bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamic HIV risk differentiation among youth: Validation of a tool for prioritization of prevention in East Zimbabwe
Authors: Moorhouse Louisa R , Gregson Simon , Imai-Eaton Jeffrey W , Mayini Justin , Dadirai Tawanda , Magoge-Mandizvidza Phyllis , Maswera Rufurwokuda , Mabaya Simbarashe , Baggaley Rachel , Low-Beer Daniel , Nyamukapa Constance , Dalal Shona
Published: September 2024

Background

Differentiating risk for HIV infection is important for providing focussed prevention options to individuals. We conducted a longitudinal study to validate a risk-differentiation tool for predicting HIV or HSV-2 acquisition among HIV-negative youth.

Setting

Population-based household survey in east Zimbabwe.

Methods

HIV and HSV-2 status and HIV behavioural risk factors were assessed in two surveys conducted 12 months apart among young people. Associations between risk-behaviours and combined HIV/HSV-2 incident infection were estimated using proportional hazards models. We calculated the sensitivity and specificity of risk-differentiation questions in predicting HIV/HSV-2 acquisition and quantified changes between surveys among low, medium, and high-risk categories.

Results

In total, 44 HIV/HSV-2 seroconversions were observed in 1812 person-years of follow up (2.43/100PY, 95%CI: 1.71-3.15); 50% of incident cases reported never having had sex at baseline. Risk of HIV/HSV-2 acquisition was higher for those reporting non-regular partners (women: HR=2.71, 95% CI:1.12-6.54, men: HR=1.37, 95%CI: 0.29-6.38) and those reporting having a partner with a sexually transmitted infection (STI) (HR=7.62 (1.22-47.51). Adding a question on non-regular partnerships increased tool sensitivity from 18.2% to 38.6%, and further to 77.3% when restricted to those who had ever had sex. Individual risk category increased for 28% of men and 17% of women over 12-months.

Conclusion

The refined risk differentiation tool identified a high proportion of youth at risk of HIV acquisition. Despite this, half of incident infections were among individuals who reported no prior sexual activity. The shifting patterns of risk behaviours underscore the need for dynamic prevention engagement strategies in high HIV prevalence or incidence settings.
Photoreceptor outer segment reflectivity with ultrahigh resolution visible light optical coherence tomography in systemic hydroxychloroquine use
Authors: Garg Anupam K. , Wang Jingyu , Alonzo Bailee , Yi Ji , Kashani Amir H.
Published: September 2024

Purpose

To evaluate outer retinal organization in normal subjects and those using hydroxychloroquine (HCQ) with ultrahigh resolution visible light optical coherence tomography (VIS-OCT).

Methods

Forty eyes of 22 adult subjects were recruited from a tertiary care retina practice including controls (20 eyes, 12 subjects, mean age 40±22yrs, mean logMAR BCVA 0.19, 90% female) and subjects with a history of HCQ use (20 eyes, 10 subjects, mean age 62±17yrs, mean logMAR BCVA 0.03, 67% female). Each subject was imaged using a custom-built VIS-OCT device (axial resolution 1.3μm) and FDA-approved OCT devices.

Results

Using VIS-OCT, control subjects demonstrate 5 and 6 hyperreflective bands in the foveal and parafoveal regions, respectively, between the outer nuclear layer and Bruch’s membrane. These bands demonstrate intensity profiles complementary to the known histopathologic distribution of rods and cones. In comparison to controls, subjects taking HCQ demonstrate blunting of all bands, particularly bands 2-4. In all cases of suspected or known toxicity, VIS-OCT demonstrated attenuation of band 3i and in no cases was there attenuation of other bands that was more severe than band 3i, suggesting that changes in the reflectivity of Band 3i may be the earliest identifiable sign of HCQ toxicity.

Conclusions

VIS-OCT of the outer retina demonstrates a unique outer retinal banding pattern corresponding to photoreceptor density profiles. There is a notable attenuation of the photoreceptor outer segment reflectivity profile associated with early HCQ toxicity. This finding may be an early, and possibly reversible, sign of HCQ toxicity, primarily impacting the cones.
Deuterium metabolic imaging of the human abdomen at clinical field strength
Authors: Wodtke Pascal , McLean Mary A , Horvat-Menih Ines , Birchall Jonathan R , Zamora-Morales Maria J , Grimmer Ashley , Latimer Elizabeth , Wylot Marta , Schulte Rolf F , Gallagher Ferdia A
Published: September 2024

Background

The Warburg effect is a hallmark of cancer and is characterized by increased glucose consumption and lactate formation. Deuterium metabolic imaging (DMI) is an emerging non-invasive MRI method for probing this metabolic reprogramming in the field of neuroimaging. Here we show the feasibility of the technique for abdominal imaging using a routine 3 T MRI system, which has previously presented significant technical challenges.

Purpose

This study aimed to translate abdominal DMI to clinical field strength by optimizing the radiofrequency coil setup, the administered dose of deuterium (2H)-labelled glucose, and the data processing pipeline for quantitative characterization of DMI signals over time in the kidney and liver, establishing a basis for routine clinical studies in the future.

Materials and Methods

Five healthy volunteers were recruited and imaged on 2 or 3 occasions, with different2H-glucose doses (totalling 13 DMI scan sessions). DMI was performed at 3 T using a flexible 20 x 30 cm22H-tuned transmit-receive surface coil. We have defined three novel quantitative parameters as metrics of metabolism and compared these between doses and organs.

