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Natural deep eutectic solvent in situ formation-based extraction method coupled to high-performance anion-exchange chromatography with pulsed amperometric detection for multiclass carbohydrates in hot pot bases.

A novel method was developed for the simultaneous extraction of fourteen multiclass carbohydrates from high-fat foods via the in situ formation of deep eutectic adducts from analytes and acetate ions. Different natural deep eutectic solvents (NADESs) composed of fructose and organic acids were tested as extraction solvents. A model NADES formulated with sodium acetate and fructose was characterized using Fourier transform infrared (FTIR) spectroscopy and hydrogen nuclear magnetic resonance (1H-NMR) spectroscopy. The critical extraction parameters were systematically optimized using multi-response surface methodology (MRSM) with a central composite design (CCD). The extract was analyzed using high-performance anion-exchange chromatography coupled with pulsed amperometric detection (HPAEC-PAD) using a sodium hydroxide-sodium acetate eluent, which did not require organic solvents. This approach exhibited good linearity over the concentration range of 0.02-10 mg L-1, with correlation coefficients (r) ranging from 0.9994 to 0.9999. The limits of detection and quantification were in the ranges of 0.06-0.42 mg kg-1 and 0.19-1.3 mg kg-1, respectively, which were significantly lower than those of liquid chromatography (LC). The protocol was successfully applied to the determination of fourteen carbohydrates in forty-five hotpot seasoning samples. The recoveries ranged from 86.3% to 104.1%, with relative standard deviations (RSDs) of 0.9-7.1%. By integrating multiple techniques, this strategy simplifies operations, shortens extraction time, and achieves baseline separation of three carbohydrate classes that exhibit poor resolution using a conventional LC method. This study describes an efficient procedure for the simultaneous determination of multiple trace-level carbohydrates in complex samples using HPAEC-PAD.

Journal Article

Understanding psychosocial adjustment in military-to-civilian transition: A latent profile analysis of ex-serving Australian Defence Force members.

Military-to-civilian transition is a critical life stage that can expose veterans to elevated risks of psychological distress, social difficulties, and reduced wellbeing. Although psychosocial factors are central to successful reintegration, little is known about distinct patterns of needs among ex-serving Australian Defence Force (ADF) members. This study used latent profile analysis (LPA) to identify psychosocial needs profiles across five domains of the Military-Civilian Adjustment and Reintegration Measure (M-CARM) in a sample of 725 ex-serving ADF members. The optimal three-class solution identified: a Low Adjustment Need (LAN) group (20.7%) reporting minimal reintegration challenges; a Cultural Adjustment Need (CAN) group (42.9%) characterized by cultural adaptation difficulties, particularly beliefs about civilians and regimentation; and a Cultural and Psychological Need (CPN) group (36.4%) showing broader challenges across beliefs about civilians, purpose and connection, regimentation, and resentment and regret. The CAN group was more likely to be male, have lower educational attainment, and have no combat deployment history. The CPN group was similarly male dominated with lower education, and was additionally characterized by Navy service, unemployment or not being in the labor force, and medical discharge. Compared with the LAN group, both CAN and CPN groups reported higher levels of depression, anxiety, posttraumatic stress, and nightmare distress, as well as poorer quality of life and greater functional impairment. These findings highlight persistent reintegration challenges among veterans and support the need for stratified support models, ranging from psychoeducation to intensive multidisciplinary care, to better address diverse psychosocial needs of ex-serving ADF members.

Australian defense force

Associations between prescribed amphetamines and spontaneous cervical artery dissection: a matched case-control study.

AIMS: To assess whether prescribed amphetamines are associated with spontaneous cervical artery dissection (sCeAD), an important cause of stroke in young adults. METHODS: We conducted a retrospective matched case-control study within a large academic health system in Chicago, Illinois. Adults aged 18-85 years with incident sCeAD were matched 1:4 to controls without dissection on age, sex, and race/ethnicity. The primary exposure was documented amphetamine prescription. Conditional logistic regression was used to estimate adjusted odds ratios (ORs) controlling for relevant vascular and clinical covariates. Sensitivity analyses included strict matched-strata and inverse probability-weighted models. RESULTS: Among 11,463 individuals, including 2,293 cases and 9,170 controls, amphetamine exposure was associated with higher odds of sCeAD (adjusted OR 1.70, 95% CI 1.18-2.46). Results were unchanged in strictly matched strata (OR 1.70, 95% CI 1.18-2.46) and remained directionally consistent after inverse probability weighting (OR 1.40, 95% CI 1.09-1.79). High-dose amphetamine exposure (≥30 mg/day) had the strongest association (OR 1.96, 95% CI 1.18-3.26), whereas low-dose exposure was not statistically significant. CONCLUSION: Prescribed amphetamines were associated with modestly increased odds of sCeAD. While these findings are observational and hypothesis-generating, they may support a possible association in susceptible patients.

