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Plain language summaryCelebrating the legacy of two decades of Parkinson's disease research in South AfricaParkinson's disease (PD) has been well-studied in Western Countries, but there are far fewer studies in other parts of the world, especially in Africa. This lack of research is partly because there are insufficient neurologists in many African countries, leading to missed or incorrect diagnoses. Stigma around PD and the absence of national disease registries also make research more difficult. To help fill this gap, our team has spent the past 20 years studying PD in South Africa. We have built a collection of almost 2,000 South African participants and report our main findings here. Overall, we found only 20 PD-causing variants in our collection of 689 unrelated PD cases. Interestingly, some of these genetic findings appear to be unique to South Africans, likely due to the unique genetic composition of the country's population. Our functional studies showed how variants in genes, such as PRKN and LRRK2, disrupt the function of mitochondria. Mitochondria are tiny structures in cells that supply the energy required for the cells to function. Cells die when they do not have the necessary energy, potentially explaining why brain cells die in PD. A third part of our research focuses on curcumin, a natural compound found in turmeric known for its antioxidant and anti-inflammatory effects. Using cell models, including cells from individuals with PD, we found that curcumin can protect cells from damage caused by paraquat, a harmful chemical which has been linked to the development of PD. However, this rescue is only seen when curcumin is given before the damage occurs. This suggests that curcumin may help prevent neuronal loss in PD. In summary, our work adds to global knowledge about the genetics, disease processes, and possible treatments for PD. It also shows what a small African laboratory can achieve, despite limited personnel and resources. Celebrating the legacy of two decades of Parkinson's disease research in South AfricaParkinson's disease (PD) has been well-studied in Western Countries, but there are far fewer studies in other parts of the world, especially in Africa. This lack of research is partly because there are insufficient neurologists in many African countries, leading to missed or incorrect diagnoses. Stigma around PD and the absence of national disease registries also make research more difficult. To help fill this gap, our team has spent the past 20 years studying PD in South Africa. We have built a collection of almost 2,000 South African participants and report our main findings here. Overall, we found only 20 PD-causing variants in our collection of 689 unrelated PD cases. Interestingly, some of these genetic findings appear to be unique to South Africans, likely due to the unique genetic composition of the country's population. Our functional studies showed how variants in genes, such as PRKN and LRRK2, disrupt the function of mitochondria. Mitochondria are tiny structures in cells that supply the energy required for the cells to function. Cells die when they do not have the necessary energy, potentially explaining why brain cells die in PD. A third part of our research focuses on curcumin, a natural compound found in turmeric known for its antioxidant and anti-inflammatory effects. Using cell models, including cells from individuals with PD, we found that curcumin can protect cells from damage caused by paraquat, a harmful chemical which has been linked to the development of PD. However, this rescue is only seen when curcumin is given before the damage occurs. This suggests that curcumin may help prevent neuronal loss in PD. In summary, our work adds to global knowledge about the genetics, disease processes, and possible treatments for PD. It also shows what a small African laboratory can achieve, despite limited personnel and resources.

Numerous studies have examined the factors contributing to the variation in disease progression among people living with HIV-1, identifying a range of genetic, immunologic and virologic factors that interact in a complex, multifactorial dynamic. However, investigating individual susceptibility to HIV-1 infection adds an additional layer of complexity. In this observational report, we focus on the case of a man (Case-2021) who previously remained HIV-1 negative despite 35 years of self-reported high-risk sexual behavior with other men while enrolled in the MACS/WIHS Combined Cohort Study (MWCCS). To understand why this individual stayed free of HIV-1 infection for so long and what led to his eventual seroconversion, we examined the available genetic, immunologic, and virologic laboratory data before and two weeks after his diagnosis of HIV-1 infection and initiation of antiretroviral therapy (ART). In addition, we looked into two other high-risk men from same group (HR-10) who have sex with men (MSM) enrolled in the MWCCS who seroconverted later in their enrollment. Furthermore, we performed similar laboratory tests to assess the effect of seasonal variations on blood biomarkers from the same clinical visit as Case-2021, including one individual who already was living with HIV-1 and another who has remained seronegative throughout their enrollment in the MWCCS. In conclusion, this Case-2021 observational report suggests that resistance to HIV-1 infection is likely multifactorial, involving high risk sexual behavior, HIV-1 variants, the genomic structure of the CCR5 receptor on CD4+ T cells, and age-related immune changes. Further study is needed to investigate both the genomic protective factors of CCR5 against HIV-1 infection and these age-related immune changes.

