bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of obstructive sleep apnea on cerebral blood flow
Authors: Postrzech-Adamczyk Katarzyna , Nahorecki Artur , Łyszczak Paweł , Skomro Robert , Szuba Andrzej
Published: February 2019

Aim: Obstructive sleep apnea (OSA) is a common disorder with growing incidence. Major risk factors for OSA are obesity, aging, gender and menopause. As life expectancy lengthens and the obesity epidemic is ongoing, we can assume that OSA will affect an increasing part of the population. Pathological consequences of this disease include an increased risk of arterial hypertension, coronary artery disease, arrhythmia, heart failure as well as cerebrovascular diseases, such as stroke, transient ischemic attack and cognitive dysfunction. The cerebrovascular system differs significantly from other vessels in the body. Brain oxygen demands constitute about 20% of the total oxygen consumed by the body.
Conclusions: OSA significantly affects the cerebral blood flow both during sleep and daily activities. This can have serious health consequences and makes the brain more vulnerable to ischemia. In this review we describe the impact of OSA on cerebral circulation during both sleep and wakefulness and we also outline the pathophysiology of these changes.
Results: In patients with other risk factors for cerebral ischemia, early screening and treatment for OSA should be introduced.
Using a PANS Simulation Approach for the Transient Flow Around the Japan Bulk Carrier
Authors: Bensow Rickard Everyd , van den Boogaard Maurits
Published: February 2019

In this study, a partially averaged Navier-Stokes (PANS) modeling approach developed based on the k-ω turbulence model has been applied to the flow around the Japan Bulk Carrier. Three different meshes have been used for a fixed physical resolution for the PANS modeling. The results are encouraging, with small-scale flow dynamics being allowed to develop on reasonably small mesh sizes, but more studies are required before reliable predictive simulations can be performed.

1. Introduction

Steady resistance and wake simulations in ship hydrodynamics are currently being performed with relatively high reliability using the Reynolds averaged Navier-Stokes (RANS) simulation approach. There are, however, a number of cases where RANS is not sufficient and a scale-resolving transient simulation approach is needed. This is well established in cases of flow around bluff bodies, e.g., vortex-induced vibrations and flow across cylinders (Pereira 2018), or for ship to ship interaction (Arslan et al. 2015), where the main interest is on global parameters, such as shedding frequency or force variation, but the transient separating flow is not well predicted by RANS simulation. It could also be that details of the transient flow behavior is part of the study, e.g. relating to propeller dynamics (Jang & Mahesh 2013; Bensow 2015; Guilmineau et al. 2017), vortex dynamics (Fureby et al. 2016; Visonneau et al. 2018), or in cavitation (Bensow 2011); in these cases, RANS modeling is inherently not able to capture the details of the governing flow physics because of the underlying averaging. However, it may also be the case where the flow is smoothly separating, or close to, as is the case for the Japan Bulk Carrier (JBC), see Visonneau et al. (2016) and further the discussion below.

Using a wall-resolved large eddy simulation (LES) approach is computationally very expensive, with an unfavorable scaling toward full-scale Re numbers (Liefvendahl & Fureby 2017), thus the attention has rather turned toward hybrid RANS/LES approaches or wall-modeled LES; this was used in many of the studies referenced previously, e.g., Guilmineau et al. (2017); Pereira (2018); Visonneau et al. (2018). Grid size estimates for different modeling approaches for simulating the JBC in model scale are given by Liefvendahl and Johansson (2018), amounting to around 2•109 for the wall-resolved LES, 150•106 for the wall-modeled LES, 50•106 for the hybrid RANS/LES, and finally 30•106 for the RANS approach, where the distance between wall-resolved LES and the others will greatly increase with the Re number. In terms of computational effort, one needs to remember that the transient flow approaches, compared with RANS, further needs to include long time-series for sampling statistics.
Arabidopsis RCD1 coordinates chloroplast and mitochondrial functions through interaction with ANAC transcription factors
Authors: Shapiguzov Alexey , Vainonen Julia P , Hunter Kerri , Tossavainen Helena , Tiwari Arjun , Järvi Sari , Hellman Maarit , Aarabi Fayezeh , Alseekh Saleh , Wybouw Brecht , Van Der Kelen Katrien , Nikkanen Lauri , Krasensky-Wrzaczek Julia , Sipari Nina , Keinänen Markku , Tyystjärvi Esa , Rintamäki Eevi , De Rybel Bert , Salojärvi Jarkko , Van Breusegem Frank , Fernie Alisdair R , Brosché Mikael , Permi Perttu , Aro Eva-Mari , Wrzaczek Michael , Kangasjärvi Jaakko
Published: February 2019

Reactive oxygen species (ROS)-dependent signaling pathways from chloroplasts and mitochondria merge at the nuclear protein RADICAL-INDUCED CELL DEATH1 (RCD1). RCD1 interacts in vivo and suppresses the activity of the transcription factors ANAC013 and ANAC017, which mediate a ROS-related retrograde signal originating from mitochondrial complex III. Inactivation of RCD1 leads to increased expression of mitochondrial dysfunction stimulon (MDS) genes regulated by ANAC013 and ANAC017. Accumulating MDS gene products, including alternative oxidases (AOXs), affect redox status of the chloroplasts, leading to changes in chloroplast ROS processing and increased protection of photosynthetic apparatus. ROS alter the abundance, thiol redox state and oligomerization of the RCD1 protein in vivo, providing feedback control on its function. RCD1-dependent regulation is linked to chloroplast signaling by 3'-phosphoadenosine 5'-phosphate (PAP). Thus, RCD1 integrates organellar signaling from chloroplasts and mitochondria to establish transcriptional control over the metabolic processes in both organelles.
Screen Time and Physical Activity Pattern of School Children (11-17 Years) from Different Cultural Regions of Punjab, India
Authors: Kaur Sukhdeep , Bains Kiran , Kaur Harpreet
Published: February 2019

Aim: To assess regional disparity in the screen time and physical activity pattern of school children (11-17 years) from Punjab (India).

