bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic ancestry contributes to somatic mutations in lung cancers from admixed Latin American populations
Authors: Carrot-Zhang Jian , Soca-Chafre Giovanny , Patterson Nick , Thorner Aaron R. , Nag Anwesha , Watson Jacqueline , Genovese Giulio , Rodriguez July , Gelbard Maya K. , Corrales-Rodriguez Luis , Mitsuishi Yoichiro , Ha Gavin , Campbell Joshua D. , Oxnard Geoffrey R. , Arrieta Oscar , Cardona Andres F. , Gusev Alexander , Meyerson Matthew
Published: September 2020

Inherited lung cancer risk, particularly in non-smokers, is poorly understood. Genomic and ancestry analysis of 1,153 lung cancers from Latin America revealed striking associations between Native American ancestry and their somatic landscape, including tumor mutational burden (TMB), and specific driver mutations in EGFR, KRAS, and STK11. A local Native American ancestry risk score predicted EGFR and KRAS mutation frequency more strongly than global ancestry, suggesting that germline genetics (rather than environmental exposure) underlie these disparities.

Significance

The frequency of somatic EGFR and KRAS mutations in lung cancer varies by ethnicity but we do not understand why. Our study suggests that the variation in EGFR and KRAS is directly associated with genetic ancestry and suggests further studies to identify germline alleles that underpin this association.
MT5-MMP controls APP and β-CTF/C99 metabolism through proteolytic-dependent and -independent mechanisms relevant for Alzheimer’s disease
Authors: García-González Laura , Paumier Jean-Michel , Louis Laurence , Pilat Dominika , Bernard Anne , Stephan Delphine , Jullien Nicolas , Checler Frédéric , Nivet Emmanuel , Khrestchatisky Michel , Baranger Kévin , Rivera Santiago
Published: September 2020

We previously discovered the implication of membrane-type 5-matrix metalloproteinase (MT5-MMP) in Alzheimer’s disease AD pathogenesis. Here we shed new light on pathogenic mechanisms by which MT5-MMP controls APP processing and the fate of amyloid beta peptide (Aβ), its precursor C99 and C83. We found in HEK carrying theAPPSwedish familial mutation (HEKswe) that MT5-MMP-mediated processing of APP that releases the soluble 95 kDa form (sAPP95), was hampered by the removal of the C-terminal non-catalytic domains of MT5-MMP. Catalytically inactive MT5-MMP variants increased the levels of Aβ and promoted APP/C99 sorting in the endo-lysosomal system. We found interaction of C99 with the C-terminal portion of MT5-MMP, the deletion of which caused a strong degradation of C99 by the proteasome, preventing Aβ accumulation. These findings reveal novel mechanisms for MT5-MMP control of APP metabolism and C99 fate involving proteolytic and non-proteolytic actions mainly mediated by the C-terminal part of the proteinase.
Towards establishing no observed adverse effect levels (NOAEL) for different sources of dietary phosphorus in feline adult diets: results from a 7 month feeding study
Authors: Coltherd Jennifer C. , Alexander Janet , Pink Claire , Rawlings John , Elliott Jonathan , Haydock Richard , Carvell-Miller Laura J. , Biourge Vincent , Molina Luis , Butterwick Richard , Logan Darren W. , Watson Phillip , Bakke Anne Marie
Published: September 2020

High dietary phosphorus (P), particularly soluble salts, may contribute to chronic kidney disease development in cats. The aim of this study was to assess the safety of P supplied at 1g/1000kcal from a highly soluble P salt in P-rich dry format feline diets. Seventy-five healthy adult cats (n=25/group) were fed either a low P control (1.4g/1000 kcal; calcium:phosphorus ratio, Ca:P 0.97) or one of two test diets with 4g/1000 kcal (4184kJ); Ca:P 1.04 or 5g/1000kcal; Ca:P 1.27, both incorporating 1g/1000kcal (4184kJ) sodium tripolyphosphate (STPP) – for a period of 30 weeks in a randomised parallel-group study. Health markers in blood and urine, glomerular filtration rate, renal ultrasound and bone density were assessed at baseline and at regular time points. At the end of the test period, responses following transition to a commercial diet (total P – 2.34g/1000kcal, Ca:P 1.3) for a 4-week washout period were also assessed. No adverse effects on general, kidney or bone (skeletal) function and health were observed. P and Ca balance, some serum biochemistry parameters and regulatory hormones were increased in cats fed test diets from week 2 onwards (p≤0.05). Data from the washout period suggest that increased serum creatinine and urea values observed in the two test diet groups were influenced by dietary differences during the test period, and not indicative of changes in renal function. The present data suggest NOAELs for feline diets containing 1g P/1000kcal (4184kJ) from STPP and total phosphorus level of up to 5g/1000kcal (4184kJ) when fed for 30 weeks.
Stochastic survival of the densest and mitochondrial DNA clonal expansion in ageing
Authors: Insalata Ferdinando , Hoitzing Hanne , Aryaman Juvid , Jones Nick S.
Published: September 2020

