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Cost-effectiveness analysis of a virtually administered pain coping skills training intervention in women with breast cancer in underserved areas.

OBJECTIVES: Women with cancer who live in medically underserved areas could benefit from behavioral pain interventions, but access is limited. A randomized trial reported that a 4-session virtual program incorporating pain coping skills training (mPCST) was effective in improving pain outcomes compared to an attention-control condition. We performed a cost-effectiveness analysis of mPCST vs. control. METHODS: Data on medical resource use, therapist time, and participants' attendance at intervention sessions and time associated with travel and using a mobile app were collected. The 5-level EuroQol 5-Dimension (EQ-5D-5L), a preference-weighted measure of health-related quality of life (HRQOL), was administered at baseline, after the intervention period, and 3 and 6 months later. Medicare payments were used to value medical resource use and therapist time to deliver mPCST. Patient time was valued using the average US wage. RESULTS: Medical resource utilization was similar for both groups, but hospitalizations trended higher in the mPCST group. EQ-5D-5L preference weights were higher by an average of 0.066 (p = 0.04) with mPCST across the follow-up period, representing an incremental gain of 0.04 quality-adjusted life years (QALYs) (95% CI: 0.00-0.08). When including the base-case cost of mPCST of \$500 vs. \$0 for the control group, the incremental cost-effectiveness ratio (ICER) was \$12,725 per QALY (95% CI: 5,566-69,343). Including the value of patient time added \$303 to mPCST costs resulting in an ICER of \$20,438 per QALY (95% CI: 9,051-111,403). SIGNIFICANCE OF RESULTS: mPCST is a cost-effective program that improves HRQOL for women with cancer living in medically underserved areas.

Humans

Co-Use of Some Substances Associated With Higher Doses in Adolescents: Findings From the Adolescent Brain Cognitive Development Study.

PURPOSE: Adolescence is a critical developmental period marked by heightened vulnerability to initiating substance use, with long-term implications for health and behavior. Nicotine, alcohol, and cannabis are the most commonly used substances among adolescents. Their use often co-occurs but few studies have described or quantified the patterns and doses of substance co-use in this vulnerable population. METHODS: We used data from six waves of the Adolescent Brain Cognitive Development study. Substance use was measured through a web-based timeline followback interview, and outcomes are operationalized into substance use quantity (in standard units), single use, and co-use (use of two substances on the same day) of alcohol, cannabis, and nicotine. Group differences of average dose in standard units between single use and co-use for each substance class were analyzed using linear mixed-effects modeling in years 4-6. RESULTS: The average dose of nicotine was significantly higher when co-used with alcohol (4.32; 95% confidence interval [CI]: 2.55-6.09; p < .001) or when co-used with cannabis (4.41; 95% CI: 2.76-6.05; p < .001) in year 6; nicotine trends were similar in years four and five. In year 6, the average dose of alcohol was higher when co-used with cannabis (1.87; 95% CI: 0.37-3.36; p = .004) or co-used with nicotine (1.64; 95% CI: 0.06-3.22; p = .03) compared to single use of alcohol. The average dose of cannabis was not significantly different when used singularly or co-used with either alcohol or nicotine in our study years. DISCUSSION: During adolescence, the co-use of substances (namely alcohol and nicotine) may lead to higher average doses compared to single-substance use.

Humans

Mendelian randomisation for rheumatology: beyond hype-what it's good for, what it can't do, and how to read it critically.