Study Design: A school-based cross sectional survey.

Place and Duration of Study: Government schools of three regions of Punjab, namely, Majha, Doaba and Malwa region, between June to December 2015.

Methodology: A survey was conducted including 1050 children, randomly selected from government schools of three regions of Punjab, namely, Majha (n=210), Doaba (n=210) and Malwa (n=630), to obtain information on their physical activity pattern (school sports, leisure time physical activity/LTPA and mode of commuting to school) and screen time.

Results: Malwa region children were spending more time (7.2 h/wk) in school sports than Majha (6.3 h/wk) and Doaba region (6.6 h/wk) children. Majha region children were spending more time (6.0 h/wk) in LTPA than Doaba (3.5 h/wk) and Malwa region (5.4 h/wk) children; whereas, Doaba (11.7 h/wk) region children had higher screen time than Majha (8.9 h/wk) and Malwa region (9.2 h/wk) children. Significant (P≤0.01) regional disparity was noted in the mean time spent by school children in LTPA and screen activities; whereas, no regional difference was found in the mean time spent in school sports. The percentage of active commuters was more from Doaba region (96%) as compared to Majha (89%) and Malwa (88%) region. Most (85, 85 and 72%) of the children from Majha, Doaba and Malwa region had low screen time, respectively.

Conclusion: Based on AAP and WHO levels, irrespective of region, school children studied had adequate physical activity level, low screen time and were mostly active commuters.
The Effect of Artemisinin-based Combination Therapy (ACT) Antimalaria Drugs on Liver Enzymes in Pregnancy
Authors: Oyeyemi Ajibade Oluwagbenga , Sonuga Ayobola Abimbola
Published: February 2019

Aims: Artemisinin-based Combination Therapies (ACTs) are employed as first-line agents in malaria chemotherapy. This study is aimed at assessing the effects of ACTs on renal function of pregnant women.

Study Design: Comparative study.

Place and Duration of Study: Pregnant women aged 18 to 50 years were recruited from antenatal clinic of Obstetrics and Gynecology Department of Ekiti State Hospital, Ado Ekiti, Nigeria between 2016 and 2018

Methodology: One hundred and eighty pregnant women were grouped into three which include:  Sixty pregnant women with malaria parasite on ACT drugs (Group A), sixty pregnant women with malaria parasite not on ACT drugs (Group B), sixty pregnant women without malaria parasite (Group C/control). Plasma Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), Alanine Transaminase (ALT) and Lactate Dehydrogenase (LDH) activities were evaluated by standard methods. The data collected were analyzed using one-way analysis of variance (ANOVA) and Student’s t test to compare the data between the test groups and control.

Results: Results showed there was a significant decrease (P=.05) in Body Mass Index in the pregnant women with malaria on ACT and those that were not on ACT when compared with control (24.1± 0.32 versus (25+ 2.30 vs 27± 1.62). A significant increase (P=.05) occurred in the levels of ALP,AST, ALT and LDH  in pregnant women with malaria not on ACT drugs when compared the control (168.45±0.19, 10.0±0.27, 8.19±0.25, 4.5±0.21) versus (143.20±0.12, 8.71±0.30, 5.99±0.21, 2.08±0.19),while no significant difference occurred in the levels of ALP,AST, ALT and LDH in pregnant women with malaria on ACT when compared with control (141.60±0.78, 8.02±0.32, 6.10±0.30, 2.75+ 0.20) vs (143.20±0.12, 8.71±0.30, 5.99±0.21, 2.08±0.19).

Conclusion: Normal therapeutic dose of ACT has no harmful effect on the liver in pregnancy.
Traditional Chinese Medicine Enhances Growth, Immune Response, and Resistance to Streptococcus agalactiae in Nile Tilapia
Authors: Abarike Emmanuel Delwin , Jian Jichang , Tang Jufen , Cai Jia , Yu Huang , Chen Lihua
Published: February 2019

Herbal supplements are suitable for improving fish health and combating diseases in fish culture. However, the mechanism of action of many herbal mixtures remains unclear. This study was conducted to evaluate the effects of traditional Chinese medicine (TCM; a mix of Astragalus membranaceus, Angelica sinensis, and Crataegus hupehensis at a ratio of 1:1:1 on a weight basis) on growth, immune response, and disease resistance in Nile tilapia Oreochromis niloticus. Experimental fish (mean ± SE weight = 57 ± 1 g) were divided into two groups: a control group and a TCM (10 g/kg) group. After 4 weeks of the experimental trial, a significant increase in weight gain and specific growth rate and a lower feed conversion ratio were observed in fish fed a TCM-supplemented diet compared with control fish. Similarly, the immune response of Nile Tilapia in the TCM group showed enhanced lysozyme, superoxide dismutase, catalase, and immunoglobulin levels compared with the control fish. In comparison with the control, fish fed TCM showed significant up-regulation of β-defensin, lysozyme, heat shock protein 70, superoxide dismutase, and catalase genes in the intestine and head-kidney tissues. After a Streptococcus agalactiae challenge, survival of Nile Tilapia in the TCM group was 70% compared with 35% in the control. These results indicate that the TCM mixture in this study can elevate the immune response and disease resistance of Nile Tilapia.
Paving the Path toward Reliable Cathode Materials for Aluminum‐Ion Batteries
Authors: Wu Feng , Yang Haoyi , Bai Ying , Wu Chuan
Published: February 2019

