bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of two pyruvate transporters inSalmonella entericaserovar Typhimurium and their biological relevance
Authors: Paulini Stephanie , Fabiani Florian D. , Weiß Anna S. , Moldoveanu Ana Laura , Helaine Sophie , Stecher Bärbel , Jung Kirsten 
Published: May 2022

SUMMARYPyruvate (CH3COCOOH) is the simplest of the alpha-keto acids and is at the interface of several metabolic pathways both in prokaryotes and eukaryotes. In an amino acid-rich environment, fast-growing bacteria excrete pyruvate instead of completely metabolizing it. The role of pyruvate uptake in pathological conditions is still unclear. In this study, we identified two pyruvate-specific transporters, BtsT and CstA, inSalmonella entericaserovar Typhimurium (S. Typhimurium). Expression ofbtsTis induced by the histidine kinase/response regulator system BtsS/BtsR upon sensing extracellular pyruvate (threshold 200 μM), whereas expression ofcstAis maximal in the stationary phase. Both pyruvate transporters were found to be important for the uptake of this compound, but also for chemotaxis to pyruvate, survival under oxidative and nitrosative stress, and persistence ofS. Typhimurium in response to gentamicin. Compared with the wild-type, the ΔbtsTΔcstAmutant has disadvantages in antibiotic persistence in macrophages, as well as in colonization and systemic infection in gnotobiotic mice. These data demonstrate the surprising complexity of the two pyruvate uptake systems inS. Typhimurium.
Arabidopsis thalianarosette growth habit is a photomorphogenic trait controlled by the TALE homeodomain protein ATH1 and involves TOR kinase
Authors: Hajibehzad Shahram Shokrian , Silva Savani S. , Peeters Niels , Stouten Evelien , Buijs Guido , Smeekens Sjef , Proveniers Marcel 
Published: May 2022

AbstractHere, we demonstrate that Arabidopsis rosette habit is abona fidephotomorphogenic trait controlled by the homeodomain protein ATH1. In light,ATH1expression at the SAM is induced by broad wavelengths, mediated through multiple photoreceptors, and requires inactivation of COP1 and PIF photomorphogenesis inhibitors. Such inducedATH1prevents elongation of rosette internodes by maintaining the rib zone area of the SAM in an inactive state. In the absence of light, Arabidopsis plants cannot complete seedling establishment after germination due to inactivity of the shoot apical meristem (SAM). Light requirement for SAM activation can be overcome by availability to the meristem of metabolizable sugars, such as sucrose. However, under these conditions plants fail to establish a typical compact rosette and display a caulescent growth habit. We show that this is due to insufficient expression ofATH1at the SAM. ATH1 induction restores rosette habit in dark-grown plants through inhibition ofPIFgene expression. Together, this suggests that a SAM-specific, double-negative ATH1-PIF feedback loop is at the basis of Arabidopsis rosette habit. Induction ofATH1expression and restoration of rosette habit in darkness also occurs at increased levels of sucrose. Both sugar and light signals that induceATH1are mediated by TOR kinase. Overall, these results support a fundamental role for ATH1 in Arabidopsis rosette habit and further strengthen a role for TOR kinase as a central hub for integration of energy and light signals controlling organogenesis at the SAM.
Wild-type IDH1 inhibition enhances chemotherapy response in melanoma
Authors: Zarei Mehrdad , Hajihassani Omid , Hue Jonathan J. , Graor Hallie J. , Rathore Moeez , Vaziri-Gohar Ali , Asara John M. , Winter Jordan M. , Rothermel Luke D. 
Published: May 2022