Humans

Pathways of onward HIV disclosure in relationships among young people living with vertically acquired HIV receiving antiretroviral therapy: A qualitative analysis from the BREATHER Plus trial, South Africa.

For young people living with HIV (YPLHIV) navigating their status since birth, managing onward disclosure of a potentially stigmatising condition in relationships is challenging, and may or may not lead to social support, with implications for wellbeing. In a clinical trial setting in KwaZulu-Natal, South Africa, we investigate how young people living with vertically acquired HIV navigate onward disclosure. Data were from the qualitative component of the BREATHER Plus randomised controlled trial evaluating the efficacy, safety and acceptability of short-cycle dolutegravir/tenofovir-based triple antiretroviral therapy (ART) in young people aged 12-19 years. We analyse data on 35 participants receiving ART engaged in clinical trials at the research site: 29 in longitudinal in-depth interviews (IDIs) and 12 across three focus group discussions (FGDs), including 6 in IDIs and FGDs. The Disclosure Processes Model was applied in the thematic analysis. Pre-disclosure was characterised by social assessments of potential confidants. During disclosure, reciprocal vulnerability and partial information-sharing were employed. Post-disclosure processes entailed linear and non-linear feedback trajectories, impacting future disclosures. The findings show that the study cohort of young people receiving ART navigated many bidirectional disclosure pathways to maintain social connections in relationships, and counselling guidelines need to be responsive to this.

Humans

Nitrogen sources and concentrations shape algal odor compounds: Key drivers of β-cyclocitral and β-ionone in water bodies of the lower Yangtze River.

Taste and odor (T&O) compounds derived from cyanobacterial blooms pose escalating threats to freshwater security worldwide, yet the drivers of specific T&O metabolites remain poorly constrained. Here, we investigated the dual effects of nitrogen (N) sources and concentrations on the production of β-cyclocitral and β-ionone, two algal-derived T&O compounds, through integrated field surveys (54 sites across lakes and rivers) in the eutrophic lower Yangtze River, China, and laboratory cultivation of typical cyanobacteria (Microcystis aeruginosa and Pseudanabaena cinerea). Our field data revealed that the concentrations of β-cyclocitral and β-ionone in lakes and rivers were not significantly different, but increased with the trophic level index. Redundancy analysis and Mantel analysis showed that Microcystis and Pseudanabaena were potentially dominant contributors to β-cyclocitral and β-ionone in the water column. Structural equation modeling and variation partitioning analysis showed that enhanced nitrate (NO3--N) significantly promoted the production of these compounds. Laboratory experiments demonstrated that inorganic N (NaNO₃) maximized total T&O yields by promoting algal biomass, whereas organic N (urea and glutamic acid) elevated the T&O production per unit biomass by 1.5- to 9.5-fold. Notably, Pseudanabaena exhibited a 2.3-fold higher β-ionone yield than Microcystis, with greater sensitivity to N concentrations. Our study highlights the critical role of nitrogen pollution, both source and concentration, in the production of T&O compounds by phytoplankton and provides reference data for managing T&O issues in rivers and shallow lakes.

Norisoprenoids

Association between fruit and vegetable intake and risk of depression: A systematic review and meta-analysis of prospective cohort studies.