Aluminum metal is a high‐energy‐density carrier with low cost, and thus endows rechargeable aluminum batteries (RABs) with the potential to act as an inexpensive and efficient electrochemical device, so as to supplement the increasing demand for energy storage and conversion. Despite the enticing aspects regarding cost and energy density, the poor reversibility of electrodes has limited the pursuit of RABs for a long time. Fortunately, ionic‐liquid electrolytes enable reversible aluminum plating/stripping at room temperature, and they lay the very foundation of RABs. In order to integrate with the aluminum‐metal anode, the selection of the cathode is pivotal, but is limited at present. The scant option of a reliable cathode can be accounted for by the intrinsic high charge density of Al3+ ions, which results in sluggish diffusion. Hence, reliable cathode materials are a key challenge of burgeoning RABs. Herein, the main focus is on the insertion cathodes for RABs also termed aluminum‐ion batteries, and the recent progress and optimization methods are summarized. Finally, an outlook is presented to navigate the possible future work.
Microstructured Fibers for the Production of Food
Authors: Sordo Federica , Janecek Emma‐Rose , Qu Yunpeng , Michaud Véronique , Stellacci Francesco , Engmann Jan , Wooster Tim J. , Sorin Fabien
Published: February 2019

Food engineering faces the difficult challenge of combining taste, i.e., tailoring texture and rheology of food matrices with the balanced intake of healthy nutrients. In materials science, fiber suspensions and composites have been developed as a versatile and successful approach to tailor rheology while imparting materials with added functionalities. Structures based on such types of physical (micro)fibers are however rare in food production mainly due to a lack of food‐grade materials and processes allowing for the fabrication of fibers with controlled sizes and microstructures. Here, the controlled fabrication of multi‐material microstructured edible fibers is demonstrated using a food compatible process based on preform‐to‐fiber thermal drawing. It is shown that different material systems based on gelatin or casein, with plasticizers such as glycerol, can be thermally drawn into fibers with various geometries and cross‐sectional structures. It is demonstrated that fibers can exhibit tailored mechanical properties post‐drawing, and can encapsulate nutrients to control their release. The versatility of fiber materials is also exploited to demonstrate the fabrication of food‐grade fabrics and scaffolds for food growth. The end results establish a new field in food production that relies on fiber‐based simple and eco‐friendly processes to realize enjoyable yet healthy and nutritious products.
Conformation‐Controlled Molecular Sieving Effects for Membrane‐Based Propylene/Propane Separation
Authors: Liu Yang , Chen Zhijie , Liu Gongping , Belmabkhout Youssef , Adil Karim , Eddaoudi Mohamed , Koros William
Published: February 2019

Membrane‐based separation is poised to reduce the operation cost of propylene/propane separation; however, identifying a suitable molecular sieve for membrane development is still an ongoing challenge. Here, the successful identification and use of a metal–organic framework (MOF) material as fillers, namely, the Zr‐fum‐fcu‐MOF possessing an optimal contracted triangular pore‐aperture driving the efficient diffusive separation of propylene from propane in mixed‐matrix membranes are reported. It is demonstrated that the fabricated hybrid membranes display a high propylene/propane separation performance, far beyond the current trade‐off limit of polymer membranes with excellent properties under industrial conditions. Most importantly, the mechanism behind the exceptional high propylene/propane selectivity is delineated by exploring theoretically the efficiency of sieving of different conformers of propane through the hypothesized triangular rigid pore‐aperture of Zr‐fum‐fcu‐MOF.
Biocatalytic Enantioselective Hydroaminations for Production of N‐Cycloalkyl‐Substituted L‐Aspartic Acids Using Two C−N Lyases
Authors: Zhang Jielin , Fu Haigen , Tepper Pieter G. , Poelarends Gerrit J.
Published: February 2019

N‐cycloalkyl‐substituted amino acids have wide‐ranging applications in pharma‐ and nutraceutical fields. Here we report the asymmetric synthesis of various N‐cycloalkyl‐substituted l‐aspartic acids using ethylenediamine‐N,N′‐disuccinic acid lyase (EDDS lyase) and a previously engineered variant of methylaspartate ammonia lyase (MAL‐Q73A) as biocatalysts. Particularly, EDDS lyase shows broad non‐natural substrate promiscuity and excellent enantioselectivity, allowing the selective addition of homo‐ and heterocycloalkyl amines (comprising four‐, five‐ and six‐membered rings) to fumarate, giving the corresponding N‐cycloalkyl‐substituted l‐aspartic acids with >99% e.e. This biocatalytic methodology offers an alternative synthetic choice to prepare difficult N‐cycloalkyl‐substituted amino acids. Given its very broad amine scope, EDDS lyase is an exceptionally powerful synthetic tool that nicely complements the rapidly expanding toolbox of biocatalysts for asymmetric synthesis of noncanonical amino acids.

