bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular Motions and Interactions in Aqueous Solutions of Thymosin‐β4, Stabilin CTD and Their 1 : 1 Complex, Studied by 1H‐NMR Spectroscopy
Authors: Bokor M. , Tantos Á. , Mészáros A. , Jenei B. , Haminda R. , Tompa P. , Tompa K.
Published: May 2020

Wide‐line 1H NMR measurements were extended and all results were interpreted in a thermodynamics‐based new approach on aqueous solutions of thymosin‐β4 (Tβ4), stabilin cytoplasmic domain (CTD), and their 1 : 1 complex. Energy distributions of potential barriers controlling the motion of protein‐bound water molecules were determined. Heterogeneous and homogeneous regions were found in the protein‐water interface. The measure of heterogeneity of this interface gives quantitative value for the portion of disordered parts in the protein. Ordered structural elements were found extending up to ∼20 % of the individual whole proteins. About 40 % of the binding sites of free Tβ4 get involved in bonds holding the complex together. The complex has the most heterogeneous solvent accessible surface (SAS) in terms of protein‐water interactions. The complex is more disordered than Tβ4 or stabilin CTD. The greater SAS area of the complex is interpreted as a clear sign of its open structure.
Introducing an Expanded Trinucleotide Repeat Tract into the Human Genome for Huntington's Disease Modeling In Vitro
Authors: Malankhanova Tuyana , Sorokin Michael , Medvedev Sergey , Zakian Suren , Malakhova Anastasia
Published: May 2020

In neurodegeneration studies, researchers are faced with problems such as limited material availability and late disease manifestation. Cell models provide the opportunity to investigate molecular mechanisms of pathogenesis. Moreover, genome editing technologies enable generation of isogenic cell models of hereditary diseases. Our protocol outlines an approach for introducing an expanded CAG repeat tract into the first exon of the HTT gene, the Huntington's disease causing mutation. The protocol allows modeling the disease at various severity levels by introducing different numbers of CAG repeats. Furthermore, the protocol can be applicable for modeling other diseases caused by trinucleotide repeat expansion. It is important to note there are many difficulties with cloning repeated sequences and amplification of GC‐rich regions. Here, we also propose troubleshooting options, which overcome these problems. The protocol is based on CRISPR/Cas9‐mediated homologous recombination with a uniquely designed donor plasmid harboring an expanded CAG tract flanked with long homology arms. © 2020 Wiley Periodicals LLC.

Basic Protocol 1: Design and assembling donor and CRISPR/Cas9‐expressing plasmids

Basic Protocol 2: Transfection of cells with plasmids and sorting GFP‐positive cells

Basic Protocol 3: PCR screening single‐cell clones and validation of the mutant HTT expression
Selective Synthesis of Symmetrical Secondary Amines from Nitriles with a Pt−CuFe/Fe3O4 Catalyst and Ammonia Borane as Hydrogen Donor
Authors: Guo Rongxiu , He GuangQi , Liu Lei , Ai Yongjian , Hu Ze‐nan , Zhang Xinyue , Tian Haimeng , Sun Hong‐bin , Niu Dun , Liang Qionglin
Published: May 2020

Hydrogenation of nitriles is an efficient and environmentally friendly route to synthesize symmetrical secondary amines, but it usually produces a mixture of amines, imines, and hydrogenolysis by‐products. Herein we report a magnetic quaternary‐component Pt−CuFe/Fe3O4 nanocatalyst system for the selective synthesis of symmetrical secondary amines with ammonia borane as hydrogen donor. The catalyst with a low Pt loading (0.456 wt%) is the source of the activity, and the d‐band electron transfer from Cu to Fe enhances the selectivity. This synergistic effect results in the transformation of benzonitrile to dibenzylamine with excellent conversion (up to 99 %) and nearly quantitative selectivity (up to 96 %) under mild reaction conditions, nevertheless, the reaction TOF is as high as up to 1409.9 h−1. A variety of nitriles are suitable for the synthesis of symmetrical secondary amines. More importantly, unwanted hydrogenolysis byproducts, especially toluene, is not detected at all. In addition, the catalyst is magnetically recoverable, and it can be reused up to five times.
LED‐NMR Monitoring of an Enantioselective Catalytic [2+2] Photocycloaddition
Authors: Skubi Kazimer L. , Swords Wesley B. , Hofstetter Heike , Yoon Tehshik P.
Published: May 2020

We report that an NMR spectrometer equipped with a high‐power LED light source can be used to study a fast enantioselective photocatalytic [2+2] cycloaddition. While traditional ex situ applications of NMR provide considerable information on reaction mechanisms, they are often ineffective for observing fast reactions. Recently, motivated by renewed interest in organic photochemistry, several approaches have been reported for in situ monitoring of photochemical reactions. These previously disclosed methods, however, have rarely been applied to rapid (<5 min) photochemical reactions. Furthermore, these approaches have not previously been used to interrogate the mechanisms of photocatalytic energy‐transfer reactions. In the present work, we describe our experimental setup and demonstrate its utility by determining a phenomenological rate law for a model photocatalytic energy‐transfer cycloaddition reaction.
Oxygen‐Defect‐Rich Cobalt Ferrite Nanoparticles for Practical Water Electrolysis with High Activity and Durability
Authors: Debnath Bharati , Parvin Sahanaz , Dixit Harsha , Bhattacharyya Sayan
Published: May 2020