Diastolic dysfunction is an important early indicator of heart failure (HF) with preserved ejection fraction (HFpEF). Type 2 diabetes mellitus (T2DM) may contribute to HFpEF, as it is associated with an increased risk of hospitalization and mortality. To investigate the association between diastolic dysfunction and T2DM in an adult population from Liverpool, accounting for age and sex. A retrospective review of 493 patient records was conducted, extracting data on diastolic function status, diabetes status, age, and sex. Echocardiographic parameters were used to assess and grade diastolic function according to the 2016 ASE/EACVI recommendations. Diastolic dysfunction was more prevalent in type 2 diabetics (71.42%) than non-diabetic patients (43.98%) (P&#x2009;<&#x2009;.05). The odds ratio of developing diastolic dysfunction was 2.636 times higher in diabetics, with 2.56 times greater odds of a higher dysfunction grade (P&#x2009;<&#x2009;.001). Age &#x2265;65&#xa0;years was associated with 4.65 times higher odds of having diastolic dysfunction, with no significant difference between genders. This retrospective cohort study demonstrates a clear and statistically significant association between T2DM, advancing age and diastolic dysfunction. This association, however, should be interpreted within the context of a clinically selected population undergoing echocardiography. Due to the metabolic alterations that are associated with diabetes and the pathophysiology of HFpEF, there is a great potential for the use antidiabetic therapies as cardioprotective agents aimed at reducing HF morbidity and mortality. Considering these results, we propose incorporating diabetes into the H2FpEF score. Key messages What is already known on this topic - the development of heart failure with preserved ejection fraction (HFpEF) has long been associated with type 2 diabetes mellitus (T2DM), with the recognition of diastolic dysfunction as an early marker of disease progression. However, data describing the relationship between diabetes and diastolic dysfunction in specific local populations remains limited. What this study adds - this study provides data from a Liverpool tertiary centre showcasing significantly higher prevalence and severity of diastolic dysfunction in patients with type 2 diabetes. These findings produce locally relevant epidemiological evidence that supports the association between diabetes and diastolic dysfunction. How this study might affect research, practice or policy - the findings of this study highlight the importance of cardiovascular assessment in patients with type 2 diabetes in certain populations with a high burden of diabetes, such as Liverpool, and may support earlier identification of individuals at risk of developing HFpEF. Future research might consider incorporating T2DM into the H&#x2082;FPEF score, to improve early risk stratification.

Cystic fibrosis (CF) results from mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, causing multisystem disease and impaired quality of life. CFTR modulators have improved pulmonary and nutritional outcomes, yet potential metabolic effects such as dyslipidemia remain a concern, particularly in adults. Pediatric data are limited. This study evaluated the effects of CFTR modulators on lipid and lipoprotein profiles in children with CF. This retrospective study was conducted at a tertiary pediatric pulmonology center. Body mass index (BMI) Z-scores, lung function tests, and serum lipid profiles were compared between baseline and six months after initiation of CFTR modulator therapy. Twenty-six patients were included finally. The median age was 11 (5.9-15.6) years; 53.8% were female, and 80.8% received elexacaftor/tezacaftor/ivacaftor. After six-month therapy, significant improvements were observed in BMI (p&#x2009;=&#x2009;0.047), FEV&#x2081; (p&#x2009;=&#x2009;0.005), and FVC Z-scores (p&#x2009;=&#x2009;0.001). Although HDL, LDL, VLDL, triglycerides, and total cholesterol increased numerically, none reached statistical significance. No difference was found between BMI changes and lipid alterations. Over six months of continuous CFTR modulator therapy, we observed improvements in pulmonary and nutritional outcomes without evidence of clinically meaningful lipid deterioration. This study adds real-world pediatric data regarding lipid profile changes during CFTR modulator therapy. While these therapies significantly improve pulmonary and nutritional outcomes, we observed no evidence of lipid deterioration over six months of treatment. These findings contribute to the evolving understanding of the systemic effects of CFTR modulators in childhood and underscore the importance of ongoing cardiometabolic evaluation as survival improves.

