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Alpha-band default mode network (DMN) connectivity declines with aging and Alzheimer's disease (AD), yet most electroencephalography (EEG) connectivity studies used pairwise (two-order) measures, such as mutual information rate (MIR). We leveraged O-information rate (OIR) to quantify three-order interactions and to separate redundant from synergistic information processing across frontal, temporal, and parietal DMN regions. We hypothesized that, extending established findings of reduced pairwise connectivity, (i) OIR (and its components) would be reduced in older versus younger adults and in AD versus healthy controls (HC); (ii) combining MIR with OIR would improve classification compared with MIR alone; and (iii) OIR measures would correlate positively with global cognition (as assessed by the Montreal Cognitive Assessment (MoCA)). Resting-state EEG from two samples-healthy adult lifespan aging (95 younger; 93 older) and AD spectrum (44 HC; 84 amnestic mild cognitive impairment [aMCI]; 41 AD)-was source-localized using eLORETA to DMN regions. Alpha band (8-13 Hz) MIR and OIR were computed through multivariate spectral analysis. Group differences were tested using t-tests or analysis of covariance (ANCOVA) with multiple comparison correction. Classification (OIR, MIR, demographic, and combined feature sets) used cross-validated logistic-regression, linear-SVM, and random-forest models, with bootstrap 95% confidence intervals and DeLong tests for AUC comparisons. OIR and its redundancy component were significantly reduced in older versus younger adults and in AD versus HC/aMCI, with no HC-aMCI differences. The synergy component showed no group differences. MIR decreased broadly with aging and fronto-parietally in AD. Regarding classification (AD spectrum dataset, cross-validated AUC), OIR-based metrics outperformed MIR (AD vs. HC: 0.93 vs. 0.73; AD vs. aMCI: 0.93 vs. 0.71; aMCI vs. HC: 0.48 vs. 0.46). Combining demographics with all information-theoretic features improved AD vs. HC (0.98; DeLong p = 0.023) but not AD vs. aMCI (0.93), where OIR alone was already at ceiling; no feature set exceeded chance for aMCI vs. HC. After correction, OIR and its redundancy component correlated positively with MoCA scores; MIR and the synergy component did not. Alpha-band three-order DMN interactions-particularly redundant information processing-decline with aging and AD and provide additional information beyond two-order connectivity for diagnostic classification. OIR offers complementary measures to traditional metrics, and future studies should examine its value when combined with more established AD biomarkers.

Follow-up of pre-licensure trial participants potentially informs a vaccine's long-term safety profile. This prospective study enrolled participants from the first clinical trials of ChAdOx1 nCoV-19 vaccine, many of whom subsequently received COVID-19 vaccines in the UK vaccination programme. Serious adverse events (SAEs) and adverse events of special interest (AESIs) were captured. AESI selection was based on Brighton Collaboration definitions. Between September 2021 and April 2022, 4470 participants enrolled (58% female, median age 50 years); 3845/4470 (86.0%) completed the study. Median follow-up was 11.77 months; total follow-up was 48,116 person-months. There were 174 SAEs and 71 AESIs (33 events recorded as both) in 195 participants, including 5 deaths. Immunology data were available for a small subset of participants; total IgG against trimeric SARS-CoV-2 spike protein tended to increase during the study. Although no emergent safety signals were detected, continued post-marketing surveillance remains imperative, particularly for neurological disorders. 2021-003382-36.

Lung cancer remains the leading cause of cancer deaths worldwide, and has persistent disparities in detection, treatment, and survivorship. Navigators, including nurses, allied health professionals, and community health workers, are central to addressing these challenges by guiding patients through care pathways and improving access to timely, high-quality care. Yet, navigators receive little lung cancer-specific training, leaving a gap in workforce preparation. How do lung cancer navigators perceive the impact of a lung cancer- specific educational workshop on their knowledge, confidence, job satisfaction, role effectiveness, and multidisciplinary care contribution? We developed the Lung Cancer Navigator Workshop, a professional development program providing lung cancer-specific education. An expert advisory board guided key curriculum content considerations, focusing on evidence-based topics such as screening, diagnosis, biomarker testing, treatment, survivorship, and stigma. The Workshop was delivered in person through didactic sessions, supplemented by optional asynchronous content. Program evaluation included immediate post-workshop testing and a nine-month follow-up survey assessing perceived changes in key outcomes. A total of 217 participants completed the Workshop. Evaluation results showed significant knowledge acquisition and sustained impact. At nine-month follow-up, more than 80% reported meaningful benefits across areas. Participants described improvements in their work, including expanding screening, standardizing diagnostic pathways, integrating risk assessments, and adopting stigma-reducing communication. Improvements were also observed in confidence and job satisfaction. Participation in a lung cancer-specific navigator training program was associated with sustained improvements in knowledge and professional outcomes. Targeted training can strengthen the navigator workforce, reduce disparities, advance care coordination, and improve outcomes.