Results

The careful positioning of a dedicated surface coil minimized unwanted gastric signals while maintaining excellent hepatic and renal measurements. The timecourses derived from the liver and kidney were reproducible and comparable across different doses, with a trend towards lower quantitative measurements with decreasing dose. An increase in the2H-water signal over time particularly in the liver, could be used as an indirect measure of metabolism.

Conclusion

DMI of the human abdomen is feasible using a routine MRI system and the metabolism measured in the kidney and liver can serve as a reference for future clinical studies. The2H-glucose dose can be reduced from 0.75 to 0.25 g/kg to minimize gastric signal without substantially affecting the reliability of organ quantification.
Phenotypic Findings Associated with Variation in Elastin
Authors: Justice Anne , Kelly Melissa A. , Bellus Gary , Green Joshua D. , Zaidi Raza , Kerrins Taylor , Josyula Navya , Luperchio Teresa R. , Kozel Beth A. , Williams Marc S.
Published: September 2024

Variation in the elastin gene (ELN) may contribute to connective tissue disease beyond the known disease associations of Supravalvar Aortic Stenosis and Cutis Laxa. Exome data from MyCode Community Health Initiative participants were analyzed forELNrare variants (mean allele frequency <1%, not currently annotated as benign). Participants with variants of interest underwent phenotyping by dual chart review using a standardized abstraction tool. Additionally, all rare variants that met inclusion criteria were collapsed into anELNgene burden score to perform a Phenome-wide Association Study (PheWAS). Two hundred and ninety-six eligible participants with relevantELNvariants were identified from 184,293 MyCode participants. One hundred and three of 254 living participants (41%) met phenotypic criteria, most commonly aortic hypoplasia, arterial dilation, aneurysm, and dissection, and connective tissue abnormalities.ELNvariation was significantly (P <2.8×10−5) associated with “arterial dissection” in the PheWAS and two connective tissue Phecodes approached significance. Variation inELNis associated with connective tissue pathology beyond classic phenotypes.

eTOC Blurb

Carriers of variants of interest in the elastin gene (ELN) were evaluated for presence of findings that could be associated with the variation. Chart review and Phenome-wide Association Studies were used. Results are consistent with variation inELNbeing associated with findings affecting elastic tissues beyond classic phenotypes.
EFFECTS OF LIFESTYLE ACTIVITY LEVEL ON ANTICIPATORY LOCOMOTOR ADJUSTMENTS FOR PEDESTRIAN CIRCUMVENTION
Authors: Boulo Joris , Simon Margaux , McFadyen Bradford J. , Blanchette Andreanne K.
Published: September 2024

Navigating public environments requires adjustments to one’s walking patterns to avoid stationary and moving obstacles. It is known that physical inactivity induces alterations in motor capacities, but the impact of inactivity on anticipatory locomotor adjustments (ALA) has not been studied. The purpose of the present study was to compare ALAs and related muscle co-contraction during a pedestrian circumvention task between active (AA) and inactive young adults (IA). Thirteen AA and thirteen IA were placed in a virtual environment simulating a public park. Participants circumvented virtual pedestrians walking towards them. Walking speed, onset of deviation, clearance, foot placement strategies and muscle co-contraction were analysed. IA exhibited slower walking speeds compared to the AA during circumvention condition but not during unobstructed walking condition. The distance at the onset of trajectory deviation was larger for IA. Both groups increased co-contraction for pedestrian circumvention at the ankle and left hip and IA displayed greater ankle co-contraction overall. No significant group differences were observed in minimum clearance. This study suggests that an inactive lifestyle influences ALAs by inducing a cautious behavior during pedestrian circumvention.
Network biology and bioinformatics-based framework to identify the impacts of SARS-CoV-2 infections on lung cancer and tuberculosis
Authors: Waaje Abdul , Sarkar Md Sumon , Islam Md Zahidul
Published: September 2024

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a coronavirus variation responsible for COVID-19, the respiratory disease that triggered the COVID-19 pandemic. The primary aim of our study is to elucidate the complex network of interactions between SARS-CoV-2, tuberculosis, and lung cancer employing a bioinformatics and network biology approach. Lung cancer is the leading cause of significant illness and death connected to cancer worldwide. Tuberculosis (TB) is a prevalent medical condition induced by the Mycobacterium bacteria. It mostly affects the lungs but may also have an influence on other areas of the body. Coronavirus disease (COVID-19) causes a risk of respiratory complications between lung cancer and tuberculosis. SARS-CoV-2 impacts the lower respiratory system and causes severe pneumonia, which can significantly increase the mortality risk in individuals with lung cancer. We conducted transcriptome analysis to determine molecular biomarkers and common pathways in lung cancer, TB, and COVID-19, which provide understanding into the association of SARS-CoV-2 to lung cancer and tuberculosis. Based on the compatible RNA-seq data, our research employed GREIN and NCBI’s Gene Expression Omnibus (GEO) to perform differential gene expression analysis. Our study exploited three RNA-seq datasets from the Gene Expression Omnibus (GEO)—GSE171110, GSE89403, and GSE81089—to identify distinct relationships between differentially expressed genes (DEGs) in SARS-CoV-2, tuberculosis, and lung cancer. We identified 30 common genes among SARS-CoV-2, tuberculosis, and lung cancer (25 upregulated genes and 5 downregulated genes). We analyzed the following five databases: WikiPathway, KEGG, Bio Carta, Elsevier Pathway and Reactome. Using Cytohubba’s MCC and Degree methods, We determined the top 15 hub genes resulting from the PPI interaction. These hub genes can serve as potential biomarkers, leading to novel treatment strategies for disorders under investigation. Transcription factors (TFs) and microRNAs (miRNAs) were identified as the molecules that control the differentially expressed genes (DEGs) of interest, either during transcription or after transcription. We identified 35 prospective therapeutic compounds that form significant differentially expressed genes (DEGs) in SARS-CoV-2, lung cancer, and tuberculosis, which could potentially serve as medications. We hypothesized that the potential medications that emerged from this investigation may have therapeutic benefits.
Rapamycin alters the feeding preference for amino acids and sugar in femaleDrosophila
Authors: Yu Guixiang , Yang Qihao , Wu Qi
Published: September 2024