The expansion of deleted mitochondrial DNA molecules has been associated with ageing1,2, particularly in skeletal muscle fibres3–5; its mechanism has remained unclear for three decades. Previous accounts have assigned a replicative advantage to the deletions6–8, but there is evidence that cells can, instead, selectively remove defective mitochondrial DNA9. Here we present a spatial model that, without a replicative advantage, but instead through a combination of enhanced density for mutants and noise, produces a wave of expanding mutations with speeds consistent with experimental data10. A standard model based on replicative advantage yields waves that are too fast. We provide a formula that predicts that wave-speed drops with copy number, consonant with experimental data. Crucially, our model yields travelling waves of mutants even if mutants are preferentially eliminated. Additionally, we predict that experimentally observed mutant loads can be produced byde novomutation rates that are drastically lower than previously thought for neutral models11. Given this exemplar of how noise, density and spatial structure affect muscle age-ing, we introduce the mechanism of stochastic survival of the densest, an alternative to replicative advantage, that may underpin other evolutionary phenomena.
Genomic signatures of the unjamming transition in compressed human bronchial epithelial cells
Authors: De Marzio Margherita , Kılıç Ayşe , Maiorino Enrico , Mitchel Jennifer , McGill Maureen , Chase Robert , Fredberg Jeffrey J. , Park Jin-Ah , Glass Kimberly , Weiss Scott T.
Published: September 2020

Epithelial tissue has the capacity to switch from a collective phase that is quiescent, solidlike and non-migratory to one that is dynamic, fluid-like and migratory. In certain physiological and pathophysiological contexts this phenotypic switch has been attributed not to the well-known epithelial-to-mesenchymal transition, EMT, but rather to the recently discovered unjamming transition, UJT. UJT has been characterized thus far mainly at functional and morphological levels whereas underlying genome-wide molecular events remain largely unexplored. Using primary human bronchial epithelial cells and one well-defined trigger of UJT –mechanical compression– here we combine temporal RNA-Seq data and Protein-Protein Interaction networks to provide the first genome-wide analysis of UJT. Our results show that compression induces a multiphasic transcriptional response characterized by an early activation of genes regulating the membrane and actomyosin structure, and a delayed activation of genes regulating the extracellular matrix and cellmatrix interactions. This biphasic response is mediated by a cascade of signaling processes that promotes actin polymerization through the recruitment of integrin-ECM adhesive complexes and promotes increased cellular motility through activation of AP-1 transcription factors via ERK and JNK pathways. These findings, taken together, show that the UJT program is not the result of any single signaling pathway but rather comprises a coordinated interplay of downstream pathways including development, fate selection, energy metabolism, cytoskeletal reorganization, and adhesive interaction with extracellular matrix.
In Silico Analysis of Effect of Non-synonymous SNPs associated with Permanent Neonatal Diabetes Mellitus on Stability and Structure of Human Insulin
Authors: Tabassum Nishat
Published: September 2020

Motivation

Proteins are the building-blocks of life. However with the deluge of data on protein sequences and their association with diseases, it is imperative to use computational tools to aid experimental analysis. Determination of the impact of disease-causing SNPs on protein’s structure is crucial in discovering how a disease affects the functions on a fundamental level and thereafter, determining potential drug targets.

Results

SNPs associated with the genetic disease permanent neonatal diabetus mellitus (PNDM) were studied to determine their impact on human insulin. Out of 16 missense variants, eight were predicted to be deleterious. 6 of the SNPs resulted in high structural differences (RMSD > 0.9, H bonds > 35). Stability changes were also determined.
RecT recombinase expression enables efficient gene editing inEnterococcus
Authors: Chen Victor , Griffin Matthew E. , Hang Howard C.
Published: September 2020

Enterococcus faeciumis a ubiquitous Gram-positive bacterium that has been recovered from the environment, food, and microbiota of mammals. Commensal strains ofE. faeciumcan confer beneficial effects on host physiology and immunity, but antibiotic usage has afforded antibiotic-resistant and pathogenic isolates from livestock and humans. However, the dissection ofE. faeciumfunctions and mechanisms has been restricted by inefficient gene editing methods. To address these limitations, here we report the expression ofE. faeciumRecT recombinase significantly improves the efficiency of recombineering technologies in both commensal and antibiotic-resistant strains ofE. faeciumand otherEnterococcusspecies such asE. duransandE. hirae. Notably, the expression of RecT in combination with clustered regularly interspaced palindromic repeat (CRISPR)-Cas9 and guide RNAs (gRNAs) enabled highly efficient scar-less single-stranded DNA recombineering to generate specific gene editing mutants inE. faecium. Moreover, we demonstrate thatE. faeciumRecT expression facilitated chromosomal insertions of double-stranded DNA templates encoding antibiotic selectable markers to generate gene deletion mutants. As further proof-of-principle, we use CRISPR-Cas9 mediated recombineering to knock out both sortase A genes inE. faeciumfor downstream functional characterization. The general RecT-mediated recombineering methods described here should significantly enhance genetic studies ofE. faeciumand other closely related species for functional and mechanistic studies.

