bluuebunny/crossref_metadata_2025 huggingface dataset:
Coupled environmental and demographic fluctuations shape the evolution of cooperative antimicrobial resistance
Authors: Hernández-Navarro Lluís , Asker Matthew , Rucklidge Alastair M. , Mobilia Mauro
Published: November 2023

There is a pressing need to better understand how microbial populations respond to antimicrobial drugs, and to find mechanisms to possibly eradicate antimicrobial-resistant cells. The inactivation of antimicrobials by resistant microbes can often be viewed as a cooperative behaviour leading to the coexistence of resistant and sensitive cells in large populations and static environments. This picture is, however, greatly altered by the fluctuations arising in volatile environments, in which microbial communities commonly evolve. Here, we study the eco-evolutionary dynamics of a population consisting of an antimicrobial-resistant strain and microbes sensitive to antimicrobial drugs in a time-fluctuating environment, modelled by a carrying capacity randomly switching between states of abundance and scarcity. We assume that antimicrobial resistance (AMR) is a shared public good when the number of resistant cells exceeds a certain threshold. Eco-evolutionary dynamics is thus characterised by demographic noise (birth and death events) coupled to environmental fluctuations which can cause population bottlenecks. By combining analytical and computational means, we determine the environmental conditions for the long-lived coexistence and fixation of both strains, and characterise afluctuation-drivenAMR eradication mechanism, where resistant microbes experience bottlenecks leading to extinction. We also discuss the possible applications of our findings to laboratory-controlled experiments.
“The Brain is…”: A Survey of The Brain’s Many Definitions
Authors: Bolt Taylor , Uddin Lucina Q.
Published: November 2023

A reader of the peer-reviewed neuroscience literature will often encounter expressions like the following: ‘the brain is a dynamic system’, ‘the brain is a complex network’, or ‘the brain is a highly metabolic organ’. These expressions attempt to define the essential functions and properties of the mammalian or human brain in a simple phrase or sentence, sometimes using metaphors. We sought to survey the most common phrases of the form ‘the brain is…’ in the biomedical literature to provide insights into current conceptualizations of the brain. Utilizing text analytic tools applied to a large sample (> 4 million) of peer-reviewed full-text articles and abstracts, we extracted several thousand phrases of the form ‘the brain is…’ and identified over a dozen frequently appearing phrases. The most used phrases included metaphors (e.g., the brain as a ‘information processor’ or ‘prediction machine’) and descriptions of essential functions (e.g., ‘a central organ of stress adaptation’) or properties (e.g., ‘a highly vascularized organ’). Comparison of these phrases with those involving other bodily organs (e.g. the heart, liver, etc.) highlighted common phrases between the brain and other organs, such as the heart as a ‘complex dynamic system’. However, the brain was unique among organs in the number and diversity of metaphors ascribed to it. The results of our analysis underscore the diversity of qualities and functions commonly attributed to the brain in the biomedical literature and suggest a range of conceptualizations that defy unification.
Rational Design of TDP-43 Derived α-Helical Peptide Inhibitors: anIn-SilicoStrategy to Prevent TDP-43 Aggregation in Neurodegenerative Disorders
Authors: Salaikumaran Muthu Raj , Gopal Pallavi P.
Published: November 2023

TDP-43, an essential RNA/DNA-binding protein, is central to the pathology of neurodegenerative diseases such as Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Pathological mislocalization and aggregation of TDP-43 disrupts RNA splicing, mRNA stability, and mRNA transport, thereby impairing neuronal function and survival. The formation of amyloid-like TDP-43 filaments is largely facilitated by the destabilization of an α-helical segment within the disordered C-terminal region. In this study, we hypothesized that preventing the destabilization of the α-helical domain could potentially halt the growth of these pathological filaments. To explore this, we utilized a range ofin-silicotechniques to design and evaluate peptide-based therapeutics. Various pathological TDP-43 amyloid-like filament crystal structures were selected for their potential to inhibit the binding of additional TDP-43 monomers to the growing filaments. Our computational approaches included biophysical and secondary structure property prediction, molecular docking, 3D structure prediction, and molecular dynamics simulations. Through these techniques, we were able to assess the structure, stability, and binding affinity of these peptides in relation to pathological TDP-43 filaments. The results of ourin-silicoanalyses identified a selection of promising peptides, which displayed a stable α-helical structure, exhibited an increased number of intramolecular hydrogen bonds within the helical domain, and demonstrated high binding affinities for pathological TDP-43 amyloid-like filaments. Additionally, molecular dynamics simulations provided further support for the stability of these peptides, as they exhibited lower root mean square deviations in their helical propensity over 100ns. These findings establish α-helical propensity peptides as potential lead molecules for the development of novel therapeutics against TDP-43 aggregation. This structure-based computational approach for rational design of peptide inhibitors opens a new direction in the search for effective interventions for ALS, FTD, and other related neurodegenerative diseases. The peptides identified as the most promising candidates in this study are currently subject to further testing and validation through both in vitro and in vivo experiments.

