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Major depressive disorder (MDD) and psychostimulant use disorder (PUD) are common, disabling psychopathologies that pose a major public health burden. They share a common behavioral phenotype: deficits in inhibitory control (IC). However, whether this is underpinned by shared neurobiology remains unclear. In this meta-analytic study, we aimed to define and compare brain functional alterations during IC tasks in MDD and PUD.
Methods
We conducted a systematic literature search on IC task-based functional magnetic resonance imaging studies in MDD and PUD (cocaine or methamphetamine use disorder) in PubMed, Web of Science, and Scopus. We performed a quantitative meta-analysis using seed-based d mapping to define common and distinct neurofunctional abnormalities.
Results
We identified 14 studies comparing IC-related brain activation in a total of 340 MDD patients with 303 healthy controls (HCs), and 11 studies comparing 258 PUD patients with 273 HCs. MDD showed disorder-differentiating hypoactivation during IC tasks in the median cingulate/paracingulate gyri relative to PUD and HC, whereas PUD showed disorder-differentiating hypoactivation relative to MDD and HC in the bilateral inferior parietal lobule. In conjunction analysis, hypoactivation in the right inferior/middle frontal gyrus was common to both MDD and PUD.
Conclusions
The transdiagnostic neurofunctional alterations in prefrontal cognitive control regions may underlie IC deficits shared by MDD and PUD, whereas disorder-differentiating activation abnormalities in midcingulate and parietal regions may account for their distinct features associated with disturbed goal-directed behavior.
The interaction of helminth infections with type 2 diabetes (T2D) has been a major area of research in the past few years. This paper, therefore, focuses on the systematic review of the effects of helminthic infections on metabolism and immune regulation related to T2D, with mechanisms through which both direct and indirect effects are mediated. Specifically, the possible therapeutic role of helminths in T2D management, probably mediated through the modulation of host metabolic pathways and immune responses, is of special interest. This paper discusses the current possibilities for translating helminth therapy from basic laboratory research to clinical application, as well as existing and future challenges. Although preliminary studies suggest the potential for helminth therapy for T2D patients, their safety and efficacy still need to be confirmed by larger-scale clinical studies.
Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.
Methods
T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9).
Results
PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges’ g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges’ g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (pcorrected = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (pcorrected = .001).
Conclusions
PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.
Background: Attitudes toward aging influence many health outcomes, yet their relationship with cognition and Alzheimer’s disease (AD) remains unknown. To better understand their impact on cognition and AD risk, we examined whether positive attitudes predict better cognition and diminished risk on AD biomarkers. Methods: A subsample of older adults with a family history of AD (n=54; women=39) from the McGill PREVENT-AD cohort participated in this study. Participants completed the Attitudes to Ageing Questionnaire (AAQ-24), providing three scores: psychosocial loss, psychological growth and physical change. Participants underwent cognitive testing (Rey Auditory Verbal Learning Test, RAVLT; Delis-Kaplan Executive Function System-Color Word Interference Test, D-KEFS-CWIT), and AD blood-based biomarker assessments (p-tau217, Aβ42/40). Regression models tested associations, adjusting for covariates (age, sex, education, depression, APOE4), and were Bonferroni corrected. Results: Positive attitudes were associated with better recall and recognition (RAVLT) and improved word reading, colour naming, switching, and inhibition (D-KEFS-CWIT) (p<0.00077), while negative attitudes showed the opposite pattern. Negative attitudes were correlated with lower Aβ42/40 ratios, while positive attitudes were linked to lower p-tau217 (p<0.0167). Conclusions: These findings demonstrate that positive attitudes predict better cognition and a lower risk profile for AD biomarkers, suggesting that life outlook may be an early disease feature or a risk factor.