The scope of any metal oxide as a catalyst for driving electrocatalytic reactions depends on its electronic structure, which is correlated to its oxygen‐defect density. Likewise, to transform a spinel oxide, such as cobalt ferrite (CoFe2O4), into a worthy universal‐pH, bifunctional electrocatalyst for the hydrogen and oxygen evolution reactions (HER and OER, respectively), oxygen defects need to be regulated. Prepared by coprecipitation and inert calcination at 650 °C, CoFe2O4 nanoparticles (NPs) require 253 and 300 mV OER overpotentials to reach current densities of 10 and 100 mA cm−2, respectively, if nickel foam is used as a substrate. With cost‐effective carbon fiber paper, the OER overpotential increases to 372 mV at 10 mA cm−2 at pH 14. The NPs prepared at 550 °C require HER overpotentials of 218, 245, and 314 mV at −10 mA cm−2 in alkaline, acidic, and neutral pH, respectively. The intrinsic activity is reflected from turnover frequencies of >3 O2 s−1 and >5 H2 s−1 at overpotentials of 398 and 259 mV, respectively. If coupled for overall water splitting, the extremely durable two‐electrode electrolyzer requires a cell potential of only 1.63 V to reach 10 mA cm−2 at pH 14. The homologous couple also splits seawater at impressively low cell voltages of 1.72 and 1.47 V at room temperature and 80 °C, respectively.
Nontargeted Analysis Strategy for the Identification of Phenolic Compounds in Complex Technical Lignin Samples
Authors: Prothmann Jens , Li Kena , Hulteberg Christian , Spégel Peter , Sandahl Margareta , Turner Charlotta
Published: May 2020

Lignin is the second most abundant biopolymer in nature and a promising renewable resource for aromatic chemicals. For the understanding of different lignin isolation and conversion processes, the identification of phenolic compounds is of importance. However, given the vast number of possible chemical transformations, the prediction of produced phenolic structures is challenging and a nontargeted analysis method is therefore needed. In this study, a nontargeted analysis method has been developed for the identification of phenolic compounds by using an ultrahigh‐performance supercritical fluid chromatography–high‐resolution multiple stage tandem mass spectrometry method, combined with a Kendrick mass defect‐based classification model. The method is applied to a Lignoboost Kraft lignin (LKL), a sodium lignosulfonate lignin (SLS), and a depolymerized Kraft lignin (DKL) sample. In total, 260 tentative phenolic compounds are identified in the LKL sample, 50 in the SLS sample, and 77 in the DKL sample.
Adult‐onset type 1 diabetic patients with less severe clinical manifestation have less risk DR‐DQ genotypes than childhood‐onset patients
Authors: Ren Wenqian , Yang Daizhi , Jiang Ziyu , Xian Yingxin , Huang Qianwen , Luo Sihui , Zheng Xueying , Yan Jinhua , Xu Wen , Yao Bin , Wang Cong‐Yi , Bei Jin‐Xin , Groop Leif , Noble Janelle A , Weng Jianping
Published: May 2020

Background

The aim of this study was to investigate differences in clinical features and HLA genotypes between adult‐onset and childhood‐onset patients with type 1 diabetes in a Chinese population.

Materials and Methods

This study enrolled 716 Han Chinese patients with type 1 diabetes from Guangdong (258 childhood‐onset and 458 adult‐onset) to compare their clinical features. Of them 214 patients with classical type 1 diabetes (100 childhood‐onset and 114 adult‐onset) were selected for HLA DR and DQ genotyping by next‐generation sequencing.

Results

Adult‐onset patients were characterized by longer duration of symptoms before diagnosis, lower frequency of DKA at disease onset, less frequent autoantibody positivity, higher serum C‐peptide concentrations, and better glycemic control. These findings were replicated in the restricted cohort of 214 patients with classical type 1 diabetes. Compared with childhood‐onset patients, adult‐onset patients had a lower frequency of the DR9 haplotype, as well as lower frequency of high‐risk DR3/DR4 and DR3/DR9 genotypes, but higher frequency of DR3/DR3 genotype and DR3/X, DR4/X or DR9/X (X, non‐risk) genotypes.

Conclusions

Adult‐onset type 1 diabetic patients with susceptible haplotypes (DR3, DR4 or DR9) were more likely to carry protective DR‐DQ haplotypes than childhood‐onset patients, which suggested the association between less risk DR‐DQ genotypes and the less severe clinical manifestation in adult‐onset patients.
Development and characterization of an Otp conditional loss of function allele
Authors: Hu Yu , Li Jiamin , Zhu Yuyuan , Li Mengqi , Lin Jianbang , Yang Lixin , Wang Chuan , Lu Zhonghua
Published: May 2020

Orthopedia (Otp) is a homeodomain transcription factor that plays an essential role in the development of hypothalamic neurosecretory systems. Loss of Otp results in the failure of differentiation of key hypothalamic neuroendocrine cell types, and pups die soon after birth. Although the constitutive knockout Otp mouse model (Otp
KO) has significantly expanded our understanding of Otp's function in vivo, a conditional loss of function Otp allele that enables tissue or cell‐type specific ablation of Otp has not been developed. Here, we used CRISPR/Cas9 gene‐editing technology to generate a conditional Otp knockout mouse line in which exon 2 of the murine Otp gene is flanked by LoxP sites (Otp
f/f). Crossing the Otp
f/f mouse with Agrp‐Ires‐cre mouse, we demonstrate the requirement for Otp in the continuous differentiation of AgRP neurons after cell fate determination. We also show that the residual AgRP neurons in Agrp‐Ires‐cre;Otp
f/f mice project to similar downstream target regions. This newly developed Otp
f/f mouse can be used to explore the functions of Otp with cell‐type or temporal specificity.
Genetic factors for short life span associated with evolution of the loss of flight ability
Authors: Ikemoto Atsushi , Sato Daiki X. , Makino Takashi , Kawata Masakado
Published: May 2020