Pharmacological interventions targeting the aging process hold significant promise for improving the quality of life in the elderly and reducing healthcare costs. Rapamycin, in particular, has exhibited significant anti-aging and lifespan-extending effects across multiple model organisms. However, chronic rapamycin administration may also lead to various adverse reactions since it reshapes energy metabolism. Here, usingDrosophila melanogasteras a model, we show that life-prolonging doses of rapamycin significantly modify animal feeding behavior. Long-term administration of rapamycin decreased protein preference in females while enhancing their sugar intake. Utilizing a chemically defined diet, we identified that changes in amino acid and sugar feeding preferences emerged as early as the second day of rapamycin treatment, preceding any detectable decline in fecundity. However, rapamycin-induced changes in macronutrient feeding preferences were not observed in males and sterile mutant females. Overall, our study suggests that the modification of feeding behavior could be a non-negligible side effect of rapamycin treatment, which is influenced by both sex and reproductive status.
Genetic deletion of NAPE-PLD induces context-dependent dysregulation of anxiety-like behaviors, stress responsiveness, and HPA-axis functionality in mice
Authors: Woodward Taylor J. , Dimen Diana , Sizemore Emily Fender , Stockman Sarah , Kazi Fezaan , Luquet Serge , Mackie Ken , Katona Istvan , Hohmann Andrea G.
Published: September 2024

The endocannabinoid (eCB) system regulates stress responsiveness and hypothalamic-pituitary-adrenal (HPA) axis activity. The enzymeN-acyl phosphatidylethanolamine phospholipase-D (NAPE-PLD) is primarily responsible for the synthesis of the endocannabinoid signaling molecule anandamide (AEA) and other structurally related lipid signaling molecules known asN-acylethanolamines (NAEs). However, little is known about how activity of this enzyme affects behavior. As AEA plays a regulatory role in stress adaptation, we hypothesized that reducing synthesis of AEA and other NAEs would dysregulate stress reactivity. To test this hypothesis, we evaluated wild type (WT) and NAPE-PLD knockout (KO) mice in behavioral assays that assess stress responsiveness and anxiety-like behavior. NAPE-PLD KO mice exhibited anxiety-like behaviors in the open field test and the light-dark box test after a period of single housing. NAPE-PLD KO mice exhibited a heightened freezing response to the testing environment that was further enhanced by exposure to 2,3,5-trimethyl-3-thiazoline (TMT) predator odor. NAPE-PLD KO mice exhibited an exaggerated freezing response at baseline but blunted response to TMT when compared to WT mice. NAPE-PLD KO mice also exhibited a context-dependent dysregulation of HPA axis in response to TMT in the paraventricular hypothalamic nucleus at a neuronal level, as measured by c-Fos immunohistochemstry. Male, but not female, NAPE-PLD knockout mice showed higher levels of circulating corticosterone relative to same-sex wildtype mice in response to TMT exposure, suggesting a sexually-dimorphic dysregulation of the HPA axis at the hormonal level. Together, these findings suggest the enzymatic activity of NAPE-PLD regulates emotional resilience and recovery from both acute and sustained stress.

Significance Statement

The endocannabinoid anandamide (AEA) regulates stress responsiveness and activity of the hypothalamic-pituitary-adrenal (HPA) axis. Currently, little is known about how an enzyme (i.e.N-acylphosphatidylethanolamine phospholipase-D (NAPE-PLD)) involved in thesynthesisof AEA affects behavior. We hypothesized that genetic deletion of NAPE-PLD would dysregulate responsiveness to stress at a behavioral and neuronal level. Our studies provide insight into potential vulnerabilities to stress and anxiety that may result from dysregulation of the enzyme NAPE-PLD in people.
Identification of 16 novel Alzheimer’s disease susceptibility loci using multi-ancestry meta-analyses of clinical Alzheimer’s disease and AD-by-proxy cases from four whole genome sequencing datasets
Authors: Willett Julian Daniel Sunday , Waqas Mohammad , Choi Younjung , Ngai Tiffany , Mullin Kristina , Tanzi Rudolph E. , Prokopenko Dmitry
Published: September 2024