AbstractMalignant melanoma is one of the most common types of cancer in the United States. Despite recent and well-described progress in melanoma treatment, advanced disease still carries a poor prognosis for many patients and chemotherapy has been appropriately abandoned as a front-line option. Wild-type isocitrate dehydrogenase 1 (wtIDH1) has recently been implicated as a metabolic dependency in cancer. The enzyme is protective to cancer cells under metabolic stress, including oxidative damage by conventional chemotherapy and nutrient limitation characteristic of the tumor microenvironment. Specifically, the cytosolic enzyme generates NADPH to maintain redox homeostasis. IDH1 also supports mitochondrial function through anaplerosis of its reaction product, α-ketoglutarate. We show that melanoma patients express higher levels of the wtIDH1 enzyme compared to normal skin tissue, and elevated wtIDH1 expression portends poor patient survival. Knockdown of IDH1 by RNA interference inhibited cell proliferation and migration under low nutrient levels. Suppression of IDH1 expression in melanoma also decreased NADPH and glutathione levels, resulting in increased reactive oxygen species. An FDA-approved inhibitor of mutant IDH1, ivosidenib (AG-120), exhibited potent anti-wtIDH1 properties under low magnesium and nutrient levels, reflective of the tumor microenvironmentin natura. Similarly, findings were replicated in murine models of melanoma. Further, wtIDH1 inhibition was synergistic to conventional anti-melanoma chemotherapy in pre-clinical models. This work points to a novel and readily available combination treatment strategy for patients with advanced and refractory melanoma.
Isolation of bat sarbecoviruses of SARS-CoV-2 clade, Japan
Authors: Murakami Shin , Kitamura Tomoya , Matsugo Hiromichi , Kamiki Haruhiko , Oyabu Ken , Sekine Wataru , Takenaka-Uema Akiko , Sakai-Tagawa Yuko , Kawaoka Yoshihiro , Horimoto Taisuke 
Published: May 2022

ABSTRACTBetacoronaviruses have caused 3 outbreaks in the past 2 decades. SARS-CoV-2, in particular, has caused a serious pandemic. As the betacoronaviruses are considered to originate from bats, surveillance of bat betacoronaviruses is crucial for understanding the mechanism of cross-species transition and potential for future outbreaks. We previously detected and characterized a SARS-CoV-2-related sarbecovirus, Rc-o319, fromRhinolophus cornutusin Japan. Here, we detected several bat sarbecoviruses of the SARS-CoV-2 clade fromR. cornutusin multiple locations in Japan, and successfully isolated them using Vero/TMPRSS2 cells stably expressingR. cornutusACE2 (Vero-RcACE2). The coding sequences of S1 region varied among isolates, whereas other genetic regions were highly conserved. Isolates were efficiently grown in Vero-RcACE2 cells, but did not replicate in Vero/TMPRSS2 cells stably expressing human ACE2, suggesting a narrow host range. Further long-term epidemiological studies of sarbecoviruses in wildlife are expected to facilitate the assessment of the risk of their spillover potential.
Predicting 3D RNA structure from solely the nucleotide sequence using Euclidean distance neural networks
Authors: Sha Congzhou M. , Wang Jian , Dokholyan Nikolay V. 
Published: May 2022

ABSTRACTFast and accurate 3D RNA structure prediction remains a major challenge in structural biology, mostly due to the size and flexibility of RNA molecules, as well as lack of diverse experimentally determined structures of RNA molecules. Unlike DNA structure, RNA structure is far less constrained by base pair hydrogen bonding, resulting in an explosion of potential stable states. Here, we propose a convolutional neural network which predicts all pairwise distances between residues in an RNA, using a recently described smooth parametrization of Euclidean distance matrices. We achieve high accuracy predictions on RNAs up to 100 nucleotides in length in fractions of a second, a factor of 107 faster than existing molecular dynamics-based methods. We also convert our coarse-grained machine learning output into an all-atom model using discrete molecular dynamics with constraints. Our proposed computational pipeline accurately predicts all-atom RNA models solely from the nucleotide sequence.
Spontaneous genomic variation as a survival strategy of nosocomial S. haemolyticus
Authors: Bouchami Ons , Machado Miguel , Carriço João André , Melo-Cristino José , de Lencastre Herminia , Miragaia Maria 
Published: May 2022