Graphical Abstract
Integrative chromatin state annotation of 234 human ENCODE4 cell types using Segway reveals disease drivers
Authors: Farahbod Marjan , Diab Abdul Rahman , Sud Paul , Kagda Meenakshi , Whaling Ian , Foroozandeh Mehdi , Goel Ishan , Daneshpajouh Habib , Hitz Benjamin , Cherry J. Michael , Libbrecht Maxwell
Published: November 2023

Towards the goal of identifying functional elements in the human genome, the fourth and final phase of the ENCODE consortium has newly profiled hundreds of human tissues using sequencing-based measurements of genomic activity such as ChIP-seq measures of transcription factor binding and histone modification. Chromatin state annotations created by segmentation and genome annotation (SAGA) methods such as Segway have emerged as the predominant integrative summary of such epigenomic data sets. Here, we present the ENCODE4 catalog of Segway annotations, a set of sample-specific genome-wide Segway chromatin state annotations for 234 ENCODE human biosamples inferred from 1,794 functional genomics experiments. We define an updated vocabulary of chromatin state terms that includes patterns of activity present only in a subset of samples or identified only with rarely-performed assays. We show that these ENCODE4 Segway annotations accurately capture both general and cell-type-specific regulatory patterns, and do so with substantially improved sensitivity relative to prior large-scale chromatin annotation sets. This catalog facilitates the downstream discovery of regulatory mechanisms which underlie diseases and traits identified by genome-wide association studies.
MechPPI: Binding Mechanism-based Machine-Learning tool for Predicting Protein-Protein Binding Affinity Changes Upon Mutations
Authors: Liu Yangying , Armstrong Grant , Tam Justin , Chen Brian Y.
Published: November 2023

Protein-protein interactions are essential for various biological processes, including signal transduction, metabolism, vesicle transport, and mitogenic processes. It’s crucial to consider them within the context of their interactions with other proteins to understand protein function. Mutations in proteins can affect their binding affinity to partner proteins by introducing various effects, such as changes in hydrophobic regions, electrostatic interactions, or hydrogen bonds. Assessing the impact of mutations on protein interactions can have implications for disease susceptibility and drug efficacy. Understanding the impact of mutations on protein-protein interactions and predicting binding affinity changes computationally can benefit both basic biology and drug development. Different computational methods offer varying levels of accuracy and efficiency, and the choice of method depends on the specific research goals and available resources. We developed MechPPI, a tool that can use potential mechanism features underlying mutation to predict the binding affinity change upon mutation. We showed MechPPI can accurately predict binding affinity change upon a single mutation, and results demonstrate the potential of MechPPI as a powerful and useful computational tool in protein design and engineering.
Oxycodone Self-Administration in Female Rats is Enhanced by Δ9-tetrahydrocannabinol, but not by Cannabidiol, in a Progressive Ratio Procedure
Authors: Nguyen Jacques D. , Grant Yanabel , Yang Celine , Gutierrez Arnold , Taffe Michael A.
Published: November 2023

Epidemiological evidence suggests that the legalization of cannabis may reduce opioid-related harms. Preclinical evidence of neuropharmacological interactions of endogenous cannabinoid and opioid systems prompts further investigation of cannabinoids as potential therapeutics for the non-medical use of opioids. In these studies female rats, previously trained to self-administer oxycodone (0.15 mg/kg/infusion) intravenously in 6 h sessions, were allowed to self-administer oxycodone after exposure to cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) by vapor inhalation and THC by injection (5.0-20 mg/kg, i.p.). Self-administration was characterized under Progressive Ratio (PR) and Fixed Ratio (FR) 1 schedules of reinforcement in 3 h sessions. THC decreased IVSA of oxycodone in a FR procedure but increased reward seeking in a PR procedure. CBD decreased the IVSA of oxycodone in the FR but not the PR procedure. The results are consistent with an anti-reward effect of CBD but suggest THC acts to increase the reinforcing efficacy of oxycodone in this procedure.
Adaptation and exogenous attention interact in the early visual cortex: A TMS study
Authors: Lee Hsing-Hao , Fernández Antonio , Carrasco Marisa
Published: November 2023

Transcranial magnetic stimulation (TMS) to early visual cortex modulates the effect of adaptation and eliminates the effect of exogenous (involuntary) attention on contrast sensitivity. Here we investigated whether adaptation modulates exogenous attention under TMS to V1/V2. Observers performed an orientation discrimination task while attending to one of two stimuli, with or without adaptation. Following an attentional cue, two stimuli were presented in the stimulated region and its contralateral symmetric region. A response cue indicated the stimulus whose orientation observers had to discriminate. Without adaptation, in the distractor-stimulated condition, contrast sensitivity increased at the attended location and decreased at the unattended location via response gain–but these effects were eliminated in the target-stimulated condition. Critically, after adaptation, exogenous attention altered performance similarly in both distractor-stimulated and target-stimulated conditions. These results reveal that (1) adaptation and attention interact in the early visual cortex, and (2) adaptation shields exogenous attention from TMS effects.
ALDH1A3-acetaldehyde metabolism potentiates transcriptional heterogeneity in melanoma
Authors: Lu Yuting , Travnickova Jana , Badonyi Mihaly , Rambow Florian , Coates Andrea , Khan Zaid , Marques Jair , Murphy Laura , Garcia-Martinez Pablo , Marais Richard , Louphrasitthiphol Pakavarin , Chan Alex H. Y. , Schofield Christopher J. , Kriegsheim Alex Von , Marsh Joseph A , Pavet Valeria , Sansom Owen J , Illingworth Robert , Patton E. Elizabeth
Published: November 2023