Alzheimer’s disease (AD) is the most prevalent form of dementia. While many AD-associated genetic determinants have been previously identified, few studies have analyzed individuals of non-European ancestry. Here, we describe a multi-ancestry genome-wide association study of clinically-diagnosed AD and AD-by-proxy using whole genome sequencing data from NIAGADS, NIMH, UKB, and All of Us (AoU) consisting of 49,149 cases (12,074 clinically-diagnosed and 37,075 AD-by-proxy) and 383,225 controls. Nearly half of NIAGADS and AoU participants are of non-European ancestry. For clinically-diagnosed AD, we identified 14 new loci - five common (FBN2,/SCL27A6, AC090115.1, DYM, KCNG1/AL121785.1, TIAM1) and nine rare (VWA5B1, RNU6-755P/LMX1A, MOB1A, MORC1-AS1, LINC00989, PDE4D, RNU2-49P/CDO1, NEO1,andSLC35G3/AC022916.1). Meta-analysis of UKB and AoU AD-by-proxy cases yielded two new rare loci (RPL23/LASP1andCEBPA/AC008738.6) which were also nominally significant in NIAGADS. In summary, we provide evidence for 16 novel AD loci and advocate for more studies using WGS-based GWAS of diverse cohorts.
Impact of Respiratory Syncytial Virus (RSV) in adults 60 years and older in Spain
Authors: Jimeno S. , Peláez A. , Calle Á. , Villarreal M. , Natalini S.
Published: September 2024

Respiratory illnesses frequently lead to hospitalisation in adults aged 60 and older, especially due to respiratory virus infectious (RVIs). This study investigates hospitalisation patterns and characteristics of RVIs at HM Hospitals from October 2023 to March 2024.

We retrospectively explored hospitalisations of patients aged 60 years and older with RVIs, gathering data on demographics, clinical profiles, comorbidities, and treatments. Outcomes included hospitalisation, ICU admissions, and mortality, independent factors associated with outcomes were identified using a multi-state model.

From October 2023 to March 2024, from a total of 3,258 hospitalisation, 1,933 (59.3%) were identified as positive for RVIs. Overall, SARS-CoV-2 was the most prevalent (52.6%), followed by influenza (32.7%) and RSV (11.8%). Most RVIs involved single infections (88.2%). Hospitalisation rates increased with age for SARS-CoV-2, influenza, and RSV, with SARS-CoV-2 showing the highest rate, followed by influenza and RSV.

In the multi-state model, RSV infection significantly increased ICU admission risk (HR: 2.1, 95%,p= 0.037). Age on admission (HR: 1.1, 95%, p < 0.001) and Charlson score (HR: 1.4, 95%,p= 0.001) were associated with transitioning from admission to death. ICU to death risks included age at admission (HR: 1.7, 95%,p< 0.001).

RVIs in adults 60 years and older are associated with high hospitalisation and mortality rates, primarily driven by influenza and SARS-CoV-2, followed by RSV. Age and comorbidities significantly impact disease severity, emphasising the need for targeted prevention and management strategies for RSV in this vulnerable population.

Funding

This studio received no funding.
WearGait-PD: An Open-Access Wearables Dataset for Gait in Parkinson’s Disease and Age-Matched Controls
Authors: Anderson Anthony J. , Eguren David , Gonzalez Michael A. , Khan Naima , Watkinson Sophia , Caiola Michael , Hirczy Siegfried S , Zabetian Cyrus P. , Mills Kelly , Moukheiber Emile , Moro-Velazquez Laureano , Dehak Najim , Motely Chelsie , Muir Brittney C. , Butala Ankur , Kontson Kimberly
Published: September 2024

Wearable movement sensors are powerful tools for objectively characterizing and quantifying movement. They enhance the precise characterization of gait, balance, and motor symptoms in Parkinson’s disease and related disorders, facilitating in-clinic and remote assessments, disease management, and therapeutic intervention development. Access to high-quality data from these sensors can accelerate discoveries in this clinical population. The WearGait-PD open-access dataset contains raw inertial measurement unit (IMU) and sensorized insole data from individuals with PD and age-matched controls, synchronized to a gait walkway reference system. IMU data include 3-degree of freedom (DOF) acceleration, rotational velocity, magnetic field strength, and orientation for each of 13 sensors on the participant’s body. Sensor insole data include absolute pressure from 16 sensors in each insole and 3-DOF acceleration and rotational velocity. Walkway data include 2D position and relative pressure for each active sensor during every footfall. Frame-by-frame annotation of participant actions during gait and balance tasks was incorporated using synchronized video cameras. All data were associated with demographic information and clinical evaluations (e.g., medications, DBS-status, MDS-UPDRS scores).
Effect of Fathers in Preemie Prep for Parents (P3) Program on Couple’s Preterm Birth Preparedness
Authors: Basir Mir A. , McDonnell Siobhan M. , Brazauskas Ruta , Kim U. Olivia , Ahamed S. Iqbal , McIntosh Jennifer J. , Pizur-Barnekow Kris , Pitt Michael B. , Kruper Abbey , Leuthner Steven R. , Flynn Kathryn E.
Published: September 2024

Objective

Evaluate the effect of fathers’ participation in the Preemie Prep for Parents (P3) program on maternal learning and fathers’ preterm birth knowledge.

Methods

Mothers with preterm birth predisposing medical condition(s) enrolled with or without the baby’s father and were randomized to the P3 intervention (text-messages linking to animated videos) or control (patient education webpages). Parent Prematurity Knowledge Questionnaire assessed knowledge, including unmarried fathers’ legal neonatal decision-making ability.

