Hypoxia pathways are closely related to LIHC tumorigenesis. To our knowledge, this is the first report of a novel CSC biomarker, mRNAsi, to predict the prognosis of LIHC. Further, we identified 21 key genes through mRNA expression network analysis, which could be potential therapeutic targets to inhibit the stemness of cancer cells in LIHC.
Association between serum erythropoietin levels and renal reversibility in patients with renal impairment from multiple myeloma
Authors: Kobayashi Hiroki , Terao Toshiki , Tsushima Takafumi , Abe Yoshiaki , Miura Daisuke , Narita Kentaro , Kitadate Akihiro , Takeuchi Masami , Matsue Kosei 
Published: April 2020

AbstractRenal impairment (RI) is a common clinical presentation in patients with multiple myeloma (MM). Despite treatment with novel agents or management strategies that focus on the disease response, some patients develop irreversible RI. This study aimed to determine the influencing, clinical variables of renal reversibility in patients with RI treated with novel drugs. We analyzed 244 patients newly diagnosed with MM retrospectively. Maximum renal response was assessed according to the criteria for the definition of renal response proposed by the International Myeloma Working Group. Major renal response was defined as the occurrence of complete renal response or partial renal response. RI (a glomerular filtration rate < 50 mL/min/1.73 m2) was observed in 110 patients (45%). In total, 56 patients (51%) achieved a major renal response. Serum erythropoietin (EPO) levels >25 mIU/mL (P < .001) and a percentage of urinary albumin excretion ≤25% (P < .001) were both significant factors that influenced the occurrence of major renal responses. Both remained significant factors associated with renal reversibility in the multivariate analysis. Patients were assigned a score of 1 each for EPO >25 mIU/mL and urinary albumin ≤25%. The estimated 6‐month rates of major renal responses of patients with scores of 2, 1, and 0 were 78.6%, 30.6%, and 0%, respectively (P < .001). In conclusion, a serum EPO level >25 mIU/mL is an independent predictive factor for major renal response and may predict renal reversibility more accurately when urinary albumin level is congruently ≤25%.
Impact of renin–angiotensin system inhibitors on outcomes after transcatheter aortic valve replacement: A meta‐analysis
Authors: Sun Yinghao , Li Jie , Li Guang , Fan Ruixin , Luo Jianfang 
Published: April 2020

AbstractObjectivesWe aimed to evaluate the impact of renin–angiotensin system (RAS) inhibitors on outcomes after transcatheter aortic valve replacement (TAVR).BackgroundThe impact of RAS inhibitors on outcomes after TAVR was unclear.MethodsA systematic review of articles comparing outcomes of patients using and not using RAS inhibitors after TAVR was performed through PubMed, Embase, and Cochrane. Primary outcome was midterm all‐cause mortality. Risk ratios (RRs) were calculated with the corresponding 95% confidence interval using random effect models.ResultsFive studies with 23,319 patients were included. Patients treated with RAS inhibitors had lower midterm all‐cause mortality after TAVR than those without RAS inhibitors in both the unmatched (13.3 vs. 17.2%, RR 0.77, p = .005) and propensity score matched cohorts (13.5 vs 16.2%, RR 0.83, p < .001). Cardiovascular mortality (10.4 vs. 15.6%, RR 0.68, p < .001), rate of heart failure readmission (12.2 vs. 14.5%, RR 0.80, p = .006), and new‐onset atrial fibrillation (14.0 vs. 23.7%, RR 0.73, p = .003) were also lower with RAS inhibitors. No difference was found between two groups regarding cerebrovascular events, myocardial infarction, major bleeding, major vascular complications, acute kidney injury, permanent pacemaker implantation, and moderate/severe paravalvular aortic regurgitation.ConclusionsRAS inhibitors were associated with lower midterm all‐cause mortality after TAVR.
Management of acute myocardial infarction during the COVID‐19 pandemic
Authors: Mahmud Ehtisham , Dauerman Harold L. , Welt Frederick G.P. , Messenger John C. , Rao Sunil V. , Grines Cindy , Mattu Amal , Kirtane Ajay J. , Jauhar Rajiv , Meraj Perwaiz , Rokos Ivan C. , Rumsfeld John S. , Henry Timothy D. 
Published: April 2020

AbstractThe worldwide pandemic caused by the novel acute respiratory syndrome coronavirus 2 has resulted in a new and lethal disease termed coronavirus disease 2019 (COVID‐19). Although there is an association between cardiovascular disease and COVID‐19, the majority of patients who need cardiovascular care for the management of ischemic heart disease may not be infected with this novel coronavirus. The objective of this document is to provide recommendations for a systematic approach for the care of patients with an acute myocardial infarction (AMI) during the COVID‐19 pandemic. There is a recognition of two major challenges in providing recommendations for AMI care in the COVID‐19 era. Cardiovascular manifestations of COVID‐19 are complex with patients presenting with AMI, myocarditis simulating an ST‐elevation myocardial infarction (STEMI) presentation, stress cardiomyopathy, non‐ischemic cardiomyopathy, coronary spasm, or nonspecific myocardial injury, and the prevalence of COVID‐19 disease in the US population remains unknown with risk of asymptomatic spread. This document addresses the care of these patients focusing on (a) varied clinical presentations; (b) appropriate personal protection equipment (PPE) for health care workers; (c) the roles of the emergency department, emergency medical system, and the cardiac catheterization laboratory (CCL); and (4) regional STEMI systems of care. During the COVID‐19 pandemic, primary percutaneous coronary intervention (PCI) remains the standard of care for STEMI patients at PCI‐capable hospitals when it can be provided in a timely manner, with an expert team outfitted with PPE in a dedicated CCL room. A fibrinolysis‐based strategy may be entertained at non‐PCI‐capable referral hospitals or in specific situations where primary PCI cannot be executed or is not deemed the best option.
Chemometrics‐assisted color histogram‐based analytical systems
Authors: Gonçalves Dias Diniz Paulo Henrique 
Published: April 2020