Despite the continued absence of a definitive biomarker for irritable bowel syndrome (IBS), research over the last three decades has identified a wide range of underlying pathophysiological abnormalities. Peripheral mechanisms include gastrointestinal infection, changes in the gut microbiome, visceral hypersensitivity, increased intestinal permeability, low-grade mucosal inflammation and altered immune function, abnormal gastrointestinal motility, and the role of serotonin, bile acid metabolism, and carbohydrate metabolism. Central mechanisms include psychological health and altered central pain processing. These central and peripheral mechanisms can act in an integrated way to cause IBS symptoms, via the gut-brain axis, supporting the concept of IBS as a disorder of gut-brain interaction. Some mechanisms can be quantified using validated tests and questionnaires, including abnormal bile acid metabolism, accelerated colonic transit, and psychological comorbidity. However, more work is needed to translate most mechanisms into reliable tests able to identify specific targets for treatment. This Review discusses the current understanding of the pathophysiology of IBS in terms of peripheral, central, and integrated mechanisms.

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Prefrontal theta burst stimulation (TBS) - induced brain activation may offer insights into the therapeutic mechanisms underlying TBS. This study aimed to compare baseline TBS-induced prefrontal hemodynamic responses in individuals with major depressive disorder (MDD) and healthy controls (HCs), and to evaluate whether changes in stimulation-evoked responses are correlated with improvements in depressive symptoms following four weeks of daily TBS. Both MDD (n = 44; 70% females) and HCs (n = 45; 60% females) underwent a concurrent TBS/functional near-infrared spectroscopy (fNIRS) paradigm. MDD participants further received 20 sessions of intermittent TBS (iTBS) of the left dorsolateral prefrontal cortex, followed by post-treatment TBS/fNIRS measurements. TBS-evoked hemodynamic responses were analyzed using repeated-measures ANOVA and t-tests. Additionally, correlation analyses were conducted to assess the relationship between depressive symptom changes and prefrontal hemodynamic response changes following treatment. Significant increases in deoxyhemoglobin concentrations were observed both during and after TBS. However, no significant differences in TBS-induced hemoglobin responses were found between MDD participants and HCs. Notably, changes in individual TBS-induced hemodynamic responses after treatment significantly correlated with symptom reductions (r = -0.488, p = 0.037). These findings suggest that TBS-induced hemodynamic responses may reflect underlying neural changes that are functionally relevant to symptom improvement, highlighting their potential as neuroimaging markers for treatment monitoring in depression.

Lung metastases in patients with metastatic rhabdomyosarcoma (RMS) have not been treated uniformly across Europe. This provides comparison of the impact of whole lung irradiation (WLI). Lung-metastatic patients included in the Cooperative Weichteilsarkom Studiengruppe-IV 2002, European Pediatric Soft Tissue Sarcoma Study Group MTS 2008 or the Soft Tissue Sarcoma Registry received four- or six-drug chemotherapy, surgery, and/or irradiation (radiotherapy) of the primary tumor. Treatment of lung lesions consisted of metastasectomy, WLI, or no local treatment according to protocols. A total of 238 patients with lung-metastatic RMS were included. Half of these patients (n = 119/238) had lung metastases only (median age, 6.6 years), mainly classified as embryonal RMS (n = 93/119, 78%). Lung-only patients underwent metastasectomy (n = 17) and/or WLI (n = 31) or no local treatment of lung metastases (n = 71). Early complete response of lung metastases was associated with favorable 3-year overall survival (p = .009). A trend toward improved event-free survival after WLI could be identified in patients ≥10 years old (hazard ratio [HR], 2.7; 95% CI, 0.8-9.6), but not in patients under 10 years old (HR, 0.86; 95% CI, 0.44-1.66). Lung-relapse-free survival (lung-RFS) was not influenced by WLI or metastasectomy in the univariable and multivariable analyses. When analyzing all lung-metastatic patients (including those with metastases in other sites, n = 238), WLI in patients older than 10 years was a significant prognostic factor (HR, 2.2; 95% CI, 1.0-4.9). The analysis failed to show a significant benefit of WLI in patients with lung-metastatic RMS, apart from the subgroup of patients older than 10 years. Lung-RFS was not influenced by WLI.