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CNOT2 as the critical gene for phenotypes of 12q15 microdeletion syndrome
Authors: Uehara Tomoko , Takenouchi Toshiki , Yamaguchi Yu , Daimon Yumi , Suzuki Hisato , Sakaguchi Yuri , Kosaki Kenjiro
Published: February 2019

Chromosome 12q15 microdeletion syndrome is characterized by intellectual disability and dysmorphic facial features, but the associations between each of the deleted genes and the phenotypes of 12q15 microdeletion syndrome remain unclear. Recently, the smallest region of overlap in 16 previously reported patients was used to define three candidate genes for the 12q15 microdeletion syndrome: CNOT2, KCNMB4, and PTPRB. Among these three candidate genes, CNOT2 maintains the structural integrity of the carbon catabolite repressor 4 (CCR4)‐negative on TATA (NOT) complex, which plays a key role in regulating global gene expression, and is essential for the enzymatic activity of the CCR4‐NOT complex. Disruption of the CCR4‐NOT complex results in dysregulation of global gene expression, and is associated with various human disease processes, including neuronal diseases. Therefore, CNOT2 haploinsufficiency might account for the neurological features of the 12q15 microdeletion syndrome. Herein, we document a 12‐year‐old female patient with mild intellectual disability and multiple structural abnormalities including cleft lip and palate and 2–3 toe syndactyly. She exhibited dysmorphic facial features such as upslanting and short palpebral fissures, micrognathia, low‐set ears, and hypoplastic antihelix. A microarray analysis showed a de novo 1.32‐Mb deletion within 12q15 that included CNOT2 and 14 other genes. Remapping of the 12q15 deletion region in the 16 previously reported patients together with that in the newly identified patient indicated that CNOT2 is the only gene that is commonly deleted. These findings suggest that CNOT2 is the prime candidate for the neurological phenotypes of the 12q15 microdeletion syndrome.
Fibrosis: Shared Lessons From the Lens and Cornea
Authors: Menko A. Sue , Walker Janice L. , Stepp Mary Ann
Published: February 2019

Regenerative repair in response to wounding involves cell proliferation and migration. This is followed by the reestablishment of cell structure and organization and a dynamic process of remodeling and restoration of the injured cells' extracellular matrix microenvironment and the integration of the newly synthesized matrix into the surrounding tissue. Fibrosis in the lungs, liver, and heart can lead to loss of life and in the eye to loss of vision. Learning to control fibrosis and restore normal tissue function after injury repair remains a goal of research in this area. Here we use knowledge gained using the lens and the cornea to provide insight into how fibrosis develops and clues to how it can be controlled. The lens and cornea are less complex than other tissues that develop life‐threatening fibrosis, but they are well characterized and research using them as model systems to study fibrosis is leading toward an improved understanding of fibrosis. Here we summarize the current state of the literature and how it is leading to promising new treatments. Anat Rec, 2019. © 2019 The Authors. The Anatomical Record published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists.
Role of CD147 (EMMPRIN/Basigin) in Tissue Remodeling
Authors: Guindolet Damien , Gabison Eric E.
Published: February 2019

CD147, also known as extracellular matrix metalloproteinase inducer (EMMPRIN) or basigin, is expressed in a variety of cell types. It is involved in the regulation of extracellular matrix (ECM) remodeling during physiological and pathological processes including wound healing, inflammatory diseases, and cancer. CD147 is a diagnostic and therapeutic target in cancer and inflammatory diseases, either directly or indirectly, by targeting CD147 partners. It can trigger matrix metalloproteinase inductions involved in ECM degradation, cell adhesion, and cell–cell interactions. It can also induce myofibroblast differentiation associated with ECM deposition and contraction. The shift from fibrosis to lysis, and vice versa, is poorly understood and could involve CD147. This article provides an overview of the role of CD147 in the regulation of ECM remodeling processes and discusses the involvement of the microenvironment in the modulation of its downstream effects. Understanding CD147 regulation could help identify new therapeutic intervention. Anat Rec, 2019. © 2019 Wiley Periodicals, Inc.
A Maleimide‐functionalized Tetraphenylethene for Measuring and Imaging Unfolded Proteins in Cells
Authors: Zhang Shouxiang , Liu Mengjie , Tan Lewis Yi Fong , Hong Quentin , Pow Ze Liang , Owyong Tze Cin , Ding Siyang , Wong Wallace W. H. , Hong Yuning
Published: February 2019

Collapse of the protein homeostasis (proteostasis) can lead to accumulation and aggregation of unfolded proteins, which has been found to associate with a number of disease conditions including neurodegenerative diseases, diabetes and inflammation. Here we report a maleimide‐functionalized tetraphenylethene (TPE)‐derivatized fluorescent dye, TPE‐NMI, which shows fluorescence turn‐on property upon reacting with unfolded proteins in vitro and in live cells under proteostatic stress conditions. The level of unfolded proteins can be measured by flow cytometry and visualized with confocal microscopy.
Spring soil temperature as a predictor of summer heatwaves over northwestern China
Authors: Yang Zhanmei , Zhang Jingyong , Wu Lingyun
Published: February 2019

Northwestern China has been increasingly affected by summer heatwaves in recent decades. In this study, we show that summer heatwave events over northwestern China are significantly correlated with the spring soil temperature over central Asia for the period of 1979–2017, irrespective of whether the data are detrended. By analyzing the physical links, we find that warmer spring soil temperature over central Asia tends to result in positive geopotential height anomalies over northern China and Mongolia including northwestern China in summer, which may subsequently lead to more heatwave events via the effects on downward solar radiation, subsidence warming and other processes. We further establish a statistical model to predict summer heatwaves over northwestern China based on the spring soil temperature over central Asia. The results show that the leave‐one‐out cross‐validation for the correlation skill is 0.56 for the period of 1979–2017. The spatial patterns are captured well in the hindcast experiments for the period of 2012–2017, with all pattern correlation coefficients ≥0.88. Our proposed prediction model can be applied to practical forecasting and may help to reduce the damage caused by summer heatwaves over northwestern China.
Succinct Syntheses of Methopholine, (±)‐Homolaudanosine, and (±)‐Dysoxyline via Metal‐free One‐Pot Double Alkylation on 1‐Methyl‐3,4‐dihydroisoquinolines
Authors: Achary Raghavendra , Kim Seulgi , Choi Yuri , Mathi Gangadhar Rao , Kim Hyun Jin , Hwang Jong Yeon , Kim Pilho
Published: February 2019