Importance

Enterococcus faeciumis widely recognized as an emerging public health threat with the rise of drug resistance and nosocomial infections. Nevertheless, commensalEnterococcusstrains possess beneficial health functions in mammals to upregulate host immunity and prevent microbial infections. This functional dichotomy ofEnterococcusspecies and strains highlights the need for in-depth studies to discover and characterize the genetic components underlining its diverse activities. However, current genetic engineering methods inE. faeciumstill require passive homologous recombination from plasmid DNA. This involves the successful cloning of multiple homologous fragments into a plasmid, introducing the plasmid intoE. faecium, and screening for double-crossover events that can collectively take up to multiple weeks to perform. To alleviate these challenges, we show that RecT recombinase enables rapid and efficient integration of mutagenic DNA templates to generate substitutions, deletions, and insertions in genomic DNA ofE. faecium. These improved recombineering methods should facilitate functional and mechanistic studies ofEnterococcus.
The activity of yeast Apn2 AP endonuclease at uracil-derived AP sites is dependent on the major carbon source
Authors: Stokdyk Kasey , Berroyer Alexandra , Grami Zacharia A. , Kim Nayun
Published: September 2020

Yeast Apn2 is an AP endonuclease and DNA 3’-diesterase that belongs to the Exo III family with homology to theE. coliexonuclease III,Schizosaccharomyces pombeeth1, and human AP endonucleases APEX1 and APEX2. In the absence of Apn1, the major AP endonuclease in yeast, Apn2 can cleave the DNA backbone at an AP lesion initiating the base excision repair pathway. In order to study the role and relative contribution of Apn2, we took advantage of a reporter system that was previously used to delineate how uracil-derived AP sites are repaired. At this reporter, disruption of the Apn1-initiated base excision repair pathway led to a significant elevation of A:T to C:G transversions. Here we show that such highly elevated A:T to C:G transversion mutations associated with uracil residues in DNA are abolished whenapn1Δ yeast cells are grown in glucose as the primary carbon source. We also show that the disruption of Apn2, either by the complete gene deletion or by the mutation of a catalytic residue, results in a similarly reduced rate of the uracil-associated mutations. Overall, our results indicate that Apn2 activity is regulated by the glucose repression pathway in yeast.
Spindle alignment is uncoupled with Kar9 symmetry breaking
Authors: Meziane Miram , Genthial Rachel , Vogel Jackie
Published: September 2020

Spindle positioning must be tightly regulated to ensure asymmetric cell divisions are successful. In budding yeast, spindle positioning is mediated by the asymmetric localization of microtubule +end tracking protein Kar9. Kar9 asymmetry is believed to be essential for spindle alignment. However, the temporal correlation between symmetry breaking and spindle alignment has not been measured. Here, we establish a method of quantifying Kar9 symmetry breaking and find that Kar9 asymmetry is not well coupled with early spindle alignment. We report the majority of asymmetric cells are not stably aligned. Rather, stable alignment, a state we define as perfect alignment, is correlated with Kar9 localization to the bud compartment, regardless of symmetry state. Our findings suggest that Kar9 asymmetry alone is insufficient for perfect alignment and reveal a possible role for Swe1 in regulating spindle alignment efficiency.
Insulin-Induced Conformational Changes in the Full-Length Insulin Receptor: Structural Insights Gained from Molecular Modeling Analyses
Authors: Yang Yong Xiao , Li Peng , Wang Pan , Zhu Bao Ting
Published: September 2020

Insulin receptor plays an important role in regulation of energy metabolism. Dysfunction of insulin receptor (IR) can lead to many disease states, such as diabetes mellitus. Deciphering the complex dynamic structure of human IR and its mechanism of activation would greatly aid in understanding IR-mediated signaling pathways and in particular, in designing new drugs (including nonpeptidal insulin analogs) to treat diabetes mellitus. Experimental evidence about IR structure has been gradually obtained by biologists over the past three decades. Based on the available experimental structures of IR in different states, here we employ molecular modeling approach to construct the full-length IR structures in different states and model its structural and conformational changes during insulin-induced IR activation. Several key possible intermediate states are constructed based on structural alignment, rotation and computational modeling. Based on the structures of the full-length IR in different states, it appears that there are two possible conformational transition pathways: one is symmetric, and the other one is asymmetric. Structural changes and motions of different domains of the full-length IR along the pathways are analyzed. The role of insulin binding to IR in facilitating the conformational transition of the receptor is modeled. Information and insights derived from our present structural modeling analyses may aid in understanding the complex dynamic, structural and conformational changes during the process of IR activation.
Deep-learning convolutional neural networks with transfer learning accurately classify COVID19 lung infection on portable chest radiographs
Authors: Kikkisetti Shreeja , Zhu Jocelyn , Shen Beiyi , Li Haifang , Duong Tim Q
Published: September 2020