AbstractStaphylococcus haemolyticus is one of the most important nosocomial human pathogens frequently isolated in bloodstream and medical devices related infections. This species is notorious for its multidrug resistance and genome plasticity. However, its mechanisms of evolution and adaptation are still poorly explored. In this study we aimed to characterize the strategies of genetic and phenotypic diversity in S. haemolyticus. Here, we analyzed an invasive S. haemolyticus strain, recovered from a bloodstream infection, for genetic and phenotypic stability after serial passage in vitro (>400 generations) in the absence and presence of sub-inhibitory concentrations of a beta-lactam antibiotic. We performed PFGE of the culture and five colonies at seven time points during stability assays were analyzed for beta-lactams susceptibility, hemolysis, mannitol fermentation and biofilm production. We compared their whole genome regarding chromosomal structure, gene content and mutations and preformed phylogenetic analysis based on core SNPs. We observed a high instability in the PFGE profiles at the different time points during serial passage in vitro in the absence of antibiotic. However, no variation was observed in PFGE patterns in the presence of beta-lactams. Analysis of WGS data for individual colonies collected at different time points showed the occurrence of six large-scale genomic deletions within the oriC environ (36 kbp-348 kbp) in the cell populations analyzed, smaller deletions in non-OriC environ region as well as non-synonymous mutations in clinically relevant genes. The regions of deletion and point mutations included genes encoding amino acid and metal transporters, resistance to environmental stress and beta-lactams, virulence, mannitol fermentation, metabolic processes and IS elements. A parallel variation was additionally detected in clinically significant phenotypic traits such as mannitol fermentation, beta-lactams resistance, hemolysis and biofilm formation. All the genetic variants analyzed were closely related in their core genome (13-292 SNPs). Our results suggest that S. haemolyticus populations are composed of subpopulations of genetic and phenotypic variants that might be affected in antibiotic and stress resistance, specific metabolic processes and virulence. The maintenance of subpopulations in different physiological states might be a strategy to adapt rapidly to a stress situation imposed by the host particularly in the hospital environment.
A novel method of identifying sewing damage in single jersey fabrics
Authors: Yıldız Esra Zeynep , Pamuk Oktay 
Published: May 2022

PurposeThis paper suggests a new method for determining the sewing damage that occurs in single jersey fabrics based on the calculation of the needle hole area. This paper also aims to investigate the effects of material type, sewing parameters, and repeated washing cycles on sewing damage by using this method.Design/methodology/approachSix knitted fabrics, differing in structure and raw material, were produced. Samples were sewn using different sewing parameters, and they were subjected to ten washing cycles. Values of average needle hole area, an objective indicator of sewing damage, were calculated before and after repeated washing cycles using image analysis software and were evaluated statistically.FindingsThe results showed that the average needle hole area calculated via the image analysis software effectively estimates sewing damage as the results obtained were compatible with those stated in the literature. Furthermore, fabric type, sewing direction, sewing thread type, and needle size significantly affected the sewing damage. However, stitch density did not affect the sewing damage. When the effect of washing cycles was compared, it was seen that washing leads to an increase in sewing damage.Originality/valueA review of the existing literature shows that no previous study has evaluated sewing damage using image analysis software. This study proposes a novel objective method to determine the sewing damage that occurs in knitted fabrics.
The effect of production system characteristics on resilience capabilities: a multiple case study
Authors: Dittfeld Hendryk , van Donk Dirk Pieter , van Huet Sam 
Published: May 2022

PurposeTo date, the literature has usually assumed that a universal approach to resilience is appropriate in which different resilience capabilities are equally important for all organizations independent of contextual characteristics. In contrast this study investigates if production process characteristics affect resilience capabilities in terms of redundancy, flexibility, agility and collaboration.Design/methodology/approachAn in-depth exploratory multiple case study was carried out in eight companies across different industries. Data were gathered through multiple interviews with key informants in each company.FindingsThe authors find differences in, and trade-offs between, resilience capabilities and practices related to redundancy, agility and collaboration induced by the different configurations of production system characteristics: especially between discrete and process industries. Further, a major influential characteristic is the production strategy employed (make-to-stock or make-to-order) which stresses or limits collaboration and redundancy.Originality/valueThis is one of the first studies to explore the effects of production system characteristics as a major contingency factor on the resilience capabilities of an organization. As such it provides valuable insights into the development of a more nuanced contingency approach to how organizations can build resilience and employ specific practices that fit their situation.
Interaction training – an enabler for improvement measures within the psychosocial risk assessment process
Authors: Backström Tomas , Berglund Rachael Tripney 
Published: May 2022