Acquisition or loss of flying ability is evolutionarily linked with maximum life span (MLS) in mammals and birds. Although ecological factors, such as extrinsic mortality, may lead to either shortened or extended life spans through natural selection, MLS is influenced by complex molecular and metabolic processes, and the genetic changes associated with flying ability that have led to either a longer or shorter MLS are unknown. Here, we examine the parallel evolution of flight in mammals and birds and investigate positively selected genes at branches where either the acquisition (in little brown bats and large flying foxes) or loss (in Adélie penguins, emperor penguins, common ostriches, emus, great spotted kiwis, little spotted kiwis, okarito brown kiwis, greater rheas, lesser rheas, and cassowaries) of flight abilities occurred. Although we found no shared genes under selection among all the branches of interest, 7 genes were found to be positively selected in 2 of the branches. Among the 7 genes, only IGF2BP2 is known to affect both life span and energy expenditure. The positively selected mutations detected in IGF2BP2 likely affected the functionality of the encoded protein. IGF2BP2, which has been reported to simultaneously prolong life span and increase energy expenditure, could be responsible for the evolution of shortened MLS associated with the loss of flying ability.
An isotopic approach to partition evapotranspiration in a mixed deciduous forest
Authors: Aron Phoebe G. , Poulsen Christopher J. , Fiorella Richard P. , Matheny Ashley M. , Veverica Timothy J.
Published: May 2020

Transpiration (T) is perhaps the largest fluxes of water from the land surface to the atmosphere and is susceptible to changes in climate, land use and vegetation structure. However, predictions of future transpiration fluxes vary widely and are poorly constrained. Stable water isotopes can help expand our understanding of land–atmosphere water fluxes but are limited by a lack of observations and a poor understanding of how the isotopic composition of transpired vapour (δT) varies. Here, we present isotopic data of water vapour, terrestrial water and plant water from a deciduous forest to understand how vegetation affects water budgets and land–atmosphere water fluxes. We measured subdiurnal variations of δ18OT from three tree species and used water isotopes to partition T from evapotranspiration (ET) to quantify the role of vegetation in the local water cycle. We find that δ18OT deviated from isotopic steady‐state during the day but find no species‐specific patterns. The ratio of T to ET varied from 53% to 61% and was generally invariant during the day, indicating that diurnal evaporation and transpiration fluxes respond to similar atmospheric and micrometeorological conditions at this site. Finally, we compared the isotope‐inferred ratio of T to ET with results from another ET partitioning approach that uses eddy covariance and sap flux data. We find broad midday agreement between these two partitioning techniques, in particular, the absence of a diurnal cycle, which should encourage future ecohydrological isotope studies. Isotope‐inferred estimates of transpiration can inform land surface models and improve our understanding of land–atmosphere water fluxes.
Depression and heart failure: the lonely comorbidity
Authors: Sbolli Marco , Fiuzat Mona , Cani Dario , O'Connor Christopher M.
Published: May 2020

Depression is a frequent and debilitating comorbidity that affects heart failure (HF) patients. Up to 30% of HF patients suffer from depression and even more have depressive symptoms. Moreover, depression carries a risk for HF, especially in high‐risk groups, and is significantly associated with worse quality of life and clinical outcomes. The pathophysiology of depression and HF is poorly understood, but both diseases share several mechanisms and risk factors, including dysregulation of platelet reactivity, inflammation, neuroendocrine function, arrhythmias, high‐risk behaviours, and social factors. Current HF guidelines advise to screen HF patients for depression and several screening questionnaires are available. Ultimately, the diagnosis of depression is based on DSM‐5 criteria. Depression treatment consists of non‐pharmacological and pharmacological therapies. Non‐pharmacological therapies, such as exercise training and cognitive‐behavioural therapy, have been shown to have beneficial effects on depressive symptoms. Selective serotonin reuptake inhibitors, the mainstay of antidepressant therapy, appear to be safe in HF but have not shown superiority over placebo in HF in short‐ and long‐term randomized clinical trials. New therapies to treat depression are under investigation and may offer the opportunity to improve depression management in HF, including N‐methyl‐D‐aspartate receptor antagonists, repetitive transcranial magnetic stimulation and omega‐3 supplementation. New technologies may offer several advantages for the screening and diagnosis of depression but they remain to be tested in future research. In this review, we examine the intersection of depression and HF, summarize the epidemiology and pathophysiology, and discuss new opportunities to diagnose and treat HF patients with depression.
Immunotherapy of CT26 murine tumors is characterized by an oligoclonal response of tissue‐resident memory T cells against the AH1 rejection antigen
Authors: Stringhini Marco , Probst Philipp , Neri Dario
Published: May 2020

