bluuebunny/crossref_metadata_2025 huggingface dataset:
Long‐term follow‐up of human papillomavirus type replacement among young pregnant Finnish females before and after a community‐randomised HPV vaccination trial with moderate coverage
Authors: Gray Penelope , Kann Hanna , Pimenoff Ville N. , Adhikari Indira , Eriksson Tiina , Surcel Heljä‐Marja , Vänskä Simopekka , Dillner Joakim , Faust Helena , Lehtinen Matti
Published: June 2020

Large scale human papillomavirus (HPV) vaccination against the most oncogenic high‐risk human papillomavirus (HPV) types 16/18 is rapidly reducing their incidence. However, attempts at assessing if this leads to an increase of nonvaccine targeted HPV types have been hampered by several limitations, such as the inability to differentiate secular trends. We performed a population‐based serological survey of unvaccinated young women over 12 years. The women were under 23‐years‐old, residents from 33 communities which participated in a community‐randomised trial (CRT) with approximately 50% vaccination coverage. Serum samples were retrieved pre‐CRT and post‐CRT implementation. Seropositivity to 17 HPV types was assessed. HPV seroprevalence ratios (PR) comparing the postvaccination to prevaccination era were estimated by trial arm. This was also assessed among the sexual risk‐taking core group, where type replacement may occur more rapidly. In total, 8022 serum samples from the population‐based Finnish Maternity Cohort were retrieved. HPV types 16/18 showed decreased seroprevalence among the unvaccinated in communities only after gender‐neutral vaccination (PR16/18A = 0.8, 95% CI 0.7‐0.9). HPV6/11 and HPV73 were decreased after gender‐neutral vaccination (PR6/11A = 0.8, 95% CI 0.7‐0.9, PR73A = 0.7, 95% CI 0.6‐0.9, respectively) and girls‐only vaccination (PR6/11B = 0.8, 95% CI 0.7‐0.9, PR73B = 0.9, 95% CI 0.8‐1.0). HPV68 alone was increased but only after girls‐only vaccination (PR68B = 1.3, 95% CI 1.0‐1.7, PRcore68B = 2.8, 95% CI 1.2‐6.3). A large‐scale, long‐term follow‐up found no type replacement in the communities with the strongest reduction of vaccine HPV types. Limited evidence for an increase in HPV68 was restricted to girls‐only vaccinated communities and may have been due to secular trends (ClinicalTrials.gov number: NCT00534638).
Post‐discharge outcomes for mothers and the mother–infant relationship following admission to a psychiatric Mother–Baby Unit
Authors: Wright Tanya , Stevens Suzanne , Reed Peter W. , Wouldes Trecia A.
Published: June 2020

Mother–Baby Unit research has focussed on maternal psychopathology over the course of an admission. Less is known about the baby's well‐being, the shared relationship, or the mother's recovery. In an initial sample of 45 women, we describe discharge and post‐discharge outcomes for maternal psychopathology (using maternal report and the Global Assessment of Function, GAF) and the mother–infant relationship (using the Child and Adult Relational Experimental Index, CARE Index). Three months post‐discharge, one third of women described themselves as “completely recovered,” one third were experiencing significant deterioration and 17% were readmitted to inpatient care. Poorer GAF scores were associated with a clinical diagnosis of comorbid personality disorder, antenatal presence of the index illness, partner illicit substance use, maternal perception of her bond, infant social withdrawal, and child protection concern. Post‐discharge, the mother–infant relationship results were concerning. Only 17% were regarded as adequate. Improvement was observed across this period in 56% but relational deterioration occurred for 35%. Maternal and relational outcomes were weakly correlated at discharge (r² = 0.29, p = 0.07) but this was lost post‐discharge (r² = 0.03, p = 0.89). The shared relationship and infant mental health should both be targets for intervention; both during MBU admission, and post‐discharge.
The risk of low risk: First time motherhood, prematurity and dyadic well‐being
Authors: Porter Lauren , van Heugten Kate , Champion Patricia
Published: June 2020

Premature birth has a well‐documented impact on infants, mothers and their dyadic interactions. First time motherhood in the context of low risk premature birth—relatively unexplored in the literature—is a specific experience that sits at the nexus of premature infancy, motherhood and the processes that underpin dyadic connection. This qualitative study analyzed semistructured interviews with first time mothers of low risk premature babies. Findings were generated in response to research questions concerning mothers’ meaning‐making, bonding and identity. Findings demonstrated that maternal meaning‐making emerged from a dyadic framework. When mothers or their infants were considered outside of a dyadic context, surplus suffering inadvertently occurred. Findings have important implications for infant mental health practice in medical settings, for postnatal support in the aftermath of premature birth, and for understanding the meaning of risk.
Epigallocatechin‐3‐gallate activates the AMP‐activated protein kinase signaling pathway to reduce lipid accumulation in canine hepatocytes
Authors: Ding Hongyan , Li Yu , Li Wei , Tao Huanqing , Liu Leihong , Zhang Cai , Kong Tao , Feng Shibin , Li Jinchun , Wang Xichun , Wu Jinjie
Published: June 2020