Cancer cellular heterogeneity and therapy resistance arise substantially from metabolic and transcriptional adaptations, but how these are interconnected is poorly understood. Here, we show that in melanoma, the cancer stem cell marker aldehyde dehydrogenase 1A3 (ALDH1A3) forms an enzymatic partnership with acetyl-CoA synthetase 2 (ACSS2) in the nucleus to couple high glucose metabolic flux with acetyl-histone H3 modification of neural crest lineage and glucose metabolism genes. Importantly, we show acetaldehyde is a metabolite source for acetyl-histone H3 modification in an ALDH1A3, dependent manner providing a physiologic function for this highly volatile and toxic metabolite. In a zebrafish model of melanoma residual disease, a subpopulation of ALDH1-high cells emerges following BRAF inhibitor treatment and targeting these with an ALDH1 suicide inhibitor, nifuroxazide, delays or prevents BRAF inhibitor drug-resistant relapse. Our work reveals that the ALDH1A3-ACSS2 couple directly coordinates nuclear acetaldehyde-acetyl-CoA metabolism with specific chromatin-based gene regulation and represents a potential therapeutic vulnerability in melanoma.

Highlights

ALDH1A3-high melanomas are in a high glucose metabolic flux and neural crest stem cell dual state.

Nuclear ALDH1A3 partners with ACSS2 to promote selective acetyl-histone H3.

Acetaldehyde is an acetyl source for ALDH1A3 dependent histone H3 acetylation.

ALDH1A3 is a master regulator and pharmaceutical target for melanoma heterogeneity.
Benchmarking of small and large variants across tandem repeats
Authors: English Adam , Dolzhenko Egor , Jam Helyaneh Ziaei , Mckenzie Sean , Olson Nathan D. , De Coster Wouter , Park Jonghun , Gu Bida , Wagner Justin , Eberle Michael A , Gymrek Melissa , Chaisson Mark J.P. , Zook Justin M. , Sedlazeck Fritz J
Published: November 2023

Tandem repeats (TRs) are highly polymorphic in the human genome, have thousands of associated molecular traits, and are linked to over 60 disease phenotypes. However, their complexity often excludes them from at-scale studies due to challenges with variant calling, representation, and lack of a genome-wide standard. To promote TR methods development, we create a comprehensive catalog of TR regions and explore its properties across 86 samples. We then curate variants from the GIAB HG002 individual to create a tandem repeat benchmark. We also present a variant comparison method that handles small and large alleles and varying allelic representation. The 8.1% of the genome covered by the TR catalog holds ∼24.9% of variants per individual, including 124,728 small and 17,988 large variants for the GIAB HG002 TR benchmark. We work with the GIAB community to demonstrate the utility of this benchmark across short and long read technologies.
Long-term effects of directional deep brain stimulation in Parkinson’s disease: a randomized clinical trial on motor and non-motor symptoms
Authors: Gharabaghi A , Cebi I , Scherer M , Bookjans P , Brunnett B , Milosevic L , Weiss D
Published: November 2023

Background

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson’s disease (PD) that is more precisely focused to the desired target structure may avoid nearby structures that are responsible for undesired side effects.

Objective

Comparing the long-term effects of STN-DBS with segmented or ring contacts on motor and non-motor symptoms in akinetic-rigid PD patients.

Methods

This study was a prospective randomized clinical trial. At 6-months postoperatively, the optimal omnidirectional (OS) and directional (DS) stimulation contacts were compared in MedOFF within a double-blind cross-over design, both acutely (within one day) and chronically, i.e., after 3-week stimulation blocks of each condition. The examination included motor and non-motor evaluations (e.g., cognition, mood and quality of life). Importantly, the stimulation intensity of the optimal DS was adjusted such that the total electrical energy delivered (TEED) was equivalent to the TEED of the optimal OS.

Results

There were no significant differences between OS and DS with regard to all outcome parameters, with 30% less stimulation intensity of the latter. Notably, OS scored (non-significantly) better than DS in all motor and non-motor measures apart from the cognitive evaluation, where OS led to a deterioration of executive functions. However, in 3 of 19 patients, the stimulation intensity of DS needed to be increased above the TEED-estimated values to reach the motor benefits of OS.

Conclusions

Reliable comparisons between OS and DS require long-term clinical evaluations. A potential differential influence on motor and non-motor symptoms needs to be investigated in future confirmatory studies.

Registration: ClinicalTrials.gov:NCT03548506
A multi-ancestry genome-wide association study identifies novel candidate loci in theRARBgene associated with hypertensive disorders of pregnancy
Authors: Mack Jasmine A. , Burkholder Adam , Akhtari Farida S. , House John S. , Sovio Ulla , Smith Gordon C.S. , Schmitt Charles P. , Fargo David C. , Hall Janet E. , Motsinger-Reif Alison A.
Published: November 2023

Background

Genetic factors related to pregnancy-related traits are understudied, especially among ancestrally diverse cohorts. This study assessed maternal contributions to hypertensive disorders of pregnancy (HDP) in multi-ancestry cohorts.