Cellular senescence is a hallmark of ageing and age-related disease and is closely associated with mitochondrial dysfunction and the accumulation of DNA damage. However, the contribution of mitochondria-nucleus communication, mitochondrial quality control (mtQC) and stress signalling to senescence remains incompletely understood. Here, we investigated the interplay between mtQC pathways and cellular stress responses in DNA damage-induced senescence using mouse embryonic fibroblasts (MEFs). MEFs deficient in the mitochondrial protease HtrA2 (proteostasis), the transcription factor Chop (integrated stress response; ISR) or the mitophagy regulator Pink1 were exposed to three mechanistically distinct DNA-damaging agents: bleomycin, etoposide and doxorubicin. Senescence was characterised using multiple complementary markers, including the proportion of high senescence-associated β-galactosidase-positive cells, nuclear size, total and nuclear p21 abundance, and transcriptional analysis of p16, p21 and genes associated with cell-cycle regulation and stress signalling. Mitochondrial dysfunction through mtQC impairment enhanced sensitivity to senescence with HtrA2 and Pink1 loss promoting increased senescence under DNA damage. Although DNA damage response (DDR) was activated as seen by changes in p21 homeostasis, this did not always correlate with senescence levels, which indicates that DDR alone cannot account for all senescence characteristics. The ISR played a modulatory role in the senescence induction, with Chop loss of function reducing senescence induction following DNA damage despite DDR activation. The different DNA damaging drugs produced different senescence outcomes, thus highlighting the importance of the stressor context in addition to the cellular homeostasis mechanisms in the overall senescence profile. This approach allowed, for the first time, to identify senescence subtypes dependent of mtQC and ISR integrity in the context of genotoxic stress.

To offer clinicians recommendations concerning breast cancer follow-up and surveillance after primary treatment. ASCO convened an Expert Panel to develop recommendations based on a systematic review and a formal consensus process. One randomized controlled trial (RCT) was identified and formed the evidentiary basis for the surveillance mammography guideline recommendation. No RCTs were identified that evaluated different follow-up approaches by risk of relapse in patients treated for early-stage breast cancer. Given the dearth of evidence identified in the systematic review of the literature, formal modified Delphi consensus-based recommendations were generated. The guideline offers recommendations on the role of a risk-based approach to the frequency and intensity of follow-up among patients with breast cancer in the adjuvant setting. Regular history, physical examination, and mammography are recommended for breast cancer follow-up. Either virtual or in-person visits can be offered. Certain patients at high risk of cancer recurrence warrant closer surveillance, such as those patients with locally advanced disease or residual disease following neoadjuvant chemotherapy. Recommendations on the use of blood-based biomarkers and supplemental imaging are provided. Guideline recommendations will be updated once additional evidence-based tools become available to better individualize surveillance.Additional information is available at www.ascopubs.org/topics/asco-guidelines/breast-cancer.

Genetically encoded nanomaterials enable the control of molecular composition and function, yet the use of the biosynthetic bacterial lipidation pathway to build hybrid protein/lipid nanostructures has not been reported. Here, we designed a versatile bacterial lipoprotein, named LipoCatch, for modular nanostructure formation. Lipidation was achieved by appending a signal peptide to the protein-encoding gene of SpyCatcher from the SpyCatcher/SpyTag protein/peptide binding pair. This protein was biosynthetically produced in E. coli and purified in the presence of detergent. LC-MS, SEC, DLS, and TEM confirmed site-specific lipidation and formation of nanoparticles with an average diameter of 13 nm. We show that LipoCatch supports two orthogonal functionalization strategies: (1) covalent modification through the SpyCatcher/SpyTag system and (2) the non-covalent incorporation of phospholipids that permits the tuning of particle size and compositions. Finally, stability studies show LipoCatch and hybrid LipoCatch/phospholipid nanostructures are tolerant to lyophilization, in contrast to phospholipid-only liposomes. Together, this proof-of-principle study establishes an engineered bacterial lipoprotein, LipoCatch, as a genetically encoded platform for building customizable bacterial lipoprotein-based biomaterials.

