bluuebunny/crossref_metadata_2025 huggingface dataset:
Alcohol study shows great similarity between self‐report, lab measures
Authors: Enos Gary
Published: May 2020

The alcohol research community likely will breathe a collective sigh of relief over new research findings showing that in‐laboratory measures of drinking are largely in concordance with self‐reported drinking levels. These findings help to validate alcohol self‐administration paradigms that are widely used in the development of alcohol treatment approaches.
Senators call for $2 billion in supplemental SAMHSA funding
Authors: Knopf Alison
Published: May 2020

As the fourth stimulus bill, the HEROES Act, awaits action by the Senate, 19 senators sent a letter last week to Senate and House leadership calling for increased investments in substance use disorder programs during the COVID‐19 pandemic. The letter, from Senators Tammy Baldwin (D‐Wisconsin) and Jeanne Shaheen (D‐New Hampshire), along with 17 other senators (all Democrats), calls for “$2 billion in funding for the Substance Abuse and Mental Health Services Administration (SAMHSA) to administer supplemental grant allocations under the Substance Abuse Prevention and Treatment (SAPT) Block Grant program and the State Opioid Response (SOR) grant program.”
From a Biosynthetic Pathway toward a Biocatalytic Process and Chemocatalytic Modifications: Three‐Step Enzymatic Cascade to the Plant Metabolite cis‐(+)‐12‐OPDA and Metathesis‐Derived Products
Authors: Löwe Jana , Dietz Karl‐Josef , Gröger Harald
Published: May 2020

A biotechnological approach toward the plant metabolite and regulator cis‐(+)‐12‐oxophytodienoic acid (cis‐(+)‐12‐OPDA) in a one‐pot process with >99% conversion, at least 90% selectivity and ≤10% of side products as well as a high diastereoselectivity (leading to d.r. of at least 90:10) is reported. The optimized organic‐synthetic enzyme cascade for preparing this bioactive and commercial molecule with pharmaceutical relevance on a gram per L scale is designed based on its biosynthetic pathway starting from cheap and readily accessible linolenic acid. Toward this end, a recombinant biocatalyst system has been prepared for carrying out the most critical two key steps in a tailored manner, thus avoiding sensitive intermediate decomposition. Furthermore, cis‐(+)‐12‐OPDA is successfully modified via a cross‐alkene metathesis reaction with conversions of up to >99%, leading to a compound library of new cis‐(+)‐12‐OPDA derivatives with different substitution pattern of the side chain at the 2‐position. By means of such a combined biotechnological and chemocatalytic route, a straightforward approach to a structurally unique oxylipin library is realized, which would be highly difficult or not accessible by pure chemical and biotechnological methods, respectively.
Psychological functioning, brain morphology, and functional neuroimaging in Klinefelter syndrome
Authors: Skakkebæk Anne , Gravholt Claus H. , Chang Simon , Moore Philip J. , Wallentin Mikkel
Published: May 2020

Klinefelter syndrome (KS; 47,XXY) impacts neurodevelopment and is associated with an increased risk of cognitive, psychological and social impairments, although significant heterogeneity in the neurodevelopmental profile is seen. KS is characterized by a specific cognitive profile with predominantly verbal deficits, preserved function in non‐verbal and visuo‐spatial domains, executive dysfunction and social impairments, and by an increased vulnerability toward psychiatric disorders. The neurobiological underpinnings of the observed neuropsychological profile have not been established. A distinct pattern of both global and regional brain volumetric differences has been demonstrated in addition to preliminary findings of functional brain alterations related to auditory, motor, language and social processing. When present, the combination of cognitive, psychological and social challenges has the potential to negatively affect quality of life. This review intends to provide information and insight to the neuropsychological outcome and brain correlates of KS. Possible clinical intervention and future directions of research will be discussed.
Ribbon of DNA Lattice on Gold Nanoparticles for Selective Drug Delivery to Cancer Cells
Authors: Zhang Shuxin , Chen Chang , Xue Chang , Chang Dingran , Xu Huo , Salena Bruno J. , Li Yingfu , Wu Zai‐Sheng
Published: May 2020

Herein, we report on the design of a programmable DNA ribbon using long‐chain DNA molecules with a user‐defined repetitive padlock sequence. The DNA ribbon can be further combined with gold nanoparticles (AuNPs) to create a composite nanomaterial that contains an AuNP core and a high‐density DNA crown carrying a cancer‐cell‐targeting DNA aptamer, a fluorescent tag for location tracking, and a cell‐killing drug. This composite material can be efficiently internalized by cancer cells and its cellular location can be tracked by fluorescence imaging. The system offers several attractive characteristics, including simple design, tunable DNA crown, high drug‐loading capacity, selective cell targeting, and pH‐sensitive drug release. These features make such a material a promising therapeutic agent.
Near‐Infrared‐III‐Absorbing and ‐Emitting Dyes: Energy‐Gap Engineering of Expanded Porphyrinoids via Metallation
Authors: Wang Yue , Ogasahara Koki , Tomihama Daisuke , Mysliborski Radomir , Ishida Masatoshi , Hong Yongseok , Notsuka Yusuke , Yamaoka Yoshihisa , Murayama Tomotaka , Muranaka Atsuya , Uchiyama Masanobu , Mori Shigeki , Yasutake Yuhsuke , Fukatsu Susumu , Kim Dongho , Furuta Hiroyuki
Published: May 2020

