Commentary: A road map for future data-driven urban planning and environmental health research.

Recent advances in data science and urban environmental health research utilise large-scale databases (100s-1000s of cities) to explore the complex interplay of urban characteristics such as city form and size, climate, mobility, exposure, and environmental health impacts. Cities are still hotspots of air pollution and noise, suffer urban heat island effects and lack of green space, which leads to disease and mortality burdens preventable with better knowledge. Better understanding through harmonising and analysing data in large numbers of cities is essential to identifying the most effective means of disease prevention and understanding context dependencies important for policy.

Systematic review of subjective validation methods for computerized colonoscopy simulators.

Introduction: In recent years, different approaches have been used to conduct a subjective assessment of colonoscopy simulators. The purpose of this paper is to review these different approaches, specifically the ones used for computerized simulators, as the first step for the design of a standard validation procedure for this type of simulators. Methods: A systematic review was conducted by searching papers after 2010 in PubMed, Google Scholar, ScienceDirect, and IEEE Xplore databases. Papers were screened and reviewed for procedures regarding the subjective validation of computerized simulators for traditional colonoscopy with an endoscope. Results: An initial search in the databases identified 2094 papers, of which 7 remained after exhaustive review and application of exclusion criteria. All studies used questionnaires for subjective validation, with "face" being the most common validity type tested, while "content" validity and "usability" were less prominent. Conclusions: A classification of subscales for testing face validity was derived from the studies. The Colonoscopy Simulator Realism Questionnaire (CSRQ) was selected as the guide to follow for the development of future questionnaires related to subjective validation. Mislabeling of the validity tested in the studies due to ambiguous interpretations of the validity types was a common occurrence observed in the reviewed studies.

Prodromal Alzheimer's Disease: Global Cognition, Cue Efficiency, and Cerebrospinal Fluid Neurofilament Light Values Predict Short-Term Conversion to Dementia.

Background: Predicting which patients with prodromal AD (pAD) will imminently convert to dementia may be paramount in a memory clinical setting, especially with potential disease-modifying therapies on the horizon. Objective: To explore a practical tool for this prediction, combining cognitive tests and cerebrospinal fluid (CSF) biomarkers. Methods: We designed a longitudinal prospective, observational, and multicenter study, enrolling patients with pAD. Inclusion criteria comprised memory complaints, Mini-Mental State Examination (MMSE) score of≥22, memory impairment as indicated by the Free and Cued Selective Reminding Test with Immediate Recall (FCSRT + IR) and/or TMA-93, Clinical Dementia Rating-Global Score (CDR-GS) of 0.5, and positive CSF Aß42/Aß40 ratio (<0.095, Euroimmun). The primary outcome was the conversion to dementia (CDR-GS≥1) within the first year of follow-up, referred to as "short-term conversion". A multiple regression logistic model was adopted to design the "Predict Short-Term Conversion" (PSTC) score. Results: Between 2020 and 2022, 83 patients were recruited. The median age was 74, with 49.4% being women. Twenty-five (30.1%) patients were classified as short-term converters. The PSTC score incorporated baseline scores on MMSE ( ≤24 = 3, >24 = 0) and FCSRT + IR Total Recall ( ≤14 = 4, >14 = 0), and CSF neurofilament light chains (NfLs) concentrations (ß=0.001299). The PSTC score demonstrated an area under the curve of 0.78 (95% CI: 0.67-0.90, p < 0.001), with a cutoff value of 5.14 presenting 76% sensitivity and 80% specificity. Conclusions: The PSTC score, comprising two relatively brief cognitive test scores and NfLs CSF concentrations, could be useful for predicting short-term converters among patients diagnosed with pAD.

Effect of the addition of exogenous progesterone and the progesterone receptor inhibitor (RU 486) on boar cryopreservation semen extenders.

Cryopreservation of porcine spermatozoa is detrimental due to their high sensitivity to cold shock, leading to changes akin to capacitation, known as cryocapacitation. These changes, including the acrosomal reaction, hypermotility induction, and protein phosphorylation, might be influenced by the presence of progesterone in seminal plasma and egg yolk, used in most freezing extenders. We tested the effect of various progesterone concentrations added to the freezing extenders (1, 10, and 100 µg/mL). At 100 µg/mL, progesterone decreased the proportion of straightness and tended to reduce viability and the proportion of progressive motility (p < 0.1). At 10 µg/mL, it increased reacted acrosomes in dead sperm (p < 0.05), protein phosphorylation rate (p < 0.05), and tended (p < 0.1) to enhance linear movement compared to the control. To counteract the capacitating effect of progesterone, we examined the effect of antiprogesterone mifepristone (RU 486) at concentrations of 5, 10, 20, 50, 100, and 200 µM, and co-incubated 10 µM of RU 486 with 10 µg/mL of progesterone. RU 486 maintained capacitation levels and motility parameters similar to the control, although high concentrations (100 µM) tended (p = 0.152) to increase protein phosphorylation. Co-incubation reduced the acrosome reaction in dead sperm, and RU 486 appeared to prevent hypermotility stabilizing motility and viability parameters compared to samples with progesterone alone. Protein phosphorylation increased and RU 486 could not restore capacitation to control levels due to its competitive antagonism for progesterone receptors, having less affinity than progesterone, which displaces RU 486 at high concentrations, allowing normal sperm capacitation.

