bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of prospective aging drug targets via Mendelian randomization analysis
Authors: Mao Rui , Li Ji , Xiao Wenqin
Published: April 2024

Aging represents a multifaceted process culminating in the deterioration of biological functions. Despite the introduction of numerous anti‐aging strategies, their therapeutic outcomes have often been less than optimal. Consequently, discovering new targets to mitigate aging effects is of critical importance. We applied Mendelian randomization (MR) to identify potential pharmacological targets against aging, drawing upon summary statistics from both the Decode and FinnGen cohorts, with further validation in an additional cohort. To address potential reverse causality, bidirectional MR analysis with Steiger filtering was utilized. Additionally, Bayesian co‐localization and phenotype scanning were implemented to investigate previous associations between genetic variants and traits. Summary‐data‐based Mendelian randomization (SMR) analysis was conducted to assess the impact of genetic variants on aging via their effects on protein expression. Additionally, mediation analysis was orchestrated to uncover potential intermediaries in these associations. Finally, we probed the systemic implications of drug‐target protein expression across diverse indications by MR‐PheWas analysis. Utilizing a Bonferroni‐corrected threshold, our MR examination identified 10 protein‐aging associations. Within this cohort of proteins, MST1, LCT, GMPR2, PSMB4, ECM1, EFEMP1, and ISLR2 appear to exacerbate aging risks, while MAX, B3GNT8, and USP8 may exert protective influences. None of these proteins displayed reverse causality except EFEMP1. Bayesian co‐localization inferred shared variants between aging and proteins such as B3GNT8 (rs11670143), ECM1 (rs61819393), and others listed. Mediator analysis pinpointed 1,5‐anhydroglucitol as a partial intermediary in the influence LCT exhibits on telomere length. Circulating proteins play a pivotal role in influencing the aging process, making them promising candidates for therapeutic intervention. The implications of these proteins in aging warrant further investigation in future clinical research.
Carbon emissions and abnormal cash holdings
Authors: Amin Abu , Hossain Ashrafee T. , Masum Abdullah‐Al
Published: April 2024

We find that companies that emit high levels of carbon tend to have lower abnormal cash holdings. We have run a battery of endogeneity tests to ensure the robustness of our findings. Our further analysis revealed that weaker internal governance, higher information asymmetry and CEO overconfidence contribute to the heterogeneity of the results. Additionally, we notice that polluting firms prefer to spend more on capital investments while allocating less toward dividends and R&D activities. Our results are consistent with agency theory, indicating that managerial preference for suboptimal investment and/or avoidance of external disciplining might contribute to lower abnormal cash holdings.
Climate risk exposure and debt concentration: Evidence from Chinese listed companies
Authors: Song Wuqi , Xu Wenshuai , Qu Wenzhou , Gong Xu
Published: April 2024

We examine the impact of firm‐level climate risk exposure (CRE) on the debt concentration choices of Chinese listed companies over the period 2010–2021. Our findings suggest that CRE prompts firms to choose debt structures with higher concentration, and this relationship holds true for both physical and transition risks. Further analysis reveals that this effect is more pronounced among firms with higher default risk, restricted access to capital, and lower accounting quality. Our findings remain solid to a battery of robustness tests. Collectively, our study sheds light on the economic consequences of through the lens of firms' debt concentration adjustments.
Intraday and interday variations of milk fatty acids in dairy cows in early and late lactation
Authors: Nagahaka Noriaki , Abe Eisuke , Hiraoka Hiroshi , Kondo Makoto
Published: April 2024

The composition of milk fatty acid (FA) was determined using Fourier‐transform mid‐infrared spectroscopy, which enables the rapid measurement of many samples. Milk FA is one indicator supporting the management of dairy cows and herds. This study aimed to determine an appropriate sampling method for milk FA in a practical farm condition based on intraday and interday variations in milk FA composition during early and late lactation stages. Milk samples were collected in the morning (07:00–08:00 h) and afternoon (16:30–17:30 h) for five consecutive days during early and late lactation. Within the day, de novo FA as the total FA basis was higher in the morning than in the afternoon, whereas preformed FA as the total FA basis was lower in the morning than in the afternoon. The weighted averages of milk FA composition according to milk yield collected in the morning and afternoon were significantly different between cows in early and late lactation; however, these were not significantly different among the consecutive five sampling days in each period. It was concluded that milk samples collected in the morning and afternoon for 1 day are suitable for milk FA determination. These results provide basic data for determining precise sampling methods for practical farms.
Design, synthesis and characterization of ethyl 3‐benzoyl‐7‐morpholinoindolizine‐1‐carboxylate as anti‐tubercular agents: In silico screening for possible target identification
Authors: Tiwari Priya , Mangubhai Gayakvad Sunitaben , Kidwai Saqib , Singh Ramandeep , Chandrashekharappa Sandeep
Published: April 2024

