bluuebunny/crossref_metadata_2025 huggingface dataset:
Congenital Malformations and Preeclampsia Associated with Integrase Inhibitor Use in Pregnancy
Authors: Smith Christiana , Fought Angela J. , Sung Joyce F. , McKinney Jennifer R. , Metz Torri D. , Fetters Kirk B. , Lazarus Sarah , Capraro Shannon , Barr Emily , Glenny Carrie , Buehler Jenna , Weinberg Adriana ,   the CHIP Perinatal Medical Team
Published: October 2022

Background

Antiretroviral therapy (ART) decreases perinatal HIV transmission, but concerns exist regarding maternal and infant safety. We compared the incidence of congenital malformations and other adverse outcomes in pregnancies exposed to integrase inhibitor (INSTI) versus non-INSTI ART.

Setting

Single-site review of all pregnancies among women living with HIV between 2008 and 2018. Methods: We used binomial family generalized estimating equations to model the relationship of congenital anomalies and pregnancy outcomes with exposure to INSTI or dolutegravir (DTG) versus non-INSTI ART. Results: Among 257 pregnancies, 77 women received ≥1 INSTI (54 DTG, 14 elvitegravir, 15 raltegravir), 167 received non-INSTI, and 3 had missing data. Forty-nine congenital anomalies were identified among 36 infants. Infants with first-trimester DTG or any first-trimester INSTI exposure had higher odds of congenital anomalies than infants with first-trimester non-INSTI exposure (OR=2.55; 95%CI=1.07-6.10; OR=2.61; 95%CI=1.15-5.94, respectively). Infants with INSTI exposure after the second trimester had no increased odds of anomalies. Women with INSTI exposure had higher odds of preeclampsia (OR=4.73; 95%CI=1.70-13.19). Among women who received INSTI, grade ≥3 laboratory abnormalities were noted in 2.6% while receiving the INSTI and 3.9% while not receiving the INSTI, versus 16.2% in women who received non-INSTI. There was no association between INSTI exposure and other pregnancy outcomes.

Conclusion

First-trimester INSTI exposure may be associated with increased rates of congenital anomalies. Use of INSTI during pregnancy was also associated with preeclampsia in our cohort. These findings underscore the need for continued monitoring of the safety of INSTI in pregnancy.
Report – Cost and Clinical Utility of WES and WGS in pediatric patients with suspected genetic disease
Authors: Douglas Michael P. , Deverka Patricia A. , Gelb Bruce , Ferket Bart , Hassmiller Lich Kristen , Stevens Smith Hadley , Norton Mary , Berg Jonathan , Slavotinek Anne , Hindorff Lucia , Phillips Kathryn
Published: October 2022

Payer coverage for Exome Sequencing (ES) is becoming commonplace (albeit in some cases with prior authorization restrictions), coverage for Genome Sequencing (GS) is rare, with most payers considering it as investigational and not medically necessary. Previous studies had identified several concerns and challenges from the payer perspective.The objective of this study is to conduct a targeted literature review of the evidence describing the cost and clinical utility of GS and ES compared to standard of care (SoC) testing in children ≤18 years with suspected genetic disease.

We conducted a systematic literature review to identify evidence for cost, diagnostic utility and clinical utility between SoC, ES, and GS in children (0-18 years) with suspected genetic diseases. We also identified list prices for individual tests from Concert Genetics. Descriptive analyses were conducted for cost and comparative effectiveness data.

We identified five studies on costs of ES and GS, as well as data from concert genetics, and 62 studies of comparative effectiveness of GS or ES in pediatric patients <18 yrs. with suspected genetic disease. We identified 2 reviews/systematic literature review, one cost savings, one micro-costing, and one cost-effectiveness analysis, in addition to the list prices from Concert Genetics which support the range of costs in the articles. List prices ranged from an average of $2264 (small panel) to $7245 for a rapid ES trio. Nearly half the studies (28/63; 44%) only reported diagnostic yield, and 18 studies with NICU/PICU patients and 18 studies of outpatients that reported a change in management. The change in management was very heterogeneous ranging from 24% to 83% depending on the patients’ suspected disorder and test type (e.g., rapid GS, rapid ES, GS). We were unable to determine if any of the GS test types (ultra-rapid GS or rapid GS or GS, range 24% - 83%) provided a greater change in clinical management rate than the ES test types (rapid ES or ES, range 35% - 83%).

There is limited evidence of GS over ES in the ability to effect change in management. Available evidence suggests that rapid over standard GS or ES is of greater benefit in the NICU/PICU setting vs. outpatient setting. Future clinical studies must include both diagnostic yield and clinical management outcomes in order to provide stakeholders with the necessary evidence to support decision-making on implementation and coverage.
OpenLabCluster: Active Learning Based Clustering and Classification of Animal Behaviors in Videos Based on Automatically Extracted Kinematic Body Keypoints
Authors: Li Jingyuan , Keselman Moishe , Shlizerman Eli
Published: October 2022