PurposeThe study objectives were to (1) identify if providing solution-focused interaction training enables managers and employees to develop and implement actions to improve their psychosocial work environment and (2) test a recontextualization of the psychosocial work environment as social structures affecting members of the workplace and verify if social interactions effectively change the local psychosocial work environment.Design/methodology/approachThe intervention involved training managers, supervisors and employees in solution-focused interaction. This study used a controlled interrupted time-series design, with an intervention and control group (CG) and pre- and post-measurements.FindingsThe psychosocial work environment improved, indicating that the training led to better social interactions, contributing to changes in the social structures within the intervention group (IG). Collective reflection between participants in the take action phase was the key to success. The recontextualization uncovered these mechanisms.Research limitations/implicationsThe present study supports a recontextualization of the psychosocial work environment as primarily decided by social structures that emerge in recurrent interactions within work teams. The same social structures also seem to be important for other features of the production system, like job performance.Practical implicationsTraining designed to enable high-quality social interactions, like dialogue and collective reflection, has proven to be effective in changing social structures. Moreover, managers may need training in facilitating the collective reflection between participants. Increased focus on social interactions within work teams is suggested for future study of organizational change processes, psychosocial work environment and practical psychosocial work environment management.Originality/valueThe intervention was delivered in the preparation phase to enable an effective take action phase. Both phases are less studied in psychosocial risk assessments research. The recontextualization has never been fully used in psychosocial research.
Past, present and future of research in relationship marketing - a machine learning perspective
Authors: Das Kallol , Mungra Yogesh , Sharma Anuj , Kumar Satish 
Published: May 2022

PurposeThis paper aims to take stock of research done in the domain of relationship marketing (RM). Additionally, this article aims to identify the potential areas of future research.Design/methodology/approachThe authors have used machine learning-based structural topic modelling using R-software to analyse the dataset of 1,905 RM articles published between 1978 and 2020.FindingsStructural topic modeling (STM) analysis led to identifying 14 topics, out of which 7 (viz. customer loyalty, customer relationship management systems, interfirm and network relationships, relationship selling, services and relationship management, consumer brand relationships and relationship marketing research) have shown a rising trend. The study also proposes a taxonomical framework to summarize RM research.Originality/valueThis is the first comprehensive review of RM research spanning over more than four decades. The study’s insights would benefit future scholars of this field to plan/execute their research for greater publication success. Additionally, managers could use the practical implications for achieving better RM outcomes.
Food delivery before and during the COVID-19 pandemic in Brazil
Authors: Liboredo Juliana Costa , Amaral Cláudia Antônia Alcântara , Carvalho Natália Caldeira 
Published: May 2022

Purpose
This study aims to understand consumer behavior related to the purchase of meals by delivery services before and during the coronavirus disease 2019 (COVID-19) pandemic in Brazil.

Design/methodology/approach
An online survey was conducted between September and October 2020. The total number of valid responses was 971.

Findings
About 55% of the participants reported a decrease in consumption or not having consumed food delivery during the pandemic. Of the total, 48.3% feared contracting COVID-19 from food delivery. A significant association was observed between fear of contracting COVID-19 from food delivery and variables such as education level (p = 0.001), observance of social distancing (p = 0.03) and food delivery consumption frequency (p < 0.001). More people were careful about cleaning food packaging (from 12.4% before to 66.1% during the pandemic, p < 0.001) and disposal (from 47.6% before to 66.4% during the pandemic, p < 0.001) and heating the food before consumption (from 7.6% before to 13.7% during the pandemic, p < 0.001) and used payment methods without approximation (from 29.8% before to 43.2% during the pandemic, p < 0.001) compared with the pre-pandemic period. More people also reported that application of security protocols during delivery (from 29.8% before to 43.2% during the pandemic, p < 0.001) and in restaurants (from 7.2% before to 25% during the pandemic, p < 0.001) and possessing knowledge about the financial difficulty of the establishment (from 4.6% before to 17% during the pandemic, p < 0.001) were the most important factors for choosing a food service.