A mild one‐pot and metal‐free condition was discovered to implement two different alkyl groups chemoselectively on 1‐methyl‐3,4‐dihydroisoquinoline (1‐Me‐DHIQ), one at the nitrogen another at the C1‐methyl group. This chemistry is compatible with various DHIQs as well as alkyl halides. Application of this chemistry facilitated the concise syntheses of methopholine, (±)‐homolaudanosine, and (±)‐dysoxyline, requiring only two steps from 6,7‐dimethoxy‐1‐Me‐DHIQ.
Ring Closure Reaction Pathway of a Diarylethene in Solution Using Femtosecond Time‐resolved Fluorescence Spectra
Authors: Seo Kiho , Eom Intae , Shim Sangdeok , Kim Chul Hoon , Joo Taiha
Published: February 2019

Photochromic ring closure reaction dynamics of 1,2‐bis(2‐methylbenzo[b]thiophene‐3‐yl)hexafluoro cyclopentene is investigated by means of time‐resolved fluorescence spectra. Compared with a single wavelength probe, direct measurement of the emission spectra during the reaction provides unambiguous and straightforward picture for the ring closure reaction pathway. We observe two different emission bands in the fluorescence of the open ring isomer. From the global analysis for the spectra, we obtain <1 ps time constant for the ring closure reaction in polar solvent. Moreover, the ring closure reaction of the compound takes place entirely on the ultrafast timescale. The unreactive parallel conformer decays to the ground state by 150 ps time constant.
Toward Second‐Generation Cardiomyogenic and Anti‐cardiofibrotic 1,4‐Dihydropyridine‐Class TGFβ Inhibitors
Authors: Längle Daniel , Werner Tessa R. , Wesseler Fabian , Reckzeh Elena , Schaumann Niklas , Drowley Lauren , Polla Magnus , Plowright Alleyn T. , Hirt Marc N. , Eschenhagen Thomas , Schade Dennis
Published: February 2019

Innovative therapeutic modalities for pharmacological intervention of transforming growth factor β (TGFβ)‐dependent diseases are of great value. b‐Annelated 1,4‐dihydropyridines (DHPs) might be such a class, as they induce TGFβ receptor type II degradation. However, intrinsic drawbacks are associated with this compound class and were systematically addressed in the presented study. It was possible to install polar functionalities and bioisosteric moieties at distinct sites of the molecules while maintaining TGFβ‐inhibitory activities. The introduction of a 2‐amino group or 7‐N‐alkyl modification proved to be successful strategies. Aqueous solubility was improved by up to seven‐fold at pH 7.4 and 200‐fold at pH 3 relative to the parent ethyl 4‐(biphenyl‐4‐yl)‐2,7,7‐trimethyl‐5‐oxo‐1,4,5,6,7,8‐hexahydroquinoline‐3‐carboxylate. The therapeutic potential of the presented DHPs was further underscored in view of a potential dual mode of action: The differentiation of committed human iPSC‐derived cardiac progenitor cells (CPCs) was potently stimulated, and the rescue of cardiac fibrosis phenotypes was observed in engineered heart tissue (EHT) constructs.
Incidence and malignancy rates of indeterminate pediatric thyroid nodules
Authors: Wang Huiying , Mehrad Mitra , Ely Kim A. , Liang Jiancong , Solórzano Carmen C. , Neblett Wallace W. , Coogan Alice C. , Weiss Vivian L.
Published: February 2019

Background

The American Thyroid Association guidelines task force currently recommends definitive thyroidectomy or lobectomy after an indeterminate thyroid biopsy in children. This recommendation is based on evidence of a greater incidence and a higher risk of malignancy compared with adults in earlier pediatric studies. Such management may lead to overtreatment and unnecessary surgery for many children in the United States.

Methods

The objective of the current study was to re‐evaluate pediatric thyroid nodules and assess the overall percentages and malignancy rates for indeterminate thyroid biopsies in children. In total, 302 pediatric thyroid fine‐needle aspirations (FNAs) were analyzed retrospectively (2001‐2018). Distribution percentages and malignancy rates were calculated for each category of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC).

Results

Two indeterminate TBSRTC groups (atypia of undetermined significance/follicular lesion of undetermined significance and follicular neoplasm/suspicious for a follicular neoplasm) had much lower distribution percentages and malignancy rates compared with earlier pediatric series and American Thyroid Association guidelines. A meta‐analysis further supported these findings and demonstrated distinctly different malignancy rates for the indeterminate groups (atypia of undetermined significance/follicular lesion of undetermined significance, follicular neoplasm/suspicious for a follicular neoplasm, and suspicious for malignancy), suggesting the need for TBSRTC category‐specific management recommendations rather than a nondiscriminatory, up‐front surgical approach.