Portable chest x-ray (pCXR) has become an indispensable tool in the management of Coronavirus Disease 2019 (COVID-19) lung infection. This study employed deep-learning convolutional neural networks to classify COVID-19 lung infections on pCXR from normal and related lung infections to potentially enable more timely and accurate diagnosis. This retrospect study employed deep-learning convolutional neural network (CNN) with transfer learning to classify based on pCXRs COVID-19 pneumonia (N=455) on pCXR from normal (N=532), bacterial pneumonia (N=492), and non-COVID viral pneumonia (N=552). The data was split into 75% training and 25% testing. A five-fold cross-validation was used. Performance was evaluated using receiver-operating curve analysis. Comparison was made with CNN operated on the whole pCXR and segmented lungs. CNN accurately classified COVID-19 pCXR from those of normal, bacterial pneumonia, and non-COVID-19 viral pneumonia patients in a multiclass model. The overall sensitivity, specificity, accuracy, and AUC were 0.79, 0.93, and 0.79, 0.85 respectively (whole pCXR), and were 0.91, 0.93, 0.88, and 0.89 (CXR of segmented lung). The performance was generally better using segmented lungs. Heatmaps showed that CNN accurately localized areas of hazy appearance, ground glass opacity and/or consolidation on the pCXR. Deep-learning convolutional neural network with transfer learning accurately classifies COVID-19 on portable chest x-ray against normal, bacterial pneumonia or non-COVID viral pneumonia. This approach has the potential to help radiologists and frontline physicians by providing more timely and accurate diagnosis.
Electrophysiological Phenotype Characterization of Human iPSC-Derived Neuronal Cell Lines by Means of High-Density Microelectrode Arrays
Authors: Ronchi Silvia , Buccino Alessio Paolo , Prack Gustavo , Kumar Sreedhar Saseendran , Schröter Manuel , Fiscella Michele , Hierlemann Andreas
Published: September 2020

Recent advances in the field of cellular reprogramming have opened a route to study the fundamental mechanisms underlying common neurological disorders. High-density microelectrode-arrays (HD-MEAs) provide unprecedented means to study neuronal physiology at different scales, ranging from network through single-neuron to subcellular features. In this work, we used HD-MEAsin vitroto characterize and compare human induced-pluripotent-stem-cell (iPSC)-derived dopaminergic and motor neurons, including isogenic neuronal lines modeling Parkinson’s disease and amyotrophic lateral sclerosis. We established reproducible electrophysiological network, single-cell and subcellular metrics, which were used for phenotype characterization and drug testing. Metrics such as burst shapes and axonal velocity enabled the distinction of healthy and diseased neurons. The HD-MEA metrics could also be used to detect the effects of dosing the drug retigabine to human motor neurons. Finally, we showed that the ability to detect drug effects and the observed culture-to-culture variability critically depend on the number of available recording electrodes.
Examining the link among green human resource management practices, green supply chain management practices and performance
Authors: Acquah Innocent Senyo Kwasi , Agyabeng-Mensah Yaw , Afum Ebenezer
Published: September 2020

Purpose

The increasing concern for the protection of the environment through pollution prevention, conservation of resources and less usage of energy has attracted several firms to align green practices with their supply chain and human resource policies and practices. This study explores the influence of green human resource management and green supply chain management practices on operational, market, financial, social and environmental performances.

Design/methodology/approach

The study uses partial least square–structural equation modeling approach to analyze the data gathered through structured questionnaires from supply chain and human resource managers in manufacturing and hospitality firms in Ghana.

Findings

It is established that green supply chain management practices play complementary partial mediating role between green human resource management and operational, market, social and environmental performances, while it plays competitive partial mediating role between green human resource management and financial performance. Subsequently, the analysis reveals that the synergy between green human resource management and green supply chain management creates the highest value in operational performance, followed by market performance, environmental performance, financial performance and social performance.

Originality/value

The study proposes and tests a conceptual model that examines the synergistic influence of green human resource management and green supply chain management on operational, market, financial, social and environmental performances.
Energy sustainability in teaching and outreach initiatives and the contribution to the 2030 Agenda
Authors: Lange Salvia Amanda , Londero Brandli Luciana , Leal Filho Walter , Gasparetto Rebelatto Bianca , Reginatto Giovana
Published: September 2020

Purpose

Considering the different roles universities can perform to contribute to sustainable development, it is through teaching and outreach that they might be able to connect to the academic and local communities the most. The purpose of this study is to investigate the extent to which energy sustainability is being considered in campus teaching and outreach activities of different higher education institutions worldwide. In this context, this exploratory study was developed.

Design/methodology/approach

Through an online survey, a group of 36 universities from all continents was inquired about the level of sustainability in energy aspects of teaching and outreach activities, including curriculum change, training courses for staff and the regularity of outreach projects.

Findings

The results allowed global analysis concerning challenges and opportunities of these educational activities. This study also touches upon the interconnection between these practices and the contribution of universities towards the 2030 Agenda, and how universities can expand their activities and contribute practically to society. In terms of practical contributions, this study provides recommendations for higher education institutions to develop further in the area of energy sustainability through teaching and outreach.