Milk fat is a crucial component for evaluating the production performance and nutritional value of goat milk. Previous research indicated that the composition of ruminal microbiota plays a significant role in regulating milk fat percentage in ruminants. Thus, this study aimed to identify key ruminal microorganisms and blood metabolites relevant to milk fat synthesis in dairy goats as a mean to explore their role in regulating milk fat synthesis. Sixty clinically healthy Xinong Saanen dairy goats at mid-lactation and of similar body weight, and similar milk yield were used in a feeding study for 15 days. Based on daily milk yield of dairy goats and the results of milk component determination on the 1st and 8th days, five goats with the highest milk fat content (H group) and five goats with the lowest milk fat content (L group) were selected for further analysis. Before the morning feeding on the 15th day of the experiment, samples of milk, blood and ruminal fluid were collected for analyses of components, volatile fatty acids, microbiota and metabolites. Results revealed that acetate content in the rumen of H group was greater compared with L group. H group had abundant beneficial bacteria including Ruminococcaceae_UCG-005, Saccharofermentans, Ruminococcaceae-UCG-002 and Prevotellaceae_UCG-3, which were important for plant cellulose and hemicellulose degradation and immune regulation. Metabolomics analysis revealed H group had greater relative concentrations of 4-acetamidobutanoic acid and azelaic acid in serum, and had lower relative concentrations of Arginyl-Alanine, SM(d18:1/12:0) and DL-Tryptophan. These altered metabolites are involved in the sphingolipid signaling pathway, arginine and proline metabolism. Overall, this study identified key ruminal microorganisms and serum metabolites associated with milk fat synthesis in dairy goats. These findings offer insights for enhancing the quality of goat milk and contribute to a better understanding of the regulatory mechanisms involved in milk fat synthesis in dairy goats.
Guideline-based tobacco treatment is infrequently offered. Electronic health record-enabled patient-generated health data (PGHD) has the potential to increase patient treatment engagement and satisfaction.
Methods:
We evaluated outcomes of a strategy to enable PGHD in a medical oncology clinic from July 1, 2021 to December 31, 2022. Among 12,777 patients, 82.1% received a tobacco screener about use and interest in treatment as part of eCheck-in via the patient portal.
Results:
We attained a broad reach (82.1%) and moderate response rate (30.9%) for this low-burden PGHD strategy. Patients reporting current smoking (n = 240) expressed interest in smoking cessation medication (47.9%) and counseling (35.8%). As a result of patient requests via PGHD, most tobacco treatment requests by patients were addressed by their providers (40.6–80.3%). Among patients with active smoking, those who received/answered the screener (n = 309 ) were more likely to receive tobacco treatment compared with usual care patients who did not have the patient portal (n = 323) (OR = 2.72, 95% CI = 1.93–3.82, P < 0.0001) using propensity scores to adjust for the effect of age, sex, race, insurance, and comorbidity. Patients who received yet ignored the screener (n = 1024) compared with usual care were also more likely to receive tobacco treatment, but to a lesser extent (OR = 2.20, 95% CI = 1.68–2.86, P < 0.0001). We mapped observed and potential benefits to the Translational Science Benefits Model (TSBM).
Discussion:
PGHD via patient portal appears to be a feasible, acceptable, scalable, and cost-effective approach to promote patient-centered care and tobacco treatment in cancer patients. Importantly, the PGHD approach serves as a real world example of cancer prevention leveraging the TSBM.
Aircraft tyres play a critical role in ensuring the safety of aircraft landings. This paper introduces a novel multi-scale analytical method for evaluating tyre impact performance, explicitly studying the effect of damage defects in the manufacturing and service process on tyre landing dynamic performance. Building on this approach, a numerical simulation of aircraft tyre static and impact load scenarios was conducted, followed by experimental validation. The study systematically compares and analyses the effects of void volume fraction, cord volume fraction and material scale factor on the maximum impact force experienced by aircraft tyre. The variations in maximum impact force arising from changes in tyre structural strength, and deformation can be explained by specific parameters. The findings of this research have significant implications for tyre design and engineering, as well as for enhancing the understanding of the factors that influence tyre performance and safety.
Objectives/Goals: Transmission-blocking vaccines hold promise for malaria elimination by reducing community transmission. But a major challenge that limits the development of efficacious vaccines is the vast parasite’s genetic diversity. This work aims to assess the genetic diversity of the Pfs25 vaccine candidate in complex infections across African countries. Methods/Study Population: We employed next-generation amplicon deep sequencing to identify nonsynonymous single nucleotide polymorphisms (SNPs) in 194 Plasmodium falciparum samples from four endemic African countries: Senegal, Tanzania, Ghana, and Burkina Faso. The individuals aged between 1 and 74 years, but most of them ranged from 1 to 19 years, and all presented symptomatic P. falciparum infection. The genome amplicon sequencing was analyzed using Geneious software and P. falciparum 3D7 as a reference. The SPNs were called with a minimum coverage of 500bp, and for this work, we used a very sensitive threshold of 1% variant frequency to determine the frequency of SNPs. The identified SNPs were threaded to the crystal structure of the Pfs25 protein, which allowed us to predict the impact of the novel SNP in the protein or antibody binding. Results/Anticipated Results: We identified 26 SNPs including 24 novel variants, and assessed their population prevalence and variant frequency in complex infections. Notably, five variants were detected in multiple samples (L63V, V143I, S39G, L63P, and E59G), while the remaining 21 were rare variants found in individual samples. Analysis of country-specific prevalence showed varying proportions of mutant alleles, with Ghana exhibiting the highest prevalence (44.6%), followed by Tanzania (12%), Senegal (11.8%), and Burkina Faso (2.7%). Moreover, we categorized SNPs based on their frequency, identifying dominant variants (>25%), and rare variants (Discussion/Significance of Impact: We identified additional SNPs in the Pfs25 gene beyond those previously reported. However, the majority of these newly discovered display low variant frequency and population prevalence. Further research exploring the functional implications of these variations will be important to elucidate their role in malaria transmission.