Cushing's Disease (CD) is caused by pituitary adenomas, leading to hypercortisolism. This condition burdens patients socioeconomically, with a reduced quality of life and higher mortality. Transsphenoidal surgery (TSS) is the first-line treatment, offering a 78% remission rate. This study aims to identify factors influencing TSS outcomes to find the predictors of remission for improved treatment planning.&#xa0;A systematic search of electronic databases was performed based on the PRISMA guideline. Studies were selected if they reported data on remission and non-remission groups. A comparative meta-analysis was performed based on the variable type. This review included 11,666 patients treated with TSS for CD, with a remission rate of 73.88%. The mean age was 39.1 years, predominantly female (75.21%), with an average follow-up of 53.29 months. Remission rates were higher in patients with positive MRI results (78.47% vs. 66.11%, P&#x2009;<&#x2009;0.01), microadenomas (79.16% vs. 64.70%, P&#x2009;<&#x2009;0.01), without cavernous sinus invasion (78.50% vs. 47.54%, P&#x2009;<&#x2009;0.01), first-time TSS (81.98% vs. 63.80%, P&#x2009;<&#x2009;0.01), selective adenectomy surgery (81.24% vs. 64.54%, P&#x2009;<&#x2009;0.01), and positive adenoma pathology (80.37% vs.54.65%, P&#x2009;<&#x2009;0.01). Patients who achieved long-term remission exhibited significantly lower immediate post-operative serum cortisol, Adrenocorticotrophic Hormone (ACTH), and urinary-free cortisol (UFC) levels. The risk of bias was low across most studies. Our systematic review and meta-analysis demonstrate MRI findings, histopathology, tumor size, post-operative cortisol, ACTH, UFC, tumor invasion, and repetition of surgery as predictors of remission. These factors should be considered in patient selection for TSS to maximize clinical benefits.

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ALK-negative anaplastic large cell lymphoma (ALCL) is a rare primary central nervous system lymphoma (PCNSL). Although DUSP22 rearrangement is considered favorable in systemic ALK-negative ALCL, survival remains poor in PCNSL. We report a case of PCNSL ALK-negative ALCL with DUSP22-IRF4 rearrangement and an unusual gain of the ALK gene (2p23), complicated by transaminitis, treated with high-dose methotrexate followed by whole-brain radiation therapy, achieving durable remission exceeding 3 years. To our knowledge, this is the first reported case in the CNS setting, suggesting that DUSP22 rearrangement and ALK gain may confer a favorable prognosis. The authors have confirmed clinical trial registration is not needed for this submission.

Freezing of gait is a debilitating walking disturbance that can severely worsen quality of life for people with Parkinson's disease. However, current Parkinson's disease treatments do not effectively address freezing of gait, leading researchers to explore cueing to mitigate the symptom. Somatosensory stimulation is an emerging cueing strategy that could be discreet and practical to mitigate freezing of gait duration. Twenty-six participants (seven females) attempted walking trials in a freeze-inducing path while wearing a functional electrical stimulation cueing device. Functional electrical stimulation cueing was activated autonomously in real time. Constrained random sampling was used to designate each trial as cueing system on or off, providing a control for within-participant analysis. A total of 576 freezing episodes were recorded with the device on. Of those, 492 were successfully stimulated. To assess cueing performance, freezing of gait time per trial in the on and off device states was calculated for each participant. On average, freezing of gait time per trial decreased from 5.84 to 5.69&#x2009;s (2.44%). Freezing of gait time per trial increased for half the participants and the other half experienced a decrease. There were no statistically significant group-level effects, though electrical stimulation cueing elicits a wide range of responses from different participants, with the technology mitigating freezing of gait for some individuals. Because functional electrical stimulation has numerous modifiable parameters that influence sensation and nervous system response, personalizing these parameters could enhance the effectiveness of freezing of gait mitigation and provide deeper insights into freezing of gait.