Depression is a leading cause of global disability, and identifying modifiable lifestyle factors is a public health priority. We conducted a systematic review and dose-response meta-analysis of prospective cohort studies examining the association between fruit and vegetable intake and incident depression. PubMed, Web of Science, Scopus, Embase, and Google Scholar were searched through November 2025. Data on study characteristics, dietary assessment, outcomes, effect estimates, and covariates were independently extracted by two reviewers. Random-effects models were used to calculate pooled relative risks (RRs), and linear and non-linear dose-response relationships were assessed. Heterogeneity was evaluated using I2, and evidence certainty was rated with GRADE. Thirteen cohorts with 385,449 participants and 26,592 depression cases were included. Highest versus lowest combined fruit and vegetable intake was associated with a 37% lower risk of depression (RR: 0.63; 95% CI: 0.50, 0.80). Each 200 g/day increase corresponded to a 16% risk reduction (RR: 0.84; 95% CI: 0.74-0.94). Separate analyses showed that fruit and vegetable intake reduced depression risk by 16% and 12%, respectively, with a non-linear dose-response for vegetables. These findings indicate that higher consumption of fruits and vegetables is associated with lower depression risk, supporting dietary strategies as a potential approach for mental health prevention. However, given the observational nature of the included studies, these results should be interpreted with caution, as residual confounding may partially account for the observed associations. Registration: This study was registered at PROSPERO (CRD420261279998).

Humans

The genomic origins and evolutionary path to a key innovation in the world's most venomous snakes.

Evolutionary innovation is a catalyst for the colonization of new environments and the adaptive radiations of major groups. Novel traits typically evolve through the modification of preexisting characters, but the genetic paths underlying their origin have been challenging to trace, and the general requirements for and relative order of different kinds of gene mutations have been difficult to assess. Here, we trace the genomic origins of four procoagulant venom toxins (factor X, factor V, group I phospholipase A2, and Kunitz-type toxins) that collectively underlie a novel, especially potent blood-clotting venom type in the recently evolved Australian brown snake and taipan clade. We find evidence for a previously unknown fifth toxin, coagulation factor VII, and show that the toxins evolved through two distinct genetic paths. The factor X and factor V toxins evolved through the sequential de novo co-option of ancestral clotting factor proteins that entailed their heterotopic expression in the venom gland, the fixation of segmental duplications containing each locus, and subsequent gain-of-function mutations that rendered factor X and factor V constitutively active. In contrast, the phospholipase A2 and Kunitz-type toxins evolved by modifying the functions of neurotoxins that were part of the venom arsenal. Our findings support models in which innovative mutations in single-copy genes precede gene duplication in the evolution of novel proteins and offer a rare view into the genesis of a complex trait that has played a central role in a major adaptive radiation.

Animals

Post-Breakup Instagram Surveillance: Attachment Style, Personality Traits, and Breakup Distress as Predictors.

The end of a romantic relationship is one of the most emotionally challenging life events. Social media platforms such as Instagram enable users to monitor an ex-partner, a behavior known as Interpersonal Electronic Surveillance (IES), which may complicate coping. This study examined associations with retrospectively reported IES on Instagram during the first 3 weeks post-breakup, focusing on attachment, personality, and breakup-related emotional distress. Previous studies suggest that higher anxious attachment and emotional distress are related to increased monitoring behaviors on Facebook. The present research extends this approach to Instagram, a popular platform among Generation Z, and additionally examines personality factors. Data from N = 232 participants (aged 18-27 years; 84 percent women), who had experienced a breakup within the past year and followed their ex-partner on Instagram, were collected using a cross-sectional online questionnaire. The survey included standardized measures and self-constructed items. Hierarchical regression analyses including breakup-related variables, mediation analyses, and independent-samples t-tests were conducted. Due to extremely low internal consistency, Agreeableness was excluded from inferential analyses. The analyses indicated that Extraversion was the only personality trait directly associated with increased IES. Attachment styles showed no direct associations after emotional distress was included in the model. Emotional distress emerged as the most consistent factor associated with IES, showing patterns consistent with indirect associations involving Neuroticism and anxious attachment, suggesting a central role of emotional distress in post-breakup surveillance behavior. These findings highlight digital monitoring as a potentially maladaptive coping strategy and underscore the importance of addressing social media use in post-breakup adjustment.

Humans

Implementing a novel digital health platform for self-management of postmenopausal osteoporosis: A qualitative study of user experiences, perspectives and implementation outcomes.