This paper presents detailed analyses of the Reynolds stresses and their budgets in temporally evolving stratified wakes using direct numerical simulation. Ensemble averaging is employed to mitigate statistical errors in the data, and the results are presented as functions of both the transverse and vertical coordinates – at time instants across the near-wake, non-equilibrium, and quasi-two-dimensional regimes for wakes in weakly and strongly stratified environments. Key findings include the identification of dominant terms in the Reynolds stress transport equations and their spatial structures, the generation and destruction processes of the Reynolds stresses, and the energy transfer between the Reynolds stress and the mean flow. The study also clarifies the effects of the Reynolds number and the Froude number. Additionally, we assess the validity of the eddy-viscosity type models and some existing closures for the Reynolds stress model, highlighting the limitations of isotropy and return-to-isotropy hypotheses in stratified flows.
Rogue waves (RWs) can form on the ocean surface due to the well-known quasi-four-wave resonant interaction or superposition principle. The first is known as the nonlinear focusing mechanism and leads to an increased probability of RWs when unidirectionality and narrowband energy of the wave field are satisfied. This work delves into the dynamics of extreme wave focusing in crossing seas, revealing a distinct type of nonlinear RWs, characterised by a decisive longevity compared with those generated by the dispersive focusing (superposition) mechanism. In fact, through fully nonlinear hydrodynamic numerical simulations, we show that the interactions between two crossing unidirectional wave beams can trigger fully localised and robust development of RWs. These coherent structures, characterised by a typical spectral broadening then spreading in the form of dual bimodality and recurrent wave group focusing, not only defy the weakening expectation of quasi-four-wave resonant interaction in directionally spreading wave fields, but also differ from classical focusing mechanisms already mentioned. This has been determined following a rigorous lifespan-based statistical analysis of extreme wave events in our fully nonlinear simulations. Utilising the coupled nonlinear Schrödinger framework, we also show that such intrinsic focusing dynamics can be captured by weakly nonlinear wave evolution equations. This opens new research avenues for further explorations of these complex and intriguing wave phenomena in hydrodynamics as well as other nonlinear and dispersive multi-wave systems.
During the COVID-19 pandemic, virtual physician visits rapidly increased among community-dwelling older persons living with dementia (PLWD) in Ontario. Rural residents often have less access to medical care compared to their urban counterparts, and it is unclear whether access to virtual care was equitable between PLWD in urban versus rural locations.
Methods:
Using population-based health administrative data and a repeated cross-sectional study design, we identified and described community-dwelling PLWD between March 2020 and August 2022 in Ontario, Canada. Poisson regression was used to calculate rate ratios (RR) and 95% confidence intervals comparing rates of virtual visits between rural and urban PLWD by key physician specialties: family physicians, neurologists and psychiatrists/geriatricians.
Results:
Of 122,751 PLWD in our cohort, 9.2% (n = 11,304) resided in rural areas. Rural PLWD were slightly younger compared to their urban counterparts (mean age = 81 vs. 82 years; standardized difference = 0.16). There were no differences across areas by sex or income quintile. In adjusted models, rates of virtual visits were significantly lower for rural compared to urban PLWD across all specialties: family physicians (RR = 0.71 [0.69–0.73]), neurologists (RR = 0.79 [0.75–0.83]) and psychiatrists/geriatricians (RR = 0.72 [0.68–0.76]).
Conclusions:
PLWD in rural areas had significantly lower rates of virtual family physician, neurologist and psychiatrist/geriatrician visits compared to urban dwellers during the study period. This finding raises important issues regarding access to primary and specialist healthcare services for rural PLWD. Future work should explore barriers to care to improve health care access among PLWD in rural communities.