The synthesis of organometallic complexes of modified 26π‐conjugated hexaphyrins with absorption and emission capabilities in the third near‐infrared region (NIR‐III) is described. Symmetry alteration of the frontier molecular orbitals (MOs) of bis‐PdII and bis‐PtII complexes of hexaphyrin via N‐confusion modification led to substantial metal dπ–pπ interactions. This MO mixing, in turn, resulted in a significantly narrower HOMO–LUMO energy gap. A remarkable long‐wavelength shift of the lowest S0→S1 absorption beyond 1700 nm was achieved with the bis‐PtII complex, t‐Pt2‐3. The emergence of photoacoustic (PA) signals maximized at 1700 nm makes t‐Pt2‐3 potentially useful as a NIR‐III PA contrast agent. The rigid bis‐PdII complexes, t‐Pd2‐3 and c‐Pd2‐3, are rare examples of NIR emitters beyond 1500 nm. The current study provides new insight into the design of stable, expanded porphyrinic dyes possessing NIR‐III‐emissive and photoacoustic‐response capabilities.
Validation of water main failure predictions: A 2‐year case study
Authors: Kahn Christopher , Damiani Aaron , Ge Shaoqing
Published: May 2020

Recent studies have shown that U.S. water mains are failing at an accelerating rate. In the meantime, water utilities are challenged by limited funding. It is important that water mains with much higher likelihood of failure (LOF) are replaced before they fail to avoid possible high consequences, such as public safety threats, high financial losses, and environmental damages. This article presents a model to evaluate the LOF of water mains using data available in geographic information systems (GIS). A case study is presented comparing 2 years of actual water main break data with the results of the model. The comparison shows a strong correlation between the model prediction and the actual break rates of main pipes; thus, it validates the robustness of the model and shows that funding can be used more efficiently by focusing on the water mains with a high LOF as predicted by the GIS model. This model has been used in New Jersey American Water's distribution systems. It can be used in other water systems to help guide water main replacement efforts.
Zinc‐induced copper deficiency, sideroblastic anemia, and neutropenia: A perplexing facet of zinc excess
Authors: Wahab Ahsan , Mushtaq Kamran , Borak Samuel G. , Bellam Naresh
Published: May 2020

Hypocupremia due to zinc products can cause sideroblastic anemia and neutropenia and mimics other serious hematological disorders. Early consideration of the copper deficiency and a thorough clinical history can prevent unnecessary interventions.
Multipolar Porphyrin‐Triazatruxene Arrays for Two‐Photon Fluorescence Cell Imaging
Authors: Zhang Jinghui , Gong Lei , Zhang Xiaoshuang , Zhu Mengliang , Su Chaorui , Ma Qing , Qi Dongdong , Bian Yongzhong , Du Hongwu , Jiang Jianzhuang
Published: May 2020

Two‐photon excited fluorescent (TPEF) materials are highly desirable for bioimaging applications owing to their unique characteristics of deep‐tissue penetration and high spatiotemporal resolution. Herein, by connecting one, two, or three electron‐deficient zinc porphyrin units to an electron‐rich triazatruxene core via ethynyl π‐bridges, conjugated multipolar molecules TAT‐(ZnP)n (n=1–3) were developed as TPEF materials for cell imaging. The three new dyes present high fluorescence quantum yields (0.40–0.47) and rationally improved two‐photon absorption (TPA) properties. In particular, the peak TPA cross section of TAT‐ZnP (436 GM) is significantly larger than that of the ZnP reference (59 GM). The δTPA values of TAT‐(ZnP)2 and TAT‐(ZnP)3 further increase to 1031 and up to 1496 GM, respectively, indicating the effect of incorporated ZnP units on the TPA properties. The substantial improvement of the TPEF properties is attributed to the formation of π‐conjugated quadrapole/octupole molecules and the extension of D‐π‐A‐D systems, which has been rationalized by density function theory (DFT) calculations. Moreover, all of the three new dyes display good biocompatibility and preferential targeting ability toward cytomembrane, thus can be superior candidates for TPEF imaging of living cells. Overall, this work demonstrated a promising strategy for the development of porphyrin‐based TPEF materials by the construction and extension of D‐π‐A‐D multipolar array.
Recent Advances in Iodine‐Promoted C−S/N−S Bonds Formation
Authors: Zhang Honghua , Wang Huihong , Jiang Yi , Cao Fei , Gao Weiwei , Zhu Longqing , Yang Yuhang , Wang Xiaodong , Wang Yongqiang , Chen Jinhong , Feng Yiyue , Deng Xuemei , Lu Yingmei , Hu Xiaoling , Li Xiangxiang , Zhang Juan , Shi Tao , Wang Zhen
Published: May 2020

Sulfur‐containing scaffold, as a ubiquitous structural motif, has been frequently used in natural products, bioactive chemicals and pharmaceuticals, particularly C−S/N−S bonds are indispensable in many biological important compounds and pharmaceuticals. Development of mild and general methods for C−S/N−S bonds formation has great significance in modern research. Iodine and its derivatives have been recognized as inexpensive, environmentally benign and easy‐handled catalysts or reagents to promote the construction of C−S/N−S bonds under mild reaction conditions, with good regioselectivities and broad substrate scope. Especially based on this, several new strategies, such as oxidation relay strategy, have been greatly developed and accelerated the advancement of this field. This review focuses on recent advances in iodine and its derivatives promoted hybridized C−S/N−S bonds formation. The features and mechanisms of corresponding reactions are summarized and the results of some cases are compared with those of previous reports. In addition, the future of this domain is discussed.
A New Class of C2‐Symmetric Chiral Cyclopentadienyl Ligand Derived from Ferrocene Scaffold: Design, Synthesis and Application
Authors: Liang Hao , Vasamsetty Laxmaiah , Li Teng , Jiang Jijun , Pang Xingying , Wang Jun
Published: May 2020