Aviation is a major source of greenhouse gases emission in the world, and the invention of sustainable aviation fuel (SAF) is a hope that this source of carbon footprint can be minimized. This article assesses the economic and environmental trade-offs of different feedstock routes in China to produce SAF considering the waste cooking oil (WCO), agricultural residues, and municipal solid waste (MSW). A cost-benefit analysis, conducted under explicit modeling assumptions including an 8% discount rate and 20-year project horizon, reveals WCO to be highly efficient in terms of conversion and large-scale emission cuts (up to 80%), but its economic viability is undermined by fluctuations in prices. The MSW and agricultural residues are more stable and cost-effective sources of alternative but need more complex conversion technologies to yield higher. The study identifies the considerable importance of the government policies, including subsidies and carbon prices, to make SAF production feasible. The research article adds new information to SAF sourcing in China, and the findings have practical suggestions on multi-feedstock strategies and technology to boost the scalability of SAF production. The future of the research should be to understand the socioeconomic effects, regional differences, and longitudinal research in order to enlighten policy and industry stakeholders of the area.

Background: The 2-benzylbenzimidazoles or nitazenes are an evolving class of highly potent mu-opioid receptor agonists. Nitazenes were originally developed in the late 1950s for pharmaceutical use as analgesics; however, due to their extreme potency and the risk of adverse health outcomes, pharmaceutical research was discontinued. Since 2019, nitazenes have emerged as illicit drugs of abuse, causing significant concern. From 2021, they have been detected in both coronial and clinical casework in Victoria, Australia. This study examined nitazene-related coronial casework in Victoria from 2021 to 2025 to explore the trends and characteristics of nitazene-related deaths. Methods: Relevant cases were identified from the Victorian Institute of Forensic Medicine's (VIFM's) case management system. Data were collated and analysed from all coronial cases where a nitazene was detected by a toxicological analysis between 1 January 2021 and 31 December 2025. Trend comparisons were made with nitazene detections reported in other countries. Results: Nitazenes were detected in 23 deaths from a total of approximately 33,108 coronial cases admitted to the VIFM for investigation over the time period. The age range was 17-45 years, with a median of 32 and with 87% of the deaths being male. The nitazenes detected were protonitazene (n = 14), metonitazene (n = 5), isotonitazene (n = 2), N-pyrrolidino etonitazene (n = 2), N-desethyl isotonitazene (n = 1), methylenedioxynitazene (n = 1) and etodesnitazene (n = 1). Two cases contained more than one nitazene; both involved protonitazene, one involved metonitazene, and the other involved N-desethyl isotonitazene and methylenedioxynitazene. The timeline of detection of these nitazenes displays similarities with emergence trends in other countries. The nitazene concentrations ranged from 0.1 to 33 ng/mL. Broad polydrug usage was evident in all cases, with other drugs co-detected in the blood including stimulants (particularly, methylamphetamine (48%) and cocaine (44%)) as well as pharmaceutical benzodiazepines (43%) and pharmaceutical opioids (22%), and 13% had 6-monoacetylmorphine detected in either blood or urine. Novel benzodiazepines (39%) were also common, including bromazolam, which was co-detected in 35% of cases. Nineteen deaths were attributed solely to nitazene-related mixed-drug toxicity, while the remaining four cases were attributed to cardiac- and pulmonary-related disease, with polydrug use deemed a contributing factor. Conclusions: This novel case series adds comprehensive toxicological information to the body of evidence reinforcing the high risk of harm associated with the use of nitazenes. It is imperative that toxicology services continue to monitor for nitazenes to promote community awareness against nitazene-related harm.

Our understanding of sex differences in reward learning has been limited due to the predominant study of males. Here, we evaluated sex differences in flexible learning in two domains: the learning of stimulus- and action-based associations and their reversals. During action-based learning, rats selected between two identical visual stimuli presented on a touchscreen, where the spatial location predicted a higher probability of reward. For stimulus-based learning, rats chose between two distinct visual stimuli presented in pseudorandom spatial locations, one of which was associated with a higher probability of reward. Reversal phases involved switching reward contingency between the two actions or stimuli. We found that females did not differ in their discrimination or reversal learning accuracy compared to males, yet they collected fewer rewards and were more likely to omit trials than males in both domains. To gain a detailed understanding of differences across conditions, we modeled animals' trial-by-trial choices using reinforcement learning (RL) models and examined their steady-state behavior to capture transitions between distinct behavioral states. Although the estimated parameters of the best-fitting RL model revealed some sex differences, the model that incorporated transitions between different behavioral states provided a better overall fit to the data. This model also revealed that across all reversal phases, females exhibited a higher transition-specific lapse rate than males, indicating greater task disengagement once there was no need for further learning. Together, our fine-grained analysis of behavior adds to a growing literature on sex differences in flexible reward learning.