Mendelian randomisation (MR) has become abundant in the literature, with variation in quality and frequent overinterpretation of causality. This creates a problem for clinical readers, reviewers, and editors: some MR studies can sharpen causal thinking, prioritise drug targets, and challenge misleading observational claims, whereas others are little more than automated exposure-outcome scans with causal claims disproportionate to the evidence. MR can strengthen causal inference when randomised trials are impractical and conventional observational studies are vulnerable to confounding, reverse causation, or selection bias. In rheumatology, credible MR can contribute to questions about disease aetiology, modifiable risk factors, therapeutic target validation, adverse-effect anticipation, and phenotype validation. However, its interpretation depends on whether the exposure is plausibly instrumentable, whether the genetic instruments are biologically defensible, whether assumptions are interrogated in ways appropriate to the design, and whether findings are triangulated with clinical, observational, experimental, and mechanistic evidence. Instead of recapitulating all methodological issues of MR, this review aims to help rheumatologists distinguish robust MR from weak or overinterpreted analyses quickly. We provide an accessible framework for reading and triaging MR studies in rheumatology. Papers that use poorly justified instruments, treat medication use as drug-target evidence, interpret genetic liability as diagnosis, rely on mechanical sensitivity analyses, ignore prior evidence or ask no clinically meaningful question can often be passed over by readers. The goal is not to discourage MR in rheumatology, but to raise the standard; useful MR should clarify causal reasoning rather than simply generate another statistically significant association.

Journal Article

Driven toward care, avoiding the end: A systematic review and meta-analysis of the relationship between death anxiety and healthcare utilisation.

Both overuse and underuse of the healthcare system have been recognised as significant problems. Relatedly, growing research has recognised the key role of death anxiety in driving various health-relevant behaviours. However, the relationship between death anxiety and healthcare utilisation has not yet been systematically explored. The current systematic review and meta-analysis addressed this gap. In total, 987 papers were screened for inclusion, of which 63 were included in the final review (Ntotal&#x202f;=&#x202f;21,271). This included 33 quantitative studies, 27 qualitative studies and 3 mixed-methods designs. In total, 17 studies contained sufficient data to be meta-analysed. Overall, the included studies highlighted a significant relationship between death anxiety and healthcare utilisation; in particular, positive associations with desire for life-prolonging treatments and contact with hospitals and medical professionals. By contrast, a negative association was found with other aspects of healthcare utilisation, including hospice use and end-of-life communication. The sample type emerged as a significant moderator, suggesting that the relationship between death anxiety and healthcare usage was strongest in non-medical samples. The current findings suggest that death anxiety plays a key role in utilisation of the healthcare system. The fear of death may need to be targeted in psychological interventions, in order to ensure maximal effectiveness of health services, and improve outcomes for healthcare users.

Humans

The psychosocial supports and interventions accessed by family members of patients with developmental and epileptic encephalopathies: A systematic review.

AIM: Family members of patients with developmental and epileptic encephalopathies (DEEs) face profound emotional, social and practical challenges, yet little is known about how they access psychosocial support. We synthesised the literature on the psychosocial support accessed by family members of patients with DEEs, including evidence-based interventions. METHOD: Four databases were searched. Two reviewers independently screened and extracted data, appraised study quality (QualSyst Tool), and determined certainty of evidence (GRADE-CERQual Framework). Data were synthesised using inductive thematic analysis. RESULTS: 28 papers comprising 27 unique studies were included and methodological quality was high overall (median&#xa0;=&#xa0;0.91, IQR&#xa0;=&#xa0;0.85-1.00). Most studies focused on parent experiences; only two included siblings' perspectives. Families reported high psychological needs which were rarely met by psychological support. Clinicians rarely provided adequate information, quality communication or addressed mental health. Families valued respite care, but experienced barriers to access. Peer support was the most common and valued resource. Three studies tested interventions and appeared feasible and acceptable for parents. However, evidence for intervention effectiveness is preliminary and limited to small, uncontrolled pilot studies. INTERPRETATION: Gaps exist in psychosocial support provision for families of patients with DEEs, including insufficient research on siblings' and grandparents' needs, and lack of evidence-based interventions. We propose evidence-informed research and implementation strategies to address these gaps.

Humans

Longitudinal Relations among Perceived Economic Stress, Teacher-Student Relationships, and Cybervictimization: Exploring Within-Person Links.