BACKGROUND: Osteoporosis self-management requires scalable support, and digital health platforms may meet this need. This study aimed to characterise the experiences and perspectives of postmenopausal women who participated in a 12-month randomised controlled trial (RCT) of a digital voice assistant (DVA) delivered osteoporosis self-management intervention, and to assess key implementation outcomes. METHODS: This was a qualitative analysis of interviews with postmenopausal women from the intervention arm (DVA group) of the RCT. The DVA program broadcast education videos, medication reminders, home-based exercise, nutrition advice and monthly quizzes through a DVA device. Semi-structured interviews were recorded, transcribed and managed in NVivo through reflexive thematic analysis, guided by the Practical Planning for Implementation and Scale-Up and Proctor's implementation outcome taxonomy frameworks. Evidence weighting summarised participant coverage and code density. RESULTS: Twenty-two of 25 (88%) DVA group participants completed semi-structured interviews. Thematic analysis identified seven themes mapped to Proctor's implementation outcomes. Evidence weighting indicated strong support for the intervention's appropriateness and acceptability, moderate support for its adoption, fidelity, feasibility and sustainability, and limited support for costs. Participants valued clear audiovisual guidance, conversation-based interactions with natural language, and flexible home-based access to self-management. CONCLUSION: Digital health platforms for osteoporosis self-management appear feasible, acceptable and sustainable among postmenopausal women. Findings indicate that these platforms are approaching readiness for evaluation in implementation-focused settings, contingent on streamlined content, reliable delivery modalities, accessible user support, clear privacy regulations and pragmatic pricing models.

Humans

Health bill beneath the plastic feast: A phthalate contamination alert from takeout food containers.

The rapid growth of takeout food consumption in China has raised concerns regarding exposure to phthalic acid esters (PAEs) from food packaging. This study investigated the presence, source, contribution, and health risk of PAEs in commonly used takeout containers. Widespread contamination was observed, with total PAE concentrations ranging from below the limit of detection to 222,000 ng/g. Diisobutyl phthalate (DIBP), dibutyl phthalate (DBP), and bis(2-ethylhexyl) phthalate (DEHP) were identified as the predominant compounds, accounting for 7.50 %, 14.7 %, and 18.7 % of the total concentration, respectively. These PAEs may originated from additives during manufacturing and potential contamination of raw materials. Human exposure assessment showed that daily exposure doses of DIBP, DBP, and DEHP via container ranged from 0.00 to 2340 ng/(kg·day) among frequent takeout consumers, contributing substantially to overall PAE body burdens. To further assess exposure and associated risks, a nationwide online questionnaire survey was conducted across China. Based on this national-scale behavioral dataset, the health risks among Chinese residents were evaluated. Although the modeled non-carcinogenic risks of DIBP, DBP, and DEHP remained within acceptable limits, the simulation suggested that approximately 70 % of participants may experience potential exceedance of the carcinogenic risk threshold for DEHP. The frequency of takeout food consumption was identified as the most important factor affecting PAE exposure. These findings underscore the importance of limiting takeout frequency and reducing reliance on plastic containers to mitigate health risks. This study provides scientific evidence to support the development of safer packaging materials and informs public health strategies.

Phthalic Acids

Effect of Bariatric Surgery on Improvement of Retinal Microvasculature in Patients With Obesity: A Systematic Review and Meta-Analysis.

Obesity is associated with adverse retinal microvascular changes, including narrower central retinal arteriolar equivalent (CRAE), wider central retinal venular equivalent (CRVE) and lower arteriovenous ratio (AVR). Although bariatric surgery improves cardiometabolic risk, its effect on retinal microvascular calibre remains uncertain. We systematically searched the Cochrane Library, PubMed, ScienceDirect and Scopus up to June 2026. Prospective cohort studies reporting CRAE, CRVE or AVR before and after bariatric surgery in patients with obesity were included. Risk of bias was assessed using the Newcastle-Ottawa Scale. Pooled mean differences (MD) with 95% confidence intervals (CI) were calculated using a random-effects model. Eight prospective cohort studies including 283 patients were included. Seven studies contributed to the CRAE and CRVE analyses, and seven contributed to the AVR analysis. Bariatric surgery was associated with a significant increase in CRAE (MD&#x2009;=&#x2009;+4.02&#x2009;&#x3bc;m, CI [0.26-7.78], p&#x2009;=&#x2009;0.04). Sensitivity analysis excluding one study showed a stronger and more consistent effect (MD&#x2009;=&#x2009;+5.41&#x2009;&#x3bc;m, CI [4.59-6.22], p&#x2009;<&#x2009;0.01). CRVE significantly decreased after surgery (MD&#x2009;=&#x2009;-6.75&#x2009;&#x3bc;m, CI [-7.42 to -6.07], p&#x2009;<&#x2009;0.01), while AVR significantly increased (MD&#x2009;=&#x2009;+0.03, CI [0.02-0.05], p&#x2009;<&#x2009;0.01). Sensitivity analyses suggested that the direction of effect was generally robust, although between-study heterogeneity was present. Bariatric surgery may be associated with favourable retinal microvascular changes in patients with obesity, reflected by increased CRAE and AVR and decreased CRVE.