A thorough search for the development of innovative drugs to treat tuberculosis, especially considering the urgent need to address developing drug resistance, we report here a synthetic series of ethyl 3‐benzoyl‐7‐morpholinoindolizine‐1‐carboxylate analogues (5a‐o) as potent anti‐tubercular agents. These morpholino‐indolizines were synthesized by reacting 4‐morpholino pyridinium salts, with various electron‐deficient acetylenes to afford the ethyl 3‐benzoyl‐7‐morpholinoindolizine‐1‐carboxylate analogues (5a‐o). All synthesized intermediate and final compounds are characterized by spectroscopic methods such as 1H NMR, 13C NMR and HRMS and further examined for their anti‐tubercular activity against the M. tuberculosis H37Rv strain (ATCC 27294—American type cell culture). All the compounds screened for anti‐tubercular activity in the range of 6.25–50 μM against the H37Rv strain of Mycobacterium tuberculosis. Compound 5g showed prominent activity with MIC99 2.55 μg/mL whereas compounds 5d and 5j showed activity with MIC99 18.91 μg/mL and 25.07 μg/mL, respectively. In silico analysis of these compounds revealed drug‐likeness. Additionally, the molecular target identification for Malate synthase (PDB 5CBB) is attained by computational approach. The compound 5g with a MIC99 value of 2.55 μg/mL against M. tuberculosis H37Rv emerged as the most promising anti‐TB drug and in silico investigations suggest Malate synthase (5CBB) might be the compound's possible target.
Visualization of the hepatic and renal cell uptake and trafficking of tetrahedral DNA origami in tumour
Authors: Zhu Shitai , Peng Hongzhen , Kong Huating , Yan Qinglong , Xia Kai , Wang Lihua , Zhu Ying , Luo Shihua
Published: April 2024

DNA nanostructures, known for their programmability, ease of modification, and favourable biocompatibility, have gained widespread application in the biomedical field. Among them, Tetrahedral DNA Origami (TDOs), as a novel DNA nanostructure, possesses well‐defined structures, multiple modification sites, and large cavities, making it a promising drug carrier. However, current understanding of TDOs' interactions with biological systems, particularly with target cells and organs, remains unexplored, limiting its further applications in biomedicine. In this work, we prepared TDOs with an average particle size of 40 nm and labelled them with Cy5 fluorescent molecules. Following intravenous injection in mice, the uptake of TDOs by different types of liver and kidney cells was observed. Results indicated that TDOs accumulate in renal tubules and are metabolized by Kupffer cells, epithelial cells, and hepatocytes in the liver. Additionally, in a tumour‐bearing mouse model, TDOs passively targeted tumour tissues and exhibited excellent tumour penetration and retention after rapid metabolism in hepatocytes. Our findings provide crucial insights for the development of TDO‐based drug delivery systems.
Population pharmacokinetics and dosing optimization of perampanel in children with epilepsy: A real‐world study
Authors: Li Sichan , Yi Jiaqin , Tuo YaLi , Nie Gang , Wang Jun , Wang Yang , Sun Dan , Liu Zhisheng
Published: April 2024

Objective

The purposes of this study were to explore the pharmacokinetics of perampanel (PER) in children with epilepsy, identify factors that contribute to pharmacokinetic variations among subjects, evaluate the connection between PER exposure and clinical outcome, and establish an evidence‐based approach for tailoring individualized antiepileptic treatment in this specific population.

Methods

In this prospective study, PER plasma concentrations and genetic information on metabolic enzymes were obtained from 194 patients younger than 18 years. The disposition kinetics of PER in pediatric patients following oral dosing were characterized using nonlinear mixed effect models. The effective range for the plasma concentration of PER was determined by assessing the efficacy and safety of PER treatment and analyzing the relationship between drug exposure and clinical response. Monte Carlo simulations were then performed to evaluate and optimize the current dosing regimens.

Results

The pharmacokinetic profile of PER was adequately described by a one‐compartment model with first‐order absorption and elimination. Body weight, total bilirubin level, and concomitant oxcarbazepine were found to have significant influences on PER pharmacokinetics. Model estimates of apparent clearance and volume of distribution were .016 ± .009 L/h/kg and 1.47 ± .78 L/kg, respectively. The effective range predicted from plasma concentration data in responders was 215–862 μg/L. Dosing scenarios stratified according to essential covariates were proposed through simulation analysis.

Significance

In this study, we captured the pharmacokinetic/pharmacodynamic characteristics of PER in pediatric epilepsy patients through analysis of real‐world data and adopted a pharmacometric approach to support an individualized dosing strategy for PER in this specific population.
Effects of comprehensive nursing interventions on wound pain in patients undergoing catheter insertion for peritoneal dialysis
Authors: Chen Chao , Wang Xiang‐Lei , Li Hui , Zuo Hong
Published: April 2024

This study investigates the effects of comprehensive nursing interventions on wound pain in patients undergoing catheter insertion for peritoneal dialysis. Sixty patients who underwent catheter insertion for peritoneal dialysis from January 2021 to January 2023 at our hospital were selected as subjects and randomly divided into an experimental group and a control group using a random number table method. The control group received routine nursing care, while the experimental group was subjected to comprehensive nursing interventions. The study compared the impact of nursing measures on visual analogue scale (VAS), self‐rating anxiety scale (SAS), self‐rating depression scale (SDS) and nursing satisfaction between the two groups. The analysis revealed that on the third, fifth and seventh days post‐intervention, the experimental group's wound VAS scores were significantly lower than those of the control group (p < 0.001). Furthermore, levels of anxiety and depression were markedly lower in the experimental group compared with the control group (p < 0.001). In addition, the nursing satisfaction rate was significantly higher in the experimental group than in the control group (96.67% vs. 73.33%, p = 0.011). This study indicates that the application of comprehensive nursing interventions in patients undergoing catheter insertion for peritoneal dialysis is highly effective. It can alleviate wound pain and negative emotions to a certain extent, while also achieving high patient satisfaction, thus demonstrating significant clinical value.
Do aposematic species have larger range sizes? A case study with neotropical poison frogs
Authors: Silveira Priscila , de Sousa Fernanda Gonçalves , Böning Philipp , Maciel Natan M. , Stropp Juliana , Lötters Stefan
Published: April 2024

Aim

Aposematic animals, i.e., those that are defended and warn potential predators through signals, are suggested to have resource‐gathering advantages against non‐aposematic ones. We here explore this in a biogeographic framework expecting that aposematic species are better dispersers, which translates into larger geographic range size.