Results

104 mothers reported living with the baby’s father; 50 participated with the father and 54 participated alone. In the P3 group, mothers participating with the father (n=33) had greater knowledge than mothers participating alone (n=21), 85% correct responses vs. 76%,p=0.033. However, there was no difference in knowledge among the control mothers, 67% vs. 60%,p=0.068. P3 fathers (n=33) knowledge scores were not different than control fathers (n=17), 77% vs. 68%,p=0.054. Parents who viewed the video on fathers’ rights (n=58) were more likely than those who did not (n=96) to know unmarried fathers’ legal inability to decide neonatal treatments, 84% vs. 41%,p<0.001.

Conclusions

Among opposite-sex cohabitating couples, fathers’ participation in the P3 program enhanced maternal learning.

Practice Implications

The P3 program’s potential to educate fathers may benefit high-risk pregnancies.
A survey of Large Language Model use in a hospital, research, and teaching campus
Authors: Gasparini Loretta , Phillipson Nitya , Capurro Daniel , Rosenberg Revital , Buttery Jim , Howley Jayne , Ranganathan Sarath , Quinlan Catherine , Selvadurai Niloufer , Wildenauer Michael , South Michael , Dimaguila Gerardo Luis
Published: September 2024

Background

The use of Large Language Models (LLMs) has exploded since November 2022 but there is sparse evidence regarding LLM use in health, medical and research contexts.

Objective

To summarise the current uses of and attitudes towards LLMs across the clinical, research and teaching contexts in our campus.

Design

We administered a survey about LLM uses and attitudes. We conducted summary quantitative analysis and inductive qualitative analysis of free text responses.

Setting

In August-September 2023, we circulated the survey amongst all staff and students across our campus (approximately n=7500), a fully integrated paediatric academic hospital and research institute.

Participants

We received 281 anonymous survey responses.

Main outcome measures

We asked about participants’ knowledge of LLMs, their current use of LLMs in professional or learning contexts, and perspectives on possible future uses, opportunities, and risks of LLM use.

Results

Over 90% of respondents have heard of LLM tools and about two-thirds have used them in their work on our campus. Respondents reported using LLMs for a range of uses, including for generating or editing text and exploring ideas. Many, but not necessarily all, respondents seem aware of the limitations and potential risks of LLMs, including privacy and security risks. Various respondents expressed enthusiasm about opportunities of LLM use, including increased efficiency.

Conclusions

Our findings show LLM tools are already widely used on our campus. Guidelines and governance are needed to keep up with practice. We have developed recommendations for the use of LLMs on our campus using insights from this survey.

What is known

The known:The use of Large Language Models (LLMs) has increased rapidly since the introduction of ChatGPT in November 2022.

The new:Most survey respondents are aware of, if not using, LLMs in their work across our hospital, research, and university campus. Diverse uses were reported, including generating or editing text and exploring ideas. There were varying attitudes towards LLMs. Perceived risks included privacy and security risks. A key perceived opportunity was increased efficiency.

The implications:LLM tools are already widely used on our campus, highlighting the need for guidelines and governance to keep up with practice.
Adaptive arousal regulation: Pharmacologically shifting the peak of the Yerkes-Dodson curve by catecholaminergic enhancement of arousal
Authors: Beerendonk Lola , Mejias Jorge F. , Nuiten Stijn A. , de Gee Jan Willem , Zantvoord Jasper B , Fahrenfort Johannes Jacobus , van Gaal Simon
Published: September 2024

Performance typically peaks at moderate arousal levels, consistent with the Yerkes-Dodson law, as confirmed by recent human and mouse pupillometry studies. Arousal states are influenced by neuromodulators like catecholamines (noradrenaline; NA and dopamine; DA) and acetylcholine (ACh). To explore their causal roles in this law, we pharmacologically enhanced arousal while measuring human decision-making and spontaneous arousal fluctuations via pupil size. The catecholaminergic agent atomoxetine (ATX) increased overall arousal and shifted the entire arousal-performance curve, suggesting a relative arousal mechanism where performance adapts to arousal fluctuations within arousal states. In contrast, the cholinergic agent donepezil (DNP) did not affect arousal or the curve. We modeled these findings in a neurobiologically plausible computational framework, showing how catecholaminergic modulation alters a disinhibitory neural circuit that encodes sensory evidence for decision-making. This work suggests that performance adapts flexibly to arousal fluctuations, ensuring optimal performance in each and every arousal state.
A genome-wide One Health study ofKlebsiella pneumoniaein Norway reveals overlapping populations but few recent transmission events across reservoirs
Authors: Hetland Marit A K , Winkler Mia A , Kaspersen Hako , Håkonsholm Fredrik , Bakksjø Ragna-Johanne , Bernhoff Eva , Delgado-Blas Jose F. , Brisse Sylvain , Correia Annapaula , Fostervold Aasmund , Lam Margaret M C , Lunestad Bjørn-Tore , Marathe Nachiket P , Raffelsberger Niclas , Samuelsen Ørjan , Sunde Marianne , Sundsfjord Arnfinn , Urdahl Anne Margrete , Wick Ryan R , Löhr Iren H , Holt Kathryn E
Published: September 2024