A new class of C2‐symmetric, chiral cyclopentadienyl ligand based on planar chiral ferrocene backbone was developed. A series of its corresponding rhodium(I), iridium(I), and ruthenium(II) complexes were prepared as well. In addition, the rhodium(I) complexes were evaluated in the asymmetric catalytic intramolecular amidoarylation of olefin‐tethered benzamides via C−H activation.
Unusual Structures of the Parent Molecules Diarsene, Distibene, and Dibismuthene: Toward Their Observation
Authors: Li Guoliang , Huang Chunxiang , Xie Yaoming , Robinson Gregory H. , Schaefer Henry F.
Published: May 2020

There is considerable interest, from both experimental and theoretical perspectives, in molecules incorporating multiple bonds between main group elements. Herein, we not only consider the parent molecules HE=EH (E=As, Sb, Bi), but also a number of their isomers. For each E2H2 molecule, a number of different structures were optimized with four different DFT methods. Final structures were determined with the coupled cluster method CCSD(T) using large basis sets, namely cc‐pVQZ‐PP, incorporating relativistic psuedopotentials. All feasible dissociation pathways are examined. For all three E2H2 molecules the trans isomer lies lowest in energy, with the cis isomer higher by 2.7 (As), 2.1 (Sb), and 1.8 (Bi) kcal mol−1, respectively. However, both cis and trans structures should be observable, as large barriers (27.7, 20.5, and 17.7 kcal mol−1) separate them. For both the cis and trans structures, in the infrared the strong E‐H stretching frequencies should also be observable. Only the cis structures have dipole moments (0.62, 0.01, and 0.83 debye, respectively), and their observation by microwave spectroscopy would be stunning. Also considered were the higher energy vinylidene‐like, pyramidal, monobridged, and linear structures. We conclude that molecules such as HSb=SbH‐Fe(CO)4, HBi=BiH‐Fe(CO)4, and related systems, should be feasible synthetic targets.
Water‐Waves Problem with Surface Tension in a Corner Domain II: The Local Well‐Posedness
Authors: Ming Mei , Wang Chao
Published: May 2020

Based on the a priori estimates in our previous work, we continue to investigate the water‐waves problem in a bounded two‐dimensional corner domain in this paper. We prove the local well‐posedness of the solution to the water‐waves system when the contact angles are less than π/16. © 2020 Wiley Periodicals LLC
Recycling of Flexible Polyurethane Foam by Split‐Phase Alcoholysis: Identification of Additives and Alcoholyzing Agents to Reach Higher Efficiencies
Authors: Vanbergen Thomas , Verlent Isabel , De Geeter Joke , Haelterman Bart , Claes Laurens , De Vos Dirk
Published: May 2020

Split‐phase alcoholysis of flexible polyurethane (PU) foam yields an apolar phase containing the recycled polyether polyol, and a lower, polar phase of the alcoholyzing agent and aromatic compounds. However, multiple purification steps are required to render the polyether polyol suitable for synthesis of new flexible PU foams; the unfavorable mass balance limits industrial applications. In this work, 2‐pyrrolidone was identified as a performant additive for accelerating the dissolution and depolymerization process. By applying a lactam to PU foam in a weight ratio of 0.1:1, the glycol to PU foam weight ratio can be decreased from 1.5:1 to only 0.5:1, without loss of purity or yield of the recycled polyether polyol. Diglycerol was discovered as a novel, promising alcoholyzing agent; it allows the recycling of the polyether polyol in high purity (97 %) and excellent yields (98 %), and after a single washing with diglycerol, a sufficiently low hydroxyl value (61 mgKOH g−1) is reached. The recycled polyether polyol can replace the virgin polyether polyol (48 mgKOH g−1) for up to 50 % in the synthesis of new flexible PU foams with effects on the foam quality that stay within the limits of generally accepted specifications. A first step towards the valorization of the lower phase was also taken by applying hydrolysis of the newly formed carbamates to toluenediamines, which are readily reintegrated in new PU foams.
Rationale and study design of OUTSTEP‐HF: a randomised controlled study to assess the effect of sacubitril/valsartan and enalapril on physical activity measured by accelerometry in patients with heart failure with reduced ejection fraction
Authors: Edelmann Frank , Jaarsma Tiny , Comin‐Colet Josep , Schorr Jessica , Ecochard Laurent , Hussain Rizwan I. , Piepoli Massimo F.
Published: May 2020

Aim

In PARADIGM‐HF, sacubitril/valsartan demonstrated superiority to enalapril in reducing mortality and morbidity in patients with heart failure (HF) with reduced ejection fraction (HFrEF). Several patient‐centred outcomes like improved physical activity and quality of life have been emphasised as important treatment goals in HF management. OUTSTEP‐HF has been designed to evaluate the effect of sacubitril/valsartan compared with enalapril on non‐sedentary daytime physical activity in patients with HFrEF.

Methods

OUTSTEP‐HF is a randomised, actively controlled, double‐blind, double‐dummy study that plans to enrol 600 ambulatory patients with symptomatic HFrEF in 19 European countries. Patients will be randomised 1:1 to receive sacubitril/valsartan 97/103 mg bid or enalapril 10 mg bid. The primary objective of the study is to assess changes from baseline (Week 0) to Week 12 in exercise capacity measured by the 6‐min walk test and in daily non‐sedentary daytime activity. Physical activity and objective sleep parameters will be measured by accelerometry using a wrist‐worn device, worn continuously from screening (Week −2) until the end of study (Week 12). As a co‐primary outcome, changes from baseline in sub‐maximal exercise capacity will be assessed by the 6‐min walk test. Patient‐ and physician‐reported questionnaires will be used to assess quality of life, changes in signs and symptoms of HF and sleep parameters.