Methods

We performed a genome-wide association study of HDP using data from the Personalized Environment and Genes Study (PEGS) cohort (USA) with validation in the UK Biobank (UKBB). We performed gene-level and gene-set analyses and tested the association of polygenic scores (PGS) for systolic blood pressure (SBP), preeclampsia (PE), and gestational hypertension (GH).

Results

We identified two novel maternal genome-wide significant associations with HDP. The lead independent variants were rs114954125 on chromosome 2 (nearLRP1B;OR (95% CI): 3.03 (2.05, 4.49);P=3.19 − 10−8) and rs61176331 on chromosome 3 (nearRARB;OR (95% CI): 3.09 (2.11, 4.53);P=7.97×10−9). We validated rs61176331 in the UKBB (P=3.73 − 10−2). When aggregating SNPs by genes,RARB(P=1.36 − 10−3) andRN7SL283P(P=2.56 − 10−2) were associated with HDP. Inflammatory and immunological biological pathways were most strongly related to HDP-associated genes. While all blood pressure and HDP-related PGS were significantly associated with HDP in PEGS, the SBP PGS was a stronger predictor of HDP (area under the curve (AUC): 0.57; R2=0.7%) compared to the PE PGS (AUC: 0.53; R2=0.2%).

Conclusion

Our study is the first to identify and validate maternal genetic variants nearRARBassociated with HDP. The findings demonstrate the power of multi-ancestry studies for genetic discovery and highlight the relationship between immune response and HDP and the utility of PGS for risk prediction.

ClinicalTrials.govIdentifier for PEGS:NCT00341237
Long-term improvement of gait with adaptive deep brain stimulation in a patient with Parkinson’s disease
Authors: Isaias Ioannis U. , Caffi Laura , Borellini Linda , Ampollini Antonella M. , Mazzoni Alberto , Pezzoli Gianni , Locatelli Marco , Palmisano Chiara
Published: November 2023

A major limitation of conventional deep brain stimulation (cDBS) of the subthalamic nucleus (STN) for Parkinson’s disease (PD) is poor efficacy and, in some cases, worsening of gait disturbances. We applied a novel DBS paradigm, which adjusts the current amplitude linearly with respect to subthalamic beta power (adaptive DBS, aDBS), in one parkinsonian patient with gait impairment and chronically stimulated with bilateral STN-cDBS. When in aDBS mode, the patient showed a consistent improvement in walking while retaining benefit on other PD-related symptoms. Spatiotemporal gait parameters and anticipatory postural adjustments, particularly the imbalance phase, significantly improved with aDBS mode. This improvement was maintained for more than five months of follow-up. Adaptive DBS can benefit gait in PD by possibly avoiding overstimulation and dysfunctional entrainment of the supraspinal locomotor network.
Comparative survey-based study of non-invasive saliva collection devices
Authors: Kil Yeokyoung (Anne) , Booeshaghi Ali S. , Pachter Lior S.
Published: November 2023

Background

We compared five saliva collection devices on their saliva collection efficiency, instruction reading rate, user difficulty ratings, and leakage of saliva, all of which are important factors in safe, easy, and efficient saliva collection. The devices evaluated were: Salivette (swab), SuperSAL (swab), SalivaBio Passive Drool, Medschenker Saliva Collection Kit (funnel), and cryovial with funnel used in SwabSeq COVID-19 surveillance tests.

Methods

56 individuals used five devices in randomized orders by first reading the device’s instruction manual while timed, then self-collecting saliva while timed, to measure the instruction reading rate and saliva collection rate, respectively. For each device, users were asked about the difficulties of instructions; assembly; and saliva collection, and whether there was leakage of saliva. Lastly, unstimulated and stimulated saliva production (=flow) rates for each user were measured. The saliva collection and instruction reading rates were normalized by the individual’s base saliva flow rate and base reading rate. The rates and difficulty ratings for devices were compared using permutation tests and one-way ANOVA.

Results

Salivette had the highest average saliva collection rate and SuperSAL had the lowest. For the instruction reading rate, Medschenker’s funnel device had the highest average and Salivette had the lowest. While all devices showed saliva leakage, passive drool had the highest fraction of leakages and the Medschenker device the lowest. Users found the instructions for Salivette the hardest and those for SwabSeq the easiest. Users found the assembly for Medschenker to be easiest and that for SuperSAL to be hardest. Users rated Salivette easiest to collect saliva with, and SuperSAL most difficult.