Mice bearing CT26 tumors can be cured by administration of L19‐mIL12 or F8‐mTNF, two antibody fusion proteins which selectively deliver their cytokine payload to the tumor. In both settings, cancer cures crucially depended on CD8+ T cells and the AH1 peptide (derived from the gp70 protein of the murine leukemia virus) acted as the main tumor‐rejection antigen, with ∼50% of CD8+ T cells in the neoplastic mass being AH1‐specific after therapy. In order to characterize the clonality of the T cell response, its phenotype, and activation status, we isolated CD8+ T cells from tumors and secondary lymphoid organs and submitted them to T cell receptor (TCR) and total mRNA sequencing. We found an extremely diverse repertoire of more than 40 000 unique TCR sequences, but the ten most abundant TCRs accounted for >60% of CD8+ T‐cell clones in the tumor. AH1‐specific TCRs were consistently found among the most abundant sequences. AH1‐specific T cells in the tumor had a tissue‐resident memory phenotype. Treatment with L19‐mIL12 led to overexpression of IL‐12 receptor and of markers of cell activation and proliferation. These data suggest that the antitumor response driven by antibody‐cytokine fusions proceeds through an oligoclonal expansion and activation of tumor‐infiltrating CD8+ T cells.
CO2 Capture by 2‐(Methylamino)pyridine Ligated Aluminum Alkyl Complexes
Authors: Yokley Timothy W. , Tupkar Hrishikesh , Schley Nathan D. , DeYonker Nathan J. , Brewster Timothy P.
Published: May 2020

A set of novel, easily synthesized aluminum complexes, Al[κ2‐N,N‐2‐(methylamino)pyridine]2R (R = Et, iBu) are reported. When subjected to 1 atm of CO2 pressure, each hemilabile pyridine arm dissociates and facilitates cooperative activation of the CO2 substrate reminiscent of a Frustrated Lewis Pair. This reaction has limited precedent for Al/N based Lewis Pair systems, and this is the first system readily shown to sequester multiple equivalents of CO2 per aluminum center. The ethyl variant then reacts further, inserting a third equivalent of CO2 into the aluminum alkyl to generate an aluminum carboxylate. Examples of this type of reactivity are rare under thermal conditions. A joint experimental/computational study supports the proposed reaction mechanism.
Thioglycerol‐Stabilized Rhodium Nanoparticles in Biphasic Medium as Catalysts in Multistep Reactions
Authors: Serrano‐Maldonado Alejandro , Reina Antonio , Portales‐Martínez Benjamín , Guerrero‐Ríos Itzel
Published: May 2020

Small rhodium nanoparticles (ca. 3.5 nm) were prepared by the decomposition of an organometallic precursor under hydrogen pressure in glycerol using 1‐thioglycerol as stabilizer. Full characterization in the solid state [HR‐TEM, EDX, XPS] showed a fcc structure for the Rh0/RhI nanoparticles capped with thiolate ligand. Reduction of different functionalities, including nitro groups and imines, was applied to tandem reductive amination of aldehydes with primary and secondary amines, and to the synthesis of N‐substituted anilines from nitrobenzene. In addition, thiolate‐capped RhNPs could be recovered and reused up to 5 runs without loss of activity nor selectivity.
Direct Exploitation of the Ethynyl Moiety in Calcium Carbide Through Sealed Ball Milling
Authors: Hosseini Abolfazl , Schreiner Peter R.
Published: May 2020

Ball milling of calcium carbide (CaC2) enables the reaction of its ethynyl moiety with organic electrophiles. This was realized simply by co‐milling CaC2 with organic substrates in a sealed jar without the need for an additive or a catalyst. Various ketones including those bearing α‐hydrogens were ethynylated in good yields at short reaction times. Aryl halides are also amenable substrates for this protocol as they furnish aryl ethynes through a benzyne intermediate. This method offers a practical and cheap alternative to the established procedures for introducing ethynyl functionalities.
Text‐based emotion detection: Advances, challenges, and opportunities
Authors: Acheampong Francisca Adoma , Wenyu Chen , Nunoo‐Mensah Henry
Published: May 2020

Emotion detection (ED) is a branch of sentiment analysis that deals with the extraction and analysis of emotions. The evolution of Web 2.0 has put text mining and analysis at the frontiers of organizational success. It helps service providers provide tailor‐made services to their customers. Numerous studies are being carried out in the area of text mining and analysis due to the ease in sourcing for data and the vast benefits its deliverable offers. This article surveys the concept of ED from texts and highlights the main approaches adopted by researchers in the design of text‐based ED systems. The article further discusses some recent state‐of‐the‐art proposals in the field. The proposals are discussed in relation to their major contributions, approaches employed, datasets used, results obtained, strengths, and their weaknesses. Also, emotion‐labeled data sources are presented to provide neophytes with eligible text datasets for ED. Finally, the article presents some open issues and future research direction for text‐based
ED.
Adaptation via pleiotropy and linkage: Association mapping reveals a complex genetic architecture within the sticklebackEdalocus
Authors: Archambeault Sophie L. , Bärtschi Luis R. , Merminod Aurélie D. , Peichel Catherine L.
Published: May 2020