Conclusion

OUTSTEP‐HF will be the largest randomised trial in HF to date to use non‐invasive accelerometry to assess whether treatment with sacubitril/valsartan improves patients' daily physical activity and exercise capacity compared with enalapril.
Synthesis of Two Epimers of Pseudopaline
Authors: Cullia Gregorio , Fanelli Roberto , Voulhoux Romé , Arnoux Pascal , Cavelier Florine
Published: May 2020

Opines are a known group of compounds characterized by an elevated polarity. Recently, two new members of this class, staphylopine and pseudopaline, have been identified in Staphylococcus aureus and Pseudomonas aeruginosa, respectively. These molecules are metal chelators that contribute to the growth of bacteria in particularly metal‐poor environment. Different evidences suggest that these molecules might have an important role in the development of pulmonary infections in humans. Considering the impact of P. aeruginosa infections in cystic fibrosis patients (prevalence up to 70 %), pseudopaline has risen interest as potential source of new therapeutic intervention. We present herein a straightforward synthetic approach for the synthesis of the two epimers of pseudopaline. Starting from a chiral building block, we attribute the absolute configuration to the two obtained diasteroisomers.
Biogeomorphology in the marine landscape: Modelling the feedbacks between patches of the polychaete worm Lanice conchilega and tidal sand waves
Authors: Damveld Johan H. , Borsje Bas W. , Roos Pieter C. , Hulscher Suzanne J. M. H.
Published: May 2020

Tidal sand waves are dynamic bedforms found in coastal shelf seas. Moreover, these areas are inhabited by numerous benthic species, of which the spatial distribution is linked to the morphological structure of sand waves. In particular, the tube‐building worm Lanice conchilegais of interest as this organism forms small mounds on the seabed, which provide shelter to other organisms. We investigate how the interactions between small‐scale mounds (height ∼dm) and large‐scale sand waves (height ∼m) shape the bed of the marine environment. To this end, we present a two‐way coupled process‐based model of sand waves and tube‐building worm patches in Delft3D. The population density evolves according to a general law of logistic growth, with the bed shear stress controlling the carrying capacity. Worm patches are randomly seeded and the tubes are mimicked by small cylinders that influence flow and turbulence, thereby altering sediment dynamics. Model results relate the patches with the highest worm densities to the sand wave troughs, which qualitatively agrees with field observations. Furthermore, the L. conchilegatubes trigger the formation of sandy mounds on the seabed. Because of the population density distribution, the mounds in the troughs can be several centimetres higher than on the crests. Regarding sand wave morphology, the combination of patches and mounds are found to shorten the time‐to‐equilibrium. Also, if the initial bed comprised small sinusoidal sand waves, the equilibrium wave height decreased with a few decimetres compared to the situation without worm patches. As the timescale of mound formation (years) is shorter than that of sand wave evolution (decades), the mounds induce (and accelerate) sand wave growth on a similar spatial scale to the mounds. Initially, this leads to shorter sand waves than they would be in an abiotic environment. However, near equilibrium the wavelengths tend towards their abiotic counterparts again. © 2020 The Authors. Earth Surface Processes and Landforms published by John Wiley & Sons Ltd
Modelling the impact of a time‐varying wave angle on the nonlinear evolution of sand bars in the surf zone
Authors: Nnafie Abdel , van Andel Niek , de Swart Huib
Published: May 2020

Sandy beaches are often characterized by the presence of sand bars, whose characteristics (growth, migration speed, etc.) strongly depend on offshore wave conditions, such as wave height and angle of wave incidence. This study addresses the impact of a sinusoidally time‐varying wave angle of incidence with different time‐means on the saturation height, migration speed and longshore spacing of sand bars. Model results show that shore‐transverse sand bars (so‐called TBR bars) eventually develop under a time‐varying wave angle. Depending on the time‐mean, amplitude and period of the varying angle of wave incidence, the mean heights and mean migration speeds of the bars can be larger or smaller than their corresponding values in the case of time‐invariant angles. Bars might not even form when the wave angle varies around a too large oblique mean value, whereas bars exist in the case of a time‐invariant wave angle. The oscillations in both bar height and migration speed are large if the period of the time‐varying wave angle is close to the adjustment timescale of the system and if large differences in the local growth and migration rates of the bars occur during one oscillation period. The oscillations in bar height are a combination of harmonics with the principal period and half the period of the time‐varying wave angle, whereas those of migration speed contain only the principal period. Bars that are subject to time‐varying wave angles have larger longshore crest‐to‐crest spacings than those which form under fixed wave angles. Physical explanations for these findings are given. © 2020 The Authors. Earth Surface Processes and Landforms published by John Wiley & Sons Ltd
Prognostic impact of B‐vitamins involved in one‐carbon metabolism in patients with diffuse large B‐cell lymphoma
Authors: Cao Yiwen , Chen Peizhan , Cai Minci , Shi Qing , Xu Pengpeng , Wang Li , He Yang , Wang Hui , Zhao Weili
Published: May 2020