Family economic hardship has been identified as a risk factor for adolescents' cybervictimization. Nevertheless, existing studies have primarily focused on objective economic conditions, and little is known about the within-person association between perceived economic stress and adolescents' cybervictimization and the mediating mechanisms underlying this association. To fill these gaps, the random intercept cross-lagged model was employed to examine the dynamic relations among perceived economic stress, teacher-student relationships, and cybervictimization. The data were obtained from a sample of 2407 Chinese adolescents (Mage = 12.75, SD = 0.58, 50.23% girls at baseline) recruited from seven schools and assessed at three time points over one year. At the between-person level, there were no significant associations among perceived economic stress, teacher-student relationships, and cybervictimization. At the within-person level, perceived economic stress positively predicted later cybervictimization over time, and this effect was unidirectional. The bidirectional relations between perceived economic stress and teacher-student relationships remained stable over time. Cybervictimization significantly and negatively predicted subsequent teacher-student relationships across time, indicating a unidirectional predictive effect. Additionally, perceived economic stress indirectly predicted cybervictimization through teacher-student relationships. The findings highlight the importance of distinguishing within-person from between-person processes and shed light on the longitudinal role of teacher-student relationships in the association between perceived economic stress and cybervictimization.

Humans

Long-term efficacy of cognitive behavioural therapy for insomnia (CBT-I) on depressive symptoms: A systematic review and meta-analysis of randomised controlled trials.

Depressive symptoms are common in individuals with persistent insomnia. Previous meta-analyses of randomised controlled trials (RCTs) showed that cognitive behavioural therapy for insomnia (CBT-I) can reduce depressive symptoms at post-treatment. However, the long-term maintenance of these improvements has never been systematically examined. To fill-in this gap, we conducted a systematic review and meta-analysis of the long-term (&#x2265;3 months) effects of CBT-I on depressive symptoms. The review was registered in PROSPERO (CRD420251146061). Only RCTs in adults with insomnia were considered. Pubmed, Scopus, Psycinfo, CINAHL, and Medline were searched up to 12 September 2025 with no predefined time constraints. From 5359 records initially retrieved, we included 53 articles reporting on 13,608 individuals. After outliers removal, random effects meta-analysis showed that CBT-I was superior to control conditions in reducing depressive symptoms at 3 [k&#x202f;=&#x202f;29, d&#x202f;=&#x202f;-.35, [95% CI: -.49 to -.21], p&#x202f;<&#x202f;.001], 6 [k&#x202f;=&#x202f;29, d&#x202f;=&#x202f;-.32, [95% CI: -.59 to -.05], p&#x202f;=&#x202f;.018], and 12 [k&#x202f;=&#x202f;10, d&#x202f;=&#x202f;-.25, [95% CI: -.39 to -.12], p&#x202f;<&#x202f;.001] months follow-ups. Results demonstrate that the effects of CBT-I on depressive symptoms are sustained throughout the year following treatment, although effects may decline over time.

Humans

Sleep stage-dependent distribution of interictal epileptiform discharges in epilepsy: A systematic review.

BACKGROUND: Sleep and epilepsy interact through complex bidirectional mechanisms. Although NREM sleep facilitates interictal epileptiform discharges (IED), the diagnostic contribution of individual sleep stages remains uncertain. In particular, it is unclear whether deeper sleep stages such as N3 provide an advantage over N2 for spike detection or localization in clinical (electroencephalography) EEG practice. METHODS: This systematic review followed PRISMA 2020 guidelines. PubMed and Web of Science were searched for studies reporting quantitative IED measures across sleep stages in patients with epilepsy. Eligible studies included scalp EEG, video-EEG, polysomnography, or intracranial recordings. Mean IED rates per minute were derived when possible. Comparisons between NREM and REM sleep and between N2 and N3 stages were performed using study level non-parametric tests. Risk of bias was assessed with the ROBINS-I tool. RESULTS: Ten observational studies including 266 patients (mean age 30.1&#xa0;years) were analyzed. IED rates were significantly higher during NREM than REM sleep (Wilcoxon signed-rank test, W&#xa0;=&#xa0;0, p&#xa0;=&#xa0;0.0019, r&#xa0;=&#xa0;0.87). No significant difference was observed between N2 and N3 sleep, although median spike rates were slightly higher during N3 than N2 (0.99 vs 0.86 IED/min). REM showed the lowest activity. CONCLUSIONS: NREM sleep consistently exhibited higher IED rates than REM sleep, reinforcing the neurophysiological association between sleep stage and epileptiform activity without establishing diagnostic superiority.