Conclusions

Adult patients with indeterminate preoperative thyroid cytopathology are followed by repeat biopsy and possibly molecular testing before undergoing definitive surgery. However, in children, the guidelines are considerably more aggressive and recommend definitive surgery after the first indeterminate thyroid biopsy. Here, the largest pediatric cohort to date with meta‐analysis is presented, and the authors propose a re‐evaluation of this up‐front approach to pediatric thyroid care.
The Relative Bioavailability and Effects of Food and Acid‐Reducing Agents on Filgotinib Tablets in Healthy Subjects
Authors: Anderson Kacey , Zheng Hao , Kotecha Mona , Cuvin Jennifer , Scott Bob , Sharma Shringi , Qin Ann Ran‐Ran , Namour Florence , Xin Yan
Published: February 2019

Filgotinib is a potent, selective Janus kinase‐1 inhibitor being developed to treat chronic inflammatory diseases. This phase 1 study in healthy subjects evaluated the relative bioavailability of filgotinib maleate tablets versus the reference tablet (filgotinib hydrochloride) and effects of food and acid‐reducing agents (ARAs) on the pharmacokinetics of filgotinib and its major metabolite. Noncompartmental pharmacokinetic parameters of filgotinib and its major metabolite were compared between the 2 tablets at 100‐ and 200‐mg doses and with or without food or ARAs. Filgotinib maleate tablets resulted in equivalent plasma exposures (area under concentration‐time curve to infinity [AUC∞] and maximum concentration [Cmax]) of filgotinib and its metabolite as the reference tablet (90%CIs of geometric least‐squares mean ratios were within the prespecified no‐effect boundary of 70% to 143%). Food intake had no effect on filgotinib AUC∞, but a high‐fat meal reduced Cmax by 20%. Coadministration of filgotinib with omeprazole or famotidine had no effect on filgotinib AUC∞, but omeprazole decreased Cmax by 27%. Neither food nor ARAs affected metabolite exposure. Single‐dose filgotinib 100 or 200 mg was well tolerated. This study supports evaluation of filgotinib maleate tablets, administered without regard to food or ARAs, in future clinical studies.
Effects of Cationic Polyacrylamide on Hydrothermal Formation of Ultralong α‐CaSO4·0.5H2O Whiskers
Authors: Wang Jing , Fan Saiying , Hou Sichao , Chen Ruosong , Xiang Lan , Yang Cheng
Published: February 2019

Herein, ultralong α‐CaSO4·0.5H2O whiskers with an average length above 500 µm and aspect ratios of 200–500 are hydrothermally produced employing trace amount (0.06 mg L−1) of cationic polyacrylamide (CPAM) as the morphology modifier. The hydrothermal formation mechanisms of α‐CaSO4·0.5H2O involving the initial nucleation of bassanite nanocrystals/nanorods and their subsequent self‐assembly into long whiskers through oriented attachment are revealed for the first time. Experimental results indicate that CPAM is electrostatically adsorbed onto the initial bassanite nanorods and results in their near‐neutral surfaces, favoring the assembly of the initial nanorods into larger aggregates, thus finally leading to the formation of ultralong α‐CaSO4·0.5H2O whiskers with high aspect ratios. Moreover, α‐CaSO4·0.5H2O whiskers are calcined to CaSO4 whiskers for the fabrication of polyvinyl chloride (PVC)/CaSO4 composites with a high impact strength and flexural strength of 42.0 KJ m−2 and 53.6 MPa, respectively, indicating that the mechanical properties of the PVC/CaSO4 composites could be significantly improved by these ultralong CaSO4 whiskers.
Two‐year‐supervised resistance training prevented diabetes incidence in people with prediabetes: A randomised control trial
Authors: Dai Xia , Zhai Lu , Chen Qingyun , Miller Joshua D. , Lu Lirong , Hsue Cunyi , Liu Lin , Yuan Xiaodan , Wei Wei , Ma Xiaojun , Fang Zhaohui , Zhao Wenpiao , Liu Yuhua , Huang Feng , Lou Qingqing
Published: February 2019

Aim

The purpose of this study is to explore the long‐term effects of aerobic training (AT), resistance training (RT), and combined training (AT + RT) on the prevention of T2D incidence in patients with prediabetes.

Materials and methods

In this randomised controlled trial, people with prediabetes (fasting glucose ≥5.6 and <7.0 mmol/L and/or 2‐h glucose ≥7.8 and <11.1 mmol/L on the 75‐g oral glucose tolerance test and/or haemoglobin A1c ≥5.7% and <6.4%) were randomly assigned to the control group, AT group, RT group, or AT + RT group. Supervised exercise programmes, including AT, RT, and AT + RT, were completed for 60 minutes per day, three non‐consecutive days per week for 24 months. The primary outcome was the incidence of T2D; secondary outcomes were blood glucose and lipid levels, including total cholesterol (TC) and standard 2‐hour oral glucose tolerance (2hPG).

Results

A total of 137 (80%) subjects with a mean age of 59 years (45 men, 92 women) entered the final analysis. After 24 months of intervention, the incidences of T2D adjusted by sex and age were significantly decreased by 74% (95% CI, 38‐89), 65% (95% CI, 21‐85), and 72% (95% CI, 36‐87) in the AT + RT, RT, and AT groups compared with the control group (HR: AT + RT 0.26 [95% CI, 0.11‐0.62], RT 0.35 [95% CI, 0.15‐0.79], and AT 0.28 [95% CI, 0.13‐0.64]). The cumulative T2D incidences were significantly lower in the AT + RT, RT, and AT groups than in the control group (21%, 26%, and 22% vs 69%). The blood glucose and lipid profiles improved more in the AT, RT, and AT + RT groups than in the control group.