Members of theKlebsiella pneumoniaespecies complex (KpSC) are opportunistic pathogens that cause severe and difficult-to-treat infections. KpSC are common in non-human niches, but the clinical relevance of these populations is disputed. Utilising 3,255 whole-genome sequenced isolates from human, animal and marine sources collected during 2001-2020 in Norway, we showed the KpSC populations in different niches were distinct but overlapping. Notably, human infection isolates showed greatest connectivity with each other, followed by isolates from human carriage, pigs, and bivalves. Nearly 5% of human infection isolates had close relatives (≤22 substitutions) amongst animal and marine isolates, despite temporally and geographically distant sampling of these sources. Infection prevention measures are essential to limit transmission within human clinical settings and reduce disease burden. However, as colonisation often precedes infection, preventing transmission that leads to colonisation, e.g. transmission between animals and humans in the community, and in the food chain, could also be beneficial.
The oocyte zinc transporterSlc39a10/Zip10is a regulator of zinc sparks during fertilization in mice
Authors: Kageyama Atsuko , Ogonuki Narumi , Wakai Takuya , Namiki Takafumi , Kawata Yui , Ozawa Manabu , Yamada Yasuhiro , Fukada Toshiyuki , Ogura Atsuo , Fissore Rafael A. , Kashiwazaki Naomi , Ito Junya
Published: September 2024

In all vertebrates studied to date, a rise(s) in intracellular calcium is indispensable for successful fertilization and further embryonic development. Recent studies demonstrated that zinc is ejected to the extracellular milieu, the ‘zinc spark’, and follows the first few calcium rises of fertilization. However, the role of the zinc sparks in fertilization and development, and the supporting influx mechanism(s) are unknown. In this study in mouse oocytes, we investigated the role of zinc transportersZip6/Slc39a6andZip10/Slc39a10. Zip10 mRNA or ZIP10 was expressed throughout folliculogenesis in oocyte or the plasma membrane, respectively. ZIP6 was also expressed in nuclear localization in oocytes and granulosa cells throughout folliculogenesis. The number of ovulated oocytes was examined in oocyte-specificZip6(Zip6d/d:Zip6flox/floxGdf9Cre/+) andZip10(Zip10d/d:Zip10flox/floxGdf9Cre/+) knockout mice, and no change was observed for either strain.Zip10d/doocytes matured and formed normal metaphase II spindles, but had lower labile zinc levels as suggested by the zinc indicator, Fluozin-3 intensity. The levels of zinc fluorescence intensity in theZip6d/dgroup were not different from theZip6f/f. Fertilization-induced calcium oscillations were present in bothZip6d/dandZip10d/doocytes, but zinc sparks were observed inZip6d/dbut not inZip10d/doocytes. Despite other events of egg activation proceeding normally inZip10d/doocytes, embryo development into blastocysts was compromised. We show here for the first time that the zinc transporter ZIP10 contributes to zinc homeostasis in oocytes and embryos, highlighting the pivotal role of this divalent cation in early development.

Classification

Major Classification: Biological Sciences

Minor Classification: Developmental Biology

Significance statement

Recent studies reported that the ejection of zinc into the extracellular milieu also called the ‘zinc spark’, occurs during mammalian fertilization including humans and all vertebrates. However, the role and molecules involved in producing these sparks remain unclear. We demonstrated for the first time that a zinc transporter,Slc39a10/Zip10,is required for the zinc sparks of fertilization in mice. In addition, ZIP10-dependent zinc signaling is not involved in the zona reaction or the block of polyspermy but it is in embryonic development. Taken together, we show here a zinc transporter-dependent signaling event has pivotal roles in fertilization and embryonic development in mice. Our findings will contribute to improving embryonic development in all mammals.
Large-scale mouse mutagenesis identifies novel genes affecting vertebral development
Authors: Ibarra-Soria Ximena , Webb Elizabeth , Mulley John F.
Published: September 2024

We analyzed the International Mouse Phenotyping Consortium (IMPC) release 19 set of 8,539 phenotyped whole-gene knockouts to identify 204 genes that alter vertebral development. These genes are broadly grouped into six categories based on their phenotype: “vertebral number” (22 genes); “vertebral processes” (35 genes); “spine shape” (16 genes); “tail morphology” (73 genes); “vertebral form” (62 genes); and “somitogenesis” (24 genes), with minimal overlap between groups. Gene expression analysis of somite trios across six developmental stages show that 182 of these genes are expressed in somites, and 60% of them show variable expression during somite maturation. A further 54% show expression changes between developmental stages. Fourteen of the 204 genes affecting vertebral development have a vertebral phenotype as their only phenotype, and for 34 genes vertebral phenotypes represent ≥50% of their total phenotypes. We find no evidence for a previous association of the majority of these genes with vertebral defects, and have therefore identified an extensive set of novel candidate genes for association with vertebral malformations in humans, including vertebral fusions, numerical variation, and scoliosis.
Constraints on the variation of physical constants, equivalence principle violation, and a fifth force from atomic experiments
Authors: Dzuba V. A. , Flambaum V. V. , Mansour A. J.
Published: September 2024

The aim of this paper is to derive limits on various forms of “new physics” using atomic experimental data. Interactions with dark energy and dark matter fields can lead to space-time variations of fundamental constants, which can be detected through atomic spectroscopy. In this study, we examine the effects of a varying nuclear mass mN and nuclear radius rN on two transition ratios: the comparison of the two-photon transition in atomic hydrogen with the hyperfine transition in Cs133 based clocks, and the ratio of optical clock frequencies in Al+ and Hg+. The sensitivity of these frequency ratios to changes in mN and rN enables us to derive new limits on the variations of the proton mass, quark mass, and the QCD parameter θ. Additionally, we consider the scalar field generated by the Yukawa-type interaction of feebly interacting hypothetical scalar particles with Standard Model particles in the presence of massive bodies such as the Sun and Moon. Using the data from the Al+/Hg+, Yb+/Cs, and Yb+(E2)/Yb+(E3) transition frequency ratios, we place constraints on the interaction of the scalar field with photons, nucleons, and electrons for a range of scalar particle masses. We also investigate limits on the Einstein equivalence principle (EEP) violating term (c00) in the Standard Model extension (SME) Lagrangian and the dependence of fundamental constants on gravity.