Humans

Analysis of the Relationship between Early Clinical Factors and Glasgow Outcome Scale in Patients With Traumatic Brain Injury.

OBJECTIVE: This study aimed to evaluate the association between early clinical factors and the Glasgow outcome scale (GOS) in patients with traumatic brain injury (TBI). METHODS: We conducted a retrospective analysis of 98 TBI patients who underwent emergency surgery between January 2021 and January 2024. Based on GOS scores at 6 months post-surgery, patients were classified into a favorable outcome group (GOS&#xa0;&#x2265;&#xa0;4, defined as moderate disability or good recovery,&#xa0;n = 58) and an unfavorable outcome group (GOS < 4, i.e., death, persistent vegetative state, or severe disability,&#xa0;n = 40). Baseline and early clinical parameters were compared between groups. Statistically significant variables from univariate analysis were entered into a multivariate logistic regression model to identify independent prognostic factors. RESULTS: Significant intergroup differences were observed in age, time from injury to surgery, bleeding site, midline shift, Glasgow coma scale (GCS) score at admission, blood glucose level, and D-dimer level (all p < 0.05). Multivariate analysis confirmed that age, time from injury to surgery, GCS score, blood glucose, and D-dimer level were independent predictors of GOS (all p < 0.05). CONCLUSION: Early clinical factors, including age, time to surgery, GCS score, blood glucose, and D-dimer level, independently influence GOS in TBI patients. Time from injury to surgery&#xa0;emerged as a potentially modifiable factor in this cohort, suggesting that minimizing delays may improve outcomes.

Humans

Disentangling oscillatory and aperiodic neural activity in autism: A spectral parameterization analysis of neurofeedback intervention.

BACKGROUND: Autism Spectrum Disorder (ASD) is characterized by atypical neural oscillations and heterogeneous alterations in excitation/inhibition (E/I) balance, the directionality of which varies across individuals, neural circuits, and developmental stages. While Alpha-band neurofeedback (NFB) is a promising intervention, its underlying neurophysiological mechanisms remain unclear, partly due to the conflation of periodic and aperiodic signals in traditional EEG analysis. METHODS: This randomized controlled trial recruited 40 children with ASD, assigned to either an experimental group (Alpha-training NFB) or a no-feedback group. Resting-state EEG and behavioral assessments (SRS, ABC) were collected pre- and post-intervention. We employed spectral parameterization to decompose neural activity into aperiodic (1/f slope, offset) and periodic (periodic alpha power, center frequency) components. RESULTS: NFB training yielded significant behavioral improvements in social cognition and relating skills. Physiologically, the experimental group exhibited a significant steepening of the aperiodic slope (increased exponent), reflecting a reduction in neural noise and potential optimization of inhibitory modulation. Furthermore, we observed enhanced periodic alpha power and an acceleration of the alpha center frequency (ACF), indicative of improved neural efficiency and maturation. These physiological shifts in frontal and occipital regions were significantly correlated with improvements in behavioral scores. CONCLUSION: Alpha-training NFB was associated with improvements in caregiver-rated behavioral scores and modulated spectral features of resting-state EEG in children with ASD. These findings validate the utility of spectral parameterization markers in evaluating neuromodulatory interventions.

Humans

Reinforcement learning-based dynamic ensemble for missense variant effect prediction and tiered prioritization of VUS.