Epigallocatechin‐3‐gallate (EGCG) plays a crucial role in hepatic lipid metabolism. However, the underlying regulatory mechanism of hepatic lipid metabolism by EGCG in canine is unclear. Primary canine hepatocytes were treated with EGCG (0.01, 0.1, or 1 μM) and BML‐275 (an AMP‐activated protein kinase [AMPK] inhibitor) to study the effects of EGCG on the gene and protein expressions associated with AMPK signaling pathway. Data showed that treatment with EGCG had greater activation of AMPK, as well as greater expression levels and transcriptional activity of peroxisome proliferator activated receptor‐α (PPARα) along with upregulated messenger RNA (mRNA) abundance and protein abundance of PPARα‐target genes. EGCG decreased the expression levels and transcriptional activity of sterol regulatory element‐binding protein 1c (SREBP‐1c) along with downregulated mRNA abundance and protein abundance of SREBP‐1c target genes. Of particular interest, exogenous BML‐275 could reduce or eliminate the effects of EGCG on lipid metabolism in canine hepatocytes. Furthermore, the content of triglyceride was significantly decreased in the EGCG‐treated groups. These results suggest that EGCG might be a potential agent in preventing high‐fat diet‐induced lipid accumulation in small animals.
Families in posets minimizing the number of comparable pairs
Authors: Balogh József , Petříčková Šárka , Wagner Adam Zsolt
Published: June 2020

Given a graded poset we say a family is centered if it is obtained by ‘taking sets as close to the middle layer as possible.’ A poset is said to have the centeredness property if for any , among all families of size in , centered families contain the minimum number of comparable pairs. Kleitman showed that the Boolean lattice has the centeredness property. It was conjectured by Noel, Scott, and Sudakov, and by Balogh and Wagner, that the poset also has the centeredness property, provided is sufficiently large compared with . We show that this conjecture is false for all and investigate the range of for which it holds. Further, we improve a result of Noel, Scott, and Sudakov by showing that the poset of subspaces of has the centeredness property. Several open questions are also given.
Synthesis, biological evaluation, and docking study of a series of 1,4‐disubstituted 1,2,3‐triazole derivatives with an indole‐triazole‐peptide conjugate
Authors: Suryapeta Srinivas , Papigani Neeraja , Banothu Venkanna , Dubey Pramod Kumar , Mukkanti Khagga , Pal Sarbani
Published: June 2020

A series of new compounds containing an indole‐triazole‐peptide conjugate were designed as potential agents possessing the dual anti‐bacterial and anticancer activities. Accordingly, 20 compounds were prepared via a multi‐step synthesis involving the copper‐catalyzed azide‐alkyne cycloaddition (CuAAC) as a key step in moderate to high yield. All the synthesized compounds were purified by chromatographic techniques and characterized by IR, 1H and 13C NMR and mass spectral data. The synthesized derivatives were screened for their antimicrobial activities against one gram‐positive (Staphylococcus aureus) and three gram‐negative (Escherichia coli, Klebsiella pneumonia, and Proteus vulgaris) bacteria using an agar‐well diffusion method. Most of the compounds showed moderate to reasonable antibacterial activities especially the compound 9e that showed good activities against all the strains. The potential of DNA gyrase inhibitory activity of this compound was assessed by using molecular docking studies in silico carried out using Autodock Vina software. The low ΔGbind value (−9.4 Kcal/mol) of compound 9e suggested its good interactions with the target protein in silico. The cytotoxic activities of some of the compounds synthesized were evaluated via a MTT assay using the human lung cancer cell line A549. Several compounds showed promising activities among which compound 9b, 9k, and 9e showed low IC50 values.
The multiple ways Wnt signaling contributes to acute leukemia pathogenesis
Authors: Soares-Lima Sheila C , Pombo-de-Oliveira Maria S , Carneiro Flávia R G
Published: June 2020

WNT proteins constitute a very conserved family of secreted glycoproteins that act as short-range ligands for signaling with critical roles in hematopoiesis, embryonic development, and tissue homeostasis. These proteins transduce signals via the canonical pathway, which is β-catenin-mediated and better-characterized, or via more diverse noncanonical pathways that are β-catenin independent and comprise the planar cell polarity (PCP) pathway and the WNT/Ca++ pathways. Several proteins regulate Wnt signaling through a variety of sophisticated mechanisms. Disorders within the pathway can contribute to various human diseases, and the dysregulation of Wnt pathways by different molecular mechanisms is implicated in the pathogenesis of many types of cancer, including the hematological malignancies. The types of leukemia differ considerably and can be subdivided into chronic, myeloid or lymphocytic, and acute, myeloid or lymphocytic, leukemia, according to the differentiation stage of the predominant cells, the progenitor lineage, the diagnostic age strata, and the specific molecular drivers behind their development. Here, we review the role of Wnt signaling in normal hematopoiesis and discuss in detail the multiple ways canonical Wnt signaling can be dysregulated in acute leukemia, including alterations in gene expression and protein levels, epigenetic regulation, and mutations. Furthermore, we highlight the different impacts of these alterations, considering the distinct forms of the disease, and the therapeutic potential of targeting Wnt signaling.
Aloe emodin relieves Ang II-induced endothelial junction dysfunction via promoting ubiquitination mediated NLRP3 inflammasome inactivation
Authors: Zhang Yi , Song Ziqing , Huang Shan , Zhu Li , Liu Tianyi , Shu Hongyan , Wang Lei , Huang Yi , Chen Yang
Published: June 2020