Quantifying natural behavior from video recordings is a key component in ethological studies. Markerless pose estimation methods have provided an important step toward that goal by automatically inferring kinematic body keypoints. The next step in behavior quantification is utilization of these features toward organizing and interpreting behavioral segments into states. In this work, we introduce a novel deep learning toolset to address this aim. In particular, we introduce OpenLabCluster which clusters segments into groups according to the similarity of kinematic body keypoints and then employs active learning approach which refines the clusters and classifies them into behavioral states. The active learning approach is an iterative semi-supervised deep learning methodology selecting representative examples of segments to be annotated such that the annotation informs clustering and classification of all segments. With these methodologies, OpenLabCluster contributes to faster and more accurate organization of behavioral segments with only a sparse number of them being annotated. We demonstrate OpenLabCluster performance on four different datasets, which include different animal species exhibiting natural behaviors, and show that it boosts clustering and classification compared to existing methods, even when all segments have been annotated. OpenLabCluster has been developed as an open-source interactive graphic interface which includes all necessary functions to perform clustering and classification, informs the scientist of the outcomes in each step, and incorporates the choices made by the scientist in further steps.
A study on RSR evaluation of health service capacity of county-level administrative areas based on entropy weight TOPSIS method in Fujian Province in China
Authors: Zhang Shengli
Published: October 2022

Objective

To identify the differences in health service capacity among county-level administrative regions in Fujian province in China, so as to provide decision-making ideas and basis for high-quality development of the county medical community system with Fujian characteristics,and to prevent health reform from diverging from the essence of meeting everyone’s health needs and improving health service capacity.

Methods

The entropy weight TOPSIS and RSR methods were used to comprehensively evaluate the health service capacity of 84 county-level administrative areas in Fujian Province in China.All data are from the official website of Fujian Provincial Bureau of Statistics.

Results

The results show that the evaluation system of health service capacity with seven indicators, including per capita GDP, number of resident population, number of health institutions, number of beds in health institutions, number of health technicians, number of licensed (assistant) doctors and number of registered nurses,has a good discrimination. The index entropy weights are 0.09, 0.11, 0.12, 0.15, 0.17, 0.19, 0.17 respectively.According to the principle of reasonable grading of normal distribution, the health service capacity is divided into three grades by the Probit value, including 13 weak ones and 14 strong ones. It is worth noting that, as a typical example of China’s health reform, the county-level health service capacity of Sanming City in Fujian Province is only in the middle, and even Ninghua County is weak.

Conclusions

The entropy weight TOPSIS and RSR methods make use of the characteristics of the data itself, avoid the influence of subjective judgment of the evaluation subject, and can quickly make classification judgment. This study uses the statistical yearbook data to construct an evaluation model of 7 indicators, which can well classify the health service capacity of 84 county-level administrative areas. According to the evaluation results of the health service capacity in Sanming City, where the health reform model has been widely praised, it suggests that the health service capacity building cannot be ignored in the health reform evaluation. An objective evaluation may provide more valuable reform recommendations.
Socioeconomic Status and Women’s Mental Health and Wellbeing in Male-Factor Infertility Marital Circumstances: A Scoping Review
Authors: Umoh Nanji R.
Published: October 2022

Background

Infertility is established where frequent intercourse and non-contraceptive use over 12 to 24-month periods do not result in live births. It is an underemphasized global public health challenge occurring mostly in countries with the highest fertility rates. Infertility can be female- or male-factor-based, combined, unexplained, or impaired. Fertility research emphasizes socio-cultural beliefs, patriarchy, insufficient distinctions between masculinity and virility, etc., as impacting women’s mental health and wellbeing. Conversely, research, policies, and interventions underemphasize the male-factor as central to reproduction. This is counter-productive for their female counterparts in the reproductive equation and contributes to gaps in reproductive health literature. Male-factor infertility, a sensitive, long-neglected public health issue caused by genetic and environmental factors, constitutes 20% of infertility cases globally. The biopsychosocial impacts of childlessness on women in male-factor infertility circumstances are almost equally deleterious across social groups and regions.

Objective

To present a scoping review of evidence on the extent to which reproductive health literature recognizes socioeconomic status as central to women’s mental health and wellbeing in male-factor infertility circumstances.

Methods

Literature was mapped across five databases (MedlinePlus, Google Scholar, PubMed, ScienceDirect and Publons Web of Science) without restrictions to geographical regions. The Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) Checklist-2018 was the review protocol.

Results

12 out of 2582 screened articles met the eligibility criteria. The impacts of childlessness on women in male-factor infertility circumstances are similar across regions, but aggravated by socioeconomic circumstances, particularly in low- and middle-income countries (LMICs) and societies that emphasize childbearing. Women with relatively high socioeconomic statuses and access to New/Assisted Reproduction Technologies (NRTs/ARTs) enjoy better mental health and wellbeing.