Location

South America.

Taxon

Poison frogs (Amphibia; Aromobatidae and Dendrobatidae).

Methods

We use 43 toxic and 26 non‐toxic poison frog species from the lowlands only as representatives of aposematic and non‐aposematic study organisms, respectively. Realised and potential geographic ranges are calculated using minimum convex polygon and species distribution modelling methods, respectively. Accounting for species body size and phylogeny, we test if both range and aposematism are correlated using linear mixed‐effects models.

Results

Aposematic and non‐aposematic species neither differ in realised nor in potential geographic range size. There was no effect on body size.

Main Conclusions

The role of aposematism is not yet as clear as suggested and determinants of poison frog range sizes are multifaceted. A more integrative approach is needed using the information on behaviour, predation risk, and reproductive biology to assess the role of aposematism on observed species distributions. Such data are not yet available for most species, neither poison frogs nor other aposematic animals.
Lesion metrics and 12‐month outcomes of very‐high power short duration radiofrequency ablation (90W/4 s) under mild conscious sedation
Authors: Calvert Peter , Koniari Ioanna , Mills Mark T. , Ashrafi Reza , Snowdon Richard , Gupta Dhiraj , Luther Vishal
Published: April 2024

Introduction

Pulmonary vein isolation (PVI) is often performed under general anaesthesia (GA) or deep sedation. Anaesthetic availability is limited in many centers, and deep sedation is prohibited in some countries without anaesthetic support. Very high‐power short duration (vHPSD—90W/4 s) PVI using the Q‐Dot catheter is generally well tolerated under mild conscious sedation (MCS) though an understanding of catheter stability and long‐term effectiveness is lacking. We analyzed lesion metrics and 12‐month freedom from atrial arrythmia with this approach.

Methods

Our approach to radiofrequency (RF) PVI under MCS is standardized and includes a single catheter approach with a steerable sheath. We identified patients undergoing Q‐Dot RF PVI between March 2021 and December 2022 in our center, comparing those undergoing vHPSD ablation under MCS (90W/MCS) against those undergoing 50 W ablation under GA (50 W/GA) up to 12 months of follow‐up. Data were extracted from clinical records and the CARTO system.

Results

Eighty‐three patients met our inclusion criteria (51 90W/MCS; 32 50 W/GA). Despite shorter ablation times (353 vs. 886 s; p < .001), the 90 W/MCS group received more lesions (median 87 vs. 58, p < .001), resulting in similar procedure times (149.3 vs. 149.1 min; p = .981). PVI was achieved in all cases, and first pass isolation rates were similar (left wide antral circumferential ablation [WACA] 82.4% vs. 87.5%, p = .758; right WACA 74.5% vs. 78.1%, p = .796; 90 W/MCS vs. 50 W/GA respectively). Analysis of 6647 ablation lesions found similar mean impedance drops (10.0 ± 1.9 Ω vs. 10.0 ± 2.2 Ω; p = .989) and mean contact force (14.6 ± 2.0 g vs. 15.1 ± 1.6 g; p = .248). Only median 2.5% of lesions in the 90 W/MCS cohort failed to achieve ≥ 5 Ω drop. In the 90 W/MCS group, there were no procedural related complications, and 12‐month freedom from atrial arrhythmia was observed in 78.4%.

Conclusion

vHPSD PVI is feasible under MCS, with encouraging acute and long‐term procedural outcomes. This provides a compelling option for centers with limited anaesthetic support.
Quantification of cell shape, intracellular flows and transport based on DIC object detection and tracking
Authors: Kale Tanvi , Khatri Dhruv , Basu Jashaswi , Yadav Shivani A. , Athale Chaitanya A.
Published: April 2024

Computational image analysis combined with label‐free imaging has helped maintain its relevance for cell biology, despite the rapid technical improvements in fluorescence microscopy with the molecular specificity of tags. Here, we discuss some computational tools developed in our lab and their application to quantify cell shape, intracellular organelle movement and bead transport in vitro, using differential interference contrast (DIC) microscopy data as inputs. The focus of these methods is image filtering to enhance image gradients, and combining them with segmentation and single particle tracking (SPT). We demonstrate the application of these methods to Escherichia coli cell length estimation and tracking of densely packed lipid granules in Caenorhabditis elegans one‐celled embryos, diffusing beads in solutions of different viscosities and kinesin‐driven transport on microtubules. These approaches demonstrate how improvements to low‐level image analysis methods can help obtain insights through quantitative cellular and subcellular microscopy.
Health communication and shared decision‐making between nurses and older adults in community setting: An integrative review
Authors: Expósito‐Jiménez Araceli , Alcaide‐Leyva J. M. , Jiménez‐Mérida María del Rocío , Martínez‐Angulo Pablo
Published: April 2024

Aim

To explore the role of health communication in Shared Decision‐Making (SDM) between nursing staff and older people in the community setting.