This article discusses initiatives to support young people who have experienced domestic violence. It is based primarily on a qualitative evaluation of a project directed at 16- to 24-year-old victims, ran by a non-governmental organization in England, and adds to existing knowledge by (1) providing insights into support that is not solely educational and (2) by including victims' own voices. Findings support the need for projects directed at this age group and demonstrate significant positive impact on victims' health and wellbeing, confidence and self-esteem, aspirations and resilience, interpersonal relationships, perceptions of safety, and ability to identify signs of unhealthy relationships.

Obsessive-compulsive disorder (OCD) is characterized by disturbing thoughts (obsessions) that initiate anxiety-reducing thoughts or behaviors (compulsions). For patients with treatment-resistant OCD (tr-OCD), neuromodulation techniques, like capsulotomy (a lesion in the anterior limb of the internal capsule) and deep brain stimulation (DBS), have emerged as interventions that likely regulate connectivity between the prefrontal cortex (PFC) and subcortical targets. Three patients (Cap-DBS1-3) underwent a failed capsulotomy followed by successful DBS. Here, we aimed to understand the brain connections disrupted by failed capsulotomy vs modulated by successful DBS. We used diffusion-weighted magnetic resonance imaging (dMRI) tractography in a control cohort with tr-OCD (n=12) and in two of the Cap-DBS patients themselves to determine connectivity profiles of the capsulotomy, volume of tissue activated (VTA), and potentially necessary tracts (VTA minus capsulotomy tracts). We used whole-brain, PFC-focused, and subcortically-focused tractography algorithms to fully explore the space of possible connections. Capsulotomy regions-of-interest (ROIs) connected with a variety of PFC and subcortical regions. VTA ROIs and potentially necessary tracts had limited and inconsistent PFC connectivity but substantial subcortical connectivity. While correlated to the average OCD connectome (r = 0.214, 95% CI [0.177, 0.251]; r = 0.756, 95% CI [0.739, 0.772]), the Cap-DBS connectomes had many edges that were stronger (z-score > 3). The connectivity profile of potentially necessary tracts for successful DBS treatment after failed capsulotomy revealed a surprising proportion of subcortical regions and inconsistent PFC involvement, highlighting an often-ignored set of connections that may be critical to effective DBS. What is already known on this topic: OCD has been conceptualized as a disorder of cortico-striato-thalamo-cortical (CSTC) circuits. Treatment targets have largely involved connections to the PFC.What this study adds: Our study shows that potentially necessary tracts for DBS treatment after failed capsulotomy involve connections to subcortical regions and not PFC.How this study might affect research, practice, or policy: This evidence of primarily subcortical involvement in treatment should encourage the use of more detailed subcortical atlases in neuromodulation circuit research and suggests that local circuit remodeling may be a mechanism of neuromodulatory OCD treatment.

Outcomes after radical cystectomy (RC) for non-muscle-invasive bladder cancer (NMIBC) are generally favorable, but a subset experiences recurrence and cancer-specific mortality (CSM). Tools to identify high-risk patients remain limited. This study aimed to identify predictors of recurrence and cancer-specific and overall mortality in pathological NMIBC treated with RC. Multicenter retrospective cohort of 1032 patients with pTis/pTa/pT1 N0 R0 disease who underwent RC (2000-2015) at nine centers. No patient received perioperative therapy. Recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) were analyzed using Cox and competing-risks regression. Discrimination assessed by Harrell's C-index. Median follow-up 45.2 mo. Lymphovascular invasion (LVI), present in 39 patients (3.8%), was independently associated with RFS (hazard ratio [HR], 2.37; 95% confidence interval [CI], 1.29-4.38; p =&#xa0;0.006) and CSS (HR, 2.59; 95% CI, 1.31-5.10; p =&#xa0;0.006). Pathological stage was not associated with RFS (p =&#xa0;0.074). Age predicted OS (HR 1.06; p&#xa0;<&#xa0;0.001). LVI-positive patients had higher 10-yr CSM (35.3% vs 13.7%; p =&#xa0;0.002). Discrimination was modest (C-index 0.59). Limitations include retrospective design and low LVI prevalence. In patients undergoing RC for pathological NMIBC, LVI identifies a small subgroup at increased risk of recurrence and CSM, while pathological stage adds little. These findings support LVI-guided surveillance and trial enrichment, but no treatment recommendations can be drawn.