Discussion/Conclusion

The Social Determinants of Health (SDHs) provided the analytical framework. The socioeconomic status influences the quality of the women’s overall wellbeing in male-factor infertility circumstances, with implications for access to and affordability of New/Assisted Reproduction Technologies (NRTs/ARTs) and other related male-factor infertility treatment options. The deleterious impacts are more for those who are unable to afford the fertility treatments. Asides this socioeconomic context of infertility, a politico-legal context exacerbates the suffering of women in male-factor infertility circumstances, through policy gaps that exist in the provision of interventions to cater to the needs of socioeconomically disadvantaged women.
Repeat polymorphisms in non-coding DNA underlie top genetic risk loci for glaucoma and colorectal cancer
Authors: Mukamel Ronen E. , Handsaker Robert E. , Sherman Maxwell A. , Barton Alison R. , Hujoel Margaux L. A. , McCarroll Steven A. , Loh Po-Ru
Published: October 2022

Many regions in the human genome vary in length among individuals due to variable numbers of tandem repeats (VNTRs). We recently showed that protein-coding VNTRs underlie some of the strongest known genetic associations with diverse phenotypes. Here, we assessed the phenotypic impact of VNTRs genome-wide, 99% of which lie in non-coding regions. We applied a statistical imputation approach to estimate the lengths of 9,561 autosomal VNTR loci in 418,136 unrelated UK Biobank participants. Association and statistical fine-mapping analyses identified 107 VNTR-phenotype associations (involving 58 VNTRs) that were assigned a high probability of VNTR causality (PIP≥0.5). Non-coding VNTRs atTMCO1andEIF3Happeared to generate the largest known contributions of common human genetic variation to risk of glaucoma and colorectal cancer, respectively. Each of these two VNTRs associated with a >2- fold risk range across individuals. These results reveal a substantial and previously unappreciated role of non-coding VNTRs in human health.
The role of uncertainty and negative feedback loops in the evolution of induced immune defenses
Authors: Asgari Danial , Stewart Alexander J. , Meisel Richard P.
Published: October 2022

Organisms use constitutive or induced defenses against pathogens, parasites, and herbivores. Constitutive defenses are constantly on, whereas induced defenses are activated upon exposure to an enemy. Constitutive and induced defenses each have costs and benefits, which can affect the type of defense that evolves in response to pathogens. Previous models that compared the two lacked mechanistic details about host defense, did not consider pathogen proliferation rates, or lacked both features. To address this gap, we developed a detailed mechanistic model of the well-characterizedDrosophila melanogasterimmune signaling network. We evaluated the factors favoring the evolution of constitutive and induced defenses by comparing the fitness of each strategy under stochastic fly-bacteria interactions. We show that an induced defense is favored when bacteria are at low density, heterogeneously distributed, or have fluctuating distributions in ways that depend on the bacterial proliferation rate. Our model also predicts that the specific negative regulators that optimize the induced response depend on the bacterial proliferation rate. We therefore conclude that an induced immune defense is favored in environments where bacterial encounters are uncertain—because of heterogeneity in spatial or temporal distributions—but that benefit depends on the mechanism of induction and pathogen properties.
Evolutionary impact of codon specific translation errors at the proteome scale
Authors: Landerer Cedric , Pöhls Jonas , Toth-Petroczy Agnes
Published: October 2022

Errors in protein synthesis can lead to non-genetic phenotypic mutations, which contribute to generating a wide range of protein diversity. There are currently no methods to measure proteome-wide amino acid misincorporations in a high-throughput fashion, limiting their detection to specific sites and few codon-anticodon pairs. Therefore, it has been technically challenging to estimate the evolutionary impact of translation errors. Here, we developed a computational pipeline, integrated with a novel mechanistic model of translation errors, which can detect translation errors across organisms and conditions. We revealed hundreds of thousands of amino acid misincorporations and a rugged error landscape in datasets ofE. coliandS. cerevisiae. We provide proteome-wide evidence of how codon choice can locally reduce translation errors. Our analysis indicates that the translation machinery prevents strongly deleterious misincorporations while allowing for advantageous ones, and the presence of missing tRNAs would increase codon-anticodon cross-reactivity and misincorporation error rates.
Semaphorin 4B is an ADAM17-cleaved inhibitor of adipocyte thermogenesis
Authors: Amin Abdulbasit , Badenes Marina , Tüshaus Johanna , de Carvalho Érsika , Burbridge Emma , Faísca Pedro , Trávníčková Květa , Barros André , Carobbio Stefania , Domingos Pedro , Vidal-Puig Antonio , Moita Luís , Maguire Sarah , Stříšovský Kvido , Lichtenthaler Stefan F. , Adrain Colin
Published: October 2022

Objective

The metalloprotease ADAM17 (also called TACE) plays fundamental roles in homeostasis by shedding key signaling molecules from the cell surface. Although its importance for the immune system and epithelial tissues is well-documented, little is known about the role of ADAM17 in metabolic homeostasis. The purpose of this study was to determine the impact of ADAM17 expression, specifically in adipose tissues, on metabolic homeostasis.

Methods

We used histopathology, molecular, proteomic, transcriptomic, in vivo integrative physiological and ex vivo biochemical approaches to determine the impact of adipose tissue-specific deletion of ADAM17 upon adipocyte and whole organism metabolic physiology.