Background

Society and healthcare services are marked by an exponentially ageing population, leading to a significant proportion of patients being older adults with highly demanding care needs. Scientific literature supports shared decision‐making as a process that engages patients in their care. However, the increasing use of technology and the consequences of the COVID‐19 pandemic have influenced how nurses communicate with older patients. Therefore, it is crucial to understand how to develop health communication to reach effective, shared decision‐making processes.

Methods

Whittemore and Knafl's integrative review method, the literature search comprised five databases: PubMed, CINALH, Web of Science, Scopus and PsycINFO.

Results

The 12 included studies were synthesised into three study patterns: (1) nurse–older patient health communication relationship, (2) older patients' perspectives and (3) nontherapeutic communication in end‐of‐life care.

Conclusion

This review underscored the crucial role of effective health communication in shaping SDM dynamics between nursing staff and older people in the community setting. Key elements included transparent information exchange, establishing trust and maintaining communication channels with informal caregiving networks. SDM actions were aligned with preserving older people's autonomy, but communication challenges persisted, particularly in end‐of‐life situations. Advanced care planning was recommended to address these shortcomings and improve communication among older people, healthcare professionals and families.

Implications

Implementing educational measures based on verbal and nonverbal health communication in nursing training could be beneficial. Nursing research could continue to develop and refine specific communication strategies adapted to the social determinants of health for diverse clinical situations regarding older adults in the community setting.

Reporting Method

The authors have adhered to relevant EQUATOR guidelines through the PRISMA 2020 checklist.

No Patient or Public Contribution.
The association between human papillomavirus infection, vaginal microecology, and cervical intraepithelial neoplasia in women from Xinjiang, China
Authors: Shi Yi , Dong Xiao yang , Yimingjiang Mai wei li dan , Ma Wen mei , Ma Zhi ping , Pang Xue lian , Zhang Wei
Published: April 2024

Purpose

This study analyzes the relationship between human papillomavirus (HPV) infection, vaginal microecology, and cervical lesions to provide a basis for the prevention and treatment of cervical cancer (CC) in the Xinjiang region.

Methods

Real‐time quantitative PCR was used for HPV genotyping and viral load. The Gram staining and dry biochemical enzyme kit were utilized to diagnose vaginal secretions. The χ2 test and Logistic regression analysis were used for statistical analysis.

Results

The HPV infection rate among women in the Xinjiang region was 30.29%, of which the single HPV infection accounts for 77%. HPV16 and HPV52 were the main infection types. There was significant differences in the HPV infection rate and infection types among the Han, Uighur, Hui, and Kazakh ethnic groups. The viral load of HPV16 and HPV52 increases with the upgrade of cervical lesions. There were significant differences in vaginal microecology evaluation indicators H2O2, SNA, LE, GUS, trichomonas, clue cells, and lactobacilli among different ethnic groups. HPV negative patients with varying grades of cervical lesions exhibit a notable variance in H2O2 and LE, which is statistically significant. Single HPV infection and high viral load HPV significantly increase the risk of CC.

Conclusions

This study indicates that HPV infection and vaginal microecology differ among ethnic groups, which have a strong correlation with the progression of CC, offering guidance on CC screening and interventions in the Xinjiang area.
Fertility outcomes in male adults with congenital hypogonadotropic hypogonadism treated during puberty with human chorionic gonadotropin and recombinant follicle stimulating hormone
Authors: Grob Francisca , Keshwani Rachna , Angley Eleanor , Zacharin Margaret
Published: April 2024

Aim

Hormone replacement therapy with testosterone for pubertal induction in boys with congenital hypogonadotropic hypogonadism (CHH) achieves virilization but not spermatogenesis. By contrast, human chorionic gonadotropin (hCG) and recombinant follicle stimulating hormone (rFSH) provides both virilization and spermatogenesis. Fertility outcomes of boys treated with recombinant therapy during adolescence have been infrequently described. We report fertility induction and pregnancy outcomes in CHH patients treated with recombinant gonadotropins during puberty.

Methods

Data of six subjects with CHH (n = 3 Kallmann syndrome & n = 3 Isolated hypogonadotropic hypogonadism) treated with hCG and FSH for pubertal induction were reviewed. Of these, five underwent subsequent fertility induction while one desired fertility at the end of pubertal induction.

Results

Partners of all subjects achieved pregnancies using hCG and rFSH, all with full term live births. All infants were clinically normal.