Conclusions

Medschenker performed well on most qualitative and quantitative metrics while SuperSAL did not perform as well. However, no single saliva collection method or device satisfies all requirements of an ideal device. A device that allows for efficient saliva collection, easy usage, and safe saliva collection without leakage could greatly help standardize saliva collection.
Partnering Early to Provide for Infants At Risk of Cerebral palsy (PĒPI ARC): Protocol for a feasibility study of a regional hub for early detection of cerebral palsy in Aotearoa New Zealand
Authors: Fletcher Angelica Allermo , Kilgour Gaela , Sandle Meghan , Kidd Sally , Sheppard Alison , Swallow Stephanie , Stott Ngaire Susan , Battin Malcolm , Korent Wyllis , Williams Sian A
Published: November 2023

Introduction

Cerebral palsy (CP) can now be diagnosed as early as three months of age in infants with identified CP risk factors, but many barriers prevent equitable access to early detection pathways. The “Partnering Early to Provide for Infants At Risk of Cerebral Palsy” feasibility study (PĒPI ARC) seeks to trial a new approach to decrease inequitable health service in Aotearoa New Zealand for high-risk infants and their families. PĒPI ARC will incorporate face-to-face clinics, an in-person and virtual Hub, and the use of telehealth to enable flexible access to CP assessments, and support for health professionals in early CP detection.

Methods and Analysis

A non-randomised feasibility study will be conducted from the tertiary Neonatal Intensive Care Unit in Wellington and includes seven regional referral centres, servicing nearly 30% of the NZ total population. Families of infants with high risk of neurodevelopmental impairment will be invited to participate, as well as health professionals interacting with the Hub. Mixed methods will be used to evaluate the i) equitable implementation of an early detection pathway, ii) acceptability, iii) demand among families and health professionals, iv) efficacy in relation to reducing the age of receipt of CP diagnosis, and v) the experiences around communication and information sharing.

Ethics and Dissemination

The New Zealand Health and Disability Ethics Committees approved this study (HDEC:2022 FULL 13434). Findings will be disseminated in peer-reviewed journals, conference presentations and via professional networks.

Registration

Australian New Zealand Clinical Trials Registry: ACTRN12623000600640

STRENGTHS AND LIMITATIONS OF THE STUDY

The New Zealand Best Practice Recommendations for early detection of CP are based on international guidelines and have been peer reviewed for the Aotearoa New Zealand context.

Local and regional health professionals have collaborated to inform the PĒPI ARC protocol with the aim to improve access to early CP assessments and early detection rates of CP.

Reduction in health inequities for Māori and Pasifika have been targeted through informed partnerships.

Resource development and planning of PĒPI ARC Hub has been co-designed with families and recognises the ecological context of Aotearoa New Zealand.

A limitation is that only high-risk infants with “newborn detectable risks” will be included in the study.
Mood computational mechanisms underlying increased risk behavior in suicidal patients
Authors: Wang Zhihao , Nan Tian , Lu Fengmei , Yu Yue , Cai Xiao , He Zongling , Luo Yuejia , Blain Bastien
Published: November 2023

Suicidal thoughts and behaviors (STB) rank among the foremost causes of death globally. While literature consistently highlights heightened risk behavior in individuals with STB and identifies mood issues as central to STB, the precise cognitive and affective computational mechanisms driving this increased risky behavior remain elusive. Here, we asked 83 adolescent inpatients with affective disorders, where 58 patients with STB (S+) and 25 without STB (S-), and 118 gender/age-matched healthy control (HC) to make decisions between certain vs. gamble option with momentary mood ratings. Choice data analyses revealed heightened risk behavior in S+compared to S-and HC. Using a prospect theory model enhanced with approach-avoidance Pavlovian parameters revealed that this rise in risky behavior resulted only from a heightened Pavlovian approach parameter in S+. Furthermore, Pavlovian approach mediated the rise in gambling choices with STB severity. Altogether, model-based choice data analysis indicated dysfunction in the Pavlovian approach system in S+individuals, leading to greater propensity for gambling in favorable outcomes regardless the lotteries expected value. Additionally, mood model-based analyses revealed reduced sensitivity to certain rewards in S+compared to S-and HC. Importantly, these computational markers generalized to healthy population (n□ = □ 747). In S+, mood sensitivity to certain reward was negatively correlated with gambling, offering a mood computational account for increased risk behavior in STB. These findings remained significant even after adjusting for demographic, clinical, and medication-related variables. Overall, our study uncovers the cognitive and affective mechanisms contributing to increased risk behavior in STB, with significant implications for suicide prevention.
Disparities in Access to, Use of, and Quality of Rehabilitation Care Following Stroke: A Scoping Review
Authors: Freburger Janet K. , Mormer Elizabeth R. , Ressel Kristin , Zhang Shuqi , Johnson Anna M. , Pastva Amy M. , Turner Rose L. , Coyle Peter C. , Bushnell Cheryl D. , Duncan Pamela W. , Jones Berkeley Sara B.
Published: November 2023

Despite the clear utility of stroke rehabilitation, our understanding of the extent of disparities in rehabilitation care across specific sociodemographic characteristics (e.g., by age, sex, race, ethnicity, rurality, socioeconomic status) is limited. In this review, we aimed to synthesize the current evidence on disparities in referral to, use of, and quality of rehabilitation following stroke; identify research gaps in our understanding of disparities in rehabilitation care; and make recommendations for future research to advance the field in identifying, understanding the causes of, and minimizing disparities. We searched three electronic databases from 1997 to 2023 for cohort, case-control, cross-sectional, observational, and mixed-method studies that examined disparities in rehabilitation care following stroke. From 7,853 records screened, we identified 49 studies that met our inclusion criteria. Findings from the studies we reviewed varied, with the most consistent findings indicating that individuals with lower socioeconomic status and those living in rural areas (vs urban) are less likely to receive rehabilitation care following stroke. Findings on racial, ethnic, and sex disparities varied with some consistent findings among specific subgroups (e.g., studies examining care in the outpatient setting) and when examining results from analyses that controlled for functional status and other measures of “need” for therapy. Several gaps in our understanding of disparities in rehabilitation care following stroke were identified. Recommendations for future work were also provided.
The Influence of Transcatheter Aortic Valve Replacement on Left Atrial Mechanics: A Systematic Review and Meta-Analysis
Authors: Meredith Thomas , Brown Lauren , Mohammed Farhan , Pomeroy Amy , Roy David , Muller David WM , Hayward Christopher , Feneley Michael , Namasivayam Mayooran
Published: November 2023