Results

ADAM17adipoq-creΔ/Δmice exhibited a hypermetabolic phenotype characterized by elevated energy consumption and increased levels of adipocyte thermogenic gene expression. On a high fat diet, these mice were more thermogenic, while exhibiting elevated expression levels of genes associated with lipid oxidation and lipolysis. This hypermetabolic phenotype protected mutant mice from obesogenic challenge, limiting weight gain, hepatosteatosis and insulin resistance. Activation of beta-adrenoceptors by the neurotransmitter norepinephrine, a key regulator of adipocyte physiology, triggered the shedding of ADAM17 substrates, and regulated ADAM17 expression at the mRNA and protein levels, hence identifying a functional connection between thermogenic licensing and the regulation of ADAM17. Proteomic studies identified Semaphorin 4B (SEMA4B), as a novel ADAM17-shed adipokine, whose expression is regulated by physiological thermogenic cues that acts to dampen thermogenic responses in adipocytes. Transcriptomic data showed that cleaved SEMA4B acts in an autocrine manner in brown adipocytes to dampen the expression of genes involved in thermogenesis, adipogenesis, lipid uptake, storage and catabolism.

Conclusion

Our findings identify a novel ADAM17-dependent axis, regulated by beta-adrenoceptors and mediated by the ADAM17-cleaved form of SEMA4B, that may act to limit uncontrolled energy depletion during thermogenesis.
Regional variations in primary percutaneous coronary intervention for acute myocardial infarction patients: A trajectory analysis using the national claims database in Japan
Authors: Itoshima Hisashi , Shin Jung-ho , Sasaki Noriko , Goto Etsu , Kunisawa Susumu , Imanaka Yuichi
Published: October 2022

v.

BACKGROUND

Previous studies have demonstrated geographical disparities regarding the quality of care for acute myocardial infarction (AMI). The aim of this study was two-folds: first, to calculate the proportion of patients with AMI who received primary percutaneous coronary interventions (pPCIs) by secondary medical areas (SMAs), which provide general inpatient care, as a quality indicator (QI) of the process of AMI practice. Second, to identify patterns in their trajectories and to investigate the factors related to regional differences in their trajectories.

METHODS

We included patients hospitalized with AMI between April 2014 and March 2020 from the national health insurance claims database in Japan and calculated the proportion of pPCIs across 335 SMAs and fiscal years. Using these proportions, we conducted group-based trajectory modeling to identify groups that shared similar trajectories of the proportions. In addition, we investigated area-level factors that were associated with the different trajectories.

RESULTS

The median (interquartile range) proportions of pPCIs by SMAs were 63.5% (52.9% to 70.5%) in FY 2014 and 69.6% (63.3% to 74.2%) in FY 2020. Four groups, named low to low (LL; n =, low to middle (LM; n = 16), middle to middle (MM; n = 68), and high to high (HH; n = 208), were identified from our trajectory analysis. The HH and MM groups had higher population densities and higher numbers of physicians and cardiologists per capita than the LL and LM groups. The LL and LM groups had similar numbers of physicians per capita, but the number of cardiologists per capita in the LM group increased over the years of the study compared with the LL group.

CONCLUSION

The trajectory of the proportion of PCIs for AMI patients identified groups of SMAs. Among the four groups, the LM group showed an increasing trend in the proportions of pPCIs, whereas the three other groups showed relatively stable trends.

vi.

Summary boxes

What is already known on this topic

The quality of health care for acute myocardial infarction (AMI) patients varies across regions.

Door-to-balloon time is associated with patient outcomes, and one of the most easily measurable indicators is the provision of rapid treatment for AMI patients.

What this study adds

The study demonstrated that there were not only cross-sectional regional differences in the proportion of PCIs for AMI patients but also differences in these trajectories.

The cross-sectional regional differences in the proportion of pPCIs were maintained in many SMAs, but there were a few SMAs that increased yearly.
Quantifying changes in the IFR and IHR over 23 months of the SARS-CoV-2 pandemic in England
Authors: Eales Oliver , Haw David , Wang Haowei , Atchison Christina , Ashby Deborah , Cooke Graham , Barclay Wendy , Ward Helen , Darzi Ara , Donnelly Christl A. , Chadeau-Hyam Marc , Elliott Paul , Riley Steven
Published: October 2022

Background

The relationship between prevalence of infection and severe outcomes such as hospitalisation and death changed over the course of the COVID-19 pandemic. The REal-time Assessment of Community Transmission-1 (REACT-1) study estimated swab positivity in England approximately monthly from May 2020 to 31 March 2022. This period covers widespread circulation of the original strain, the emergence of the Alpha, Delta and Omicron variants and the rollout of England’s mass vaccination campaign.

Methods

Here, we explore this changing relationship between prevalence of swab positivity and the infection fatality rate (IFR) and infection hospitalisation rate (IHR) over 23 months of the pandemic in England, using publicly available data for the daily number of deaths and hospitalisations, REACT-1 swab positivity data, time-delay models and Bayesian P-spline models. We analyse data for all age groups together, as well as in two sub-groups: those aged 65 and over and those aged 64 and under.

Results

During 2020, we estimated the IFR to be 0.67% and the IHR to be 2.6%. By late-2021/early-2022 the IFR and IHR had both decreased to 0.097% and 0.76% respectively. Continuous estimates of the IFR and IHR of the virus were observed to increase during the periods of Alpha and Delta’s emergence. During periods of vaccination rollout, and the emergence of the Omicron variant, the IFR and IHR of the virus decreased. During 2020, we estimated a time-lag of 19 days between hospitalisation and swab positivity, and 26 days between deaths and swab positivity. By late-2021/early-2022 these time-lags had decreased to 7 days for hospitalisations, and 18 days for deaths.