One‐carbon metabolism (OCM) plays a pivotal role in both the stability and integrity of DNA and is mainly regulated by B‐vitamins. This study aims to investigate the clinical relevance of B‐vitamins and single nucleotide polymorphisms (SNPs) on OCM‐related genes in diffuse large B‐cell lymphoma (DLBCL). A total of 322 newly diagnosed DLBCL patients who received rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone‐based immunochemotherapy were recruited into this study. The serum levels of B‐vitamins (folate, vitamin B2 [riboflavin], vitamin B6 [pyridoxal 5′‐phosphate], and vitamin B12 [cobalamin]), as well as SNPs on methylenetetrahydrofolate reductase, methionine synthase (MTR), MTR reductase (MTRR) and cystathionine gamma‐lyase (CTH) genes, were assessed at diagnosis. The prognostic values were estimated using the Kaplan‐Meier method and Cox proportional hazards regression methods. Overall, the low serum concentration of folate and vitamin B2, as well as the presence of CTH1364 TT genotype, were significantly associated with poor treatment response in DLBCL. Multivariate analysis indicated that compared with patients in the medium and high serum folate tertiles, low serum folate tertile patients had both significantly inferior progression‐free survival (P = .033, Tertile 2 vs Tertile 1, and P = .031, Tertile 3 vs Tertile 1) and overall survival time (P < .001, Tertile 2 vs Tertile 1, and P = .001, Tertile 3 vs Tertile 1). Compared with patients in the medium and high serum vitamin B2 tertiles, low serum vitamin B2 tertile patients had both significantly inferior progression‐free survival (P = .006, Tertile 2 vs Tertile 1, and P = .001, Tertile 3 vs Tertile 1) and overall survival time (P = .030, Tertile 2 vs Tertile 1, and P = .255, Tertile 3 vs Tertile 1). In conclusion, alterations in B‐vitamin metabolism significantly affected disease progression and had a prognostic impact on DLBCL.
The role of snow processes and hillslopes on runoff generation in present and future climates in a recently constructed watershed in the Athabasca oil sands region
Authors: Biagi Kelly M. , Carey Sean K.
Published: May 2020

Mine reclamation in the Athabasca oil sands region Canada, is required by law where companies must reconstruct disturbed landscapes into functioning ecosystems such as forests, wetlands, and lakes that existed in the Boreal landscape prior to mining. Winter is a major hydrological factor in this region as snow covers the landscape for 5–6 months and is ~25% of the annual precipitation, yet few studies have explored the influence of winter processes on the hydrology of constructed watersheds. One year (2017–2018) of intensive snow hydrology measurements are supplemented with 6 years (2013–2018) of meteorological measurements from the constructed Sandhill Fen watershed to: (a) understand snow accumulation and redistribution, snowmelt timing, rate, and partitioning, (b) apply a physically based model for simulating winter processes on hillslopes, and (c) evaluate the impact of soil prescriptions and climate change projections on winter processes in reclaimed systems. The 2017–2018 snow season was between November and April and snow water equivalent (SWE) ranged between 40 and 140 mm. Snow distribution was primarily influenced by topography with little influence of snow trapping from developing vegetation. Snow accumulation was most variable on hillslopes and redistribution was driven by slope position, with SWE greatest at the base of slopes and decreased toward crests. Snowmelt on hillslopes was controlled by slope aspect, as snow declined rapidly on west and south‐facing slopes, compared with east and north‐facing slopes. Unlike results previously reported on constructed uplands, snowmelt runoff from uplands was much less (~30%), highlighting the influence of different construction materials. Model simulations indicate that antecedent soil moisture and soil temperature have a large influence on partitioning snowmelt over a range of observed conditions. Under a warmer and wetter climate, average annual peak SWE, and snow season duration could decline up to 52% and up to 61 days, respectively, while snowmelt runoff ceases completely under the warmest scenarios. Results suggest considerable future variability in snowmelt runoff from hillslopes, yet soil properties can be used to enhance vertical or lateral flows.
Decreased numbers of metachromatic cells in nasal swabs in Japanese cedar pollinosis following sublingual immunotherapy
Authors: Otsuka Kuninori , Otsuka Hirokuni , Matsune Shoji , Okubo Kimihiro
Published: May 2020

Background and Objective

Nasal symptoms were reduced following allergen‐specific sublingual immunotherapy (SLIT) for allergic rhinitis. The mechanisms underlying the effectiveness of SLIT for Japanese cedar pollinosis are poorly understood. We studied changes in the numbers of metachromatic cells, eosinophils, and neutrophils following SLIT for Japanese cedar pollinosis.

Methods

Nasal swabs were taken in the preseason (n = 32) and in pollinosis season (n = 49) from subjects given sublingual drop immunotherapy for an average duration of 1.5 years. The numbers of metachromatic cells (mast cells and basophils), eosinophils and neutrophils were determined and compared with those from untreated subjects in preseason (n = 65) and in season (n = 54).

Results

SLIT subjects had a significantly reduced frequency of moderate to most severe symptoms in comparison to untreated subjects in preseason (P < .001, the Mann‐Whitney U test), and (P < .00001) in season. Metachromatic cell counts in nasal swabs of SLIT subjects in preseason and in season were lower than those of untreated subjects (P = .014, the Mann‐Whitney U test) and (P = .00001) respectively. Eosinophil numbers in SLIT subjects were not significantly different than in untreated subjects in both preseason (P = .29) and in season (P = .09). However, when SLIT subjects in season were divided into those with greater than or equal to 1.5 years, or <1.5 years of SLIT duration, the degree of eosinophilia in those with SLIT greater than or equal to 1.5 years was significantly lower (P = .011) than in untreated patients, but not in those with SLIT less than 1.5 years (P = .9). There were no significant differences in neutrophil numbers in nasal swabs between untreated and SLIT subjects in preseason and in season.