Recent studies have revealed that aloe emodin (AE), a natural compound from the root and rhizome of Rheum palmatum L., exhibits significant pharmacologic activities. However, the pharmacologic relevance of the compound, particularly for cardiovascular disease, remains largely unknown. Here, we hypothesized that AE could improve endothelial junction dysfunction through inhibiting the activation of NOD-like receptor family pyrin domain containing-3 (NLRP3) inflammasome regulated by NLRP3 ubiquitination, and ultimately prevent cardiovascular disease. In vivo, we used confocal microscopy to study the expression of tight junction proteins zonula occludens-1/2 (ZO-1/2) and the formation of NLRP3 inflammasome in coronary arteries of hypertension. And the experimental serum was used to detect the activation of NLRP3 inflammasome by ELISA assay. We found that AE could restore the expression of the endothelial connective proteins ZO-1/2 and decrease the release of high mobility group box1 (HMGB1), and also inhibited the formation and activation of NLRP3 inflammasome. Similarly, in vitro, our findings demonstrated that AE could restore the expression of the tight junction proteins ZO-1/2 and decrease monolayer cell permeability that related to endothelial function after stimulation by angiotensin II (Ang II) in microvascular endothelial cells (MECs). We also demonstrated that AE could inhibit Ang II-induced NLRP3 inflammasome formation and activation, which were regulated by NLRP3 ubiquitination in MECs, as shown by fluorescence confocal microscopy and Western blot. Together with these changes, we revealed a new protection mechanism of AE that inhibited NLRP3 inflammasome activation and decreased the release of HMGB1 by promoting NLRP3 ubiquitination. Our findings implicated that AE exhibited immense potential and specific therapeutic value in hypertension-related cardiovascular disease in the early stage and the development of innovative drugs.
The neuroactive substances and associated muscle system in Rhipidocotyle campanula (Digenea, Bucephalidae) from the intestine of the pike Esox lucius
Authors: Kreshchenko Natalia , Terenina Nadezhda , Nefedova Darya , Mochalova Natalia , Voropaeva Ekaterina , Movsesyan Sergey
Published: June 2020

We report about the muscular system and the serotonergic and FMRFamidergic components of the nervous system of the Bucephalidae trematode, Rhipidocotyle campanula, an intestinal parasite of the pike. We use immunocytochemical methods and confocal scanning laser microscopy (CLSM). The musculature is identified by histochemical staining with fluorescently labeled phalloidin. The body wall musculature of R. campanula contains three layers of muscle fibres – the outer thin circular, intermediate longitudinal and inner diagonal muscle fibres running in two opposite directions. The digestive system of R. campanula possess of a well‐developed musculature: radial, longitudinal and circular muscle elements are detected in the pharynx, circular and longitudinal muscle filaments seen in the oesophagus, and longitudinal and the circular muscle fibres were found in the intestinal wall. Specific staining indicating the presence of actin muscle filaments occurs in the cirrus sac localized in the posterior body region. The frontal region of anterior attachment organ, the rhynchus, in R. campanula is represented by radial muscle fibres. The posterior part of the rhynchus comprise of radial muscles forming the organ's wall, and several strong longitudinal muscle bundles. Serotonergic and FMRFamidergic structures are detected in the central and peripheral compartments of the nervous system of R. campanula, that is, in the paired brain ganglia, the brain commissure, the longitudinal nerve cords, and connective nerve commissures. The innervations of the rhynchus, pharynx, oesophagus and distal regions of the reproductive system by the serotonergic and FMRFamidergic nervous elements are revealed. We compare our findings obtained on R. campanula with related data for other trematodes.
Intrinsic disorder in protein sense‐antisense recognition
Authors: Dayhoff Guy W. , van Regenmortel Marc H. V. , Uversky Vladimir N.
Published: June 2020

In addition to the well‐established sense‐antisense complementarity abundantly present in the nucleic acid world and serving as a basic principle of the specific double‐helical structure of DNA, production of mRNA, and genetic code‐based biosynthesis of proteins, sense‐antisense complementarity is also present in proteins, where sense and antisense peptides were shown to interact with each other with increased probability. In nucleic acids, sense‐antisense complementarity is achieved via the Watson‐Crick complementarity of the base pairs or nucleotide pairing. In proteins, the complementarity between sense and antisense peptides depends on a specific hydropathic pattern, where codons for hydrophilic and hydrophobic amino acids in a sense peptide are complemented by the codons for hydrophobic and hydrophilic amino acids in its antisense counterpart. We are showing here that in addition to this pattern of the complementary hydrophobicity, sense and antisense peptides are characterized by the complementary order‐disorder patterns and show complementarity in sequence distribution of their disorder‐based interaction sites. We also discuss how this order‐disorder complementarity can be related to protein evolution.
Elucidation of cellular targets and exploitation of the receptor‐binding domain of SARS‐CoV‐2 for vaccine and monoclonal antibody synthesis
Authors: Baig Abdul Mannan , Khaleeq Areeba , Syeda Hira
Published: June 2020