Originality/value

Energy is a sustainability aspect relatively well covered by actions on campus operations, but there is a paucity of studies connecting this topic to teaching and outreach activities. This study is an approach to not only fill this gap but also reinforce the university role and contribution to the Sustainable Development Goals.
Word‐of‐mouth communication and search
Authors: Campbell Arthur , Leister C. Matthew , Zenou Yves
Published: September 2020

We develop a word‐of‐mouth search model where information flows from the old to the new generation for an experience good with unknown quality. We study the features of the social network that determine product quality and welfare and characterize the demand‐side (under provision of search effort) and supply‐side (inefficient entry by firms) factors that result in inefficiencies. One striking result is to show that the more connected but also the less‐unequal a friendship network is (in the sense of second order stochastic dominance of the degree distribution), the less can disreputable (low‐quality) firms thrive in equilibrium.
The Neurophysiology of Implicit Alcohol Associations in Recently Abstinent Patients With Alcohol Use Disorder: An Event‐Related Potential Study Considering Gender Effects
Authors: Tschuemperlin Raphaela Martina , Batschelet Hallie Margareta , Moggi Franz , Koenig Thomas , Roesner Susanne , Keller Anne , Pfeifer Philippe , Soravia Leila Maria , Stein Maria
Published: September 2020

Background

Neuroscientific models of alcohol use disorders (AUDs) postulate an imbalance between automatic, implicit, and controlled (conscious) processes. Implicit associations towards alcohol indicate the automatically attributed appeal of alcohol‐related stimuli. First, behavioral studies indicate that negative alcohol associations are less pronounced in patients compared to controls, but potential neurophysiological differences remain unexplored. This study investigates neurophysiological correlates of implicit alcohol associations in recently abstinent patients with AUD for the first time, including possible gender effects.

Methods

A total of 62 patients (40 males and 22 females) and 21 controls performed an alcohol valence Implicit Association Test, combining alcohol‐related pictures with positive (incongruent condition) or negative (congruent condition) words, while brain activity was recorded using 64‐channel electroencephalography. Event‐related potentials (ERPs) for alcohol‐negative and alcohol‐positive trials were computed. Microstate analyses investigated the effects of group (patients, controls) and condition (incongruent, congruent); furthermore, possible gender effects in patients were analyzed. Significant effects were localized with standardized low‐resolution brain electromagnetic topography analysis.

Results

Although no behavioral group differences were found, ERPs of patients and controls were characterized by distinct microstates from 320 ms onwards. ERPs between conditions differed only in patients with higher signal strength during incongruent trials. Around 600 ms, controls displayed higher signal strength than patients. A gender effect mirrored this pattern with enhanced signal strength in females as opposed to male patients. Around 690 ms, a group‐by‐valence interaction indicated enhanced signal strength in congruent compared to incongruent trials, which was more pronounced in controls.

Conclusions

For patients with AUD, the pattern, timing, and source localization of effects suggest greater effort regarding semantic and self‐relevant integration around 400 ms during incongruent trials and attenuated emotional processing during the late positive potential timeframe. Interestingly, this emotional attenuation seemed reduced in female patients, thus corroborating the importance of gender‐sensitive research and potential treatment of AUD.
Artificial light may change flight patterns of bats near bridges along urban waterways
Authors: Barré K. , Spoelstra K. , Bas Y. , Challéat S. , Kiri Ing R. , Azam C. , Zissis G. , Lapostolle D. , Kerbiriou C. , Le Viol I.
Published: September 2020

Artificial light at night (ALAN) is considered as a major threat to biodiversity, especially to nocturnal species, as it reduces availability, quality and functionality of habitats. However, its effects on the way species use landscape elements such as rivers are still largely understudied, especially the effect of crossing infrastructure lighting on bridges. These elements are nevertheless key commuting and foraging habitats in heavily urbanised landscapes for several taxa such as bats that are particularly affected by ALAN. We studied the effects of the illumination of facades and undersides of bridges on the relative abundance of pipistrelle bats, on their 3D distribution and their behavioural response (i.e. flight speed) close to bridges. We set‐up an innovative approach based on a microphone‐array to reconstruct positions and flight trajectories in 3D. We studied the effect of lighting on bats in the close proximity of six similar bridges, mostly differentiated by the presence or absence of lighting (3 lit and 3 unlit). All bridges cross the same waterway, within a uniformly and highly urbanized agglomeration (Toulouse, France). We found that bat activity was 1.7 times lower in lit sites. Bats tended to keep a larger distance, and to fly faster close to illuminated bridges. These results suggest that bridge lighting strongly reduces habitat availability and likely connectivity for bats. In that case, results call for switching off the illumination of such bridges crossing riverine ecosystems to preserve their functionality as habitats and corridors for bats.
Non‐Pecuniary Effects of Sugar‐Sweetened Beverage Policies
Authors: Ahn Sunjin , Lusk Jayson L.
Published: September 2020

Debate about the economic impacts of sugar‐sweetened beverage (SSB) taxes have largely focused on pecuniary effects, but evidence has emerged that taxes could also convey information about what consumers “should” be doing. Disentangling the pecuniary and non‐pecuniary (or non‐price) effects using market data is a significant challenge. To address this issue, we study consumer choices in a simulated market environment in experimental conditions where we vary the reasons respondents are given for the cause of the price hike. We also study responses to a ban on large‐sized sodas, where the stated causes of the ban are randomly varied across respondents. We utilized random parameter logit models and use difference‐in‐difference estimates to identify the non‐pecuniary effect of a SSB tax and a large soda ban on SSB market shares. Our initial study, conducted in 2016, revealed significant non‐pecuniary effects, with soda choices falling less dramatically when subjects knew prices increased because of a soda tax. However, replications and extensions conducted in 2019 show no consistent non‐pecuniary effects. There is considerable heterogeneity across respondents in the difference‐in‐difference estimates, which is only partially explained by demographic or measured attitudinal variables. Results of this study emphasize the importance of carrying out replications and suggest, at least in the context of our experiment, non‐pecuniary effects are small relative to the traditional economic drivers.
Inappropriate activation of invariant natural killer T cells and antigen‐presenting cells with the elevation of HMGB1 in preterm births without acute chorioamnionitis
Authors: Kato Masahiko , Negishi Yasuyuki , Shima Yoshio , Kuwabara Yoshimitsu , Morita Rimpei , Takeshita Toshiyuki
Published: September 2020