Individuals can engage in a variety of study strategies that influence later recall. The effects can be complex and are often diagnostic of underlying memory processes. For example, producing items by reading them aloud yields a crossover pattern: Early list items are recalled more accurately when studied silently, whereas later items benefit from being read aloud. When aloud and silent items alternate within a list, this contrast produces a characteristic sawtooth serial-position curve in which aloud items form the peaks and silent items the troughs. According to the revised feature model, these interactions arise from encoding mechanisms: Production both disrupts rehearsal-primarily affecting early serial positions-and adds distinctive features that benefit later items. Crucially, because these mechanisms operate prior to retrieval and do not depend on how recall is initiated, the revised feature model predicts that the interaction between production and serial position should appear regardless of whether recall proceeds forward (from first to last) or backward (from last to first). That is, changing the output order should not undo encoding-based differences that have already shaped the memory traces. In six experiments, we tested this a priori prediction by manipulating recall direction in immediate serial recall. Consistent with expectations, the interactions associated with the production effect were observed in both forward and backward recall, despite the substantial performance differences typically observed between the two tasks. These findings are consistent with the encoding-based predictions of the revised feature model, and the model provides a principled account of the patterns observed across the experiments. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

Mutations in the MAPT gene encoding tau protein can be causative for frontotemporal lobar degeneration, FTLD-tau. Preclinical mouse models expressing these disease-causing MAPT alleles have successfully modeled biochemical and neuropathological phenomena similar to those seen in human FTLD-tau. One such model, rTg4510, features P301L human tau primarily expressed in the forebrain under the control of a Tet-off system, using the CaMKII promoter to drive transgene expression. While this model allows temporal manipulation of the transgenic tau, many experiments do not require such manipulation, and the bigenic tet-off system adds to the costs of simple transgenics, introduces additional genetic variation, and increases animal usage. Here, we have generated and characterized mice that constitutively overexpress P301L human tau under the CaMKII promoter. The initial founder and offspring were produced in the FVB/N background where we identified a line of constitutive "cTauP301L" mice that stably expresses the 0N4R isoform of P301L human tau at levels comparable to the rTg4510 mouse. The cTauP301L line features a relatively small deletion at the transgene insertion site and demonstrates no overt motor phenotype. There was, however, unexpectedly high early lethality on the FVB background that was mitigated after just one crossing to C57BL/6 mice. In both backgrounds, TauP301L expression resulted in an age-dependent accumulation of tau and gliosis that occur prominently in the forebrain and hippocampus. In transgenic F1 B6/FVB mice, spatial memory deficits were detected by 6&#xa0;months of age. Overall, this new cTauP301L model recapitulates disease-associated pathology and memory deficits, with limited disruption of the murine genome and a lack of longevity-restricting motor phenotypes. The cTauP301L mouse is a robust, new alternative to existing mouse models of tauopathy.

Chylothorax is a medical condition characterised by the abnormal accumulation of lymphatic fluid in the pleural cavity. In its congenital form, chylothorax develops as a result of an idiopathic abnormality in the thoracic duct. Congenital chylothorax (CCT) is the leading cause of pleural effusion in infants, a condition where excess fluid builds up in the space between the lungs and the chest wall. This scoping review includes a wide range of published studies from 1980 to January 2024, obtained from multiple reputable databases, including Google Scholar, PubMed, Springer and BioMed Central. Effective management strategies are crucial for improving outcomes in infants with CCT. Timely drainage of pleural fluid is essential to alleviate respiratory distress and prevent further complications. Appropriate nutritional care is also critical, as it helps in supporting the neonate's overall health and recovery. Early intervention and continuous monitoring can significantly improve the likelihood of a positive outcome. What the study adds. Congenital chylothorax (CCT) is a serious but rare condition in newborns. CCT is characterised by the accumulation of lymphatic fluid in the pleural space with subsequent respiratory distress. This scoping review of recent literature describes current concepts in the aetiology, diagnosis and treatment of CCT in newborns, emphasising the importance of timely diagnosis and a multidisciplinary strategy. The review integrates available evidence on CCT, emerging diagnostic strategies such as lymphangiography and lymphoscintigraphy, and treatments such as video-assisted thoracoscopic surgery, to provide clinicians with practice-informed choice.Implications of the findings. Early management and tailored intervention can improve results in infants with CCT. Improvements in morbidity and mortality have demonstrated the importance of new management strategies.

