bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractEpidemiological 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

SummaryTranscranial 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

AbstractCancer 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.HighlightsALDH1A3-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

AbstractTandem 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

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

AbstractBackgroundGenetic 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.MethodsWe 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).ResultsWe 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%).ConclusionOur 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

ABSTRACTA 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

AbstractBackgroundWe 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.Methods56 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.ResultsSalivette 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.ConclusionsMedschenker 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

ABSTRACTIntroductionCerebral 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 AnalysisA 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 DisseminationThe 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.RegistrationAustralian New Zealand Clinical Trials Registry: ACTRN12623000600640STRENGTHS AND LIMITATIONS OF THE STUDYThe 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

AbstractSuicidal 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

AbstractDespite 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

AbstractBackgroundThe 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.ObjectivesTo quantify associations between TAVR and LA remodelling by pooling available data from published observational studies.MethodsA 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).ResultsTwelve 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%).ConclusionThe afterload reduction afforded by TAVR is associated with significant haemodynamic and morphological up-stream LA changes.Condensed AbstractThe 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.