Conclusion

One of mechanisms underlying the effectiveness of sublingual drop immunotherapy for Japanese cedar pollinosis is a reduction of the number of metachromatic cells in preseason and in season. Eosinophilia was also reduced in season in those given SLIT for greater than or equal to 1.5 years.
Molecular characterisation of TP53 mutated squamous cell carcinomas of the lung to identify putative targets for therapy
Authors: Haakensen Vilde D. , Khadse Anand , Sandhu Vandana , Halvorsen Ann Rita , Solberg Steinar K. , Jørgensen Lars H. , Brustugun Odd Terje , Kure Elin H. , Helland Åslaug
Published: May 2020

Personalised cancer treatment depends on identification of therapeutically relevant biological subgroups of patients for assessing effect of treatment and to discover new therapeutic options. By analyses in heterogeneous patient populations, the effects may be lost in noise. Squamous cell carcinoma of the lung is a major killer worldwide. Despite recent advances, mortality is high and response to therapies varies greatly from patient to patient. Target search in biologically relevant subgroups may identify treatment options not so far discovered. A total of 198 patients undergoing surgery for squamous cell carcinomas of the lung were included in the study. The tumours were analysed for copy number alterations (n = 152) and gene expression from tumour (n = 188) and normal lung (n = 21), with both data levels present in 140 patients. We studied alterations in tumours harbouring mutations in TP53 and in previously published gene expression subtypes. Genes with consistent alterations in both genomic levels were identified as putative biomarkers. Results were validated in TCGA. The most convincing biomarker in TP53 mutated squamous cell carcinomas of the lung was BIRC5 with amplification in 36% of mutated samples, 5% in wild‐type samples and a 17%‐fold change of expression between TP53 mutated tumours and normal lung tissue. BIRC5 was significantly altered in the classical and primitive subtypes. We suggest BIRC5 as a putative predictive biomarker and putative druggable target in squamous cell lung carcinomas harbouring TP53 mutation or classified as classical and primitive subtypes.
The impact of high‐fidelity simulation on knowledge, critical thinking, and clinical decision‐making for the management of pre‐eclampsia
Authors: Akalin Ayse , Sahin Sevil
Published: May 2020

Objective

To investigate the impact of high‐fidelity simulation on nursing students’ knowledge, critical thinking, and clinical decision‐making in the management of pre‐eclampsia, and to explore the students’ views and learning experiences.

Methods

A mixed‐methods design study was conducted on 107 third‐year nursing students. The students were randomly assigned to the control group (n=54) or the experimental group (n=53). The students in the experimental group attended the simulation training using a high‐fidelity simulator, while the students in the control group attended only the classical training on “the management of pre‐eclampsia.”

Results

Knowledge (P<0.001), critical thinking (P<0.05), and clinical decision‐making (P<0.05) scores of students in the experimental group increased after the simulation. In the focus group interviews, five themes were identified: learning development; closing the gap between theory and practice; confident decision‐making and self‐confidence; professional preparation; and recommendations.

Conclusion

High‐fidelity simulation is efficacious for improving the management of pre‐eclampsia among nursing students.
CNN based musical instrument identification using time‐frequency localized features
Authors: Dutta Arindam , Sil Dibakar , Chandra Aniruddha , Palit Sarbani
Published: May 2020

In this paper, the authors make an attempt to solve the convoluted problem of identifying musical instruments based on their audio excerpts, using a deep convolutional neural network. Continuous wavelet transform of audio signals are realized through Morse wavelet and two‐dimensional feature maps are formed, which are then fed to a simple yet robust convolutional neural network. The outcome is appreciable in the sense that training the model with just 20% of the data and testing on the rest gives a classification accuracy of 85%.
Addressing social stressors in a brief motivational interview improve mental health symptoms for Latinx heavy drinkers
Authors: Lee Christina S. , Rosales Robert , Colby Suzanne M. , Martin Rosemarie , Cox Koriann , Rohsenow Damaris J.
Published: May 2020

Objective

Depressive and anxiety symptoms co‐occur with hazardous drinking among Latinxs. This secondary analysis of a clinical trial to reduce hazardous drinking (motivational interviewing adapted to address social stressors [CAMI] vs. motivational interviewing [MI]) examined effects on anxiety/depressive symptoms. Discrimination and acculturation were examined as moderators.

Methods

Latinx (n = 296) hazardous drinkers (2+ occasions/month of heavy drinking; 4/5 drinks/occasion, females/males) were randomized to CAMI/MI. Generalized estimating equations analyzed how treatment conditions and interactions were related to depressive and anxiety symptoms after controlling for covariates.

Results

Baseline symptoms (anxiety, depression) exceeded clinical thresholds (Anxiety ≥8, M = 14.62, SD = 13.52; Depression ≥ 12, M = 18.78, SD = 12.57). Cultural adaptation of motivational interviewing (CAMI) showed significantly lower anxiety and depressive symptoms (6/12 months, respectively) than MI. CAMI with high baseline discrimination reported significantly less depression than MI (12 months).

Conclusions

Explicitly addressing social stressors may be a beneficial adjunct to treatment for Latinx drinkers.
Arginase‐II promotes melanoma migration and adhesion through enhancing hydrogen peroxide production and STAT3 signaling
Authors: Yu Yi , Ladeiras Diogo , Xiong Yuyan , Boligan Kayluz Frias , Liang Xiujie , von Gunten Stephan , Hunger Robert E. , Ming Xiu‐Fen , Yang Zhihong
Published: May 2020