A 32-year-old woman with panhypopituitarism following surgical resection, chemotherapy, and radiotherapy for a pituitary germinoma underwent assisted reproductive treatment. Management involved comprehensive hormone replacement therapy, ovulation induction with exogenous gonadotropins, in vitro fertilization (IVF), and thromboprophylaxis with low molecular weight heparin due to a diagnosed thrombophilia. A fresh embryo transfer resulted in a successful singleton pregnancy. The pregnancy progressed uneventfully and reached full term and a healthy neonate was delivered. This case highlights the feasibility of pregnancy in women with complex endocrine and thrombotic conditions and adds to the limited literature supporting IVF in women with significant hypothalamic-pituitary axis compromise.

A 35-year-old female patient presenting with photosensitive erythema initially consulted a general practitioner. After a dermatological evaluation, she was diagnosed with anti-TIF1&#x3b3;-positive dermatomyositis (DM). Due to a painful axillary lymph node, further ultrasound investigation led to the diagnosis of adenocarcinoma of unknown primary origin with paraneoplastic DM, initiating a complex, interdisciplinary treatment approach. A novel approach was initiating an immunotherapy due to cancer despite a paraneoplastic autoimmune disease, which adds to the literature that immunotherapy is not generally contraindicated in these patients. The treatment protocol was found in a combination of dose-dense corticosteroids, chemotherapy, immunotherapy, surgery, and radiotherapy. The treatment protocol led to a complete remission of both DM and neoplastic disease. This case underlines the importance of an individual and careful interdisciplinary treatment protocol with regularly evaluating the therapeutic outcome of symptoms and adverse effects.

The robust Dutch rose, also known as the Rosa hybrida is distinguished by its vibrant colors, superior product quality, and extended vase life. These rose varieties, originating from Netherlands, have proven highly successful in Indian agricultural conditions and the international export industry. The dataset consists of a total of 1,995 high resolution petal image collected during this research, encompassing petal color categories, such as red, yellow, white, pink, purple, orange, bi-color, and multi-color, as well as health statuses including fresh, dry, and diseased petals. The primary purpose of this dataset is to support machine learning activities in agriculture and specifically for tasks such as automatic petal health evaluation and rose variety categorization. Although the rose flower is scientifically rich and has a wide range of industrial uses, it has not been given much attention in machine learning, especially when compared to other plant-based datasets. This study adds to the accuracy of quality assessment through the use of modern computer vision and machine learning methods, thus helping the agriculture sector, rose-based edible product making, and flavor development industries.

This systematic review and meta-analysis evaluated the fluency- enhancing effect of DAF alone in individuals with developmental stuttering. Following PRISMA 2020 guidelines, we searched multiple databases for studies published between 2000 and 2024. Eligible studies examined DAF conditions applied to speech tasks with stuttering-related outcomes. Meta-analyses were conducted using a random-effects model, with subgroup analyses by disfluency type, delay time, speech task, stuttering severity, and participant age. Of the 194 records screened, eight studies involving a total of 98 participants in total met the inclusion criteria, and five studies involving 61 participants were eligible for quantitative synthesis. Each study included 8-20 participants ranging from school-age children to adults. Most participants were male, and stuttering severity ranged from mild to severe. DAF conditions were evaluated using oral reading and spontaneous speech/monologue tasks. Meta-analysis revealed no significant overall benefit of DAF compared with normal auditory feedback (NAF; mean difference = -1.46, 95% CI [-4.83, 1.91]). DAF alone does not consistently reduce disfluencies; however, specific populations and conditions may derive greater benefits from it. Larger, well-controlled studies are needed to clarify its therapeutic potential and clinical applications. What is already known on this subject Delayed auditory feedback (DAF) has been reported to improve fluency in people who stutter and is used in several assistive devices. However, its independent effect remains unclear because DAF is often combined with other altered auditory feedback conditions. What this study adds to existing knowledge This systematic review and meta-analysis evaluated the exclusive effect of DAF on stuttering. The results indicate that DAF alone does not consistently reduce disfluency compared with NAF, although certain conditions (e.g., shorter delays or reading tasks) may show greater benefits. What are the potential or actual clinical implications of this work? Clinicians should interpret the fluency-enhancing effects of DAF cautiously when used alone. Further well-controlled studies are needed to determine which individuals and speech contexts may benefit most from DAF-based interventions.