Conclusion

This study provides early evidence of proof of concept of use of gonadotropin induction of puberty being beneficial in subsequent fertility outcome.
CO2 emissions–economic growth nexus: Validity of EKC in oil‐exporting and oil‐importing countries
Authors: Tokpah Joseph Tuakolon , Saliminezhad Andisheh , Ozdeser Huseyin
Published: April 2024

The purpose of this study is to examine and compare the validity of the environmental Kuznets curve and the relationship between carbon dioxide emissions, per capita GDP, fossil fuel consumption, oil prices and foreign direct investment in advanced oil‐importing and oil‐exporting countries from 1970 to 2020. The researchers consider these nations for their dependency on oil resources and their different economic characteristics. The Westerlund (Oxford Bulletin of Economics and Statistics, 2007, 69, 709) co‐integration test shows that the studied variables are co‐integrated in the long run in both panels of the countries. The pooled mean group‐autoregressive distributed lag (PMG‐ARDL) model established by Pesaran et al. (Journal of the American Statistical Association, 1999, 94, 621), which assesses the short‐ and long‐run nexus between the variables of interest, detects statistically significant associations, providing evidence to support the hypothesis of EKC in both groups. Furthermore, foreign direct investment and fossil fuel consumption have long‐term positive effects on CO2 emissions. The main difference between both groups of countries is that oil price has a positive effect on CO2 emissions in oil‐exporting countries, while it has a negative effect on environmental degradation in oil‐importing countries. The study suggests increasing investment in renewable energy infrastructure by encouraging research and development, providing subsidies and tax incentives for renewable energy companies and promoting large‐scale renewable energy projects as they contribute to environmental quality.
A Korean Picture Bride as an Immigrant Woman Entrepreneur: Gender, Mobility, and Hawaii's Lodging Businesses
Authors: Bae Jin Suk
Published: April 2024

This article aims to analyze the autobiographical records left by Chun Yun‐hee, who came to Hawaii in 1915 as a Korean picture bride, through the lenses of gender, family, labor, and entrepreneurship. First, this article examines the motivations and causes for her transcountry mobility during Korea's Japanese colonial era and subsequent local‐level relocations within the Hawaiian Islands. Second, it sheds light on her labor and economic activities in the period after her migration to the United States, particularly focusing on her involvement in Hawaii's lodging business. It examines why and how she entered and operated lodging businesses, specifically in terms of capital, labor, and customers; how gender and geographical conditions affected her entrepreneurial activities; and how she interpreted the meaning of her work. It is expected that this study will contribute to an improved understanding of not only immigrant women entrepreneurs in general but also the economic adaptation processes and the role of social networks among Korean picture brides in particular.
Lessons learned from conducting a community‐based, nurse‐led HIV prevention trial with youth experiencing homelessness: Pivots and pitfalls
Authors: Santa Maria Diane M. , Fernandez‐Sanchez Higinio , Nyamathi Adey , Lightfoot Marguerita , Quadri Yasmeen , Paul Mary , Jones Jennifer Torres
Published: April 2024

Objective

This article highlights key lessons learned while conducting a nurse‐led community‐based HIV prevention trial with youth experiencing homelessness (YEH), focusing on sexually transmitted infections testing and treatment, intervention sessions, community partnerships, and participant recruitment and retention.

Design

The insights and experiences shared aim to inform future research and the design of interventions targeting populations at high risk, particularly when facing unanticipated challenges. By addressing these areas, the article contributes to the decision‐making for the design and delivery of effective strategies to improve the health outcomes among marginalized populations.

Results

The findings underscore the importance of flexibility and active participant engagement, cultivating strong relationships with community partners, utilizing technology and social media, and fostering a diverse research team that represents the heterogeneity of youth experiencing homelessness across race/ethnicity, gender identity, sexual orientation, and lived experiences.

Conclusions

These recommendations aim to enhance participant access, engagement, and retention, while promoting rigorous research and meaningful study outcomes for YEH.
Genome‐wide association study of adult plant resistance to spot blotch in an elite Canadian two‐row barley germplasm collection
Authors: Tucker James R. , Badea Ana , Fernando W. G. Dilantha , Hiebert Colin W. , Woitas Alexander C. , Beattie Aaron D.
Published: April 2024

Spot blotch, caused by Bipolaris sorokiniana, is a growing concern for barley (Hordeum vulgare) production in most humid, temperate growing regions of the world. Under epidemic conditions, this disease can reduce yields significantly. Reduction of kernel plumpness is associated with lower malt extract and consequently grain quality. Enhanced resistance to this disease is a major goal of western Canadian two‐row barley breeding programmes; however, two‐row barley is considered to be more susceptible than six‐row barley. Plant–pathogen interactions observed for Canadian germplasm are polygenic, where quantitative breeding methods could be beneficial for the development of resistant germplasm. A germplasm panel consisting of 200 two‐row, spring barley genotypes with differential reaction to spot blotch was evaluated at Brandon, Manitoba (MB), and Melfort, Saskatchewan (SK), over eight site years. Genome‐wide association study was conducted using a 50k single‐nucleotide polymorphism (SNP) Illumina iSelect genotyping array. The most‐resistant germplasm was found to carry Midwest Six‐rowed Durable Resistant Haplotype (MSDRH) alleles at the loci located on chromosomes 1H (Rcs‐qtl‐1H‐11_10764), 3H (Rcs‐qtl‐3H‐11_10565) and 7H (Rcs‐qtl‐7H‐11_20162, Rcs5 locus), where the 3H locus was found to be the most under‐represented in Canadian germplasm. Additional marker‐trait associations within nurseries were identified on chromosomes 1H, 2H and 4H. Several of the SNP markers identified were found to be polymorphic within the Canadian two‐row germplasm panel and thus could be useful for enhancing spot blotch resistance in two‐row barley for development of resistant cultivars.
Reviewing workplace innovation as a plea for a practical approach
Authors: Oeij Peter R. A. , Dhondt Steven
Published: April 2024