Problem

Acute chorioamnionitis (aCAM) associated with microbial infection is a primary cause of preterm birth (PB). However, recent studies have demonstrated that innate immunity and sterile inflammation are causes of PB in the absence of aCAM. Therefore, we analyzed immune cells in the decidua of early to moderate PB without aCAM.

Method of study

Deciduas were obtained from patients with PB at a gestational age of 24+0 to 33+6 weeks without aCAM in pathological diagnosis. The patients were divided into two groups as follows: patients with labor and/or rupture of membrane (ROM) (no aCAM with labor and/or ROM: nCAM‐w‐LR), and patients without labor and/or ROM (no aCAM without labor and/or ROM: nCAM‐w/o‐LR). The immune cells and high mobility group box 1 (HMGB1) levels in the decidua were analyzed using flow cytometry. Co‐culture of CD56+ cells with dendritic cells (DCs) and macrophages obtained from the decidua was also performed in the presence of HMGB1.

Results

The nCAM‐w‐LR group demonstrated an accumulation of iNKT cells, and increased expression of HMGB1, TLR4, receptors for advanced glycation end products, and CD1d on DCs and macrophages. HMGB1 facilitated the proliferation of iNKT cells co‐cultured with DCs and macrophages, which was found to be inhibited by heparin.

Conclusions

Inappropriate activation of innate immune cells and increased HMGB1 expression may represent parturition signs in human pregnancy. Therefore, control of these cells and HMGB1 antigenicity may be represent a potential therapeutic target for the prevention of PB.
Recommendations for prenatal, intrapartum, and postpartum care during COVID‐19 pandemic in India
Authors: Sharma Jai B. , Sharma Eshani , Sharma Sangeeta , Singh Janmeeta
Published: September 2020

The pandemic of coronavirus disease (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has affected more than 19.7 million persons worldwide with 7 28 013 deaths till August 10, 2020. It has put an unprecedented workload on healthcare systems with special reference to labor rooms and obstetrics as deliveries cannot be stopped or postponed. Preparing their facilities using triage (COVID‐positive patients, COVID‐suspect patients, and COVID‐negative patients) can help to better utilize the limited resources and help in prevention of spread of disease, and improve maternal and perinatal outcome. There is a need for proper training of healthcare providers for judicious use of personal protective equipment (PPE) for optimum outcome. Fortunately, the available literature suggests that there is no substantial increased risk of acquiring COVID‐19 in pregnancy or its increased virulence in pregnancy and labor and there are no adverse effects on fetus and neonate with negligible fetal transmission rate. Nevertheless, utmost care is needed to manage such pregnancies, their prenatal care, and labor. This review aimed to highlight the main recommendations applied in Indian maternities for better management of pregnancy during the COVID‐19 pandemic.
Unpayable debt
Authors: GUÉRIN ISABELLE , KUMAR SANTOSH
Published: September 2020

In recent decades rural South India has witnessed the profound effects of financialization, effects that include growing sexual puritanism, changing kinship patterns, and the redefinition of caste hierarchies. For Dalit women, these transformations have given rise to new forms of debt, sexuality, and sexual‐economic exchanges. Although such exchanges can be compatible with sexual desire and pleasure, Dalit women are nonetheless trapped in new forms of unpayable debt. Their debts, though quantifiable and financial, retain a strong moral component associated with new norms of chastity and monogamy. Far from being mere passive objects of exchange, Dalit women challenge their unpayable debt and struggle to exist both as creditworthy financial subjects and as subjects of desire. In contesting the norms of forced sexuality, these women challenge researchers to rethink the concepts of debt and unpayable debt through the lens of gender and sexuality. [debt, unpayable debt, exchange, obligations, sexuality, gender, feminist anthropology, financialization, India]
Leader‐Follower Congruence in Need for Achievement and Work Outcomes: The Mediating Role of Leader‐Member Exchange
Authors: Cai Di , Cai Yahua , Sun Yan , Xu Ruibing , Feng Baoyi
Published: September 2020

While several studies have investigated the effect of employees’ need for achievement on their work‐related outcomes, how leader‐follower congruence in need for achievement is related to critical workplace outcomes remains underexplored. Integrating person‐environment theory and similarity‐attraction theory, this study investigated the influences of leader‐follower congruence in need for achievement on followers’ job performance and job well‐being through the mediating effect of leader‐member exchange (LMX). Using cross‐level polynomial regression and response surface analysis to analyze the data from 391 leaders and 1,124 followers, we found that leader‐follower congruence in need for achievement had a positive effect on followers’ job performance and job well‐being though the mediating role of LMX. The theoretical and managerial implications are further discussed.
GeogEd: A new research group founded on the reciprocal relationship between geography education and the geographies of education
Authors: West Harry , Hill Jennifer , Finn Matt , Healey Ruth L. , Marvell Alan , Tebbett Natalie
Published: September 2020