Transthyretin amyloid cardiomyopathy (ATTR-CM) is an infiltrative cardiomyopathy that may occur in hereditary or wild-type forms. Although more than 150 transthyretin (TTR) variants have been reported, the c.128G&#x2009;>&#x2009;A (p.Ser43Asn) variant is rare, and data from Asian populations remain limited. This report describes a mainland Chinese family carrying the rare TTR c.128G&#x2009;>&#x2009;A (p.Ser43Asn) variant. The proband, a 51-year-old Chinese man, presented with exertional chest tightness and dyspnea. Electrocardiography showed left ventricular hypertrophy, while echocardiography demonstrated concentric left ventricular wall thickening, reduced systolic function, and relative apical sparing on strain imaging. Technetium-99&#x2005;m pyrophosphate [(99&#x2005;m)Tc-PYP] scintigraphy showed grade 3 myocardial uptake, and monoclonal protein assessment, including serum and urine immunofixation electrophoresis and serum free light-chain testing, did not support light-chain amyloidosis. Genetic testing identified a heterozygous c.128G&#x2009;>&#x2009;A (p.Ser43Asn) missense variant in the TTR gene. Tafamidis was initiated after diagnosis. On follow-up, the proband remained in New York Heart Association functional class II, with persistent structural cardiac abnormalities on echocardiography. Family investigation identified additional affected relatives and carriers of the same variant, supporting a hereditary pattern of disease in this pedigree. This family report expands the clinical spectrum associated with the rare TTR c.128G&#x2009;>&#x2009;A (p.Ser43Asn) variant and adds to the limited data available from Asian populations.

Independent outdoor ambulation is a key rehabilitation goal after stroke, but it is unclear whether instrumented gait analysis adds prognostic information beyond conventional clinical measures. Do spatiotemporal gait parameters provide incremental predictive value beyond clinical assessments-independent of admission Functional Ambulation Category (FAC)-for outdoor ambulation in subacute stroke patients? We retrospectively analysed 137 subacute stroke inpatients with admission FAC 2-3 (89 outdoor, 48 indoor-only ambulators at discharge); one patient was excluded for an implausible step time. Admission FAC was excluded from candidate predictors to avoid overlap with the outcome. Hierarchical logistic regression compared a clinical model (Motricity Index [MI], time since onset) with one adding GAITRite-derived spatiotemporal parameters, using likelihood-ratio and DeLong tests with Firth-penalised sensitivity analysis. Model 1 achieved near-perfect discrimination (AUC = 0.995, 95% CI 0.984-0.999). Adding affected-side single- and double-support percentages (Model 2) significantly improved fit (likelihood-ratio &#x3c7;&#xb2; = 9.39, p&#x202f;=&#x202f;0.009; AUC = 0.998); the AUC difference was not significant by DeLong's test (p&#x202f;=&#x202f;0.262). Firth-penalised analyses produced concordant, stable coefficients. MI and gait velocity were the strongest single predictors (both AUC = 0.981); bootstrap optimism was &#x2264;&#x202f;0.002. Beyond a near-perfect clinical model, affected-side support-phase parameters add statistically detectable model information (improved fit and calibration) rather than a clinically decisive gain in discrimination, which is constrained by a ceiling effect. Their value is best understood as quantifying paretic-limb weight-bearing and balance-related gait quality not captured by bedside scales, in subacute stroke inpatients with admission FAC 2-3. The Youden cut-offs (MI &#x2265; 40, velocity &#x2265; 32.1&#x202f;cm/s, single support &#x2265; 29.7%) are hypothesis-generating and require external validation before clinical use.