Humans

The effect of olfactory training and odor exposure on visual selective attention.

Olfactory training (OT) is a well-established, non-invasive intervention that improves olfactory function by repeated, structured exposure to odorants. Beyond sensory outcomes, it also influences multiple aspects of cognition. Yet, its influence on attention, a fundamental process underlying many cognitive domains, remains unclear. This study examined the impact of a 12-week OT program on visual selective attentional performance and the effect of on-task odor exposure. Ninety-four healthy participants were initially included, and randomized into OT or placebo groups. Participants completed the d2 Test of Attention simultaneously with and without odor exposure in a randomized sequence at baseline, post-training, and a follow-up four weeks after stopping the training. The d2 test measures commission errors, omission errors, and concentration performance. Ninety-three participants (OT=51, placebo=42) completed baseline measurement, 74 (OT=39, placebo=35) returned for post-training session, and 57 participants (OT=29, placebo=28) returned for the follow-up appointment. Results showed that OT did not significantly improve d2 test performance. In the primary model, on-task PEA exposure reduced commission errors compared to the odorless condition, suggesting a possible transient effect of olfactory input on the inhibitory control in the context of the d2 attentional test. This effect, however, was no longer significant once the follow-up data were included and should be regarded as preliminary. Overall, these findings raise the possibility of a distinction between relatively long-term OT and short-term odor exposure: while OT did not improve visual selective attention, brief on-task odor exposure may transiently enhance inhibitory control during attentional tasks, a possibility that remains to be confirmed.

Humans

Frequency of Human Brucellosis Complications in West Asia: A Systematic Review and Meta-Analysis.

BACKGROUND: Brucellosis is a multi-systemic zoonotic infection. The West Asia/Middle East region is an important global hotspot for brucellosis. This systematic review and meta-analysis aimed to aggregate and synthesize all the available evidence regarding the complications of brucellosis in West Asia/Middle East region. METHODS: PubMed, Embase, Scopus, Web of Science, Google Scholar, and Proquest were searched. Selection of studies, data extraction, and the risk of bias assessment were performed in duplicate. Data extraction was performed for 254 complications. Meta-analysis was performed using a random-effects model with Freeman-Tukey double arcsine transformation. Where applicable small-study effects was assessed using funnel plots and Egger's test. Separate by-country, by-age, and by-publication-decade subgroup analyses were performed if feasible. RESULTS: Out of 9518 results, 240 studies (260 references) were included. The majority of the included studies were conducted in Turkey (n&#x2009;=&#x2009;177). The reported complications varied and different complication categorization systems were detected. The highest pooled estimate was observed for musculoskeletal involvement (50%, 95%CI: 39%-61%, I2&#x2009;=&#x2009;96.63%). The evidences is up-to-date until March 4, 2024. CONCLUSIONS: Some complications such as the complications of the eye were not reported in all the countries. Therefore, it's recommended to determine the relative frequency of those complications in regions without such reports. The pooled estimates of different complications of brucellosis were different. There's a need for the standardization of the reporting of the complications of brucellosis to achieve comparability between studies and across different regions.

Brucellosis

An Integrated Proteomics and Genomics Approach to Identify Essential Protein Kinases During Human Trophoblast Development.