The pandemic caused by novel severe acute respiratory syndrome coronavirus (SARS‐CoV‐2) has resulted in over 452 822 deaths in the first 20 days of June 2020 due to the coronavirus virus disease 2019 (COVID‐19). The SARS‐CoV‐2 uses the host angiotensin‐converting enzyme 2 (ACE2) receptor to gain entry inside the human cells where it replicates by using the cell protein synthesis mechanisms. The knowledge of the tissue distribution of ACE2 in human organs is therefore important to predict the clinical course of the COVID‐19. Also important is the understanding of the viral receptor‐binding domain (RBD), a region within the spike (S) proteins, that enables the entry of the virus into the host cells to synthesize vaccine and monoclonal antibodies (mAbs). We performed an exhaustive search of human protein databases to establish the tissues that express ACE2 and performed an in‐depth analysis like sequence alignments and homology modeling of the spike protein (S) of the SARS‐CoV‐2 to identify antigenic regions in the RBD that can be exploited to synthesize vaccine and mAbs. Our results show that ACE2 is widely expressed in human organs that may explain the pulmonary, systemic, and neurological deficits seen in COVID‐19 patients. We show that though the S protein of the SARS‐CoV‐2 is a homolog of S protein of SARS‐CoV‐1, it has regions of dissimilarities in the RBD and transmembrane segments. We show peptide sequences in the RBD of SARS‐CoV‐2 that can bind to the major histocompatibility complex alleles and serve as effective epitopes for vaccine and mAbs synthesis.
A prospective study of medication management during transitions from hospital to residential care: a 10‐year follow‐up to the MedGap study
Authors: Elliott Rohan A. , Boutros Yvonne , Tran Tim , Taylor Simone E.
Published: June 2020

Background

Problems with continuity of medication administration after discharge from hospitals to residential care facilities (RCFs) have been reported in Australia and internationally. The MedGap study in 2009 reported a significant decline in post‐discharge missed or delayed doses and locum doctor call‐outs at RCFs following implementation of a hospital pharmacy‐prepared interim residential care medication administration chart (IRCMAC).

Aim

To determine whether reductions in missed or delayed doses and locum doctor call‐outs were sustained nearly 10 years after the IRCMAC was implemented, and evaluate RCFs' use of IRCMACs and discharge medications supplied in original packaging.

Method

Structured telephone interviews with nurses at 52 RCFs were conducted approximately 48‐h after discharge for randomly selected patients discharged from hospitals within a major metropolitan health service in Melbourne, Australia in 2018. Results were compared with pre‐ and post‐intervention data collected using the same method in 2009. Primary endpoints were the proportion of patients for whom the RCF used the hospital‐supplied IRCMAC and discharge medications, and the incidence of missed or significantly delayed medication doses in the first 24 h post‐discharge. The number of locum doctor call‐outs was a secondary endpoint.

Results

RCFs received IRCMACs for 71/73 (97.3%) patients and used them for 61/71 (85.9%). Hospital‐supplied medication, in original packaging, was received for 65/73 (89.0%) patients and used for 59/65 (90.8%). One or more doses were missed or significantly delayed for 2/73 (2.7%) patients and locum doctors were called for nine patients (12.3%), which was similar to the 2009 post‐intervention study (6/226, 2.7% and 25/226, 11.1%, respectively) and significantly lower than the 2009 pre‐intervention study (37/202, 18.3% and 66/202, 32.7%, respectively; P < 0.01 for both endpoints). Nearly 100% of RCF staff believed IRCMACs and hospital‐supplied medication improved continuity of care.

Conclusion

Hospital pharmacy‐prepared IRCMACs and discharge medication in original packaging were highly used and valued by RCF staff, and associated with sustained low rates of missed and delayed doses and locum doctor call‐outs.
Prevalence and Risk of Metastatic Thyroid Cancers and Management Outcomes: A National Perspective
Authors: Al‐Qurayshi Zaid , Sullivan Christopher B. , Pagedar Nitin , Lee Grace S. , Tufano Ralph , Kandil Emad
Published: June 2020

Objectives

Examine the prevalence and risk of metastasis in thyroid cancers and management outcomes.

Study design

Retrospective analysis of the National Cancer Database, 2004–2014.

Methods

The study population included adult (≥ 18 years) patients with thyroid cancer. Analysis included multivariate logistic regression and Cox hazard ratio modeling.

Results

A total of 152,979 patients were included. Distant metastasis was reported in 1,867 (1.22%) patients. The distribution of metastatic cases based on pathology and tumor size were as follows in descending order: papillary thyroid carcinoma (PTC) 1 to 4 cm (30.53%), PTC > 4 cm (19.34%), undifferentiated (UTC) > 4 cm (14.14%), PTC < 1 cm (8.46%), follicular thyroid carcinoma (FTC) > 4 cm (7.28%), FTC 1 to 4 cm (5.52%), medullary thyroid cancer (MTC) ≤ 4 cm (3.96%), MTC > 4 cm (3.91%), UTC ≤ 4 cm (3.32%), Hürthle (HCC ) > 4 cm (2.09%), and HCC 1 to 4 cm (1.45%). Significant predictors of distant metastasis, while controlling for tumor pathology and size, included older age, male gender, non‐White minorities, presence of multiple comorbidities, minimal, gross extrathyroidal extension (ETE), lymphovascular invasion (LVI), and concomitant central and lateral lymph node metastasis (LNM) (P < .05 each). The risk of distant metastasis in the absence of nodal metastasis, ETE, and LVI was highest for FTC > 4 cm.

Conclusion

Although the risk of metastasis in well‐differentiated thyroid carcinoma (WDTC) is low, the prevalence of metastatic thyroid cancer is highest in WDTC population because it is the most common type of thyroid cancer. Certain pathological features, including minimal ETE and central LNM, are associated with a higher prevalence of metastatic disease.