Elevated arginase type II (Arg‐II) associates with higher grade tumors. Its function and underlying molecular mechanisms in melanoma remain elusive. In the present study, we observed a significantly higher frequency of Arg‐II expression in melanoma of patients with metastasis than those without metastasis. Silencing Arg‐II in two human melanoma cell lines slowed down the cell growth, while overexpression of native but not a catalytically inactive Arg‐II promoted cell proliferation without affecting cell death. Treatment of cells with arginase inhibitor also reduced melanoma cell number, demonstrating that Arg‐II promotes melanoma cell proliferation dependently of its enzymatic activity. However, results from silencing Arg‐II or overexpressing native or the inactive Arg‐II as well as treatment with arginase inhibitor showed that Arg‐II promotes melanoma metastasis‐related processes, such as melanoma cell migration and adhesion on endothelial cells, independently of its enzymatic activity. Moreover, the treatment of the cells with STAT3 inhibitor suppressed Arg‐II‐promoted melanoma cell migration and adhesion. Furthermore, catalase, but not superoxide dismutase, prevented STAT3 activation as well as increased melanoma cell migration and adhesion induced by overexpressing native or the inactive Arg‐II. Taken together, our study uncovers both activity‐dependent and independent mechanisms of Arg‐II in promoting melanoma progression. While Arg‐II enhances melanoma cell proliferation through polyamine dependently of its enzymatic activity, it promotes metastasis‐related processes, that is, migration and adhesion onto endothelial cell, through mitochondrial H2O2‐STAT3 pathway independently of the enzymatic activity. Suppressing Arg‐II expression rather than inhibiting its enzymatic activity may, therefore, represent a novel strategy for the treatment of melanoma.
BMPER is upregulated in obesity and seems to have a role in pericardial adipose stem cells
Authors: Pérez Laura M. , de Lucas Beatriz , Gálvez Beatriz G.
Published: May 2020

Pericardial adipose tissue (PAT), a visceral fat depot enveloping the heart, is an active endocrine organ and a source of free fatty acids and inflammatory cytokines. As in other fat adult tissues, PAT contains a population of adipose stem cells; however, whether these cells and/or their environment play a role in physiopathology is unknown. We analyzed several stem cell‐related properties of pericardial adipose stem cells (PSCs) isolated from obese and ex‐obese mice. We also performed RNA‐sequencing to profile the transcriptional landscape of PSCs isolated from the different diet regimens. Finally, we tested whether these alterations impacted on the properties of cardiac mesoangioblasts isolated from the same mice. We found functional differences between PSCs depending on their source: specifically, PSCs from obese PSC (oPSC) and ex‐obese PSC (dPSC) mice showed alterations in apoptosis and migratory capacity when compared with lean, control PSCs, with increased apoptosis in oPSCs and blunted migratory capacity in oPSCs and dPSCs. This was accompanied by different gene expression profiles across the cell types, where we identified some genes altered in obese conditions, such as BMP endothelial cell precursor‐derived regulator (BMPER), an important regulator of BMP‐related signaling pathways for endothelial cell function. The importance of BMPER in PSCs was confirmed by loss‐ and gain‐of‐function studies. Finally, we found an altered production of BMPER and some important chemokines in cardiac mesoangioblasts in obese conditions. Our findings point to BMPER as a potential new regulator of PSC function and suggest that its dysregulation could be associated with obesity and may impact on cardiac cells.
Talazoparib Exposure‐Efficacy Analysis in Patients With Advanced Breast Cancer and Germline BRCA1/2 Mutations in the EMBRACA Trial
Authors: Yu Yanke , Elmeliegy Mohamed , Litton Jennifer K. , Tudor Iulia Cristina , Czibere Akos , Zheng Jenny , Wang Diane D.
Published: May 2020

In the phase 3 EMBRACA trial, treatment with the poly(ADP‐ribose) polymerase inhibitor, talazoparib, led to significantly improved progression‐free survival (PFS) compared with chemotherapy (hazard ratio, 0.54; 95% confidence interval, 0.41‐0.71; P < .0001). We conducted an exposure‐efficacy analysis using EMBRACA data from 285 patients who were treated with talazoparib and had available pharmacokinetic parameters to evaluate the effect of talazoparib exposure (time‐varying average talazoparib concentration [Cavg,t]) and other baseline variables on PFS. Graphical examination of the relationship between Cavg,t and PFS and a Cox proportional model were used. Exposure‐response analyses showed that higher talazoparib exposure, absence of visceral disease, lower baseline lactate dehydrogenase levels, and disease‐free interval >12 months were independent covariates associated with longer PFS. The association of talazoparib exposure with PFS (higher exposure, longer PFS) suggests the recommended starting dose of 1 mg once daily (the maximum tolerated dose) is appropriate.
Estimation of the basic reproduction number, average incubation time, asymptomatic infection rate, and case fatality rate for COVID‐19: Meta‐analysis and sensitivity analysis
Authors: He Wenqing , Yi Grace Y. , Zhu Yayuan
Published: May 2020

The coronavirus disease‐2019 (COVID‐19) has been found to be caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). However, comprehensive knowledge of COVID‐19 remains incomplete and many important features are still unknown. This manuscript conducts a meta‐analysis and a sensitivity study to answer the questions: What is the basic reproduction number? How long is the incubation time of the disease on average? What portion of infections are asymptomatic? And ultimately, what is the case fatality rate? Our studies estimate the basic reproduction number to be 3.15 with the 95% CI (2.41‐3.90), the average incubation time to be 5.08 days with the 95% CI (4.77‐5.39) (in day), the asymptomatic infection rate to be 46% with the 95% CI (18.48%‐73.60%), and the case fatality rate to be 2.72% with 95% CI (1.29%‐4.16%) where asymptomatic infections are accounted for.
Early risk factors of the exacerbation of coronavirus disease 2019 pneumonia
Authors: Wang Chang‐Zheng , Hu Shun‐Lin , Wang Lin , Li Min , Li Huan‐Tian
Published: May 2020