In the developing human placenta, three subtypes of trophoblast cells, cytotrophoblasts (CTBs), extravillous trophoblasts (EVTs), and syncytiotrophoblasts (STBs), mediate critical functions essential for a successful pregnancy. CTBs constitute the stem/progenitor compartment and differentiate into STBs and EVTs within the floating and anchoring villi, respectively. STBs establish the maternal-fetal exchange interface and secrete human chorionic gonadotropin (hCG), a hormone vital for the maintenance of early pregnancy. EVTs anchor the maternal endometrium and invade the uterine tissue to remodel maternal cells, supporting implantation and progression of pregnancy. In this study, we used human trophoblast stem cells (hTSCs) as a model system and performed quantitative, label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS) to profile the proteome and phosphoproteome in TSC stem state (analogous to undifferentiated CTBs) and following their differentiation to STBs and EVTs. Through a multiomics approach, we integrated our proteomics data with global gene expression profiles to correlate cell-type specific gene and protein expression during human trophoblast development. We also identified global phosphoproteome and analyzed kinases that are specifically active in hTSC stem state, as well as in differentiated STBs and EVTs. We experimentally validated specific kinases, such as BUB1B, PAK6, PKYMT1, and TNIK, that are essential for maintaining the hTSC stem-state. Additionally, atypical protein kinase C isoforms PKC&#x3b6; are essential for STB development, whereas PTK2B, SRC, TRIO, and LYN are important for EVT development. Our findings highlight key kinases uniquely required for specific stages of trophoblast development during human placentation and suggest that pharmacological inhibition of these kinases could negatively impact the placentation process during pregnancy.

Humans

Variations in the viral hepatitis C prevalence and treatment status by material hardship and cumulative risk among people who inject drugs.

People who inject drugs (PWID) are disproportionately impacted by viral hepatitis C (HCV). Among PWID, homelessness, poverty, and material insecurity elevate infectious disease risk. We hypothesized a positive association between material hardship (difficulty accessing basic needs) and lifetime diagnosis of HCV, and a negative association between cumulative risk (material hardship and years since first injection) and HCV treatment. From 2021-22, we conducted a survey among community-recruited PWID that included items on HCV outcomes, material hardship (a sum score of usually (4) to never (1) having difficulty finding food, clothing, shelter, restrooms, and showers in the past 3 months), and years since injection drug use initiation. We developed a latent variable, cumulative risk, by combining individual scores of material hardship indicators and years since first injection drug use. Among our sample of PWID (n&#x2009;=&#x2009;471), 246 (53%) participants reported lifetime HCV diagnosis and 27% of those who tested positive for HCV reported ever or current treatment (n&#x2009;=&#x2009;67). In modified-Poisson regression, a one-unit increase in material hardship score was associated with a 3% (OR: 1.03, 95% CI: 1.01%, 1.05%) increase in odds of HCV diagnosis. In latent modeling, among PWID testing positive for HCV, a one-unit increase in cumulative risk score was associated with a 0.28 (OR: -0.28, 95% CI: -0.50, -0.06), decrease in the Z-score odds of receiving HCV treatment. Findings emphasize structural interventions to strengthen material security and co-delivering basic needs with health services to improve HCV-related outcomes among PWID.

HCV

Non-coding RNAs and Mitochondrial Dysfunction in Alzheimer's Disease: A Systematic Review.

Alzheimer's disease (AD) is responsible for 70% of dementia cases worldwide, with tau hyperphosphorylation and amyloid-&#x3b2; plaque accumulation representing its core pathological hallmarks. Genetic predisposition, oxidative stress, and neuroinflammation contribute to disease onset and progression. Non-coding ribonucleic acids (ncRNAs) are a class of RNAs which control gene expression and whose dysregulation in AD patients has been linked to amyloid production, neuroinflammation, and mitochondrial dysfunction, which ranges from impaired energy metabolism to disrupted mitochondrial biogenesis and dynamics. Our descriptive systematic review surveyed the involvement of ncRNAs in mitochondrial dysfunction in AD across experimental and clinical literature. We identified multiple microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) that directly regulate mitophagy, mitochondrial biogenesis, mitochondrial autophagic, and apoptotic pathways, mitochondrial dynamics, and protein import mechanisms in AD models. Among the most important candidates demonstrating clinical dysregulation, miR-140 and lncRNA NEAT1 regulate mitophagy, while miR-9, miR-34a, miR-146a, miR-155, and miR-485 are implicated in mitochondrial biogenesis and miR-204 in mitochondrial autophagy. LncRNA BDNF-AS, miR-148a-3p, miR-21-5p, and miR-103a-3p emerged as regulators of the mitochondrial apoptosis pathway with confirmed clinical dysregulation. Multiple ncRNAs control mitochondrial dynamics, of which miR-195, miR-124, and miR-455-3p have also been studied in AD patients. Additionally, several ncRNAs were found to indirectly regulate mitochondrial fission, autophagy, and apoptosis, although the underlying mechanisms require further characterization. Thus, while ncRNA-centered AD research is in its early stages, current mechanistic and translational evidence supports mitochondrially relevant ncRNAs as promising candidates for biomarker and therapeutic development.