Level of Evidence

NA Laryngoscope, 131:237–244, 2021
Technological capabilities and internationalization of high‐tech ventures: The moderating role of strategic orientations
Authors: Chung Jee Yong , Yoon Woojin
Published: June 2020

Venture firms' technological capabilities play a critical role in their internationalization. Applying a contingency‐based approach to the internationalization of technology‐based ventures, this study analyzes the moderating effects of strategic orientation on the relationship between technological capabilities and internationalization. The statistical analysis indicates that different strategic orientation types moderate the relationship between technological capabilities and internationalization in different directions. These findings suggest that strategic orientation offers an important context for understanding the internationalization of technology‐based ventures.
Expanded carrier screening in Chinese patients seeking the help of assisted reproductive technology
Authors: Xi Yanping , Chen Guangquan , Lei Caixia , Wu Junping , Zhang Shuo , Xiao Min , Zhang Wenbi , Zhang Yueping , Sun Xiaoxi
Published: June 2020

Background

Expanded carrier screening (ECS) has emerged as an effective approach to identify at‐risk couples (ARCs)—before they initiate attempts at reproduction—who possess a high probability of having a child affected by severe recessive diseases. The objective of this study was to evaluate the clinical utility of ECS in Chinese patients seeking the help of assisted reproductive technology (ART).

Methods

An ECS test, which covers 201 genes implicated in 135 recessive (autosomal or X‐linked) diseases, was routinely offered to all ART patients in a single genetics and in vitro fertilization clinic. Additional options for preimplantation or prenatal genetic diagnosis were discussed and offered to all ARCs. All ECS results were aggregated and the clinical decisions of the ARCs were surveyed.

Results

A total of 2,923 ART patients, representing 1,462 couples, were screened. Overall, 46.73% of the individuals were found to be the carriers for at least 1 of the 135 diseases. Of the tested couples, 2.26% (n = 33) were identified as ARCs. As of the completion of this study, 21 (63.6%) ARCs have decided to avert an affected pregnancy with the help of preimplantation genetic testing for monogenetic conditions. The cumulative carrier rate of the 187 autosomal recessive genes in the ECS panel for the 2,836 Han Chinese individuals without a family history was estimated to be 45.91%. The estimated at‐risk couple rate indicates that the screening for only the top 31 genes with gene carrier rates >0.5% would identify more than 94% of the ARCs identified by screening all 187 genes.

Conclusion

Our study demonstrates that ESC yields a significant clinical value for ART patients in China. In addition, by estimating the yields of the ECS panel, we identify genes that are appropriate for screening the Han population.
Disrupted minor intron splicing is prevalent in Mendelian disorders
Authors: Olthof Anouk M. , Rasmussen Jeffrey S. , Campeau Philippe M. , Kanadia Rahul N.
Published: June 2020

Background

Splicing is crucial for proper gene expression, and is predominately executed by the major spliceosome. Conversely, 722 introns in 699 human minor intron‐containing genes (MIGs) are spliced by the minor spliceosome. Splicing of these minor introns is disrupted in diseases caused by pathogenic variants in the minor spliceosome, ultimately leading to the aberrant expression of a subset of these MIGs. However, the effect of variants in minor introns and MIGs on diseases remains unexplored.

Methods

Variants in MIGs and associated clinical manifestations were identified using ClinVar. The HPO database was then used to curate the related symptoms and affected organ systems. Results: We found pathogenic variants in 211 MIGs, which commonly resulted in intellectual disability, seizures and microcephaly. This revealed a subset of MIGs whose aberrant splicing may contribute to the pathogenesis of minor spliceosome‐related diseases. Moreover, we identified 51 pathogenic variants in minor intron splice sites that reduce the splice site strength and can induce alternative splicing.

Conclusion

These findings highlight that disrupted minor intron splicing has a broader impact on human diseases than previously appreciated. The hope is that this knowledge will aid in the development of therapeutic strategies that incorporate the minor intron splicing pathway.
sensaas: Shape‐based Alignment by Registration of Colored Point‐based Surfaces
Authors: Douguet Dominique , Payan Frédéric
Published: June 2020

sensaas is a tool developed for aligning and comparing molecular shapes and sub‐shapes. Alignment is obtained by registration of 3D point‐based representations of the van der Waals surface. The method uses local properties of the shape to identify the correspondence relationships between two point clouds containing up to several thousand colored (labeled) points. Our rigid‐body superimposition method follows a two‐stage approach. An initial alignment is obtained by matching pose‐invariant local 3D descriptors, called FPFH, of the input point clouds. This stage provides a global superimposition of the molecular surfaces, without any knowledge of their initial pose in 3D space. This alignment is then refined by optimizing the matching of colored points. In our study, each point is colored according to its closest atom, which itself belongs to a user defined physico‐chemical class. Finally, sensaas provides an alignment and evaluates the molecular similarity by using Tversky coefficients. To assess the efficiency of this approach, we tested its ability to reproduce the superimposition of X‐ray structures of the benchmarking AstraZeneca (AZ) data set and, compared its results with those generated by the two shape‐alignment approaches shaep and shafts. We also illustrated submatching properties of our method with respect to few substructures and bioisosteric fragments. The code is available upon request from the authors (demo version at https://chemoinfo.ipmc.cnrs.fr/SENSAAS).
On the solution of a boundary value problem associated with a fractional differential equation
Authors: Sevinik Adigüzel Rezan , Aksoy Ümit , Karapinar Erdal , Erhan İnci M.
Published: June 2020