Conclusion

RT and RT plus AT were as effective as isolated AT in preventing progression to T2D.
Linking warming effects on phenology, demography, and range expansion in a migratory bird population
Authors: Alves José A. , Gunnarsson Tómas G. , Sutherland William J. , Potts Peter M. , Gill Jennifer A.
Published: February 2019

Phenological changes in response to climate change have been recorded in many taxa, but the population‐level consequences of these changes are largely unknown. If phenological change influences demography, it may underpin the changes in range size and distribution that have been associated with climate change in many species. Over the last century, Icelandic black‐tailed godwits (Limosa limosa islandica) have increased 10‐fold in numbers, and their breeding range has expanded throughout lowland Iceland, but the environmental and demographic drivers of this expansion remain unknown. Here, we explore the potential for climate‐driven shifts in phenology to influence demography and range expansion. In warmer springs, Icelandic black‐tailed godwits lay their clutches earlier, resulting in advances in hatching dates in those years. Early hatching is beneficial as population‐wide tracking of marked individuals shows that chick recruitment to the adult population is greater for early hatched individuals. Throughout the last century, this population has expanded into progressively colder breeding areas in which hatch dates are later, but temperatures have increased throughout Iceland since the 1960s. Using these established relationships between temperature, hatching dates and recruitment, we show that these warming trends have the potential to have fueled substantial increases in recruitment throughout Iceland, and thus to have contributed to local population growth and expansion across the breeding range. The demographic consequences of temperature‐mediated phenological changes, such as the advances in lay dates and increased recruitment associated with early hatching reported here, may therefore be key processes in driving population size and range changes in response to climate change.
Age‐specific distributed lag models for heat ‐ related mortality
Authors: Heaton M. J. , Olenick C. R. , Wilhelmi O.
Published: February 2019

Distributed lag (DL) models have been consistently used throughout the years to assess the cumulative impact of multiple days of high heat on public health. DL models, however, are often used on an aggregate level (e.g., city or census tracts) in spite of the fact that the effect of heat on health is individual specific, leading to possible ecological fallacies. To capture more individualized effects of heat on health, we propose a negative binomial regression model where the effect of lagged temperatures is age specific. Utilizing principles of predictive process models, we place appropriate smoothness and decay constraints on the associated DL surfaces. Furthermore, we borrow strength across ages to facilitate the estimation of the age‐specific DL function. Using death certificate data from the Texas Department of State Health Services, we show how different ages are impacted by consecutive days of high heat.
Experimental investigation on smoke spread characteristics and smoke layer height in tunnels
Authors: Xu Zhisheng , Zhao Jiaming , Liu Qiulin , Chen Hongguang , Liu Yaohui , Geng Zhongyang , He Lu
Published: February 2019

A series of experiments were carried out in a model‐scale tunnel with dimension of 6.0 m × 1.0 m × 0.7 m to investigate the smoke spread behaviors and the typical smoke layer height. Alcohol was employed as fuel, and the heat release rate was set to be 9.5, 18.4, 30.1, and 63.5 kW, respectively. The temperature profile in the tunnel was measured, and the buoyant flow stratification conditions were visualized by a laser sheet. The experiment results show that the N percentage rule would greatly influence by subjective factors. As the N (10, 20, 30) value increases, the smoke layer height also increases. The results calculated by the buoyancy frequency method were more accurate. Fan's prediction method (Fan WC, Wang QG, Jiang FH. Concise Guide of Fire Science. He Fei: University of Science and Technology of China Press; 1995.161 p.) does not accurately evaluate the smoke layer thickness in tunnel fire. An enhanced empirical formula for predicting the smoke layer thickness in the one‐dimensional horizontal spread stage was proposed. It is shown that the empirical formula could well predict the smoke layer thickness by comparing with the experimental data of previous studies.
Residual response of fire‐damaged high‐strength concrete beams
Authors: Agrawal Ankit , Kodur Venkatesh
Published: February 2019

This paper presents results from an experimental study on residual capacity of fire‐damaged high‐strength concrete (HSC) beams. Four reinforced concrete (RC) beams, fabricated with HSC, were first subject to structural loading and fire exposure with a distinct cooling phase and then loaded to failure upon cooldown to ambient conditions to evaluate residual capacity. Temperatures, deflections, and spalling in the beams were monitored during heating and cooling phases of fire exposure. Further, residual capacity, strains at critical section, and crack patterns (failure mode) of fire‐damaged beams were recorded during residual capacity tests. Results from experiments indicate that the load level during fire exposure, duration of heating phase, rate of cooling, extent (type) of spalling, and duration of postcooling storage influence residual deformations and also residual capacity of RC beams. Further, fire‐damaged HSC beams can recover 40% to 70% of their flexural capacity with respect to their room temperature design capacity provided they survive the entire duration of fire exposure.
Genesis and mineralization age of the quartz‐vein‐type scheelite deposits in Eastern Yanbian, Northeast China: Constraints on the regional tectonic setting
Authors: Chen Cong , Ren Yun‐sheng , Wu Tao‐tao , Yang Qun , Shang Qing‐qing
Published: February 2019