Conclusion

Even though many populations have high levels of immunity to SARS-CoV-2 from vaccination and natural infection, waning of immunity and variant emergence will continue to be an upwards pressure on IHR and IFR. As investments in community surveillance are scaled back, alternative methods should be developed to accurately track the ever changing relationship between infection, hospitalisation and death.
FBXL4 suppresses mitophagy by restricting the accumulation of NIX and BNIP3 mitophagy receptors
Authors: Nguyen-Dien Giang Thanh , Kozul Keri-Lyn , Cui Yi , Townsend Brendan , Kulkarni Prajakta Gosavi , Ooi Soo Siang , Marzio Antonio , Carrodus Nissa , Zuryn Steven , Pagano Michele , Parton Robert G. , Lazarou Michael , Millard Sean , Taylor Robert W. , Collins Brett M. , Jones Mathew J.K. , Pagan Julia K.
Published: October 2022

Cells selectively remove damaged or excessive mitochondria through mitophagy, a specialized form of autophagy, to maintain mitochondrial quality and quantity. Mitophagy is induced in response to diverse conditions, including hypoxia, cellular differentiation, and mitochondrial damage. However, the mechanisms by which cells remove specific dysfunctional mitochondria under steady-state conditions to fine-tune mitochondrial content are not well understood. Here, we report that SCFFBXL4, an SKP1/CUL1/F-box protein ubiquitin ligase complex, localizes to the mitochondrial outer membrane in unstressed cells and mediates the constitutive ubiquitylation and degradation of the mitophagy receptors NIX and BNIP3 to suppress basal levels of mitophagy. We demonstrate that, unlike wild-type FBXL4, pathogenic variants of FBXL4 that cause encephalopathic mtDNA depletion syndrome (MTDPS13), do not efficiently interact with the core SCF ubiquitin ligase machinery or mediate the degradation of NIX and BNIP3. Thus, we reveal a molecular mechanism that actively suppresses mitophagy via preventing NIX and BNIP3 accumulation and propose that excessive basal mitophagy in the FBXL4-associated mtDNA depletion syndrome is caused by dysregulation of NIX and BNIP3 turnover.
Olfactory chemosensation extends lifespan through TGF-β signaling and UPR activation
Authors: De-Souza Evandro A. , Thompson Maximillian A. , Taylor Rebecca C.
Published: October 2022

Animals rely on chemosensory cues to survive in pathogen-rich environments. InC. elegans, pathogenic bacteria are known to trigger aversive behaviors through neuronal perception, and to activate molecular defenses throughout the animal. This suggests that neurons may be able to coordinate the activation of organism-wide defensive responses upon pathogen perception. We find that exposure to volatile pathogen-associated compounds induces cell non-autonomous activation of the endoplasmic reticulum unfolded protein response (UPRER) in peripheral tissues followingxbp-1splicing in neurons. This odorant-induced UPRERactivation is dependent upon transforming growth factor beta (TGF-β) signaling and leads to extended lifespan and enhanced clearance of toxic proteins. Our data suggest that the cell non-autonomous UPRERrewires organismal proteostasis in response to pathogen detection, pre-empting the arrival of proteotoxic stress. Thus, chemosensation of particular odors may be a novel way to manipulate stress responses and longevity.
Multiscale Modeling of MT1-MMP-Mediated Cell Migration: Destabilization of Cell-Matrix Adhesion
Authors: Andasari V. , Zaman M.
Published: October 2022

One of several ways MT1-MMP promotes cell migration is by modifying cell adhesion properties. MT1-MMP directly processes cell adhesion properties by shedding cell transmembrane receptors that attach cells to the extracellular matrix (ECM). The shedding leads to the destabilization and disassembly of firm cell-matrix adhesion that holds cells in their stationary position, prompting cells to migrate. In this paper, we present a multiscale mathematical model of single cell migration driven by MT1-MMP destabilization of cell-matrix adhesion. The dynamics of MT1-MMP are modeled using a system of differential equations that are integrated with the Cellular Potts Model (CPM) for a combined modeling at the intracellular and cellular scale, respectively. The CPM is extended to include a local feedback mechanism from MT1-MMP on the membrane that enhances cell membrane fluctuations, resulting in actively migrating cells. The results of computational simulation show that MT1-MMP is capable of destabilizing strong cell-matrix adhesion and stimulating cell migration, and at the same time, also producing cell polarization and motile cell morphology.
Anin vivoavian model of human melanoma to perform rapid and robust preclinical studies
Authors: Jarrosson Loraine , Dalle Stéphane , Costechareyre Clélia , Tang Yaqi , Grimont Maxime , Plaschka Maud , Lacourrège Marjorie , Teinturier Romain , Le Bouar Myrtille , Maucort-Boulch Delphine , Eberhardt Anaïs , Castellani Valérie , Caramel Julie , Delloye-Bourgeois Céline
Published: October 2022