Originality/value
To the best of the authors’ knowledge, this is the first study to explore consumers’ fear of contracting COVID-19 from food delivery and consumer behavior related to food delivery services during the pandemic in Brazil – that is, way to order and payment methods, as well as concern and care related to the purchase of these foods.
Angiotensin II receptor blockers (ARBs) and manufacturing contamination: A retrospective National Register Study into suspected associated adverse drug reactions
Authors: Salim Hamisha , Jones Alan M. 
Published: May 2022

AimsThe aim of this study was to determine if any suspected adverse drug reactions (ADRs) observed with the use of angiotensin II receptor blockers (ARBs) could be linked to either (a) their unique respective physicochemical and pharmacological profiles and (b) the recently disclosed suspected carcinogenic manufacturing contaminants found in certain sartan drug class batches.MethodsThe pharmacology profiles of ARBs were data‐mined from the Chemical Database of bioactive molecules with drug‐like properties, European Molecular Biology Laboratory (ChEMBL). Suspected ADR data (from 01/2016–10/2022, inclusive) and prescribing rates of ARBs over a 5‐year prescribing window (from 09/2016 to 08/2021, inclusive) were obtained via analysis of the United Kingdom Medicines and Healthcare products Regulatory Authority (MHRA) Yellow Card drug analysis profile and Open prescribing databases, respectively.ResultsThe overall suspected ADRs and fatalities per 100 000 prescriptions identified across the ARBs studied were found to be different between the sartan drug class members (chi‐squared test, P < .05). There is a greater relative rate of reports for valsartan across all investigated organ classes of ADRs, than other ARBs, despite valsartan's more limited pharmacological profile and similar physicochemical properties to other sartans. The disparity in ADR reporting rates with valsartan vs other ARBs could be due to the dissimilarity in formulation excipients, patient factors and publicity surrounding batch contaminations, amongst others. Cancer‐related ADRs and fatalities per 100 000 prescriptions identified across the ARBs studied are not statistically significant (chi‐squared test, P > .05) based on the datasets used over the 5‐year period.ConclusionNo connection between ARB pharmacology and their suspected ADRs could be found. No conclusion between sartan batch contaminations and increased suspected cancer‐related ADRs was found.
The role of placebo response in the efficacy outcome assessment in viloxazine extended‐release pivotal trials in paediatric subjects with attention‐deficit/hyperactivity disorder
Authors: Nasser Azmi , Gomeni Roberto , Wang Zhao , Hull Joseph T. , Busse Gregory D. , Melyan Zare , Fava Maurizio , O'Neal Welton , Rubin Jonathan 
Published: May 2022

Aims: Four Phase 3 studies evaluated efficacy and safety of viloxazine extended‐release in the treatment of attention‐deficit/hyperactivity disorder (ADHD). The primary efficacy objective—change from baseline in ADHD Rating Scale‐5 (ADHD‐RS‐5) Total score at end of study (EOS)—was not met in one of the studies (812P304). A band‐pass analysis was performed to evaluate the impact of placebo response on the results.Methods: The distribution of placebo response at EOS of each trial was evaluated. The 2.5th and 97.5th percentiles of the distribution of ADHD‐RS‐5 Total score were used as boundaries for the band‐pass analysis. An independent mixed model for repeated measures analysis was conducted for each trial using all eligible data (active and placebo) from the total and band‐pass filtered populations.Results: The 2.5th and 97.5th percentiles at EOS were 3.5 and 53.5, respectively. Application of the band‐pass filter (filtering out all subjects [active, n = 305 (32.1%) and placebo, n = 134 (33.5%)] of clinical sites with placebo scores <3.5 or >53.5) revealed statistically significant improvement at the primary endpoint (600‐mg/d viloxazine ER vs. placebo) in Study 812P304 (mean [confidence interval] = 4.9537 [0.5405–9.3669]), previously masked by a high placebo response (mean [confidence interval] = 3.5756 [−0.3332–7.4844]). The outcome of the analysis indicated that the impact of the band‐pass adjustment is greater when placebo response is higher.Conclusion: This analysis indicated that a higher placebo response in Study 812P304 confounded the assessment of treatment effect. Application of the band‐pass methodology confirmed the positive results of the 3 prior studies and the signal detection confounder in the fourth study.