The transport process of a relativistic electron beam (REB) in high-density and degenerate plasmas holds significant importance for fast ignition. In this study, we have formulated a comprehensive theoretical model to address this issue, incorporating quantum degeneracy, charged particle collisions and the effects of electromagnetic (EB) fields. We model the fuel as a uniform density region and particularly focus on the effect of quantum degeneracy during the transport of the REB, which leads to the rapid growth of a self-generated EB field and a subsequently significant self-organized pinching of the REB. Through our newly developed hybrid particle-in-cell simulations, we have observed a two-fold enhancement of the heating efficiency of the REB compared with previous intuitive expectation. This finding provides a promising theoretical framework for exploring the degeneracy effect and the enhanced self-generated EB field in the dense plasma for fast ignition, and is also linked to a wide array of ultra-intense laser-based applications.
Opioid use disorder (OUD) is a devastating condition with frequent suicidality, contributing to overdose deaths. Theta burst stimulation (TBS) to the dorsolateral prefrontal cortex (DLPFC) is used to treat major depressive disorder (MDD) and is effective in treating suicidal ideation. We piloted a randomized, double-blind, sham-controlled trial of bilateral rTMS for patients with OUD and MDD experiencing suicidality.
Methods
Sequential bilateral TBS was delivered guided by structural neuroimaging: continuous TBS to the right then intermittent TBS to the left DLPFC, daily (20 treatments). The primary objective was to determine the feasibility of this population. The primary clinical outcome was the scale for suicidal ideation (SSI), secondary outcomes included depressive symptoms and opioid cue-induced craving. ClinicalTrials.gov: NCT04785456.
Results
Eighty-seven individuals were pre-screened. The most common reasons for ineligibility included being unreachable by the study team, difficulty with scheduling/travel requirements, and medical/psychiatric instability. Six participants (5:1 M:F) were enrolled (3/arm), four had a fentanyl use history; two completed per protocol (1/arm). Of the participants with follow-up data, SSI scores decreased in 2/3 in the sham arm and 2/2 in the active arm; depression and opioid craving scores decreased in all participants.
Conclusion
We present the first data piloting a structural neuroimaging-guided, multi-session rTMS treatment course in outpatients with suicidality and OUD in the current North American context. Recruitment and retention were the main challenges given the highly unstable medical and psychosocial context of this patient population. Future trials should consider a suitable environment to improve the feasibility of delivering this treatment.
In recent years, the rapid convergence of artificial intelligence (AI) and low-altitude flight technology has driven significant transformations across various industries. These advancements have showcased immense potential in areas such as logistics distribution, urban air mobility (UAM) and national defense. By adopting the AI technology, low-altitude flight technology can achieve high levels of automation and operate in coordinated swarms, thereby enhancing efficiency and precision. However, as these technologies become more pervasive, they also raise pressing ethical or moral concerns, particularly regarding privacy, public safety, as well as the risks of militarisation and weaponisation. These issues have sparked extensive debates. In summary, while the integration of AI and low-altitude flight presents revolutionary opportunities, it also introduces complex ethical challenges. This article will explore these opportunities and challenges in depth, focusing on areas such as privacy protection, public safety, military applications and legal regulation, and will propose strategies to ensure that technological advancements remain aligned with ethical or moral principles.
While the cross-sectional relationship between internet gaming disorder (IGD) and depression is well-established, whether IGD predicts future depression remains debated, and the underlying mechanisms are not fully understood. This large-scale, three-wave longitudinal study aimed to clarify the predictive role of IGD in depression and explore the mediating effects of resilience and sleep distress.
Methods
A cohort of 41,215 middle school students from Zigong City was assessed at three time points: November 2021 (T1), November 2022 (T2) and November 2023 (T3). IGD, depression, sleep distress and resilience were measured using standardized questionnaires. Multiple logistic regression was used to examine the associations between baseline IGD and both concurrent and subsequent depression. Mediation analyses were conducted with T1 IGD as the predictor, T2 sleep distress and resilience as serial mediators and T3 depression as the outcome. To test the robustness of the findings, a series of sensitivity analyses were performed. Additionally, sex differences in the mediation pathways were explored.