The problem of the existence and uniqueness of solutions of boundary value problems (BVPs) for a nonlinear fractional differential equation of order 2<α ≤ 3 is studied. The BVP is transformed into an integral equation and discussed by means of a fixed point problem for an integral operator. Conditions for the existence and uniqueness of a fixed point for the integral operator are derived via b‐comparison functions on complete b‐metric spaces. In addition, estimates for the convergence of the Picard iteration sequence are given. An estimate for the Green's function related with the problem is provided and employed in the proof of the existence and uniqueness theorem for the solution of the given problem. Illustrative examples are presented to support the theoretical results.
Mitochondrial Dysfunction is a Key Pathway that Links Saturated Fat Intake to the Development and Progression of NAFLD
Authors: Meex Ruth C. R. , Blaak Ellen E.
Published: June 2020

Non‐Alcoholic fatty liver disease (NAFLD) is the most common form of liver disease and is characterized by fat accumulation in the liver. Hypercaloric diets generally increase hepatic fat accumulation, whereas hypocaloric diets decrease liver fat content. In addition, there is evidence to suggest that moderate amounts of unsaturated fatty acids seems to be protective for the development of a fatty liver, while consumption of saturated fatty acids (SFA) appears to predispose toward hepatic steatosis. Recent studies highlight a key role for mitochondrial dysfunction in the development and progression of NAFLD. It is proposed that changes in mitochondrial structure and function are key mechanisms by which SFA lead to the development and progression of NAFLD. In this review, it is described how SFA intake is associated with liver steatosis and decreases the efficiency of the respiratory transport chain. This results in the production of reactive oxygen species and damage to nearby structures, eventually leading to inflammation, apoptosis, and scarring of the liver. Furthermore, studies demonstrating that SFA intake affects the composition of mitochondrial membranes are presented, and this process accelerates the progression of NAFLD. It is likely that events are intertwined and reinforce each other, leading to a constant deterioration in health.
Role of the cholesterol hydroxyl group in the chemical exchange saturation transfer signal at −1.6 ppm
Authors: Chang Yu‐Chi , Liu Hong‐Qing , Chang Jung‐Hsuan , Chang Yu‐Yen , Lin Eugene C.
Published: June 2020

Chemical exchange saturation transfer (CEST) can provide metabolite‐weighted images in the clinical setting; therefore, understanding the origin of each CEST signal is essential to revealing the changes in diseases at the molecular level, which would provide further insight for diagnoses and treatments. The CEST signal at −1.6 ppm is attributed to the choline methyl group of phosphatidylcholines. The methyl groups have no exchangeable protons, so the corresponding CEST signals must result from the relayed nuclear Overhauser effect (rNOE); however, the detailed mechanism remains unclear. Cholesterol is a major component of biological membranes, and its content is closely related to the dynamics and phases of these lipids. However, cholesterol has a hydroxyl group, which could participate in proton exchange to complete the rNOE process. In this study, we used liposomes containing cholesterol and its analogs (5α‐cholestane and progesterone), which presumably have similar capabilities of influencing lipid bilayers, and found that the steroid hydroxyl group is the key to inducing the rNOE at −1.6 ppm. Our results suggest that the origin of the rNOE at −1.6 ppm likely requires an intermolecular NOE between the proton of the choline methyl group and that of the cholesterol hydroxyl group, and a chemical exchange between the cholesterol hydroxyl group and bulk water. However, the phenomenon in which the rNOE at −1.6 ppm appears when the cholesterol concentration is high seems to contradict the in vivo results, suggesting a more complicated mechanism associated with the rNOE at −1.6 ppm in biological membranes.
Area deprivation is associated with poorer overall survival in children with acute lymphoblastic leukemia
Authors: Schraw Jeremy M. , Peckham‐Gregory Erin C. , Rabin Karen R. , Scheurer Michael E. , Lupo Philip J. , Oluyomi Abiodun
Published: June 2020

Background

Few studies have evaluated social determinants of outcomes disparities for children with acute lymphoblastic leukemia (ALL). We investigated the association of area deprivation index (ADI), a measure of neighborhood socioeconomic disadvantage, with overall survival (OS) among children and adolescents with ALL.

Procedure

We obtained demographic and clinical data, geocoded addresses at diagnosis, and vital status on all Texas children diagnosed with ALL from 1995 to 2011 (N = 4104). Using the US Census Bureau 2010 geography, we computed ADI scores for all census tracts in Texas and grouped the tracts into quartiles: least, third‐most, second‐most, and most disadvantaged. We mapped children to ADI quartiles based on residence at diagnosis, and estimated OS using Cox regression adjusting for sex, race/ethnicity, age, and metropolitan/nonmetropolitan residence.

Results

Five‐year OS ranged from 89% (95% confidence interval [CI] 87‐91%) for children in the least disadvantaged tracts to 79% (95% CI 76‐81%) for children in the most disadvantaged tracts (P = 4E‐7). An elevated hazard ratio (HR) for death was observed for children in the most disadvantaged tracts (HR 1.57, 95% CI 1.23‐2.00), and trends toward increased mortality were observed in the third‐most and second‐most disadvantaged tracts (HR 1.23, 95% CI 0.97‐1.57 and HR 1.27, 95% CI 0.99‐1.62, respectively). In stratified analyses, area disadvantage was more strongly associated with OS in males than females.