Genomic mapping of the loci associated with phenotypic evolution has revealed genomic “hotspots,” or regions of the genome that control multiple phenotypic traits. This clustering of loci has important implications for the speed and maintenance of adaptation and could be due to pleiotropic effects of a single mutation or tight genetic linkage of multiple causative mutations affecting different traits. The threespine stickleback (Gasterosteus aculeatus) is a powerful model for the study of adaptive evolution because the marine ecotype has repeatedly adapted to freshwater environments across the northern hemisphere in the last 12,000 years. Freshwater ecotypes have repeatedly fixed a 16 kilobase haplotype on chromosome IV that contains Ectodysplasin (Eda), a gene known to affect multiple traits, including defensive armor plates, lateral line sensory hair cells, and schooling behavior. Many additional traits have previously been mapped to a larger region of chromosome IV that encompasses the Eda freshwater haplotype. To identify which of these traits specifically map to this adaptive haplotype, we made crosses of rare marine fish heterozygous for the freshwater haplotype in an otherwise marine genetic background. Further, we performed fine-scale association mapping in a fully interbreeding, polymorphic population of freshwater stickleback to disentangle the effects of pleiotropy and linkage on the phenotypes affected by this haplotype. Although we find evidence that linked mutations have small effects on a few phenotypes, a small 1.4-kb region within the first intron of Eda has large effects on three phenotypic traits: lateral plate count, and both the number and patterning of the posterior lateral line neuromasts. Thus, the Eda haplotype is a hotspot of adaptation in stickleback due to both a small, pleiotropic region affecting multiple traits as well as multiple linked mutations affecting additional traits.
Individual antecedents of workplace victimisation: The role of negative affect, personality and self‐esteem in junior doctors' exposure to bullying at work
Authors: Samsudin Ely Zarina , Isahak Marzuki , Rampal Sanjay , Rosnah Ismail , Zakaria Mohd Idzwan
Published: May 2020

Previous studies have indicated that junior doctors commonly experience workplace bullying and that it may adversely impact medical training and delivery of quality healthcare. Yet, evidence on the precursors of bullying among them remains elusive. Drawing on the individual‐disposition hypothesis, the present paper examined the relationships of negative affect, personality and self‐esteem with workplace bullying among junior doctors. Multilevel analysis of a universal sample (n = 1074) of junior doctors working in the central zone of Malaysia using mixed effects logistic regression was performed. The results indicate that participants with moderate (AOR 4.40, 95% CI 2.20‐8.77) and high degree (AOR 13.69, 95% CI 6.46‐29.02) of negative affect as well as high degree of neuroticism (AOR 2.99, 95% CI 1.71‐5.21) have higher odds of being bullied compared to their counterparts. The findings present evidence that individual traits are associated with junior doctors' exposure to bullying. While victim blaming should be avoided, this suggest that antibullying measures with an interpersonal focus should be considered when developing antibullying initiatives targeted at junior doctors. This includes primary intervention such as cognitive training, secondary interventions such as resource enhancement building and conflict management skills training, and tertiary interventions such as counselling.
Spatiotemporal variability of alpine precipitable water over arid northwestern China
Authors: Wu Lei , Li Changbin , Wang Liuming , He Zhibin , Zhang Yuan , Wang Wanrui , Yang Linshan , Wei Jianmei , Xie Xuhong
Published: May 2020

For a better understanding of the precipitable water in the arid northwestern China (NWC), we surveyed the water vapour variability on both sides of the alpine range crests based on the Tropical Rainfall Measuring Mission monthly precipitation data (TRMM 3B43). There were 12 target zones and 23 subzones in six mountain systems representatively selected according to alpine hydrogeomorphology. They were used for comparative analyses in time and space. Comparisons between the two sides of the range crests revealed that there is more precipitable water on the south slopes of the Qilian, Altun, Kunlun, and Altai Mountains, on the north slope of the Tian Mountains, and on the east slope of Helan Mountains. High correlations were detected between precipitable water for both sides of the range crests in target zones, while low correlations were found among precipitable water separately averaged in the Kunlun, Tian, and Qilian Mountains including both sides of the range crests. The proportion of precipitable water during the rainy season gradually increased from west to east along the mountains. Temporally, precipitation presented synchronous increases or decreases on the two sides of the range crests in most of the target zones during the time period from 1998 to 2016, and an overall increase in alpine annual precipitable water was found in the area, except for the decrease in the Altun and western Tian Mountains. The summer decay dominated the decrease in these two target zones, while strengthened conveyance was observed in other seasons, especially in spring and autumn, which compensated for, and led to, total increases in precipitable water in most of the target zones. All of the above findings were indicative of differences in vapour transport from outside areas into diverse alpine systems in the arid NWC, which could be schematically evidenced by the spatial patterns of monthly and annual water vapour conveyance retrieved from the TRMM precipitation data.
Numerical investigation of avulsions in gravel‐bed braided rivers
Authors: Yang Haiyan
Published: May 2020