Results
(1) IGD was independently associated with depression at baseline (T1: adjusted odds ratio [AOR] = 4.76, 95% confidence interval [CI]: 3.79–5.98, p < 0.001), 1 year later (T2: AOR = 1.42, 95% CI: 1.16–1.74, p < 0.001) and 2 years later (T3: AOR = 1.24, 95% CI: 1.01–1.53, p = 0.042); (2) A serial multiple mediation effect of sleep distress and resilience was identified in the relationship between IGD and depression. The mediation ratio was 60.7% in the unadjusted model and 33.3% in the fully adjusted model, accounting for baseline depression, sleep distress, resilience and other covariates. The robustness of our findings was supported by various sensitivity analyses; and (3) Sex differences were observed in the mediating roles of sleep distress and resilience, with the mediation ratio being higher in boys compared to girls.
Conclusions
IGD is a significant predictor of depression in adolescents, with resilience and sleep distress serving as key mediators. Early identification and targeted interventions for IGD may help prevent depression. Intervention strategies should prioritize enhancing resilience and improving sleep quality, particularly among boys at risk.
Postpartum maternal diet quality has been linked with optimal infant feeding practices. However, whether maternal diet quality during pregnancy influences infant feeding practices remains unclear. The present study explored the relationship between maternal diet quality in pregnancy and infant feeding practices in Australian women. A brief 15-item FFQ was used to collect maternal dietary data (n 469). Diet quality was calculated using a modified 2013 Dietary Guideline Index (DGI). Multivariable linear and logistic regressions with adjustment for covariates were used to examine associations between maternal diet quality in pregnancy and infant feeding practices: infant feeding mode, breast-feeding duration and timing of solids introduction. Higher DGI score during pregnancy was associated with higher odds of breast-feeding than formula/mixed feeding (adjusted OR (AOR) 1·03, 95 % CI 1·00, 1·07), longer breast-feeding duration (adjusted β 0·09, 95 % CI 0·03, 0·15) and higher odds of breast-feeding for ≥ 6 months (AOR 1·04, 95 % CI 1·02, 1·07) than for < 6 months. Associations between maternal DGI score and breast-feeding variables were moderated by maternal country of birth, with significant associations observed in Australian-born mothers only. No association was found between maternal DGI score and timing of solids introduction. Higher maternal diet quality was associated with better infant feeding practices, and the association was moderated by country of birth. Our findings provide evidence to support the initiation of dietary interventions to promote diet quality during pregnancy, particularly among Australian-born women. Further research could explore underlying mechanisms linking maternal diet quality and infant feeding practices.
Polygenic scores (PGSs) have garnered increasing attention in the clinical sciences due to their robust prediction signals for psychopathology, including externalizing (EXT) behaviors. However, studies leveraging PGSs have rarely accounted for the phenotypic and developmental heterogeneity in EXT outcomes. We used the National Longitudinal Study of Adolescent to Adult Health (analytic N = 4,416), spanning ages 13 to 41, to examine associations between EXT PGSs and trajectories of antisocial behaviors (ASB) and substance use behaviors (SUB) identified via growth mixture modeling. Four trajectories of ASB were identified: High Decline (3.6% of the sample), Moderate (18.9%), Adolescence-Peaked (10.6%), and Low (67%), while three were identified for SUB: High Use (35.2%), Typical Use (41.7%), and Low Use (23%). EXT PGSs were consistently associated with persistent trajectories of ASB and SUB (High Decline and High Use, respectively), relative to comparison groups. EXT PGSs were also associated with the Low Use trajectory of SUB, relative to the comparison group. Results suggest PGSs may be sensitive to developmental typologies of EXT, where PGSs are more strongly predictive of chronicity in addition to (or possibly rather than) absolute severity.
In this article, we delve into the optimal scheduling challenge for many-to-many on-orbit services, taking into account variations in target accessibility. The scenario assumes that each servicing satellite is equipped with singular or multiple service capabilities, tasked with providing on-orbit services to multiple targets, each characterised by distinct service requirements. The mission’s primary objective is to determine the optimal service sequence, orbital transfer duration and on-orbit service time for each servicing satellite, with the ultimate goal of minimising the overall cost. We frame the optimal scheduling dilemma as a time-related colored travelling salesman problem (TRCTSP) and propose an enhanced firefly algorithm (EFA) to address it. Finally, experimental results across various scenarios validate the effectiveness and superiority of the proposed algorithm. The principal contribution of this work lies in the modeling and resolution of the many-to-many on-orbit service challenge, considering accessibility variations — a domain that has, until now, remained unexplored.