Conclusions

Neighborhood socioeconomic disadvantage is associated with inferior OS in this analysis of over 4100 children with ALL, highlighting the substantial contributions of social‐environmental factors to childhood cancer survival. This association was stronger in males than females.
Bidirectional mass transfer‐based generation of plasma‐activated water mist with antibacterial properties
Authors: Sysolyatina Elena V. , Lavrikova Aleksandra Y. , Loleyt Roman A. , Vasilieva Elena V. , Abdulkadieva Mariam A. , Ermolaeva Svetlana A. , Sofronov Aleksey V.
Published: June 2020

Plasma‐activated water mist (PAWM) is obtained by the ignition of plasma within an air–vapor mixture. PAWM demonstrates significant antibacterial properties, decreasing loads of foodborne pathogens by a factor of 35.5 for Listeria monocytogenes, 166 for Salmonella Typhimurium, and 266 for Escherichia coli O157:H7 within 15 s. Bacterial biofilms have a similar species‐dependant susceptibility. Biofilms of L. monocytogenes, Salmonella Typhimurium, and E. coli O157:H7 are destroyed by 44%, 77%, and 71%, respectively, after being treated for 2 min. Obtained results suggest importance of short‐lived radicals, because PAWM condensate is not bactericidal. A new model of PAW generation as a cyclic process of oxidation reactive nitrogen species by reactive oxygen species, which occurs during effective bidirectional mass transfer between heavily humid air and water mist in plasma discharge, is presented.
Effect of Heating Rate on Ignition Characteristics of Newly Prepared and Aged Aluminum Nanoparticles
Authors: Jin Xiao , Li Shengji , Yang Yihang , Yang Yanjing , Huang Xuefeng
Published: June 2020

Aluminum (Al) nanoparticles have been widely applied in propellants, but the ageing of Al nanoparticles will result in the degradation of propellant ignition performance. This paper experimentally investigates the ignition characteristics of newly prepared and aged Al nanoparticles, and improves the ignition performance of aged Al nanoparticles through elevating the heating rate. It was observed that, despite newly prepared or aged Al nanoparticles, their ignition included three stages: stage I – heating, stage II – melting, and stage III – evaporation. The temperature rise and time in stage I, melting temperature, and time in stage II and ignition temperature in stage III were separately discussed. It is found that the duration of each stage during the ignition of aged Al nanoparticles was much longer than that of newly prepared Al nanoparticles, testifying that ignition temperature of Al nanoparticles increased and ignition delay time elongated due to ageing. At elevated power density, the heating rate of Al nanoparticles increased, the heating, melting, and evaporating time shortened. The difference of ignition delay time between newly prepared and aged Al nanoparticles was significantly reduced. It means that the ignition performance can be improved through increasing the heating rate. Simultaneously, the energy conversation equation of each stage was built and discussed. It will be beneficial to deeply understand the ignition process and reveal the ignition mechanism of aged Al nanoparticles.
Unified Lagrangian‐Hamiltonian Formalism for Contact Systems
Authors: de León Manuel , Gaset Jordi , Lainz Manuel , Rivas Xavier , Román‐Roy Narciso
Published: June 2020

We present a unified geometric framework for describing both the Lagrangian and Hamiltonian formalisms of contact autonomous mechanical systems, which is based on the approach of the pioneering work of R. Skinner and R. Rusk. This framework permits to skip the second order differential equation problem, which is obtained as a part of the constraint algorithm (for singular or regular Lagrangians), and is especially useful to describe singular Lagrangian systems. Some examples are also discussed to illustrate the method.
Linking rapid forecast error growth to diabatic processes
Authors: Sánchez Claudio , Methven John , Gray Suzanne , Cullen Mike
Published: June 2020

The predictability of high‐impact weather events over the North Atlantic is controlled by synoptic‐scale systems and the mesoscale structures embedded within them. Despite forecast uncertainty being greatest at small scales at the initial time, forecast error projects strongly onto synoptic and larger scales within days. Different stages of error growth have previously been identified including: convective instability, baroclinic instability and the influence of divergent outflow on the tropopause position, and interactions between disturbances at tropopause level. Evidence is presented for "predictability barriers" (PBs) identified with events on certain validation dates during the North Atlantic Waveguide and Downstream impact Experiment (NAWDEX) where ensemble spread grows more quickly than usual, but ensemble‐mean forecast error grows even faster. An advective mechanism for diabatic influence on the development of tropopause ridges is hypothesised to be linked to the PB events. A semi‐geostrophic balance tool is used to attribute the response of the 3D ageostrophic flow to geostrophic and diabatic forcing, enabling a novel diagnostic for Diabatically Induced Ageostrophic Advection (DIAA) of potential vorticity. It is shown that predictability barriers are linked to events with strong diabatic influence on tropopause advection during the NAWDEX period. Error growth exceeds ensemble spread rate by approximately 4/3 during strong DIAA events, showing that predictive skill is considerably lower in these situations.
Treatment of chronic GvHD with mesenchymal stromal cells induces durable responses: A phase II study
Authors: Boberg Erik , Bahr Lena , Afram Gabriel , Lindström Carina , Ljungman Per , Heldring Nina , Petzelbauer Peter , Garming Legert Karin , Kadri Nadir , Le Blanc Katarina
Published: June 2020