Published by the American Physical Society
2024
Ternary structure of Plasmodium vivax
N-myristoyltransferase with myristoyl-CoA and inhibitor IMP-0001173
Authors: Bolling Cydni , Mendez Alex , Taylor Shane , Makumire Stanley , Reers Alexandra , Zigweid Rachael , Subramanian Sandhya , Dranow David M. , Staker Bart , Edwards Thomas E. , Tate Edward W. , Bell Andrew S. , Myler Peter J. , Asojo Oluwatoyin A. , Chakafana Graham
Published: September 2024

Plasmodium vivax is a major cause of malaria, which poses an increased health burden on approximately one third of the world's population due to climate change. Primaquine, the preferred treatment for P. vivax malaria, is contraindicated in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency, a common genetic cause of hemolytic anemia, that affects ∼2.5% of the world's population and ∼8% of the population in areas of the world where P. vivax malaria is endemic. The Seattle Structural Genomics Center for Infectious Disease (SSGCID) conducted a structure–function analysis of P. vivax
N-myristoyltransferase (PvNMT) as part of efforts to develop alternative malaria drugs. PvNMT catalyzes the attachment of myristate to the N-terminal glycine of many proteins, and this critical post-translational modification is required for the survival of P. vivax. The first step is the formation of a PvNMT–myristoyl–CoA binary complex that can bind to peptides. Understanding how inhibitors prevent protein binding will facilitate the development of PvNMT as a viable drug target. NMTs are secreted in all life stages of malarial parasites, making them attractive targets, unlike current antimalarials that are only effective during the plasmodial erythrocytic stages. The 2.3 Å resolution crystal structure of the ternary complex of PvNMT with myristoyl-CoA and a novel inhibitor is reported. One asymmetric unit contains two monomers. The structure reveals notable differences between the PvNMT and human enzymes and similarities to other plasmodial NMTs that can be exploited to develop new antimalarials.
A trusted B2B relationship quality in the Asian market: effects of salespeople's attributes
Authors: Lii Yuan-Shuh , Ding May-Ching , Lee Shanchih
Published: September 2024

Purpose

The research applied service-dominant logic of marketing theory, a customer-centered and relational that principally grounded in service relationships and actor networks. In actor networks, salespeople provide their skills and knowledge, such as expertise, service quality, ethics and shared value to cocreate value for buyers. Therefore, this study explores the attributes of salespeople that influence the quality of the relationship (trust and satisfaction) and, as a result, loyalty in the context of the business-to-business (B2B) relationship in the Taiwan market.

Design/methodology/approach

A causal relationship and survey research design are applied. The study collected 266 valid responses from B2B account managers representing various companies and industries. Structural equation modeling (SEM) was applied to test the hypotheses.

Findings

The results showed that salespeople’s expertise demonstrated the most significant influence on both trust and satisfaction, followed by ethics, service quality and share value, in a descending order of impact. Consequently, trust and satisfaction had a significant impact on customer loyalty.

Practical implications

The four attributes of salespeople play a pivotal role in establishing lasting relationships and maximizing the customer lifetime value. To achieve long-term success in customer interactions and relationships, a well-rounded salesperson should diligently strive to excel in all these attributes.

Originality/value

The novelty and contribution of this study are twofold. First, investigating the quality of the relationship in the context of Taiwanese manufacturers in a B2B setting is still rare, and this is the study first to explore the Taiwanese B2B relationship with its global customers. As Taiwanese manufacturers play a pivotal role in the global supply chain, the research findings have symbolic meaning and practical implications for global business partners. Second, drawing from service-dominant logic theory, this research takes an integrative view by examining the attributes (expertise, service quality, shared value and ethics) that influence and establish a quality trusting relationship and consumer loyalty in the B2B context.
Understanding the political connections of Portuguese companies through their board members
Authors: Ferreira Paulo , Oliveira Jonas , Azevedo Graça
Published: September 2024

Purpose

This study aims to analyse the political connections of Portuguese companies through the members of the board of directors, exploring how these connections influence, in particular, the composition and characteristics of the boards.

Design/methodology/approach

The research used a strategy based on analysing the financial statements and curriculum vitae of the directors of Portuguese companies listed on Euronext Lisbon from 2014 to 2019. The political connections of board members were examined, considering the variables identified in the existing literature.

Findings

The results indicate that companies with political connections maintain these relationships for long periods and have a greater number of members on the board of directors compared to companies without such connections. Directors with political experience tend to occupy non-executive positions, suggesting that companies may value political contacts more than the management skills of these directors. It was also found that there are politically connected directors who belong to multiple boards and that women appointed to the board are less likely to have a political background, reflecting male dominance in Portuguese politics.