Workplace innovation (WPI) approaches share the ‘advancement’ of work as a commonality, that is, the notion of good jobs and its relation with good business performance. How WPI approaches contribute to the advancement of work is discussed in this ‘narrative review’ of the WPI literature, which intends to provide direction to future study and implementation of advanced work. A human‐centric theoretical position is chosen with regard to WPI, good work and well‐performing organisations. The heart of the review is investigating the roots of WPI and its historical development along the lines of four different research streams: sociology and organisation research, safety science and organisation research, economic strategy and human resources research, and psychology and behavioural research. These streams are evaluated from their contribution to advanced work, ‘good jobs’. In this review of WPI as a plea for a practical approach, we conclude how the streams connect to the conceptualisation of WPI and human‐centricity, discuss the implications for practice and some limitations, and make recommendations for future research.
Genes, in context
How Life Works: A User’s Guide to the New Biology
Philip Ball
University of Chicago Press, 2023. 552 pp.
Authors: Goldman Michael A.
Published: April 2024

As biologists have long known, the genome is only one piece in the puzzle of life
Roger Guillemin (1924–2024)
Authors: Rivier Catherine
Published: April 2024

Father of neuroendocrinology
Rare wooden artifacts show the smarts of early Neanderthals
Authors: Curry Andrew
Published: April 2024

Complex tools from 300,000-year-old deposit at Schöningen in Germany point to a “wood age”
Efflux pump effects on levofloxacin resistance in
Mycobacterium abscessus
Authors: Teng Tianlu , Chen Suting , Huo Fengmin , Jia Junnan , Zhao Liping , Jiang Guanglu , Wang Fen , Chu Naihui , Huang Hairong
Published: April 2024

Mycobacterium abscessus (M. abscessus
) inherently displays resistance to most antibiotics, with the underlying drug resistance mechanisms remaining largely unexplored. Efflux pump is believed to play an important role in mediating drug resistance. The current study examined the potential of efflux pump inhibitors to reverse levofloxacin (LFX) resistance in
M. abscessus
. The reference strain of
M. abscessus
(ATCC19977) and 60 clinical isolates, including 41
M. abscessus
subsp.
abscessus
and 19
M
.
abscessus
subsp.
massilense
, were investigated. The drug sensitivity of
M. abscessus
against LFX alone or in conjunction with efflux pump inhibitors, including verapamil (VP), reserpine (RSP), carbonyl cyanide 3-chlorophenylhydrazone (CCCP), or dicyclohexylcarbodiimide (DCC), were determined by AlarmarBlue microplate assay. Drug-resistant regions of the
gyrA
and
gyrB
genes from the drug-resistant strains were sequenced. The transcription level of the efflux pump genes was monitored using qRT-PCR. All the tested strains were resistant to LFX. The drug-resistant regions from the
gyrA
and
gyrB
genes showed no mutation associated with LFX resistance. CCCP, DCC, VP, and RSP increased the susceptibility of 93.3% (56/60), 91.7% (55/60), 85% (51/60), and 83.3% (50/60) isolates to LFX by 2 to 32-fold, respectively. Elevated transcription of seven efflux pump genes was observed in isolates with a high reduction in LFX MIC values in the presence of efflux pump inhibitors. Efflux pump inhibitors can improve the antibacterial activity of LFX against
M. abscessus in vitro
. The overexpression of efflux-related genes in LFX-resistant isolates suggests that efflux pumps are associated with the development of LFX resistance in
M. abscessus
.
ABC transporter inhibition by beauvericin partially overcomes drug resistance in
Leishmania tropica
Authors: Al Khoury Charbel , Thoumi Sergio , Tokajian Sima , Sinno Aia , Nemer Georges , El Beyrouthy Mark , Rahy Kelven
Published: April 2024

Leishmaniasis is a neglected tropical disease infecting the world’s poorest populations. Miltefosine (ML) remains the primary oral drug against the cutaneous form of leishmaniasis. The ATP-binding cassette (ABC) transporters are key players in the xenobiotic efflux, and their inhibition could enhance the therapeutic index. In this study, the ability of beauvericin (BEA) to overcome ABC transporter-mediated resistance of
Leishmania tropica
to ML was assessed. In addition, the transcription profile of genes involved in resistance acquisition to ML was inspected. Finally, we explored the efflux mechanism of the drug and inhibitor. The efficacy of ML against all developmental stages of
L. tropica
in the presence or absence of BEA was evaluated using an absolute quantification assay. The expression of resistance genes was evaluated, comparing susceptible and resistant strains. Finally, the mechanisms governing the interaction between the ABC transporter and its ligands were elucidated using molecular docking and dynamic simulation. Relative quantification showed that the expression of the ABCG sub-family is mostly modulated by ML. In this study, we used BEA to impede resistance of
Leishmania tropica
. The IC
50
values, following BEA treatment, were significantly reduced from 30.83, 48.17, and 16.83 µM using ML to 8.14, 11.1, and 7.18 µM when using a combinatorial treatment (ML + BEA) against promastigotes, axenic amastigotes, and intracellular amastigotes, respectively. We also demonstrated a favorable BEA-binding enthalpy to
L. tropica
ABC transporter compared to ML. Our study revealed that BEA partially reverses the resistance development of
L. tropica
to ML by blocking the alternate ATP hydrolysis cycle.
Loss of function of metabolic traits in typhoidal
Salmonella
without apparent genome degradation
Authors: Machado Leopoldo F. M. , Galán Jorge E.
Published: April 2024