Background

The morphology and function of the left atrium (LA) are intimately tied to left ventricular loading conditions. Data pertaining to the effect of transcatheter aortic valve replacement (TAVR) on LA function and geometry are scarce.

Objectives

To quantify associations between TAVR and LA remodelling by pooling available data from published observational studies.

Methods

A systematic review and meta-analysis were performed. Eligible studies needed to report serial LA STE data, before and after TAVR. Other outcome data included LA area and indexed volume (LAVi) and standard chamber measurements. Outcomes were stratified by timing of follow-up echocardiography: early (<6mo) or late (≥6mo).

Results

Twelve studies were included, comprising 1,066 patients. The mean overall reduction in LAVi was 2.72mls/m2following TAVI (95% CI 1.37-4.06, p <0.01, low heterogeneity: I2= 0%). LA reservoir function improved overall by a mean difference of 3.71% (95% CI 1.82-5.6, p<0.01), though there was significant heterogeneity within the pooled studies (I2= 87.3%). Significant improvement in reservoir strain was seen in both early follow up (MD 3.1%, p<0.01) and late follow up studies (MD 4.48%, p=0.03), but heterogeneity remained high (I2= 65.23% and 94.4%, respectively). Six studies reported change in LA booster/contractile function, which recovered in the early follow-up studies (MD 2.26, p<0.01), but not in the late group (MD 1.41, p=0.05). Pooled improvement in LA booster function was 1.96% (95% CI 1.11-2.8, p<0.01, low heterogeneity: I2= 0%).

Conclusion

The afterload reduction afforded by TAVR is associated with significant haemodynamic and morphological up-stream LA changes.

Condensed Abstract

The morphology and function of the left atrium (LA) are intimately tied to left ventricular loading conditions. LA function, measured with speckle-tracking echocardiography (STE), has been demonstrated to provide independent prognostic information for a range of cardiomyopathic states and valvular diseases. We sought to better understand the effect of transcatheter aortic valve replacement (TAVR) on LA function and geometry by performing a systematic review and meta-analysis. Key findings are that, following TAVR, the left atrium negatively remodels (reduces in size), and this is associated with improved distensibility, as quantified by an improvement in reservoir function.
Exploring the association between housing insecurity and mental health among renters: A systematic review
Authors: Talmatzky Mira , Nohr Laura , Knaevelsrud Christine , Niemeyer Helen
Published: November 2023

Adverse social and economic conditions negatively impact mental health and well-being. The present systematic review is the first to investigate the association between housing insecurity and mental health outcomes among renters, with a focus on housing affordability and instability. We followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive search was conducted in December 2022 across four databases (MEDLINE, PsycINFO, Web of Science, and ASSIA). Quantitative studies from OECD (Organisation for Economic Co-operation and Development) member countries were eligible for inclusion if they investigated housing insecurity by examining at least one independent variable related to housing affordability and/or instability, and included at least one mental health-related outcome among adult renters. Due to heterogeneity of the identified studies, we performed a narrative synthesis. Twenty-two studies met the inclusion criteria, of which 14 applied a longitudinal design, five a cross-sectional design, and three a quasi-experimental design. Among the nine studies examining housing affordability, six reported significant associations between unaffordable rent and poor mental health in low-income renters. Regarding housing instability, 12 out of 14 studies reported significant associations between unstable housing and renters’ mental health issues. Measures of housing insecurity varied, with rent-to-income ratio and forced moves being most commonly employed. Mental health outcomes focused primarily on overall mental health, well-being, and depressive symptoms, while few studies explored other mental health outcomes. The findings suggest that experiencing unaffordable or unstable housing has a negative impact on renters’ overall mental health and depressive symptoms. Housing insecurity poses a significant challenge for renters in OECD countries, highlighting the need for policymakers to implement supportive housing policies and tenure protection measures in order to improve renters’ housing security and ultimately public health.
Automated Long-Term Monitoring of the Heat-Seeking Behavior of Mosquitoes
Authors: Sakuma Chisako , Maekawa Emi , Kanuka Hirotaka
Published: November 2023

Heat is one of the critical cues female mosquitoes use to find vertebrate hosts, particularly in the final step of attraction (touching down on hosts) before the initiation of blood-sucking. To prevent vector-borne diseases such as malaria and dengue fever, which are transmitted via mosquito blood-sucking, it is essential to understand the dynamics and mechanisms of the heat-seeking behavior of mosquitoes. An automated device to quantify CO2-activated heat-seeking behavior with continuous monitoring for up to a week was established. The device is based on the infrared beam break method; it can simultaneously monitor three independent mosquito behaviors (touchdown on a heated target, feeding, and locomotion activity) by using several pairs of infrared laser sensors. This protocol describes brief instructions for the device's construction, directions for use, and possible issues and solutions.
Segmenting the customers of system delivery projects based on data heterogeneity
Authors: Haverila Matti , Haverila Kai Christian , McLaughlin Caitlin
Published: November 2023

Purpose

This paper aims to examine project management segments based on customer satisfaction drivers and loyalty rather than traditional demographic or behavioural variables.