Gravel‐bed braided rivers are highly energetic fluvial systems characterized by frequent in‐channel avulsions, which govern the morphodynamics of such rivers and are essential for them to maintain a braided planform. However, the avulsion mechanisms within natural braided rivers remain unclear due to their complicated hydraulic and morphodynamic processes. Influenced by neighbouring channels, avulsions in braided rivers may differ from those of bifurcations in single‐thread rivers, suggesting that avulsions should be studied within the context of the entire braid network. In this study, braiding evolution processes in gravel‐bed rivers were simulated using a physics‐based numerical model that considers graded bed‐load transport by dividing sediment particles into multiple size fractions and vertical sediment sorting by dividing the riverbed into several vertical layers. The numerical model successfully produced braiding processes and avulsion activities similar to those observed in a laboratory river. Results show that bend evolution of the main channel was the fundamental process controlling the occurrence of avulsions in the numerical model, with a cyclic process of channel meandering by lateral migration that transitioned to a straight channel pattern by avulsion. The radius of bend curvature for triggering avulsions in the numerical model was measured and it was found that the highest probability for a channel bend to generate an avulsion occurs when its radius of curvature is approximately 2.0–3.3 times the average anabranch width. Other types of avulsion were also observed that did not occur specifically at meander bends, but upstream meander evolution indirectly influenced such avulsions by altering channel pattern and discharge to those locations. This study explored the processes and mechanisms of several types of avulsion, and proposed factors controlling their occurrence, namely increasing channel curvature, high shear stress, tributary discharge, riverbed gradient and upstream channel pattern, with high shear stress being a direct indicator. Furthermore, avulsions in a typical gravel‐bed braided river, the Waimakariri River in New Zealand, were analysed using sequential Google Earth maps, which confirmed the conclusions derived from the numerical simulation.
Impacts of the Samarco Tailing Dam Collapse on Metals and Arsenic Concentration in Freshwater Fish Muscle from Doce River, Southeastern Brazil
Authors: Ferreira Frederico Fernandes , de Freitas Mariella Bontempo Duca , Szinwelski Neucir , Vicente Natállia , Medeiros Laila Carine Campos , Schaefer Carlos Ernesto Gonçalves Reynaud , Dergam Jorge Abdala , Sperber Carlos Frankl
Published: May 2020

On November 2015, Samarco tailings dam in Mariana, Minas Gerais, Brazil, collapsed, releasing 62 million tons of tailings that advanced through 668 km of the Doce River and adjacent floodplain. Although the collapse was the worst environmental disaster in Brazil, little is known about its consequences to aquatic biota. Here we evaluate the effects of the tailings mudflow on metal and As concentration in fish and how concentration correlates with water and fish characteristics. We quantified semitotal amounts of Ag, Al, As, Cd, Cr, Cu, Fe, Hg, Mn, Ni, Pb, and Zn in fish muscle tissue using inductively coupled plasma mass spectrometry (ICP-MS) in 255 individuals (34 species) sampled in unaffected and affected areas along the Doce River basin. Arsenic and Hg were higher in fish from affected sites, likely due to turbulent mixing of previously sedimented material by the giant tailings wave. Silver and Zn concentrations were higher in unaffected sites. Arsenic concentration in Geophagus brasiliensis decreased with increasing fish weight. Copper and Zn decreased with increasing fish weight considering the whole assembly of fish. The tailings mudflow increased water conductivity, and conductivity increased Al concentration in fish, so we expected a larger Al concentration in fishes from affected sites. However, the observed Al concentration in fishes from affected sites was lower than expected by water conductivity. Thus, the tailings mudflow reduced Al uptake or accumulation in fishes. Mercury decreased with increasing water conductivity in both unaffected and affected sites considering all species and in G. brasiliensis alone. Despite the relatively low concentration range of metals and As found in fish, fishes from sites affected by the Fe ore tailings mudflow showed higher As and Hg concentration, compared to fishes from unaffected sites. The higher As and Hg in affected sites require further detailed monitoring to ensure safeguards of human health by fishing activity along the Doce River. Integr Environ Assess Manag 2020;16:622–630. © 2020 SETAC
Time trends of neoadjuvant chemotherapy for early breast cancer
Authors: Riedel Fabian , Hoffmann Ann Sophie , Moderow Mareike , Heublein Sabine , Deutsch Thomas M. , Golatta Michael , Wallwiener Markus , Schneeweiss Andreas , Heil Joerg , Hennigs André
Published: May 2020

Neoadjuvant chemotherapy (NACT) in early breast cancer (EBC) enables in vivo sensitivity testing and less radical surgery as compared to primary surgery and adjuvant chemotherapy (ACT). The aim of our study is to illustrate trends of systemic treatment of EBC. The study analyzed chemotherapy usage and time trends for patients with EBC treated at 104 German breast units between January 2008 and December 2017. The data were obtained through a quality‐controlled benchmarking process. Altogether, 124 084 patients were included, of whom 46 279 (37.3%) received chemotherapy. For 44 765 of these cases, detailed information on systemic treatment and surgery were available. Overall use of chemotherapy declined from 42.0% in 2008 to 32.0% in 2017. During that same time, the proportion of NACT increased from 20.0% to 57.7%, irrespective of tumor subtype. The pathological complete response (pCR) rate (defined as ypT0 ypN0) at surgery after NACT increased from 15.0% to 34.2%. The results from this large cohort from the clinical routine reflect the refined indications for chemotherapy in EBC.
Impact of uterus‐preserving surgery on Stage I primary mucinous epithelial ovarian carcinoma: A multi‐institutional study with propensity score‐weighted analysis
Authors: Yoshihara Masato , Kajiyama Hiroaki , Tamauchi Satoshi , Iyoshi Shohei , Yokoi Akira , Suzuki Shiro , Kawai Michiyasu , Nagasaka Tetsuro , Takahashi Kunihiko , Matsui Shigeyuki , Kikkawa Fumitaka
Published: May 2020

Objective

To investigate the clinical characteristics of women with Stage I primary mucinous epithelial ovarian carcinoma (mEOC) and evaluate the impact of uterus‐preserving surgery (UPS) in terms of survival prognosis.

Methods

A regional multi‐institutional retrospective study conducted between January 1986 and March 2017 by reviewing records of the Tokai Ovarian Tumor Study Group. Clinical and pathologic data and survival outcomes were assessed for women with Stage I primary mEOC. The baseline imbalance between women with and those without UPS was adjusted by an inverse probability of treatment weighting method using the propensity score (PS) of independent clinical variables.