BACKGROUND: Accurate classification of missense variants remains a challenging task despite major advances in genomics. Numerous computational models have been developed to assist in variant classification, but often require repeated integration and benchmarking efforts. Ensemble methods have been proposed to overcome the limitations of single predictors, but mostly rely on fixed, predefined weights that constrain their ability to capture interactions among predictive signals. METHODS: We present GenixRL, a dynamic ensemble framework that reformulates model fusion as a reinforcement learning optimization problem. GenixRL uses a Q-learning agent to learn a policy that dynamically weights the probabilistic outputs of complementary predictors, including BayesDel (addAF and noAF), ClinPred, and MetaRNN. Replacing static weighting with policy learning allows GenixRL to adaptively identify optimal weightings and substantially improve classification accuracy. RESULTS: In benchmark evaluation against 25 state-of-the-art predictors, GenixRL achieved an AUROC of 0.9644 on an independent ClinVar dataset. On saturation genome editing assays for BRCA1 and BRCA2, GenixRL achieved the best performance and ranked highest on 14 of 17 clinically significant genes in a zero-shot evaluation. Applied to uncertain and conflicting ClinVar variants, GenixRL enabled tiered, evidence-based prioritization of hundreds of thousands of variants as likely pathogenic or pathogenic with high confidence, supported by orthogonal population evidence from gnomAD. CONCLUSION: GenixRL advances pathogenicity prediction for missense variants and provides an adaptive ensemble that sorts variants of uncertain significance into tiered candidates for expert curation and functional validation.

Mutation, Missense

Emotional and Cognitive Processes Underlying Persuasion, Moderating Factors, and Physiological Reactions: A Systematic Review.

Persuasion is a type of social influence aiming to produce changes in others' attitudes or behaviors. This study explores the relationship between emotions and persuasion, principal moderating factors, and physiological reactions during persuasive attempts. Following PRISMA guidelines, 28 empirical articles were analyzed, addressing emotions, affective/cognitive orientations, framing effects, and psychophysiological reactions. Mixed findings emerged regarding emotions, with fear appeals being effective in health education, while more recent studies favor the use of positive persuasive messages to increase behavior intention. Principal moderating factors included personal relevance, need for cognition (NFC) and need for affect (NFA), thought confidence, vulnerability, and efficacy beliefs. Psychophysiological studies revealed distinct physiological arousal during persuasion processing compared to a rest state. In addition, a greater misalignment between current behavior and the persuasive attempt led to perceived freedom threat and psychological reactance. These insights enhance persuasive effectiveness and deepen understanding of persuasion processes, guiding future research directions.

Humans

Complement component C4 and neuroimaging in psychiatry: A systematic review.

INTRODUCTION: Genomic, transcriptomic, and proteomic studies suggest that the complement system contributes to the pathophysiology of various psychiatric disorders partly through neurodevelopmental effects linked to C4A protein levels variations. We conducted a systematic review to characterize how brain micro- and macrostructure and connectivity vary with proxies of in vivo brain C4A protein levels in both psychiatric and general-population cohorts. METHODS: We used Medline, Web of Science, and Embase, and included all studies published before April 14, 2025. Inclusion criteria were: (1) inclusion of healthy controls and/or individuals with psychiatric disorders assessed according to recognized diagnostic manuals (DSM or ICD); (2) use of MRI-based neuroimaging; and (3) use of genomic, transcriptomic and/or proteomic approaches as proxies of in vivo brain C4A proteins levels. RESULTS: From 317 identified articles, 11 were included. Associations between C4A levels and brain structure were heterogeneous across regions. Only the mOFC, dlPFC, and entorhinal cortex were implicated in more than one study. Findings for the mOFC and dlPFC varied by the type of metrics and clinical status, whereas higher C4A levels were more consistently associated with smaller entorhinal cortex surface area and cortical thickness in pediatric, middle-aged, and older general-population cohorts. In addition, one study found higher genetically predicted C4A expression to be associated with higher TSPO levels. CONCLUSION: The limited number of available studies and their methodological heterogeneity make synthesis challenging. However, biological hypotheses such as excessive synaptic pruning or broader inflammatory effects on the brain may provide plausible explanatory frameworks for the reported associations.

Humans

Frequent readmissions after hospitalization for alcohol withdrawal: a systematic review and meta-analysis.