Salmonella enterica
serovar Typhi and Paratyphi A are the cause of typhoid and paratyphoid fever in humans, which are systemic life-threatening illnesses. Both serovars are exclusively adapted to the human host, where they can cause life-long persistent infection. A distinct feature of these serovars is the presence of a relatively high number of degraded coding sequences coding for metabolic pathways, most likely a consequence of their adaptation to a single host. As a result of convergent evolution, these serovars shared many of the degraded coding sequences although often affecting different genes in the same metabolic pathway. However, there are several coding sequences that appear intact in one serovar while clearly degraded in the other, suggesting differences in their metabolic capabilities. Here, we examined the functionality of metabolic pathways that appear intact in
S
. Typhi but that show clear signs of degradation in
S
. Paratyphi A. We found that, in all cases, the existence of single amino acid substitutions in
S
. Typhi metabolic enzymes, transporters, or transcription regulators resulted in the inactivation of these metabolic pathways. Thus, the inability of
S
. Typhi to metabolize Glucose-6-Phosphate or 3-phosphoglyceric acid is due to the silencing of the expression of the genes encoding the transporters for these compounds due to point mutations in the transcriptional regulatory proteins. In contrast, its inability to utilize glucarate or galactarate is due to the presence of point mutations in the transporter and enzymes necessary for the metabolism of these sugars. These studies provide additional support for the concept of adaptive convergent evolution of these two human-adapted
S. enterica
serovars and highlight a limitation of bioinformatic approaches to predict metabolic capabilities.

IMPORTANCE

Salmonella enterica
serovar Typhi and Paratyphi A are the cause of typhoid and paratyphoid fever in humans, which are systemic life-threatening illnesses. Both serovars can only infect the human host, where they can cause life-long persistent infection. Because of their adaptation to the human host, these bacterial pathogens have changed their metabolism, leading to the loss of their ability to utilize certain nutrients. In this study we examined the functionality of metabolic pathways that appear intact in
S
. Typhi but that show clear signs of degradation in
S
. Paratyphi A. We found that, in all cases, the existence of single amino acid substitutions in
S
. Typhi metabolic enzymes, transporters, or transcription regulators resulted in the inactivation of these metabolic pathways. These studies provide additional support for the concept of adaptive convergent evolution of these two human-adapted
S. enterica
serovars.
Neogene to modern foreland basin development in the Sub-Andean zone of southern Bolivia and northern Argentina, 21–23°S
Authors: Ferroni Felipe R. , DeCelles Peter G. , Veramendi Jaime Oller
Published: April 2024

The Sub-Andean retroarc region is a unique example of an active continental-scale retroarc foreland basin system. Heavily targeted for hydrocarbon exploration, the region hosts a large volume of subsurface data coupled to surface studies dedicated to refining its evolution in time and space. This paper presents a regional correlation of stratigraphic markers from seismic reflection and well logs across the Sub-Andean foothills at 23–21°S in southern Bolivia and northern Argentina, which reveals the contrasting along-strike history of Mesozoic to Cenozoic tectonics that preceded the foreland basin setting. Supported by published geochronological data and new zircon U-Pb maximum depositional ages, we describe the depositional transition from pre-Andean to Andean stratigraphy and discrete episodes of foreland basin subsidence and shortening. Based on interpreted stratigraphic breaks, we define the extent and stepwise evolution of this foreland basin, which was characterized by the progressive eastward migration of foreland basin depozones. Based on restored thickness profiles, we present flexural models of basin subsidence for the Sub-Andean foothills region. The modeling of discrete episodes of foreland basin subsidence refines the widely accepted bimodal elastic strength in the foreland basin at 21–23°S, which is weaker in the western ranges (~20 km effective elastic thickness) and stronger eastward (>40 km). Modeling results also reveal minimum values of subsidence rates (up to 1.2 mm/yr) in the sequential foredeep depozones and suggest that the modeled tectonic load migration—as constrained by the record of syntectonic strata—probably increased over time through the incorporation of Sub-Andean rocks into the orogenic wedge.
Supplemental Material: Recycling of Paleo-Tethyan oceanic crust: Geochemical record from Early–Middle Triassic igneous rocks in the East Kunlun Orogen in western China
Authors: Yedan Hu , Ma Li-Tao , et al.
Published: April 2024

Analytical methods, Figures S1–S6, and Tables S1–S7. 
Comparative effectiveness of sotrovimab versus no treatment in non-hospitalised high-risk COVID-19 patients in north west London: a retrospective cohort study
Authors: Drysdale Myriam , Galimov Evgeniy R , Yarwood Marcus James , Patel Vishal , Levick Bethany , Gibbons Daniel C , Watkins Jonathan D , Young Sophie , Pierce Benjamin F , Lloyd Emily J , Kerr William , Birch Helen J , Kamalati Tahereh , Brett Stephen J
Published: April 2024

Background

We assessed the effectiveness of sotrovimab vs no early COVID-19 treatment in highest-risk COVID-19 patients during Omicron predominance.

Methods

Retrospective cohort study using the Discover dataset in North West London. Included patients were non-hospitalised, aged ≥12 years and met ≥1 National Health Service highest-risk criterion for sotrovimab treatment. We used Cox proportional hazards models to compare HRs of 28-day COVID-19-related hospitalisation/death between highest-risk sotrovimab-treated and untreated patients. Age, renal disease and Omicron subvariant subgroup analyses were performed.