The Eastern Yanbian area, Northeast China is tectonically located in the easternmost margin of the Xing'an Mongolian Orogenic Belt, which is a key area for providing important evidence of mineral deposits to constrain the tectonic evolution of the Paleo‐Asian Ocean. Five quartz‐vein‐type scheelite deposits have been identified in the eastern Yanbian area. These deposits are hosted within the late Palaeozoic metamorphic and granitic rocks and form under the identical hydrothermal mineralization. Zircon U–Pb ages and whole‐rock geochemistry of the ore‐hosting biotite granite and Sm–Nd ages of scheelite crystals within quartz veins are presented in this paper. Zircon U–Pb dating of the biotite granite yields a weighted mean age of 251.9 ± 2.2 Ma (mean standard weighted deviation (MSWD) = 4), and Sm–Nd dating of scheelite samples yields an isochron age of 251.7 ± 2.9 Ma (MSWD = 0.87), which constrains the scheelite mineralization in Eastern Yanbian to the late Permian. Our results, integrated with published geochronological data, indicate three periods of Phanerozoic W mineralization in Northeast China, (a) Cambrian, (b) late Permian (this work), and (c) Jurassic. Geochemical data reveal that the biotite granite is a calc‐alkaline I‐type granite, and it exhibits enrichment in large‐ion lithophile and light rare earth elements and depletion in high‐field‐strength and heavy rare earth elements (especially in Nb and Ta), consistent with the characteristics of arc magma. The subduction‐related biotite granite intrusion and quartz‐vein‐type scheelite mineralization together indicate that the Paleo‐Asian Ocean had not closed before the late Permian in the Eastern Yanbian area, and its final closure occurred in the Early‐Middle Triassic. The late Permian subduction of the Paleo‐Asian Ocean induced the partial melting of the lower crust, thus forming the magmatic arc activity and related quartz‐vein‐type scheelite mineralization, which clearly justifies the proposed tectonic–metallogenic model.
Evaluation of dalbavancin on length of stay in acute bacterial skin and skin structure infections
Authors: Jones Bruce M. , Hersey Roby , Taylor Colleen , Bland Christopher M.
Published: February 2019

Purpose

Acute bacterial skin and skin structure infections (ABSSSI) are common reasons for hospital admission. A pathway to shift care to the outpatient setting sooner could decrease length of stay (LOS). Our not‐for‐profit community health system has developed a novel practice of partnering with hospitalists as part of a multidisciplinary early discharge of hospitalized patients with dalbavancin for ABSSSI. The primary purpose of this study was to evaluate outcomes associated with this process.

Methods

This was a retrospective evaluation of an ongoing, prospective process between March 2016 and March 2017. The process involves the hospitalist or infectious diseases pharmacist evaluating patients as possible candidates for dalbavancin therapy. Patients were included if their infection was consistent with cellulitis, abscess, or post‐operative wound infection and they received dalbavancin immediately after discharge from the hospital. The primary outcome was hospital LOS with secondary outcomes of direct cost per case and 30‐day readmission rate. Hospital LOS and 30‐day readmission rate were benchmarked to national averages and internal data from the same time frame the year prior.

Results

Forty four patients were identified who had received dalbavancin during the time period and met criteria for study inclusion. For the primary outcome of hospital LOS, patients discharged to receive dalbavancin had a mean LOS of 4.3 days similar to published national average (4.95 days in 2011) and lower than internal data (8 days). For secondary outcomes, mean total direct cost per case was $2989 and five patients (11.4%) were readmitted within 30 days similar to published national (16%) and internal data (8.6%).

Conclusion

Patients discharged to receive dalbavancin had a LOS and overall 30‐day readmission rate below published national data for ABSSSI. Further study is needed to evaluate this process as an effective means to shorten LOS in the management of ABSSSI.
Recent Advances in the Schiff Bases and N‐Heterocyclic Carbenes as Ligands in the Cross‐Coupling Reactions: A Comprehensive Review
Authors: Kumar Sumit
Published: February 2019

Cross‐coupling reactions, namely, the Suzuki–Miyaura, Heck, Sonogashira, Hiyama, Negishi, Kumada, and Hartwig–Buchwald, are the most powerful approaches in the formation of C–C, C–N, C–O, and C–S bonds for the complex organic scaffolds in drugs, natural products, organic materials, and fine chemicals. The nitrogen‐based ligands have upper hands in these reactions because they are air stable, inexpensive, and easier to handle than the phosphorous counterparts. In this perspective, Schiff bases and N‐heterocyclic carbenes have been explored extensively in terms of novel design and preparation as ligands in the coupling reactions. Facile recovery and reusability of these ligands make them eco‐friendly and economical. A comprehensive outline on the progress in Schiff bases–metal complexes and NHC–metal complexes that mediated cross‐coupling reactions with recent examples highlighted is reported (160 references).
Ultrastructure of the scolex of Orygmatobothrium schmittii (Cestoda: Phyllobothriidea)
Authors: Mutti Leonardo Damian , Ivanov Verónica A.
Published: February 2019

The ultrastructure of the scolex of Orygmatobothrium schmittii (Cestoda: Phyllobothriidae) was studied using histochemistry, scanning, and transmission electron microscopy. The central bothridial structure resulted in a glandulomuscular organ formed by a mass of syncytial glands and radial muscles, with glycoprotein secretions potentially adhesive. Among the sensory receptors found on the scolex, a particular type was found surrounding the glandulomuscular organ, which might be related in the regulation of the secretions. The internal structure of the microtriches revealed a diversity of configurations according to their morphotype and distribution on the scolex. Microtriches with larger caps are thought to be useful for attachment purposes. In addition, the thick bounding membranes of the attachment organs and the circular musculature in the bothridia, seem to aid to the attachment of the scolex to the mucosa of the host.
Bracketing of premature beats arising from the left bundle branch
Authors: Park Jeong‐Wook , Ha Yeong‐Woong , Kim Sung‐Hwan , Oh Yong‐Seog
Published: February 2019

Fascicular premature ventricular contractions (PVCs) can arise from anywhere in the His Purkinje system, but PVCs originating from the left bundle branch (LBB) are rarely reported. We report the case of PVC arising from the LBB, and also describe the electrophysiological features that might indicate the bracketing of the fascicular PVC focus.