BACKGROUND: Alcohol use disorder and alcohol withdrawal syndrome impose substantial clinical and economic burdens, with repeated hospitalizations being common. We aimed to systematically review readmission rates following inpatient detoxification, assess variation across study designs and hospital settings, and identify key risk and protective factors. METHODS: We performed a literature search in Embase and Pubmed on 10/04/2026 focusing on studies assessing in hospital alcohol detoxification. Exclusion criteria included studies on substance use other than alcohol and outpatient or residential treatment. Main outcome was rehospitalization, and meta-analysis was performed to estimate pooled readmission proportions. Secondary outcomes were risk factors and protective factors influencing the rate of rehospitalization. RESULTS: Twenty-five studies were included. The pooled proportion of readmissions following alcohol detoxification was estimated at 17% (95% CI: 14%-21%; 13 studies, n&#xa0;=&#xa0;287,896) within 1&#xa0;month, increasing to 44% (95% CI: 36%-52%; 8 studies, n&#xa0;=&#xa0;2,877) at 1&#xa0;year. Substantial between-study heterogeneity was observed. Subgroup analyses found no significant differences by hospital setting or time period. Findings for study aim and study design were mixed and based on limited data A small number of studies suggested associations with housing stability, employment, and treatment engagement. CONCLUSIONS: This meta-analysis suggests that approximately one in six patients are readmitted within 1&#xa0;month and nearly half within 1&#xa0;year after inpatient alcohol detoxification. However, readmission rates varied considerably across settings and populations. Future research should evaluate targeted interventions to reduce readmissions among high-risk patient groups.

Humans

Sex- and development-specific transcriptomic profiling of venom and silk genes in the wolf spider Pardosa astrigera provides insights into ecological adaptation and predatory strategies.

Spider venom and silk glands are two major secretory systems that contribute to prey capture, defense, and reproduction, but their sex- and development-specific molecular regulation in wandering wolf spiders remains poorly understood. Here, the transcriptome of Pardosa astrigera, an important agricultural natural enemy in China, revealed significant sex- and development-associated molecular differentiation among adult females, adult males, and spiderlings. A total of 100,025 unigenes were obtained, of which 23,852 were functionally annotated, providing a comprehensive transcriptomic resource for this species. Differential expression patterns showed marked variation among groups, with 531, 1792, and 832 DEGs detected in PAF vs PAS, PAM vs PAS, and PAF vs PAM, respectively. These genes were mainly associated with metabolic, oxidation-reduction, cuticle development, MAPK signaling, and lysosome pathways. Fifteen co-expression modules revealed distinct expression patterns. The turquoise, pink, yellow, and red modules were development-related, whereas the blue module was male-biased. Venom- and spidroin-related genes were distributed across multiple modules, suggesting coordinated regulation. Overall, 42 venom peptides, 21 venom proteins, and 11 spidroins were identified. Representative genes showed strongly biased expression, including spiderling-biased U3_Pp1a and U5_Pp1e, female-biased U4_Pp1a, and male-biased SMase D_108750 and PaTuSp_108466. These findings reveal sex- and development-biased expression patterns of venom- and silk-related candidate genes in P. astrigera and may provide molecular insights into ecological adaptation and predatory strategies in wandering wolf spiders.

Animals

Psychotherapy vs antidepressants in heart failure: Impact of adherence.

BACKGROUND: Depression affects nearly half of patients with heart failure (HF), which is associated with increased morbidity and reduced health-related quality of life (HRQoL). This secondary per-protocol analysis of a previously published randomized trial evaluated the behavioral activation (BA) versus antidepressant medication (MEDS) among patients with depression and HF who adhered to study interventions. METHODS: This analysis is based on a pragmatic randomized comparative-effectiveness trial conducted from 2018 to 2022, with a 1-year follow-up. 416 participants diagnosed with HF and a DSM-5 depressive disorder were randomized to BA or MEDS, and the current analysis examined outcomes according to treatment adherence. OUTCOMES: The primary outcome was depressive symptom severity (PHQ-9) at 6&#xa0;months, and the secondary outcomes were physical and mental HRQoL (SF-12v2-PC and SF-12v2-MC, respectively) and HF-specific HRQoL (Kansas City Cardiomyopathy Questionnaire; KCCQ) overall and clinical scores (KCCQ-OS and KCCQ-CS), at 3, 6, and 12&#xa0;months. High adherence was defined as completion of >75-100% of intervention components. Overall adherence rates were similar between BA and MEDS. At 6&#xa0;months, among patients with >75-100% adherence who followed treatment as directed in both arms, BA was associated with higher Mental HRQoL (SF-12v2-MC: 5.22; 95% CI: 0.72 to 9.72; p&#xa0;=&#xa0;0.023) and higher HF-specific HRQoL (KCCQ-OS: 16.08; 95% CI: 7.20 to 24.97; p&#xa0;<&#xa0;0.001); (KCCQ-CS: 16.04; 95%CI: 7.05 to 25.02; p&#xa0;<&#xa0;0.001) compared to MEDS. There were no significant differences in depressive symptoms or physical HRQoL at 6&#xa0;months. INTERPRETATION: Both BA and MEDS were equally effective treatments for depression in HF. However, among highly adherent patients, BA was associated with greater improvements in mental and HF-specific HRQoL than MEDS. FUNDING/SUPPORT: The study was funded by PCORI Award Number: 2017C2-7716.