Results

Among 4730 women with malignant ovarian tumors, 185 had Stage I primary mEOC and were included in the study. The mean age was 47.6 years (range 12–87 years), and 56 (30.3%) women underwent UPS. After PS‐based adjustment, women in the UPS group did not have a poorer prognosis regarding overall survival (P=0.776) or recurrence‐free survival (P=0.683). Even after age stratification, there was no statistical difference in survival outcomes between the UPS and non‐UPS groups.

Conclusion

UPS was not associated with decreased survival and may be a treatment option for women with Stage I primary mEOC irrespective of age.
A Comprehensive Updated Review on SARS‐CoV‐2 and COVID‐19
Authors: Ren Yunzhao R. , Golding Amit , Sorbello Alfred , Ji Ping , Chen Jianmeng , Saluja Bhawana , Witzmann Kimberly , Arya Vikram , Reynolds Kellie S. , Choi Su‐Young , Nikolov Nikolay P. , Sahajwalla Chandrahas
Published: May 2020

This literature review aims to provide a comprehensive current summary of the pathogenesis, clinical features, disease course, host immune responses, and current investigational antiviral and immunomodulatory pharmacotherapies to facilitate the development of future therapies and measures for prevention and control.
The novel coronavirus disease (COVID‐19) complicated by pulmonary embolism and acute respiratory distress syndrome
Authors: Li Ting , Cheng Guang‐Shing , Pipavath Sudhakar N. J. , Kicska Gregory A. , Liu Liangjin , Kinahan Paul E. , Wu Wei
Published: May 2020

Acute respiratory distress syndrome and coagulopathy played an important role in morbidity and mortality of severe COVID‐19 patients. A higher frequency of pulmonary embolism (PE) than expected in COVID‐19 patients was recently reported. The presenting symptoms for PE were untypical including dyspnea, which is one of the major symptoms in severe COVID‐19, especially in those patients with acute respiratory distress syndrome (ARDS). We reported two COVID‐19 cases with coexisting complications of PE and ARDS, aiming to consolidate the emerging knowledge of this global health emergency and raise the awareness that the hypoxemia or severe dyspnea in COVID‐19 may be related to PE and not necessarily always due to the parenchymal disease.
The novel coronavirus SARS‐CoV‐2: From a zoonotic infection to coronavirus disease 2019
Authors: dos Santos Bezerra Rafael , Valença Ian N. , de Cassia Ruy Patrícia , Ximenez João P. B. , da Silva Junior Wilson A. , Covas Dimas T. , Kashima Simone , Slavov Svetoslav N.
Published: May 2020

The novel coronavirus (CoV), severe acute respiratory syndrome (SARS)‐CoV‐2 is an international public health emergency. Until now, the intermediate host and mechanisms of the interspecies jump of this virus are unknown. Phylogenetic analysis of all available bat CoV complete genomes was performed to analyze the relationships between bat CoV and SARS‐CoV‐2. To suggest a possible intermediate host, another phylogenetic reconstruction of CoV genomes obtained from animals that were hypothetically commercialized in the Chinese markets was also carried out. Moreover, mutation analysis was executed to suggest genomic regions that may have permitted the adaptation of SARS‐CoV‐2 to the human host. The phylogenetic analysis demonstrated that SARS‐CoV‐2 formed a cluster with the bat CoV isolate RaTG13. Possible CoV interspecies jumps among bat isolates were also observed. The phylogenetic tree reconstructed from CoV strains belonging to different animals demonstrated that SARS‐CoV‐2, bat RaTG13, and pangolin CoV genomes formed a monophyletic cluster, demonstrating that pangolins may be suggested as SARS‐CoV‐2 intermediate hosts. Three AA substitutions localized in the S1 portion of the S gene were observed, some of which have been correlated to structural modifications of the S protein which may facilitate SARS‐CoV‐2 tropism to human cells. Our analysis shows the tight relationship between SARS‐CoV‐2 and bat SARS‐like strains. It also hypothesizes that pangolins might have been possible intermediate hosts of the infection. Some of the observed AA substitutions in the S‐binding protein may serve as possible adaptation mutations in humans but more studies are needed to elucidate their function.
Hepatitis C virus alternative reading frame protein (ARFP): Production, features, and pathogenesis
Authors: Mohamadi Mahdi , Azarbayjani Kimia , Mozhgani Sayed‐Hamidreza , Bamdad Taravat , Alamdary Ashkan , Nikoo Hadi Razavi , Hashempour Tayebeh , Hedayat Yaghoobi Mojtaba , Ajorloo Mehdi
Published: May 2020

Earlier observation suggests that hepatitis C virus (HCV) is a single‐stranded RNA virus which encodes at least 10 viral proteins. F protein is a novel protein which has been discovered recently. These studies suggest three mechanisms for the production of this protein concerning ribosomal frameshift at codon 10, initial translation at codons 26 and 85 or 87. In this study, the association between protein F and chronicity of hepatocellular carcinoma (HCC) has been reviewed. Evidence suggests that humoral immune system can recognize this protein and produce antibodies against it. By detecting antibodies in infected people, investigators found that F protein might have a role in HCV infection causing chronic cirrhosis and HCC as higher prevalence was found in patients with mentioned complications. The increment of CD4+, CD25+, and FoxP3+ T cells, along with CD8+ T cells with low expression of granzyme B, also leads to weaker responses of the immune system which helps the infection to become chronic. Moreover, it contributes to the survival of the virus in the body through affecting the production of interferon. F protein also might play roles in the disease development, resulting in HCC. The existence of F protein affects cellular pathways through upregulating p53, c‐myc, cyclin D1, and phosphorylating Rb. This review will summarize these effects on immune system and related mechanisms in cellular pathways.
Sex‐linked roles of the CRF1 and the CRF2 receptor in social behavior
Authors: Piccin Alessandro , Contarino Angelo
Published: May 2020