Design/methodology/approach

Data were gathered over 18 consecutive months, and 3,129 surveys were completed using a questionnaire. The statistical methods included partial least squares (PLS) structural equation modelling, finite mixture segmentation, prediction-oriented segmentation (PLS-POS) and multi-group analysis (PLS-MGA).

Findings

The findings indicate the existence of three segments among system delivery project customers based on the differences in the strengths of the path coefficients in the customer-centric structural model. In Segment 1, satisfaction based on the proposal was crucial for loyalty, with the value-for-money construct negatively impacting the repurchase intent construct. Segment 2 had a solid value-for-money orientation. In Segment 3, the critical path indicated that satisfaction drove repurchase intention, with satisfaction based mainly on the installation.

Originality/value

The research contributes to the segmentation theory by introducing a new way to segment the systems delivery projects customers based on the perceived strength of the relationships in a customer-centric structural model, which aligns with traditional segmentation theory in a way that most segmentation analyses do not. A new segmentation approach to the domain of project management theory is presented. Based on the results, treating the system delivery project customer base as a single homogenous group can lead to managerially misleading conclusions.
Tailoring modifications in labrenzin synthesis: a‐la‐carte production of pathway intermediates
Authors: Kačar Dina , Cañedo Librada M. , Rodríguez Pilar , Schleissner Carmen , de la Calle Fernando , García José Luis , Galán Beatriz
Published: November 2023

Pederin‐family polyketides today constitute a group of more than 30 molecules being produced as natural products by different microorganisms across multitude of ecological niches. They are mostly known for their extreme cytotoxic activity and the decades of long exploration as potential antitumor drugs. The difference in their potency and biological activity lies in the tailoring modifications of the core molecule. Despite the isolation of many pederin‐like molecules until the date, only marine bacterium Labrenzia sp. PHM005 was reported as a cultivable producer and able to be genetically modified. Here, we study the role of tailoring enzymes from the lab gene cluster responsible for methylation and hydroxylation of labrenzin core molecule. We managed to produce a spectrum of differently tailored labrenzin analogs for the development of future drugs. This work constitutes one‐step forward in understanding the biosynthesis of pederin‐family polyketides and provides the tools to modify and overproduce these anticancer drugs in a‐la‐carte manner in Labrenzia sp. PHM005, but also in other producers in the future.
Cynical people desire power but rarely acquire it: Exploring the role of cynicism in leadership attainment
Authors: Stavrova Olga , Ehlebracht Daniel , Ren Dongning
Published: November 2023

Do cynical individuals have a stronger desire for power and are they more likely to acquire power at work? The negative consequences of cynicism—for cynics themselves and the people around them—render the examination of these questions particularly important. We first examined the role of cynicism in power motives. Results showed that more cynical individuals have a greater desire for power to avoid exploitation by others (and less so to exploit others; Study 1) and score higher on dominance (but not prestige or leadership) motives (Study 2). The subsequent two studies examined the role of cynicism in power attainment at work. A study of virtual teams (Study 3) showed that more cynical individuals were less likely to emerge as group leaders, and a prospective study of ~9000 employees followed for up to 10 years (Study 4) showed that cynicism predicted a lower likelihood of attaining a leadership position in organizations. Taken together, more (vs. less) cynical individuals have a stronger power—in particular, dominance—motive but they are not more successful at power acquisition. These findings inform the literature on cynicism and power and highlight the importance of cynical worldviews for leadership attainment.
Nitric oxide and thiols: Chemical biology, signalling paradigms and vascular therapeutic potential
Authors: Dent Matthew R. , DeMartino Anthony W.
Published: November 2023

Nitric oxide (•NO) interactions with biological thiols play crucial, but incompletely determined, roles in vascular signalling and other biological processes. Here, we highlight two recently proposed signalling paradigms: (1) the formation of a vasodilating labile nitrosyl ferrous haem (NO–ferrohaem) facilitated by thiols via thiyl radical generation and (2) polysulfides/persulfides and their interaction with •NO. We also describe the specific (bio)chemical routes in which •NO and thiols react to form S‐nitrosothiols, a broad class of small molecules, and protein post‐translational modifications that can influence protein function through catalytic site or allosteric structural changes. S‐Nitrosothiol formation depends upon cellular conditions, but critically, an appropriate oxidant for either the thiol (yielding a thiyl radical) or •NO (yielding a nitrosonium [NO+]‐donating species) is required. We examine the roles of these collective •NO/thiol species in vascular signalling and their cardiovascular therapeutic potential.
Parenting stress in families of children with disabilities: Impact of type of disability and assessment of attending paediatricians
Authors: Scheibner Cora , Scheibner Maxi , Hornemann Frauke , Arélin Maria , Hennig Yvonne Doris , Kiep Henriette , Wurst Ulrike , Merkenschlager Andreas , Gburek‐Augustat Janina
Published: November 2023

Background

Parents of children with developmental disorders (DD) or disabilities report greater parenting stress than parents of typically developing children. To minimise this stress, stressful factors need to be known and stress needs to be recognised early. The present cross‐sectional study aims to systematically assess and compare parenting stress in families of children with various types of disabilities. In addition, the assessment of parenting stress by attending paediatricians will be evaluated.