Metastatic melanoma patients carrying a BRAFV600mutation can be treated with BRAF inhibitors (BRAFi), in combination with MEK inhibitors (MEKi), but innate and acquired resistance invariably occurs. Resistance can involve transcriptional- and epigenetic-based phenotypic adaptations, as yet unpredictable. Predicting patient response to targeted therapies is crucial to guide clinical decision. We describe here the development of a highly efficient patient-derived xenograft model adapted to patient melanoma biopsies, using the avian embryo as a host (AVI-PDX™). In thisin vivoparadigm, we depict a fast and reproducible tumor engraftment of patient samples within the embryonic skin, preserving key molecular and phenotypic features. We show that sensitivity and resistance to BRAFi/MEKi targeted therapies can be reliably modeled in these AVI-PDX™, as well as synergies with other drugs, such as HDACi. We further provide proof-of-concept that the AVI-PDX™models the diversity of responses of melanoma patients to BRAFi/MEKi, within days, hence positioning it as a valuable tool for the design of personalized medicine assays and for the evaluation of novel combination strategies.
Tissue-specific transcriptomes reveal mechanisms of microbiome regulation in an ancient fish
Authors: Thorstensen Matt J. , Weinrauch Alyssa M. , Bugg William S. , Jeffries Ken M. , Anderson W. Gary
Published: October 2022

The lake sturgeon (Acipenser fulvescens) is an ancient, octoploid fish faced with conservation challenges across its range in North America but a lack of genomic resources has hindered molecular research in the species. To support such research we aimed to provide a transcriptomic database from 13 tissues: brain, esophagus, gill, head kidney, heart, white muscle, liver, glandular stomach, muscular stomach, anterior intestine, pyloric cecum, spiral valve, and rectum. The transcriptomes for each tissue were sequenced and assembled individually from a mean of 98.3 million (±38.9 million std. dev.) reads each. In addition, an overall transcriptome was assembled and annotated with all data used for each tissue-specific transcriptome. All assembled transcriptomes and their annotations were made publicly available as a scientific resource. The non-gut transcriptomes provide important resources for many research avenues, however, the gut represents a compartmentalized organ system with compartmentalized functions and the sequenced gut tissues were from each of these portions. Therefore, we focused our analysis on mRNA transcribed in different tissues of the gut and explored evidence of microbiome regulation. Gene set enrichment analyses were used to reveal the presence of photoperiod and circadian-related transcripts in the pyloric caecum, which may support periodicity in lake sturgeon digestion. Similar analyses were used to identify different types of innate immune regulation across the gut, while analyses of unique transcripts annotated to microbes revealed heterogeneous genera and genes among different gut tissues. The present results provide a scientific resource and information about the mechanisms of compartmentalized function across gut tissues in a phylogenetically ancient vertebrate.
Assessment of upper limb movement disorders using wearable sensors during functional tasks: a systematic review
Authors: Vanmechelen Inti , Haberfehlner Helga , De Vleeschhauwer Joni , Van Wonterghem Ellen , Feys Hilde , Desloovere Kaat , Aerts Jean-Marie , Monbaliu Elegast
Published: October 2022

Background

Studies aiming to objectively quantify upper limb movement disorders during functional tasks using wearable sensors have recently increased, but there is a wide variety in described measurement and analyzing methods, hampering standardization of methods in research and clinics. Therefore, the primary objective of this review was to provide an overview of sensor set-up and type, included tasks, sensor features and methods used to quantify movement disorders during upper limb tasks in multiple pathological populations. The secondary objective was to select the most sensitive sensor features for symptom detection and quantification and discuss application of the proposed methods in clinical practice.

Methods

A literature search using Scopus, Web of Science, and PubMed was performed. Articles needed to meet following criteria: (1) participants were adults/children with a neurological disease, (2) (at least) one sensor was placed on the upper limb for evaluation of movement disorders during functional tasks, (3) comparisons between: groups with/without movement disorders, sensor features before/after intervention, or sensor features with a clinical scale for assessment of the movement disorder. (4) Outcome measures included sensor features from acceleration/angular velocity signals.

Results

A total of 101 articles were included, of which 56 researched Parkinson’s Disease. Wrist(s), hand and index finger were the most popular sensor locations. The most frequent tasks for assessment were: finger tapping, wrist pro/supination, keeping the arms extended in front of the body and finger-to-nose. The most frequently calculated sensor features were mean, standard deviation, root-mean-square, ranges, skewness, kurtosis and entropy of acceleration and/or angular velocity, in combination with dominant frequencies and power of acceleration signals. Examples of clinical applications were automatization of a clinical scale or discrimination between a patient/control group or different patient groups.

Conclusion

Current overview can support clinicians and researchers to select the most sensitive pathology-dependent sensor features and measurement methodologies for detection and quantification of upper limb movement disorders and for the objective evaluations of treatment effects. The insights from Parkinson’s Disease studies can accelerate the development of wearable sensors protocols in the remaining pathologies, provided that there is sufficient attention for the standardisation of protocols, tasks, feasibility and data analysis methods.
Genome-wide association study identifies multiple HLA loci for sarcoidosis susceptibility
Authors: Liao SY , Jacobson S , Hamzeh NY , Culver DA , Barkes BQ , Mroz P , Macphail K , Pacheco K , Patel DC , Wasfi YS , Koth LL , Langefeld CD , Leach S , White E , Montgomery C , Maier LA , Fingerlin TE ,   GRADs investigators
Published: October 2022

Sarcoidosis is a complex systemic disease. Our study aimed to 1) identify novel alleles associated with sarcoidosis susceptibility; 2) provide an in-depth evaluation of HLA alleles and sarcoidosis susceptibility; 3) integrate genetic and transcription data to identify risk loci that may more directly impact disease pathogenesis.