In 2019, the Higher Education Research Group (HERG) formally became the Geography and Education Research Group (GeogEd). What may appear as a simple change in name masks a renewed understanding of the synergies between geography education (at all levels) and the geographies of education. In this paper we contextualise that change through the relationships between the two inter‐related fields. We suggest that these fields are integrally linked, iteratively and reciprocally, and that research across both is vital for a truly holistic understanding of each. We reflect on the discussions and process of forming the new Geography and Education Research Group, which we trust is sensitive to the historic remit of HERG while being inclusive to those working in geography and education beyond higher education. We conclude by looking ahead to a renewed, inclusive, and progressive Research Group, aspiring to be more diverse and enabling fruitful discussions across the geography and education nexus.
Laparoscopic repair of inguinal hernia in a patient with a ventriculoperitoneal shunt: A case report
Authors: Ishiguro Yui , Ishikawa Takahisa , Hamada Takumi , Okada Naoki , Nakagawa Takahito , Kobayashi Seiji , Ogasawara Kazuhiro , Takahashi Hiromasa , Taketomi Akinobu
Published: September 2020

Laparoscopic surgery in patients with a ventriculoperitoneal (VP) shunt is reportedly associated with increased intracranial pressure secondary to high intraperitoneal pressure and retrograde infection due to intraperitoneal infection. We herein report the first case of transabdominal preperitoneal (TAPP) inguinal hernia repair without catheter manipulation for a patient with a VP shunt. A 69‐year‐old man with a VP shunt was suspected to have an inguinal hernia based on symptoms and examination findings. With a pneumoperitoneum pressure of 10 mm Hg, the VP shunt was not clamped and mesh was placed while confirming cerebrospinal fluid outflow from the tip of the catheter. The patient developed no shunt‐associated complications and was discharged 3 days postoperatively. TAPP inguinal hernia repair without catheter manipulation is a potential surgical option for patients with a VP shunt.
A cross sectional study of psychotropic medicine use in Australia in 2018: A focus on polypharmacy
Authors: Brett Jonathan , Pearson Sallie‐Anne , Daniels Benjamin , Wylie Claire E. , Buckley Nicholas A.
Published: September 2020

Aims

To examine prescribed psychotropic medicine use on a given day in Australia (25 September 2018; World Pharmacists Day), with a focus on psychotropic polypharmacy.

Methods

We used a 10% sample of individual‐level nationwide dispensing claims to examine psychotropic medicine use on a given day. We estimated the prevalence of psychotropic medicine use in all ages stratified by age and sex. We also calculated the observed vs expected (had medicines been randomly combined) prevalence of psychotropic combinations used. We focused on combinations of clinical significance as well combinations of psychotropics with medicines prescribed to manage cardiovascular risk and disease.

Results

Serotonin reuptake inhibitors, serotonin–noradrenalin reuptake inhibitors/noradrenaline reuptake inhibitors, tricyclic antidepressants and gabapentinoids dominated psychotropic use. The use of any psychotropic as a proportion of people in the Australian population increased with age, peaking at the 85–89 year age group and declining thereafter. Combinations of medicines from the same subclass generally occurred at lower than expected frequencies. However, combinations including atypical antipsychotics occurred more frequently than expected; e.g. 7.4× with anticonvulsants and 2.2× with other atypical antipsychotics. This was also the case for combinations of sedatives, e.g. anxiolytic with hypnotic benzodiazepines (3.8×). Lipid‐lowering drugs and antidiabetic medicines were combined with psychotropics at frequencies close to those expected had they been randomly combined.

Conclusion

Psychotropic use in older adults and certain psychotropic combinations that are not well supported with evidence remain prevalent and greater consideration of the drivers of this potentially inappropriate prescribing is required.
Levamisole induced toxic epidermal necrolysis: A case report
Authors: Rohilla Rachna , Jain Arihant
Published: September 2020

Stevens‐Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life‐threatening immune‐mediated hypersensitivity reactions. Various drugs, such as Non Steroidal Anti‐inflammatory drugs (NSAIDS), allopurinol, anticonvulsants and antibiotics, have been implicated as triggering agent of SJS/TEN. Levamisole is frequently used as an antihelminthic and as an immunomodulator in cases of nephrotic syndrome. However, levamisole has not been reported as a trigger for SJS/TEN. The current case describes levamisole‐induced TEN in a 15‐year‐old male who presented to emergency with erythematous lesions, blistering and denudation of skin involving up to 30% of body surface area. Algorithm of drug causality for epidermal necrolysis scoring was applied for causality assessment and a relationship was found to be “possible”. Immediate withdrawal of levamisole along with a short course of corticosteroids and cyclosporine led to improvement in signs and symptoms. Clinicians should be aware of the possible association of levamisole and SJS/TEN.
Denser brain capillary network with preserved pericytes in Alzheimer's disease
Authors: Fernandez‐Klett Francisco , Brandt Lasse , Fernández‐Zapata Camila , Abuelnor Basim , Middeldorp Jinte , Sluijs Jacqueline A. , Curtis Maurice , Faull Richard , Harris Laura W. , Bahn Sabine , Hol Elly M. , Priller Josef
Published: September 2020