Methods

We surveyed 611 parents about their parenting stress at the Children's Development Center (CDC). Three questionnaires, including the German versions of the Parenting Stress Index (PSI) and Impact on Family Scale (IOFS), were used to evaluate parenting stress. Furthermore, attending paediatricians assessed of the child's type of disability and their perception of parenting stress in a separate questionnaire.

Results

Fifty‐five percent of all parents reported stress at a clinically relevant level, 65% in the child domain and 39% in the parent domain of the PSI. Parenting stress differed significantly across diagnostic categories (p < 0.01) and was associated with childhood disability related issues of behaviour, sleep or feeding issues. Parenting stress was often underestimated by the paediatricians, especially when the children had disabilities perceived as less severe. In one‐third of parents with clinically relevant total stress, paediatricians reported low stress levels. Parent‐reported financial problems, social isolation, and partnership conflicts were not suspected by paediatricians in ≥85% of cases.

Conclusions

Clinically relevant parenting stress was found more often than in comparable studies. An assessment of parenting stress by paediatricians may be complicated by time constraints in medical appointments, the mainly child‐centred consultation, or restricted expression of parents' stress. Paediatricians should move from a purely child‐centred to a holistic, family‐centred approach to treatment. Routine screening of parenting stress using standardised questionnaires could be helpful to identify affected families.
Addressing endoscopic ultrasound‐guided hepaticogastrostomy complications with a spiral dilator for plastic stent placement
Authors: Kawaguchi Shinya , Takeda Shodai , Satoh Tatsunori
Published: November 2023

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Virtual reality used in undergraduate orthodontic education
Authors: Chen Dongru , Liu Xiangqi , Liu Yuanbo , Wang Xi , Zheng Jinxuan , Wu Liping
Published: November 2023

Introduction

Undergraduate dental students frequently have reduced clinical experience which presents a challenge for their dental education. Previously, we developed a virtual reality (VR) simulating the whole clinical treatment process of a patient with angle Class II division 1 malocclusion, and the VR also helped to explain some important orthodontic concepts. As a novel teaching tool, this study aims to compare the effects of VR versus traditional case analysis by Power Point (PPT) in inspiring student learning motivation and evaluating learning experience.

Materials and Methods

A randomized, cross‐over, stratified sampling method was taken to divide the fourth‐year undergraduate dental students equally into two groups. The two groups were crossed over to use VR and PPT.

Results

For the whole study, results indicated that students in the VR group showed higher learning motivation (including attention, relevance, confidence and satisfaction) than in the PPT group, but the differences between VR and PPT groups were not very big, and the median of the differences located at 0. For learning experience, students thought VR to be more useful, more enjoyable and more engaging, but the median of differences also located at 0. Notably, the majority of students had higher recommendations for VR than PPT, and the median difference located at 1. However, when the two phases were analysed separately, some items showed no significant differences between VR and PPT learning.

Conclusion

VR is a very useful adjunct to education compared to traditional case analysis by PPT, but we cannot exaggerate its benefits. Educators should make good use of VR to solve the difficult problems in education.
Effects of disaster education on children's risk perception and preparedness: A quasi‐experimental longitudinal study
Authors: Yildiz Ayse , Dickinson Julie , Priego‐Hernández Jacqueline , Teeuw Richard , Shaw Rajib
Published: November 2023

The aim of this study was to examine the effects of a disaster education intervention on children's risk perception and preparedness. It also sought to advance longitudinal studies, during an 18‐month time period, of risk perception and preparedness by using a quasi‐experimental methodology in child‐centred disaster research. This study used a quasi‐experimental longitudinal research design to measure the effects of disaster education on children. These effects were examined on children's risk perception and preparedness in the Van and Kocaeli provinces of Türkiye during the 18‐month period, with a sample of 720 school children. Experimental and control groups were randomly allocated, controlling for age, school grade and school enrolment. The disaster education intervention was designed to improve the children's awareness of natural hazards and their knowledge of disaster risk reduction using discussion, visual materials and interactive teaching of emergency management. The results indicate that the disaster education intervention had a positive effect on children's risk perception and perceived importance of preparedness in both study locations. It also helped children to understand the risks and hazards in their living environments. More importantly, this study showed that disaster education enhanced the protective measures taken by children for disasters. This is the first study using the quasi‐experimental longitudinal research design to measure the effects of disaster education on children's risk perception and the importance of preparedness. The findings are of relevance for organisations such as government departments and non‐government organisations when designing or improving disaster education programmes.