We report a genome-wide association study of 1,335 sarcoidosis cases and 1,264 controls of European descent (EA) and investigate associated alleles in a study of African Americans (AA: 1,487 cases and 1,504 controls). The EA cohort was recruited from National Jewish Health, Cleveland Clinic, University of California San Francisco, and Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis. The AA cohort was from a previous study with subjects enrolled from multiple United States sites. HLA alleles were imputed and tested for association with sarcoidosis susceptibility. Expression quantitative locus and colocalization analysis were performed using a subset of subjects with transcriptome data.

49 SNPs inHLA-DRA, -DRB9, -DRB5, -DQA1, andBRD2genes were significantly associated with sarcoidosis susceptibility in EA. Among them, rs3129888 was also a risk variant for sarcoidosis in AA. Classical HLA alleles DRB1*0101, DQA1*0101, and DQB1*0501, which are highly correlated, were also associated with sarcoidosis. rs3135287 nearHLA-DRAwas associated withHLA-DRAexpression in peripheral blood mononuclear cells and bronchoalveolar lavage.

In summary, we identified several novel SNPs and three HLA alleles associated with sarcoidosis susceptibility in the largest EA population evaluated to date using an integrative analysis of genetics and transcriptomics. We also replicated our findings in an AA population.
Isolation and crystal and molecular structures of [(C5H2Br3)2Fe], [(C5HBr4)2Fe] and [(C5Br5)(C5Br4HgBr)Fe]
Authors: Blockhaus Tobias , Sünkel Karlheinz
Published: October 2022

The reaction of [(C5H3Br2)2Fe] with lithium tetramethylpiperidinide (LiTMP) in a 1:10 molar ratio in tetrahydrofuran yields, after quenching with C2H2Br4, a mixture of the polybromoferrocenes [C10H10–n
Br
n
Fe] with n = 4–9, from which single crystals of bis(1,2,3-tribromocyclopentadienyl)iron(II), [Fe(C5H2Br3)2], and bis(1,2,3,4-tetrabromocyclopentadienyl)iron(II), [Fe(C5HBr4)2Fe], were obtained by a combination of chromatography and fractional crystallization. Treatment of `[C10(HgOAc)10Fe]' with KBr3 yields a mixture of polybromoferrocenes [C10H10–n
Br
n
Fe] with n = 8–10 and bromomercurioferrocenes [C10H9–n
Br
n
(HgBr)Fe] with n = 7–9, from which single crystals of (1-bromomercurio-2,3,4,5-tetrabromocyclopentadienyl)(1,2,3,4,5-pentabromocyclopentadienyl)iron(II), [FeHgBr(C5Br4)(C5Br5)], were obtained by fractional crystallization. The crystal structures of all the compounds show Br...Br, Br...H and sometimes Br...Cp...π (Cp is a ring centroid) interactions, as well as π–π interactions. The findings are supported by Hirshfeld analyses.
Synthesis and crystal structure of 2-(1,3-dithietan-2-ylidene)cyclohexane-1,3-dione
Authors: Kellou Sabah , Brihi Ouarda , Chetioui Souheyla , Salah Eddine Lemallem , Abdelali Fiala , Boudjada Ali
Published: October 2022

The title compound, C8H8O2S2, contains a cyclohexane-1,3-dione ring, which has a twist-boat conformation. The C2S2 ring is close to planar (r.m.s. deviation = 0.023 Å) and the dihedral angle between the mean planes of the cyclohexane and 1,3-dithietane rings is 9.1 (3)°. Short intramolecular S...O contacts occur [2.719 (5) and 2.740 (5) Å]. In the crystal, the molecules are linked by weak C—H...S hydrogen bonds and short [3.165 (5) Å] S...O contacts, forming (010) layers. The prevalence of these interactions is illustrated by an analysis of the three-dimensional Hirshfeld surface and by two-dimensional fingerprint plots.
ESG dimensions and bank performance: an empirical investigation in Italy
Authors: Menicucci Elisa , Paolucci Guido
Published: October 2022

Purpose

This study aims to investigate the impact of environmental performance, social responsibility and corporate governance (ESG) on bank performance (BP) in the Italian banking sector. It analyzes the relationships between 10 dimensions of ESG pillars and BP indicators during the period 2016–2020.

Design/methodology/approach

This study examines a sample of 105 Italian banks and develops three econometric models to verify the effect of ESG initiatives on BP indicators. The independent variables are the ESG dimensions collected from the Refinitiv database, whereas the explanatory variables are performance indicators measured through accounting and market variables.