Research limitations/implications

The main limitations of this study include the small number of listed companies in the sample, which may affect the statistical robustness of the results, as well as the use of secondary sources, which may not capture all relevant policy linkages. In addition, the results are specific to the Portuguese context and may not be generalisable to other countries or other regions of the world.

Originality/value

This study contributes to the understanding of political connections in Portuguese companies, offering valuable insights into how these connections influence board composition and can impact corporate strategy and governance. The findings of this study can be especially useful for business leaders looking to optimise the formation of their boards of directors.
Size matters: the influence of supplier size on buyer's usage of mediated power in positive and negative supplier-induced disruptions
Authors: Chu Yu (Jade) , Duan Yanji
Published: September 2024

Purpose

While size asymmetry in buyer–supplier relationships has been studied in non-disruption contexts, this research explores how supplier size influences positive and negative supply chain disruptions. Anchoring on the commitment-trust theory (CTT), we explore buyer commitment as a mediating variable and examine how buying firms' mediated power usage depends on different supplier sizes and types of supplier-induced disruptions.

Design/methodology/approach

Through two scenario-based behavioral experiments, we discover different patterns in buyers' use of mediated power, contingent on the types of supplier-induced disruptions.

Findings

In negative disruptions, buyers prefer more mediated power with large suppliers to control uncertainties, using reward or coercive power strategies. In positive disruptions, we find opposite results, indicating different buyers' perceptions and actions are contingent on both the supplier size and the types of disruptions. These findings underscore the complex interplay between supplier size, buyer commitment and mediated power strategies, revealing that disruption type significantly shapes buyer responses.

Research limitations/implications

This paper extends the CTT framework by considering new antecedents and outcomes. We also provide a more comprehensive understanding of buyer behavior when facing positive and negative supplier-induced disruptions. Our study has limitations. Through vignette-based behavioral experiments, there is a risk that scenarios may not accurately represent real-life situations and that decision-making dynamics could be oversimplified. Future research should incorporate nuanced measurements and conduct additional qualitative research for a comprehensive understanding.

Originality/value

This study enriches the understanding of the buyer-supplier relationship by expanding the CTT framework for a more comprehensive picture. We also offer nuanced insights into size dynamics and disruption types, emphasizing tailored strategies in supply chain management. The findings underscore the importance of understanding these nuances to employ tailored strategy in a business-to-business (B2B) context, as mediated power is contingent on multiple factors.
Analyzing the impact of country-of-origin, geographical indication and wine world on low-involvement generation Z potential consumers’ attitudes toward wine ads
Authors: Purcini Gabriela , Medeiros Barretta Leonardo Medeiros , Ferreira Luciana , Lourenção Marina
Published: September 2024

Purpose

This study aims to compare the influence of origin types (country-of-origin – COO versus geographic indication – GI) and wine worlds (new versus old wine country – represented by Brazil and Italia, respectively) on the attitude of low-involvement Generation Z potential consumers from Brazil toward wine ads.

Design/methodology/approach

The authors conducted a two (COO vs GI) by two (New vs Old World) within-subject experimental design with 98 Brazilians from Generation Z. Latin square was used to systematically counterbalances the sequence in which participants were exposed to ads.

Findings

The results reveal that potential consumers’ attitudes are more positive when a COO is used in wine advertisements than when a GI is used. Besides, the consumers’ conative response is more positive when an Old World country (Italy) is used in wine ads than when New World country (Brazil) is used.

Research limitations/implications

This study expands existing literature by showing that, in wine ads, COO information elicits more positive responses than GI. It also suggests a preference among potential consumers for Old over New World wines in purchase, recommendation and consumption decisions.

Practical implications

The wine advertisements for the market segment investigated should highlight the COO instead of geographical indication (GI). Besides, the authors point out the importance of promoting the concept of GI among low-involvement Generation Z potential consumers.

Originality/value

To the best of the authors’ knowledge, this is the first study to assess potential consumers’ attitudes toward wine ads, comparing COO and GI and determining which geographical cue elicits more positive consumer attitudes: origin types (COO vs GI) or wine worlds (Old vs New).
Optimization of high-speed reducer in electric vehicle based on analysis of lubrication
Authors: Jia Fuchun , Liu Xianghuan , Fu Yao
Published: September 2024

Purpose

The purposes of this paper are optimization of high speed reducer in electric vehicles based on the analysis of lubrication and verification of simulation accuracy and optimization results.

Design/methodology/approach

The traditional CFD method presents poor applicability to complex geometric problems due to grid deformity. Therefore, moving particle semi-implicit (MPS) method is applied in this study to simulate lubrication of the reducer and analyze the influence of input speed and lubrication system design on the distribution. According to the results, the reducer is optimized. Meanwhile, the experiments for lubrication and churning power loss is carried out to verify the accuracy of simulation and optimization effects.

Findings

The flow field of lubricant inside the reducer is obtained. The lubrication system of reducer needs to be improved. Simulation and experiment show that the optimization is sufficient and efficient.

Originality/value

According to the simulation of lubrication, the reducer is optimized. The lubrication experimental setup is established. The conclusion of paper can provide the method and tool for reducer in electric vehicle.

Peer review

The peer review history for this article is available at: https://publons.com/publon/10.1108/ILT-04-2024-0123/