Steroid-refractory chronic graft-vs-host disease (cGvHD) contributes to morbidity after allogeneic hematopoietic stem cell transplantation. Here, we report on 11 patients with severe, refractory cGvHD treated with repeated infusions of allogeneic bone marrow-derived mesenchymal stromal cells (MSC) over a 6- to 12-month period. Six patients responded to MSC treatment following National Institutes of Health response criteria, accompanied by improvement in GvHD-related symptoms and quality of life. This response was durable, with systemic immunosuppressive therapy withdrawn from two responders, and a further two free from steroids and tapering calcineurin inhibitors. All responders displayed a distinct immune phenotype characterized by higher levels of naïve T cells and B cells before treatment compared with the nonresponders, and a significantly higher fraction of CD31+ naïve CD4+ T cells. MSC treatment was associated with significant increases in naïve T cells, B cells, and Tregs 7 days after each infusion. Skin biopsies showed resolution of epidermal pathology. CXCL9 and CXCL10 showed differential responses in responder and nonresponder patients. Our data support the use of MSC infusions as treatment for steroid-refractory cGvHD with durable responses. We propose CXCL9 and CXCL10 as early biomarkers for responsiveness to MSC treatment. Our results highlight the importance of the MSC recipient immune phenotype in promoting treatment response. This trial was registered at www.ClinicalTrials.gov as #NCT01522716.
In‐situ imaging of Li‐ion migration at interfaces in an all solid Li‐ion battery
Authors: Takata Keiji , Osaka Ryuma , Matsushita Yuki , Nakanishi Taiki
Published: June 2020

We investigated the migration of Li ions at an interface between a LixTi5O12 (LTO) and a solid electrolyte in an all‐solid Li‐ion battery. The optical reflection of LTO changes with variations in the Li content because the band structures of LTO vary with the changes in the Li content. This enables us to observe Li‐ion migration in the interface between the LTO and the solid electrolyte using an optical microscope. To observe the LTO particles optically, they were coated on an indium tin oxide on a glass substrate. Variations in Li migration caused by charging/discharging were clearly observed through the changes in the reflection of the LTO. LTO changed between an insulator Li4Ti5O12 of the spinel structure and a conductor Li7Ti5O12 of the rock‐salt structure according to the changes in the Li content. The spinel LTO has a bandgap energy of approximately 2 eV. When electron–hole pairs were generated, electric strains were produced. Surface force microscopy detected the strains and imaged the distribution of lithiation/delithiation of LTO. Interfacial conduction between a sputtered LTO and Li3PO4 particles was imaged with high spatial resolution.
Decision‐making logics and high‐tech entrepreneurial opportunity identification: The mediating role of strategic knowledge integration
Authors: Guo Runping , Lv Xingqun , Wang Yuan , Chaudhry Peggy E. , Chaudhry Sohail S.
Published: June 2020

In the era of Industry 4.0 and Made in China 2025 initiatives, this research is focused on exploring how entrepreneurial decision‐making logics contribute to opportunity identification by combining effectuation theory and knowledge‐based theory under high uncertainty through strategic knowledge integration in emerging economies, such as the Chinese economy. Empirical data were collected from 196 entrepreneurs and top executives in Chinese high‐tech new ventures using an interview survey. An established mediation model's assessment approach was used to test hypotheses through multivariate linear regression analyses. The analysis results show that both effectuation and causation have positive effects on opportunity identification. Also, emergent/planned knowledge integration plays a fully mediating role in the relationship between effectuation/causation and opportunity identification. This research contributes to the literature by providing empirical evidence to explain the problem of entrepreneurial opportunity identification under high uncertainty through the lens of effectuation theory. It facilitates the development of effectuation theory and enriches the literature on strategic knowledge integration. Moreover, our findings have important managerial implications for high‐tech new ventures to effectively recognize new opportunities in the context of emerging economies.
The effect of the top soil layer on moisture and evaporation dynamics
Authors: Li Zhen , Vanderborght Jan , Smits Kathleen M.
Published: June 2020

Understanding the effect of the top soil layer on surface evaporation and water distribution is critical to modeling hydrological systems. However, the dependency of near‐surface soil moisture and fluxes on layering characteristics remains unclear. To address this uncertainty, we investigate how the arrangement of soil horizons affects the evaporation and soil moisture, specifically, the near‐surface soil moisture, through the combination of numerical simulations and evaporation experiments. The characteristics of fluxes and moisture from different soil profiles are then used to understand the soil layering conditions. Results show that the top soil layer can significantly affect the evolution of soil moisture profiles and evaporation dynamics, the extent of which depends on the layering sequence, thickness, and properties of each layer. The soil systems consisting of a thick coarse (C) layer overlying a fine (F) layer, or a very thin F layer overlying a C layer exhibit near‐surface moisture, temperature and fluxes nearly identical to that of a homogeneous C system; in these cases, a homogeneous C soil could be used to represent the above two layered systems. However, some soil profiles cannot be described by a single set of soil properties, nevertheless, they show distinct characteristics that can serve as indicators for soil layering conditions, e.g., “first slowly then rapidly” decreasing dynamics of near‐surface soil moisture. As some characteristics are not unique to layered soil, the combined information including the near‐surface soil moisture defined at different depths and evaporation behavior of an entire drying cycle can be used to better characterize the layering conditions.
Pesticides and herbicides
Authors: Choudri B. S. , Charabi Yassine , Al‐Nasiri Noura , Al‐Awadhi Talal
Published: June 2020

This paper highlights a review of scientific papers published in the year 2019 regarding pesticides and herbicides. The scientific review presented in this paper includes the presence and occurrence of pesticides and herbicides in the environment. The entire review divided into different sections, which are grouped into four main sections. Each of these sections provides studies conducted on toxicology, ecological risk assessment, strategies of treatment, policies, modeling, and guidelines regarding pesticides and herbicides management.

Practitioners points

This paper highlights the review of scientific literature published in the year 2019.

The review includes the presence and occurrence of pesticides and herbicides in the environment.

The review focuses on toxicology, ecological risk assessment, strategies of treatment, policies, modelling and guidelines regarding pesticides and herbicides management.

The literature review covers selected papers relevant to the topic.