Dysfunctional social behavior is a major clinical feature of mood, anxiety, autism spectrum, and substance‐related disorders, and may dramatically contribute to the poor outcome of these diseases. Nevertheless, the mechanisms underlying social behavior deficits are still largely unknown. The corticotropin‐releasing factor (CRF) system, a major coordinator of the stress response, has been hypothesized to modulate social behavior. CRF signaling is mediated by two receptor types, termed CRF1 and CRF2. Using the three‐chamber task for sociability (i.e., preference for an unfamiliar conspecific vs. an object), this study demonstrates that CRF2 receptor null mutation (CRF2−/−) reduces sociability in female mice but increases it in male mice. Both female and male CRF2−/− mice display a preference for social odor cues over neutral cues, indicating that sex‐ and CRF2 receptor‐dependent sociability is not due to altered olfaction or impaired social cues discrimination. Moreover, treatment with the CRF1 receptor‐preferring antagonist, antalarmin, consistently induces sociability in non‐social mice but disrupts it in social mice, independently of CRF2 receptor deficiency. Sex, CRF2 receptor deficiency, or antalarmin affect locomotor activity during the three‐chamber test. However, throughout the study CRF1 and CRF2 receptor‐linked sociability is independent of locomotor activity. The present findings highlight major functions for the CRF system in the regulation of social behavior. Moreover, they provide initial evidence of sex‐linked roles for the CRF1 and the CRF2 receptor, emphasizing the importance of sex as a major biological variable to be taken into consideration in preclinical and clinical studies.
Retrospectively assessed subjective effects of initial opioid use differ between opioid misusers with opioid use disorder (OUD) and those who never progressed to OUD: Data from a pilot and a replication sample
Authors: Agrawal Arpana , Jeffries Paul W. , Srivastava A. Benjamin , McCutcheon Vivia V. , Lynskey Michael T. , Heath Andrew C. , Nelson Elliot C.
Published: May 2020

Attempts to identify opioid users with increased risk of escalating to opioid use disorder (OUD) have had limited success. Retrospectively assessed subjective effects of initial opioid misuse were compared in a pilot sample of opioid misusers (nonmedical use ≤60 times lifetime) who had never met criteria for OUD (N = 14) and heroin‐addicted individuals in treatment for OUD (N = 15). Relative to opioid misusers without a lifetime OUD diagnosis, individuals with OUD reported greater euphoria and other positive emotions, activation, pruritus, and internalizing symptoms. Consistent with these findings, proxy Addiction Research Center Inventory (ARCI) Amphetamine Group, and Morphine Benzedrine Group scale mean item scores were significantly higher in those with OUD. Replication was attempted in opioid misusers with (N = 25) and without OUD (N = 25) who were assessed as part of an ongoing genetic study. We observed similar significant between‐group differences in individual subjective effect items and ARCI scale mean item scores in the replication sample. We, thus confirm findings from prior reports that retrospectively assessed subjective responses to initial opioid exposure differ significantly between opioid users who do, and do not, progress to OUD. Our report extends these findings in comparisons limited to opioid misusers. Additional research will be necessary to examine prospectively whether the assessment of subjective effects after initial use has predictive utility in the identification of individuals more likely to progress to OUD.
Biomechanical comparison of distal femoral fracture fixation: Analysis of non‐locked, locked, and far‐cortical locked constructs
Authors: Riedel Matthew D. , Oppizzi Giovanni , O'Hara Nathan N. , Zhang Chunyang , Koh Kyung , Slobogean Gerard P. , Zhang Li‐Qun , O'Toole Robert V.
Published: May 2020

To assess whether far‐cortical locking (FCL) screws alter the fracture site strain environment and allow shorter bridge plate constructs for supracondylar femoral fractures, we tested the fracture site displacement under force of synthetic left femora with a 5‐cm metaphyseal fracture gap, modeling comminution. Five models of nine constructs were tested (three types of diaphyseal screws [nonlocking, locking, and FCL] and two plate lengths [13 holes and 5 holes]). Long plate models using three or four diaphyseal screws (working length 13.5 or 7.5 cm, respectively) were compared with short plates with three diaphyseal screws (working length 7.5 cm). Models were loaded axially and torsionally; 100 cycles in random order. Primary outcome measures were axial and torsional fracture site stiffness. FCL screws decreased rotational stiffness 19% (P < .01) compared with baseline nonlocking screws in the same plate and working length construct, mirroring the effect (20% decrease in stiffness, P < .01) of nearly doubling the nonlocking construct working length (7.5‐13.5 cm). Similarly, FCL screws decreased axial stiffness 23% (P < .01) in the same baseline comparison. Fracture site displacement under loading comparable to a long working length nonlocked plate construct was achieved using a shorter FCL plate construct. By closely replicating the biomechanical properties of a long plate construct, a fracture site strain environment considered favorable in promoting fracture healing might still be achievable using a shorter plate length. Clinical Significance: It might be possible to optimize fracture site strain environment and displacement under loading using shorter FCL plate constructs. Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 00:00–00, 2020.