Humans

Infertility treatment in women with epilepsy: A systematic review.

BACKGROUND: The impact of assisted reproductive technologies (ART) on seizure control in women with epilepsy remains incompletely understood. METHODS: A systematic review was conducted according to PRISMA guidelines. EMBASE, MEDLINE, CINAHL, Scopus, and the Cochrane Library were searched from inception to March 2025. Eligible studies included observational studies and case-based reports involving women undergoing infertility treatment. RESULTS: A total of 1216 publications were identified, of which four studies met the inclusion criteria, including case reports, a case series, and a cohort study. These studies included 16 women aged 25-46&#xa0;years undergoing infertility treatment, all but one of whom had epilepsy. Interventions involved in vitro fertilization (IVF), ovulation induction, and hormonal therapies. Patients were treated with a range of antiseizure medications (ASMs), including carbamazepine, clobazam, lamotrigine, levetiracetam, oxcarbazepine, valproate, and zonisamide, either as monotherapy or in combination. Seizure frequency was generally stable, with most patients maintaining baseline seizure control. Seizure exacerbations were uncommon and primarily associated with hormonal therapy and reduced ASM levels, particularly reduced lamotrigine levels. Reported events included breakthrough seizures in the setting of decreased lamotrigine concentrations, seizure clusters associated with follitropin beta, and a new-onset seizure following dehydroepiandrosterone exposure. Across studies, multiple ART attempts resulted in live births with different ASM regimens, as well as in patients not receiving ASMs. CONCLUSION: Available evidence suggests that ART is feasible in women with epilepsy, with most patients maintaining stable seizure control. Hormonal therapy may affect ASM pharmacokinetics and seizure threshold, thereby warranting close monitoring. Larger prospective studies are needed to better define ASM-specific effects and optimize care.

Humans

Innovation-related perception as a key driver of alternative protein acceptance: evidence from an early-stage model for cultivated meat and algae-/microalgae-based alternative protein products in Italy.

Alternative proteins are increasingly considered part of the transition toward more sustainable food systems, yet their diffusion depends critically on consumer acceptance. This study investigates the early-stage acceptance of two alternative protein categories in Italy-cultivated meat and algae-/microalgae-based alternative protein products. Focusing on the first three phases of acceptance, the analysis examines how innovation-related perception (IRP) shapes consumer perceived value (CPV), consumer perceived risk (CPR), and subsequent affective (AFF), cognitive (COG), and conative (CON) responses. Data were collected through an online survey administered to 238 Italian respondents and analysed using partial least squares structural equation modelling (PLS-SEM). The results show that IRP is the main upstream driver of early-stage acceptance in both product domains: more favourable perceptions strongly increase perceived value and reduce perceived risk. In turn, CPV exerts a much stronger influence than CPR on both affective and cognitive attitudes. A tentative cross-model comparison suggests only a descriptive variation in the final transition toward conative acceptance: affective and cognitive responses were both significant in the two models, with a relatively larger affective coefficient for cultivated meat and more balanced coefficients for algae-/microalgae-based products. Overall, the findings support a process-based interpretation of alternative protein acceptance and highlight the central role of innovation-related perception in shaping early consumer responses. These results provide relevant implications for communication strategies, product positioning, and policy actions aimed at improving the acceptability of alternative proteins in food cultures characterised by strong culinary traditions.

Italy