Pericytes are vascular mural cells that surround capillaries of the central nervous system (CNS). They are crucial for brain development and contribute to CNS homeostasis by regulating blood–brain barrier function and cerebral blood flow. It has been suggested that pericytes are lost in Alzheimer's disease (AD), implicating this cell type in disease pathology. Here, we have employed state‐of‐the‐art stereological morphometry techniques as well as tissue clearing and two‐photon imaging to assess the distribution of pericytes in two independent cohorts of AD (n = 16 and 13) and non‐demented controls (n = 16 and 4). Stereological quantification revealed increased capillary density with a normal pericyte population in the frontal cortex of AD brains, a region with early amyloid β deposition. Two‐photon analysis of cleared frontal cortex tissue confirmed the preservation of pericytes in AD cases. These results suggest that pericyte demise is not a general hallmark of AD pathology.
Bisphosphonates for delivering drugs to bone
Authors: Sun Shuting , Tao Jianguo , Sedghizadeh Parish P. , Cherian Philip , Junka Adam F. , Sodagar Esmat , Xing Lianping , Boeckman Robert K. , Srinivasan Venkatesan , Yao Zhenqiang , Boyce Brendan F. , Lipe Brea , Neighbors Jeffrey D. , Russell R. Graham G. , McKenna Charles E. , Ebetino Frank H.
Published: September 2020

Advances in the design of potential bone‐selective drugs for the treatment of various bone‐related diseases are creating exciting new directions for multiple unmet medical needs. For bone‐related cancers, off‐target/non‐bone toxicities with current drugs represent a significant barrier to the quality of life of affected patients. For bone infections and osteomyelitis, bacterial biofilms on infected bones limit the efficacy of antibiotics because it is hard to access the bacteria with current approaches. Promising new experimental approaches to therapy, based on bone‐targeting of drugs, have been used in animal models of these conditions and demonstrate improved efficacy and safety. The success of these drug‐design strategies bodes well for the development of therapies with improved efficacy for the treatment of diseases affecting the skeleton.

LINKED ARTICLES

This article is part of a themed issue on The molecular pharmacology of bone and cancer‐related bone diseases. To view the other articles in this section visithttp://onlinelibrary.wiley.com/doi/10.1111/bph.v178.9/issuetoc
Synergistic effect of ibrutinib and CD19 CAR‐T cells on Raji cells in vivo and in vitro
Authors: Liu Meijing , Wang Xuelin , Li Zheng , Zhang Rui , Mu Juan , Jiang Yanyu , Deng Qi , Sun Lei
Published: September 2020

Ibrutinib might improve the efficacy of anti‐CD19 chimeric antigen receptor (CD19 CAR) T‐cell therapy in chronic lymphocytic leukemia (CLL). We studied the possibility and mechanism of the synergistic effect of ibrutinib and CAR‐T cells in other types of lymphoma. In this study, we selected the CD19 CAR‐T cells of a patient with lymphoma who failed in his CD19 CAR‐T‐cell therapy and a dose of 8 mg/kg/d ibrutinib. Subcutaneous and tail vein tumorigenic mice were established with Raji cells. The differences in the synergistic effect between these 2 models were compared by bioluminescence imaging (BLI) monitoring and flow cytometry (FCM). The expression of the STAT‐3 signaling pathway was assessed by western blot analysis. There was no synergistic effect of ibrutinib and CD19 CAR‐T cells in vitro. Programmed cell death‐ligand 1 (PD‐L1) was expressed in 0.23 ± 0.06% of Raji cells. In the subcutaneous tumorigenic model, the luciferase signal was reduced significantly in the group receiving ibrutinib combined with CD19 CAR‐T cells. Moreover, the proportion of CD19 CAR‐T cells was higher in the polytherapy group than in the CAR‐T‐cell monotherapy group. However, we did not get an analogous synergistic effect in the tail vein tumorigenic model. STAT‐3 signaling pathway expression in the residual tumor cells did not differ between those with and those without ibrutinib, suggesting that the IL‐10/STAT‐3/PD‐L1 pathway was not involved in the synergistic effect. Therefore, some other mechanism might be a target for ibrutinib. Our results provide evidence for the use of ibrutinib in polytherapy for other types of B‐cell lymphoma.
Creating a culture of participation: Early childhood education and care educators in the face of change
Authors: Weckström Elina , Karlsson Liisa , Pöllänen Sinikka , Lastikka Anna‐Leena
Published: September 2020

This study reports on critical participatory research in an early childhood education and care centre in Finland. The objective was to study which elements are critical in the development and construction of a culture of participation. The data comprise conversations, team meetings and educators' diaries. Data were analysed using thematic analysis. The results indicated that a culture of participation requires four elements: (a) a shared understanding of the image of the child, (b) a shared understanding of professional development, (c) leadership and (d) a shared we‐narrative that enables the comprehensive understanding, promotion and maintenance of a culture of participation.