AbstractThis review systematizes for the first time the here called “Chemometrics‐assisted color histogram‐based analytical systems” under the acronym CACHAS. A comprehensive discussion of the fundamentals, general characteristics, and applications are presented in order to direct practical aspects for developing methods that use color histograms as input data for the construction of chemometric models. For this, analytical information is rapidly acquired using a simple image acquisition device (such as digital camera, webcam, scanner, or smartphone), without need for any image processing, other than extraction of the histograms, which are constructed by counting the frequency distribution of the different color tones (conveniently specified through a color space) of all pixels delimited by a region of interest in a digital image. As a consequence, CACHAS have been increasingly used for qualitative and quantitative purposes in food, agricultural, forensic, biomedical, and microbiological analysis, reinforcing the principles of green analytical chemistry.
Potential impact of family history–based screening guidelines on the detection of early‐onset colorectal cancer
Authors: Gupta Samir , Bharti Balambal , Ahnen Dennis J. , Buchanan Daniel D. , Cheng Iona C. , Cotterchio Michelle , Figueiredo Jane C. , Gallinger Steven J. , Haile Robert W. , Jenkins Mark A. , Lindor Noralane M. , Macrae Finlay A. , Le Marchand Loïc , Newcomb Polly A. , Thibodeau Stephen N. , Win Aung Ko , Martinez Maria Elena 
Published: April 2020

BackgroundInitiating screening at an earlier age based on cancer family history is one of the primary recommended strategies for the prevention and detection of early‐onset colorectal cancer (EOCRC), but data supporting the effectiveness of this approach are limited. The authors assessed the performance of family history–based guidelines for identifying individuals with EOCRC.MethodsThe authors conducted a population‐based, case‐control study of individuals aged 40 to 49 years with (2473 individuals) and without (772 individuals) incident CRC in the Colon Cancer Family Registry from 1998 through 2007. They estimated the sensitivity and specificity of family history–based criteria jointly recommended by the American Cancer Society, the US Multi‐Society Task Force on CRC, and the American College of Radiology in 2008 for early screening, and the age at which each participant could have been recommended screening initiation if these criteria had been applied.ResultsFamily history–based early screening criteria were met by approximately 25% of cases (614 of 2473 cases) and 10% of controls (74 of 772 controls), with a sensitivity of 25% and a specificity of 90% for identifying EOCRC cases aged 40 to 49 years. Among 614 individuals meeting early screening criteria, 98.4% could have been recommended screening initiation at an age younger than the observed age of diagnosis.ConclusionsOf CRC cases aged 40 to 49 years, 1 in 4 met family history–based early screening criteria, and nearly all cases who met these criteria could have had CRC diagnosed earlier (or possibly even prevented) if earlier screening had been implemented as per family history–based guidelines. Additional strategies are needed to improve the detection and prevention of EOCRC for individuals not meeting family history criteria for early screening.
Acute Myeloid Leukemia Minimal Residual Disease Detection: The Difference from Normal Approach
Authors: Wood Brent L. 
Published: April 2020

AbstractThe identification of residual leukemia following therapy, termed minimal or measurable residual disease (MRD), has emerged as one of the most important prognostic factors for patients with acute leukemia, including acute myeloid leukemia (AML). Flow cytometry is a preferred method for MRD detection due to its general applicability and the rapid results that it makes available. In this article, the basic protocol outlines a simple and efficient method for the labeling of hematopoietic cells from bone marrow or peripheral blood with a panel of monoclonal antibodies designed both to highlight patterns of normal maturation and allow identification of neoplastic hematopoietic progenitor populations with a high degree of sensitivity and specificity. The method was developed in a clinical laboratory setting for the diagnosis of myeloid stem cell disorders and neoplasms, and has been extensively validated both technically and clinically for the detection of MRD in AML. © 2020 The Authors.Basic Protocol: Staining and flow cytometry for AML minimal residual disease detectionSupport Protocol: Analysis and interpretation of data for AML minimal residual disease detection
Self‐Assembly, Adaptive Response, and in,out‐Stereoisomerism of Large Orthoformate Cryptands
Authors: Löw Henrik , Mena‐Osteritz Elena , Mullen Kathleen M. , Jäger Christof M. , von Delius Max 
Published: April 2020

AbstractWe report on triethylene glycol‐based orthoformate cryptands, which adapt their bridgehead configurations in response to metal templates and intramolecular hydrogen bonding in a complex manner. In contrast to smaller 1.1.1‐orthoformate cryptands, the inversion from out,out‐2.2.2 to in,in‐2.2.2 occurs spontaneously by thermal homeomorphic isomerization, i. e., without bond breakage. The global thermodynamic minimum of the entire network, which includes an unprecedented third isomer (in,out‐2.2.2), could only be reached under conditions that facilitate dynamic covalent exchange. Both inversion processes were studied in detail, including DFT calculations and MD simulations, which were particularly helpful for explaining differences between equilibrium compositions in solvents chloroform and acetonitrile. Unexpectedly, the system could be driven to the in,out‐2.2.2 state by using a metal template with a size mismatch with respect to the out,out‐2.2.2 cage.