Alzheimer Disease

Risk of stroke in SLE: a systematic review and meta-analysis.

UNLABELLED: The association between SLE and composite stroke, ischaemic stroke and haemorrhagic stroke remains incompletely understood. This meta-analysis aims to assess the risk of stroke in patients with SLE. METHODS: Data sources included PubMed, Embase, the Cochrane Library and reference lists of included studies. This meta-analysis included cohort studies evaluating whether stroke risk is associated with SLE. The risk of bias was assessed using the Newcastle-Ottawa Quality Assessment Scale (NOS). Risk ratios (RRs) with 95% CIs were pooled using a random-effects model, and publication bias was assessed with funnel plots and Egger's test. RESULTS: A total of 25 cohort studies involving 5&#x2009;220&#x2009;837 individuals were included in this meta-analysis, which were published between 2001 and 2026. The pooled analysis demonstrated a significantly increased risk of stroke in patients with SLE (RR of 2.60, 95%&#x2009;CI 2.21 to 3.05, I&#xb2;=97.9%, p<0.001). The risk of composite stroke (RR of 2.83, 95%&#x2009;CI 2.25 to 3.57, I&#xb2;=98.0%, p<0.001), ischaemic stroke (RR of 2.34, 95%&#x2009;CI 1.75 to 3.12, I&#xb2;=97.6%, p<0.001) and haemorrhagic stroke (RR of 2.66, 95%&#x2009;CI 1.57 to 4.49, I&#xb2;=96.2%, p<0.001) was also increased in SLE. Despite the large heterogeneity, the sensitivity analysis indicated that the results were robust, and there was little evidence of publication bias. CONCLUSION: The risk of composite stroke, ischaemic stroke and haemorrhagic stroke is increased in SLE. PROSPERO REGISTRATION NUMBER: CRD420261294082.

Humans

Antiadalimumab Antibodies in Patients With Inflammatory Ocular Diseases: Incidence and Clinical Outcomes.

PURPOSE: To determine the incidence, effect on adalimumab drug levels, and clinical consequences of antiadalimumab antibody formation, and to assess potential risk factors. DESIGN: Retrospective clinical cohort study. PARTICIPANTS: One hundred twenty-eight patients treated with adalimumab who underwent antiadalimumab antibody monitoring. METHODS: Beginning October 2023, regularly scheduled antiadalimumab antibody and adalimumab level testing was begun. Using staggered entry analysis, anchored observation to treatment initiation, incidence was calculated. Time-updated models evaluated risk factors for antiadalimumab antibody formation. MAIN OUTCOME: Incidence of antiadalimumab antibodies. RESULTS: Antiadalimumab antibodies developed in 37 of 128 patients for a rate of 0.077 per person-year (PY) (95% confidence interval [CI] 0.055/PY, 0.104/PY). Median serum adalimumab concentrations were significantly lower in antiadalimumab antibody-positive blood samples (2.6 &#xb5;g/mL; interquartile range 0.8, 7.0) than in antibody-negative samples (10.2 &#xb5;g/mL; interquartile range 6.9, 15.1), P < .00001. In time-updated analyses, there was a suggestion that concomitant immunosuppression was associated with a reduced risk of antiadalimumab antibodies (odds ratio [OR] 0.64; 95% CI 0.37, 1.10; P = .10) and weekly adalimumab dosing was associated with a reduced risk (OR 0.62; 95% CI 0.42, 0.91; P = .01). Antiadalimumab antibodies were associated with active ocular inflammation (OR 3.68; 95% CI 1.99, 6.82; P < .00001). CONCLUSIONS: Antiadalimumab antibodies occur commonly among patients treated with long-term adalimumab, with a cumulative incidence of nearly 50% by 8 years of therapy. Antibody formation was associated with lower serum adalimumab levels and active ocular inflammation.

Humans