Women in the perimenopause need individualised advice to meet their specific health needs. Health needs may include the management of unscheduled bleeding, perimenopausal symptom control, and provision of contraception. Although the benefits of intra-uterine hormonal devices are well established to manage abnormal bleeding, provide contraception, and progestogenic opposition for hormonal replacement therapy, there are many women who choose not to use these methods. This article presents three cases of women presenting in the perimenopause where alternative medical management is offered with newer hormonal therapies: Drovelis, Dydrogesterone and Dienogest. In each case, consideration is made to the management of bleeding, perimenopausal symptom control, and provision of contraception.

Epidemiological and phylogenetic evidence linking raw meat and raw dog food (RDF) feeding with dogs shedding antibiotic-resistant (ABR) Escherichia coli is strong. However, evidence for close phylogenetic relatedness between E. coli from meat/RDF and those causing opportunistic human infections is limited, partly due to non-contemporaneous sampling. Here, we characterised ABR E. coli from meat/RDF in Bristol, UK in 2022/23, and measured their phylogenetic relatedness to isolates causing human urinary tract and bloodstream infections in Bristol in 2023. We monitored ABR E. coli positivity in raw chicken, beef, pork and lamb from 15 large-chain stores and chicken-based RDF from 15 pet stores, selecting 200 E. coli for Illumina WGS. E. coli causing 1,182 human infections were sequenced, irrespective of resistance phenotype. Significant phylogenetic relatedness between meat and RDF E. coli was observed, consistent with common supply-chain origins. Phylogroup A/B1 and B2 E. coli dominated meat/RDF and human isolates, respectively. Resistance to antibiotics predominantly used in farmed animals dominated meat/RDF isolates; resistance to antibiotics extensively used in humans dominated human isolates. Four meat/RDF-infection E. coli pairs (three ST69 and one ST117) differed by <20 core-genome SNPs, representing 2% of meat/RDF and 0.2% of human infection-causing E. coli. Each ST69 meat/infection pair member carried identical antibiotic resistance genes. Using contemporaneous, geographically focussed sampling, close phylogenetic relatedness between meat/RDF and human infection isolates was identified but was rare. Whilst transmission and risk cannot be inferred, these findings support the integration of raw meat and RDF into One Health ABR surveillance structures.

Delirium is a serious condition characterized by an acute change in attention, arousal, and sleep disturbance. It is common in inpatients with Parkinson disease (PD) but is frequently missed or misidentified due to overlapping symptoms, such as cognitive impairment, hallucinations, and sleep disturbances. While clinical tools often measure only a snapshot of delirium, wearable devices could facilitate the identification and ongoing monitoring of delirium, including continuous assessment of activity and sleep patterns, which are frequently disrupted. Establishing feasibility is essential before wearable technologies can be implemented in routine clinical care. This study aimed to determine the feasibility and acceptability of using wearable devices in inpatients with PD, with and without delirium. Participants were recruited from an ongoing prospective cohort study comprising inpatients with PD. Delirium was diagnosed using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria and assessed daily. Participants were invited to wear Axivity AX6 devices attached to their lumbar region (lower back) and/or wrist for up to 7 days. Feasibility was assessed in terms of recruitment, device placement, nonsecurement, wear time, and compliance. Acceptability, practicality, and clinical constraints were recorded and compared between groups. Participants were predominantly older adults with advanced PD and high levels of frailty and cognitive impairment. The wearable device recruitment rate was 75.4% (46/61), comprising 68 admissions. Delirium was identified in 64.7% (44/68) of admissions. The wrist-worn device showed greater participant acceptability, with 98.5% (67/68) of participants wearing a device on the wrist compared to 38.2% (26/68) of participants wearing a lumbar device (25/68, 36.8%, wore both). Wrist placement was more practical, rated as "somewhat" or "very easy" to secure in 95.5% (64/67) of cases compared to 69.2% (18/26) for lumbar placement (P<.001). Clinical constraints such as injury or pain and low level of arousal were associated with lumbar nonsecurement. These findings indicate that wrist-worn devices are more practical and acceptable in acutely unwell patients. Wear time compliance for both placements tended to be lower in delirium cases but comparable overall (>83% for each location, P>.05). This is the first study to evaluate the feasibility of using wearable devices in inpatients with PD with and without delirium. Wearable devices were feasible, and the wrist-worn devices demonstrated greater participant acceptability and practicality, with fewer clinical constraints. These findings provide important guidance for the design and implementation of future digital health studies in this population and may ultimately support earlier recognition and management of delirium while enabling continuous, objective monitoring of delirium-related changes not captured by standard clinical assessments.