Results

We included 599 sotrovimab-treated patients and 5191 untreated patients. Compared with untreated patients, the risk of COVID-19 hospitalisation/death (HR 0.50, 95% CI 0.24, 1.06; p=0.07) and the risk of COVID-19 hospitalisation (HR 0.43, 95% CI 0.18, 1.00; p=0.051) were both lower in the sotrovimab-treated group; however, statistical significance was not reached. In the ≥65 years and renal disease subgroups, sotrovimab was associated with a significantly reduced risk of COVID-19 hospitalisation, by 89% (HR 0.11, 95% CI 0.02, 0.82; p=0.03) and 82% (HR 0.18, 95% CI 0.05, 0.62; p=0.007), respectively.

Conclusions

Risk of COVID-19 hospitalisation in sotrovimab-treated patients aged ≥65 years and with renal disease was significantly lower compared with untreated patients. Overall, risk of hospitalisation was also lower for sotrovimab-treated patients, but statistical significance was not reached.
Understanding three approaches to reporting sudden unexpected infant death in the USA
Authors: Erck Lambert Alexa B , Parks Sharyn , Bergman Kristin , Cottengim Carri , Woster Andrew , Shaw Esther , Ma Hongyan , Heitmann Rachel , Riehle-Colarusso Tiffany , Shapiro-Mendoza Carrie
Published: April 2024

Introduction

In the USA each year, there are approximately 3400 sudden unexpected infant (<1 year of age) deaths (SUID) which occur without an obvious cause before an investigation. SUID includes the causes of death (COD) undetermined/unknown, sleep-related suffocation/asphyxia and sudden infant death syndrome (SIDS); these are often called SUID subtypes. Three common ways SUID subtypes are grouped (SUID subtype groups) include International Classification of Diseases (ICD) Codes, SUID Case Registry Categories or Child Death Review (CDR)-Assigned Causes. These groups are often used to monitor SUID trends and characteristics at the local, state and national levels. We describe and compare the characteristics of these three SUID subtype groups.

Discussion

SUID subtype groups are distinct and not directly interchangeable. They vary in purpose, strengths, limitations, uses, history, data years available, population coverage, assigning entity, guidance documentation and information available to assign subtypes.

Conclusion

Making informed decisions about which SUID subtype group to use is important for reporting statistics, increasing knowledge of SUID epidemiology and informing prevention strategies.
ECCRINE SPIRADENOMA AS A DIFFERENTIAL FOR TENDON SHEATH GCT OF THE HAND — A DIAGNOSTIC DILEMMA
Authors: Bhat Vikram G. K. , Mane Prajwal , Pinto Deepak John Victor , Das Rajdeep
Published: April 2024

Eccrine spiradenoma is a rare tumor arising from the sweat glands. It usually presents itself in the head and neck region, with only a few reported cases in the literature of hand eccrine spiradenomas. It is usually seen in the age group of 15–35 years. Here, we report a case of a patient in her 50s presenting a mass over the dorsum of the hand and clinically closely mimicking tendon sheath giant cell tumor (GCT). Investigations supported the clinical diagnosis and provided extra information on possible malignant transformation. A surgical excision was performed and sent for histopathological examination which confirmed the diagnosis. It is also interesting to notice from our case that the need for histopathological evidence should not be neglected despite ultrasonography and Magnetic Resonance Imaging (MRI) being very useful as diagnostic investigations.
Finite dimensional Frobenius–Perron algebras
Authors: Xu Yongjun , Liu Yikun
Published: April 2024

Motivated by the Frobenius–Perron (FP) theory of endofunctors of a [Formula: see text]-linear category, we introduce the notion of a FP algebra. This notion can be seen as a generalization of a fusion algebra, and is related to the PP theory of endofunctors of the categories of finite dimensional representations of Taft algebras. Our main result is to classify such algebras with small dimensions according to their FP dimension vectors. Moreover, we introduce the notion of a FP Hopf algebra which can be used to categorify a FP algebra via the Green ring of the Hopf algebra.
Optical Anapole Modes of the Hybrid Ring-Disk Nanoantenna for Electric Field Enhancement
Authors: Xu Xinchen , Lv Jingwei , Yang Lin , Liu Wei , Mu Haiwei , Lv Yan , Chu Paul K. , Liu Chao
Published: April 2024

A promising design combining low loss, high refractive index dielectric materials with metal nanoparticles, and local plasma resonance is described for ring-disk nanoantenna. A hybrid Au ring Si disk structure with chain gaps is constructed and the distributions of the electric field and near-field enhancement of the electric fields are analyzed by numerical simulation utilizing the multipole decomposition method. The electric field strength can be enhanced efficiently using metals to improve the anapole mode response of dielectric materials with large refractive indexes. Additional enhancement of the electric field is achieved by opening the chain gap to create high-intensity hot spots inside the disk. The chain comprises 14 normal octahedrons and a few tips are created by intersecting octahedrons. The electric field is greatly enhanced at the tips where there are high-intensity hot spots. The effectiveness of this structure as a refractive index sensor is assessed. The scattering cross-section (SCS) and wavelength shifts result in a maximum sensitivity of 210[Formula: see text]nm/RIU. The results validate the design concept and the hybrid structure boasting large electric field enhancement and excellent optical sensing properties have large potential in nonlinear photonics.