The purpose of this study was to investigate the early risk factors for the exacerbation of coronavirus disease 2019 (COVID‐19) pneumonia. Restrospective analysis of clinical data of 85 patients infected with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), including gender, age, comorbidities, symptoms, blood routine, clotting profile, biochemical examination, albumin, myocardial enzyme profile, inflammatory markers, and chest computed tomography (CT). All laboratory examinations were measured within first 24 hours after admission, and chest CT was performed before admission. A total of 56 (65.9%) patients had a history of exposure to the Huanan seafood market in Wuhan. Fever and dry cough accounted for the highest percentage of all symptoms. Male COVID‐2019 patients were more likely to develop severe pneumonia. Patients with severe and critical conditions are older and have higher rates of hypertension (P = .003) and coronary heart disease (P = .017). All severe and critical patients infected with SARS‐CoV‐2 showed bilateral lung involvement and have more multiple lobes involvement than common patients (P < .001). Severe and critical patients showed higher white blood cell count (P = .006), neutrophil (NEU) count (P = .001), NEU% (P = .002), procalcitonin (P = .011), C‐reactive protein (P = .003), prothrombin time (P = .035), D‐dimer (P = .025), aspartate aminotransferase (P = .006), and lower lymphocyte (LYM) count (P = .019), LYM% (P = .001), albumin (P < .001). Logistic regression analysis showed that NEU count is an independent risk factor for deterioration, with the threshold of 6.5 × 109·L−1. We concluded that the laboratory independent risk factor for the progression of COVID‐19 pneumonia is NEU count. In addition, COVID‐19 patients with bilateral lung involvement or multiple lobes involvement should be taken seriously and actively treated to prevent deterioration of the disease.
Serum KL‐6 concentrations as a novel biomarker of severe COVID‐19
Authors: d'Alessandro Miriana , Cameli Paolo , Refini Rosa Metella , Bergantini Laura , Alonzi Valerio , Lanzarone Nicola , Bennett David , Rana Giuseppe Domenico , Montagnani Francesca , Scolletta Sabino , Franchi Federico , Frediani Bruno , Valente Serafina , Mazzei Maria Antonietta , Bonella Francesco , Bargagli Elena
Published: May 2020

Severe acute respiratory syndrome coronavirus 2–induced direct cytopathic effects against type I and II pneumocytes mediate lung damage. Krebs von den Lungen‐6 (KL‐6) is mainly produced by damaged or regenerating alveolar type II pneumocytes. This preliminary study analyzed serum concentrations of KL‐6 in patients with coronavirus disease (COVID‐19) to verify its potential as a prognostic biomarker of severity. Twenty‐two patients (median age [interquartile range] 63 [59‐68] years, 16 males) with COVID‐19 were enrolled prospectively. Patients were divided into mild‐moderate and severe groups, according to respiratory impairment and clinical management. KL‐6 serum concentrations and lymphocyte subset were obtained. Peripheral natural killer (NK) cells/µL were significantly higher in nonsevere patients than in the severe group (P = .0449) and the best cut‐off value was 119 cells/µL. KL‐6 serum concentrations were significantly higher in severe patients than the nonsevere group (P = .0118). Receiver operating characteristic analysis distinguished severe and nonsevere patients according to KL‐6 serum levels and the best cut‐off value was 406.5 U/mL. NK cell analysis and assay of KL‐6 in serum can help identify severe COVID‐19 patients. Increased KL‐6 serum concentrations were observed in patients with severe pulmonary involvement, revealing a prognostic value and supporting the potential usefulness of KL‐6 measurement to evaluate COVID‐19 patients' prognosis.
Dietary supplementation with citrus extract alters the plasma parameters, circulating amino acid profiles and gene expression of small intestinal nutrient transporters in Chinese yellow‐feathered broilers
Authors: Yu Miao , Li Zhenming , Wang Gang , Cui Yiyan , Rong Ting , Tian Zhimei , Liu Zhichang , Li Jiazhou , Chen Weidong , Ma Xianyong
Published: May 2020

BACKGROUND

This study evaluated the effects of citrus extract (CE) on growth performance, plasma amino acid (AA) profiles, intestinal development and small intestine AA and peptide transporter expression levels in broilers. A total of 540 one‐day‐old yellow‐feathered broilers were fed a basal diet without any antibiotic (control group), or a basal diet containing 10 mg kg−1zinc bacitracin (antibiotic group), or a basal diet supplemented with 10 mg kg−1CE (CE group). After 63 days of feeding, two broilers per pen were slaughtered to collect tissues for further analysis.

RESULTS

Results showed that CE increased (P < 0.05) the final body weight and average daily gain from day 1 to 63, and decreased (P < 0.05) the feed/gain ratio from day 1 to 63. Dietary CE supplementation increased (P < 0.05) plasma total protein, albumin and glucose concentration, and decreased (P < 0.05) urea concentration. CE supplementation increased (P < 0.05) the villus height in the ileum and the villus height/crypt depth in the jejunum and ileum, but decreased (P < 0.05) the crypt depth in the jejunum and ileum. CE supplementation increased (P < 0.05) most plasma essential AA concentrations. Additionally, CE supplementation upregulated (P < 0.05) ASCT1, b0,+AT, B0AT1, EAAT3, rBAT, y+LAT2 and PepT1 expression in the jejunum, and b0,+AT, EAAT3, rBAT, y+LAT2, CAT1 and PepT1 in the ileum.

CONCLUSIONS

Collectively, our results indicated that CE supplementation promotes intestinal physiological absorption of AAs by upregulating gene expression of small intestinal key AA and peptide transporters, thereby enhancing the growth performance of broilers. © 2020 Society of Chemical Industry