Biomechanical studies have shown that non-spherical (NS) humeral head designs in total shoulder arthroplasty (TSA) may provide superior restoration of native anatomy, improved mechanics, and enhanced stability when compared with spherical heads. This systematic review critically evaluates the literature on NS designs in anatomic TSA. Following the PRISMA guidelines, PubMed, Cochrane, and Google Scholar (pages 1-20) were searched from inception till November 2025. Extracted data included biomechanical data such as glenohumeral kinematics, range of motion (ROM), anatomic replication, contact mechanics, and coverage, and clinical data such as radiographic outcomes, ROM, patient-reported outcome measures (PROMs), and implant-related complications. Twelve biomechanical and nine clinical studies comprising a total of 647 patients were included. Most of the biomechanical data were contradictory with some studies reporting no differences in the assessed outcomes between the designs, while most reported it to be better in NS head designs. Coverage was uniformly reported to be better with NS head designs. As for clinical data, radiographic outcomes, ROM, and PROMs all improved post-operatively with one study reporting better ROM in patients with NS TSA compared to the standard TSA. Biomechanical and clinical data report similar and sometimes improved outcomes in using non-spherical head designs for TSA. III.

Autistic adults experience significant physical and mental health inequities yet remain underrepresented in clinical research, with few randomised controlled trials to guide care. Randomised controlled trials (RCTs) of selective serotonin reuptake inhibitors (SSRIs) are limited, underpowered, and rarely focused on anxiety. Anticipating recruitment challenges in a large RCT ("STRATA") evaluating sertraline for anxiety in autistic adults, we embedded qualitative research to support recruitment, retention, and monitoring trial acceptability. We organised our findings into the theoretical framework of acceptability (TFA) constructs to assess the acceptability of trial design and delivery for autistic adults. We conducted 64 interviews with autistic adults at different trial stages. Data were analysed thematically and mapped to the seven TFA constructs. Participants considered involvement in a blinded medication RCT acceptable across the TFA domains, which they weighed differently when reflecting on anticipated versus experienced aspects of participation. STRATA was a low-burden, ethically sound, and methodologically coherent study for most participants, who reported minimal trade-offs, potential benefits, and self-efficacy in managing anxiety and research participation. Acceptability of trial participation is dynamic and multidimensional, which can be enhanced by meaningful involvement of autistic people throughout the research cycle, accessible participant information design, and responsive ongoing engagement.Lay AbstractAutistic adults often experience poorer physical and mental health than the general population. Yet they are rarely included in clinical research. There have been very few high-quality studies (RCTs) testing medications for anxiety in this group. Most existing studies are small and focus on other outcomes. They don't provide clear guidance for care. To help address this gap, the STRATA trial tested whether the medication sertraline (an SSRI) can reduce anxiety in autistic adults. Recruiting participants for such trials can be challenging. We included a qualitative study to better understand what helps or hinders people from joining and staying in the trial. We aimed to explore what aspects of the STRATA trial made it easier or more appealing for autistic adults to take part. We used a framework called the theoretical framework of acceptability (TFA) to define acceptability in this context. We interviewed 64 autistic adults at different stages of the trial, including 2 who chose not to take part. Most participants found the trial acceptable when assessed against the seven aspects of the TFA (i.e., how someone feels about taking part, how much effort is needed, whether taking part fits with a person's values, how well someone understands the study, what someone may have to give up, whether the study is likely to help, and how confident someone feels about taking part). In summary, they felt positive about taking part. They thought the study was ethical and easy to understand and believed it could benefit them. Many also felt more confident in managing their anxiety and contributing to research. STRATA is one of the largest studies of its kind; 318 autistic adults took part across the United Kingdom and Australia. The trial had a very high retention rate. Ninety-two per cent of participants stayed until the main outcome point, and 87% completed the full 52&#x2009;weeks. How acceptable clinical trials like STRATA are may change during their course, and researchers need to be responsive. To do this well, researchers should involve autistic people meaningfully throughout the research process and from an early stage. Researchers also need to respect individual communication needs and provide clear and accessible information. These approaches were central to STRATA and supported by other studies.