Findings

The findings show that ESG policies negatively affect operational and market performance in the banking sector, suggesting that Italian banks have not fully embraced strong sustainability procedures. However, the relationships between ESG dimensions are mixed if measured individually. The results show a significant positive impact of emission and waste reductions on financial and operating performance, but regarding social aspects, it is proved that better product responsibility decreases accounting performance.

Research limitations/implications

This study offers an in-depth examination of ESG practices in relation to current and future performance. In particular, the findings provide practitioners and academics with an actual set of predictors in the ESG area to improve BP.

Originality/value

To the best of the authors’ knowledge, this is the only study that has investigated the impact of ESG issues on BP in Italy. Few prior studies have used all dimensions of ESG policies at a disaggregated level to investigate their effect on various performance indicators.
Fostering customer loyalty across countries in hospitality and tourism: a meta-analysis of cultural values as moderators
Authors: Qi Xiaoxiao , Shi Da , Huang Zixuan , Chang Wen
Published: October 2022

Purpose

This study aims to meta-analyze the moderating roles of Hofstede’s four cultural values in the antecedent–tourist loyalty link.

Design/methodology/approach

Based on 35 independent studies, a meta-regression was conducted to determine whether the heterogeneity of 11 antecedent–tourist loyalty relationships could be explained by four dimensions of Hofstede’s cultural values. Furthermore, this study tested how these relationships were contingent on each cultural value dimension, reinforced by robustness tests involving subgroup analyses.

Findings

The intensity of all associations significantly varied by at least one cultural value dimension, namely, power distance, individualism, masculinity or uncertainty avoidance.

Research limitations/implications

This meta-analytic study enriches the relevant literature by referring to a large, diverse sample to enhance the robustness of the moderating role of tourists’ national culture in loyalty formation and revealing the moderating effect of national culture in 11 antecedent–tourist loyalty links more than in extant literature.

Originality/value

For the body of knowledge of culture-moderated tourist loyalty formation, to the best of the authors’ knowledge, this study is the pioneering meta-analytic effort. It also first offers an original contribution to moderator analysis meta-analytic studies of tourist loyalty by identifying a new moderator, i.e. national culture.
Board committees and financial performance: exploring the effects of gender diversity in the emerging economy of India
Authors: Singhania Shubham , Singh Jagvinder , Aggrawal Deepti
Published: October 2022

Purpose

This study aims to highlight the impact of introducing women directors to board committees, thereby empowering them to contribute to decision-making, and as a result, influence firms’ financial performance in an emerging economy.

Design/methodology/approach

This study uses a fixed-effects panel data regression model to test the impact of gender diversity on corporate boards as well as board committees on firms’ financial performance. Two widely used diversity measures, the Blau index and the Shannon index, have been used to enhance the robustness of the results.

Findings

The findings suggest that gender diversity on prominent board committees (remuneration committee and nomination committee) positively affects firms’ financial performance when measured by the market-based performance measure, but it is insignificant when measured through accounting-based performance indicator. Furthermore, the benefits of gender diversity accrue to the firms only when women are part of prominent committees and are engaged in governance mechanisms, rather than just being appointed on corporate boards as a means of tokenism.

Originality/value

This study is among the first to investigate the relationship between gender diversity and financial performance through the lens of committee assignments. Moreover, the unique cultural and institutional setting offered by India, which is an emerging economy, provides a fertile ground for understanding the role of women leaders in the workforce.
Development of binational radiation therapy quality indicator reports for prostate cancer treatment using registry data
Authors: Chmiel Edward , Pase Marie , Evans Melanie , Johnson Maggie , Millar Jeremy , Papa Nathan
Published: October 2022

Introduction

Quality indicators (QIs) are metrics which seek to allow comparison of clinicians' and institutes' practice to best evidence‐based practice. The Australia and New Zealand Prostate Cancer Outcomes Registry (PCOR–ANZ) is a bi‐national clinical quality registry with coverage estimated to be over 60% of the men newly diagnosed with prostate cancer. We outline the production and ambition of institute‐level QI reports to benchmark performance for radiation therapy in the treatment of prostate cancer.

Methods

An expert clinician panel was assembled to create a list of candidate QIs based on a comprehensive literature review, and on modified Delphi‐method and expert‐consensus voting. A separate implementation group—including, clinicians, epidemiologists, data managers and data scientists—employed an evidence‐ and consensus‐ based approach to generate an effective QI report designed for automated production and regular distribution to participating institutes. Feedback from the recipient clinicians was sought to enable refinement of these reports.

Results

Seven QIs, including three related to post‐treatment symptoms, were deemed feasible to analyse with the currently available data. Utilising an existing report template employed for benchmarking of surgical indicators, a novel radiation therapy report was generated using registry data in a secure analytical environment. The first, beta version of these reports have been produced and confidentially distributed. It is planned to automatically generate these reports biannually and iteratively refine them based on the clinician input.

Conclusion

QI reports for the treatment of prostate cancer by radiation oncologists have been produced using data from Australia and New Zealand patients. These are being disseminated to institutes on a six‐monthly basis allowing comparisons to de‐identified peers. The reports aim to facilitate improving patient outcomes, deepen engagement with the radiation oncology community and increase the breadth of PCOR–ANZ coverage. Additional QIs will be included in future iterations of these reports as data matures.