Metabolic-Associated Fatty Liver Disease and Cognitive Performance in Type 2 Diabetes: Basal Data from the Phytate, Neurodegeneration and Diabetes (PHYND) Study.

The effect of liver fibrosis on mild cognitive impairment (MCI) and dementia risk in type 2 diabetes mellitus (T2DM) patients is unclear. Therefore, we performed a prospective cross-sectional study on 219 patients with T2DM and older than 60 years to evaluate the association between liver fibrosis, liver steatosis, and cognitive impairment. The Montreal Cognitive Assessment (MoCA) was used to screen for MCI or dementia. Liver fibrosis was estimated using the non-invasive Fibrosis-4 (FIB-4) score, and liver steatosis was assessed with the hepatic steatosis index. The mean age was 71 ± 6 years, 47% were women and according to MoCA cut-off values, 53.88% had MCI and 16.43% had dementia. A moderate or high risk of advanced fibrosis was significantly higher in patients with MCI or dementia compared to those with normal cognition (p < 0.001). After adjusting for confounders, a FIB-4 score greater than 1.54 was associated with MCI or dementia (p = 0.039). Multivariate analysis identified age over 70.5 years, antiplatelet medication use, and a FIB-4 score above 1.54 as the most relevant risk factors. Liver fibrosis, but not liver steatosis, is associated with MCI or dementia in older T2DM patients, suggesting that FIB-4 score might be a simple biomarker for the detection of cognitive impairment.

Evaluation of the effects of a gamified, fully immersive and stroke-specific virtual reality intervention for improving disability and quality of life in patients with stroke in the subacute phase: study protocol of the RESET randomised trial.

Stroke is the leading cause of disability and the second cause of death worldwide. The increasing burden of stroke underscores the importance of optimising rehabilitation protocols. Virtual reality (VR) can improve poststroke prognosis. A VR software combining gamification, full immersion and stroke specificity (ie, the Development and validation of a novel viRtual rEality software for improving diSability and quality of lifE in patients with sTroke (RESET) software) might substantially improve disability and quality of life (QoL). However, this technology is still very scarce. The RESET trial aims to assess the effects of an early 10-week gamified, fully immersive and stroke-specific VR intervention (ie, starting at week 3 poststroke) on disability and QoL in people with stroke in the subacute phase. People with ischaemic or haemorrhagic stroke (n=94) aged ≥ 18 years will be randomised to receive (1) usual care (UC), (2) commercial VR or (3) gamified, fully immersive and stroke-specific VR (RESET). The three groups will receive UC (ie, three sessions/week of 90 min of standard rehabilitation). The VR groups will additionally receive three VR sessions of 20 min per week. The outcome measures will be assessed at baseline (week 2 from stroke occurrence), week 13 (approximately 90 days from the event) and week 26 (approximately 6 months from the event). The primary outcome is disability measured with the Barthel Index. Secondary outcomes include QoL, upper-extremity and lower-extremity motor function, gross manual dexterity, handgrip strength and cognitive function. This study will unravel the effects of a gamified, fully immersive and stroke-specific VR software on disability and QoL in patients with stroke in the early subacute phase.Trial registration number: NCT06132399.

Impact of Driver Mutations on Metastasis-Free Survival in Uveal Melanoma: A Meta-Analysis.

The prognosis of uveal melanoma is significantly influenced by the risk of metastasis, which varies according to clinical and genetic features. Driver mutations can predict the likelihood of disease progression and survival, although the data in the literature are inconsistent. This meta-analysis aimed to evaluate the prognostic significance of driver mutations, including GNAQ, GNA11, BAP1, and SF3B1, in the advancement of uveal melanoma. A comprehensive search of databases yielded relevant studies, and data from 13 studies (848 eyes) were synthesized to assess the impact of these mutations on metastasis-free survival. The BAP1 mutation and negative immunohistochemistry were associated with a higher risk of metastasis (logHR = 1.44, 95% CI 1.05-1.83). GNAQ, GNA11, and SF3B1 mutations did not show a significant increase in risk. In summary, BAP1 has proven to reliably predict the likelihood of disease progression in uveal melanoma, while further studies are needed to establish the significance of other driver mutations.

Selective Synthesis of Boron-Functionalized Indenes and Benzofulvenes by BCl3-Promoted Cyclizations of ortho-Alkynylstyrenes.

A selective, metal-free synthesis of boron-functionalized indenes and benzofulvenes via BCl3-mediated cyclization of o-alkynylstyrenes is described. The method allows precise control over product formation by adjusting reaction conditions. These borylated products were utilized in diverse C-B bond derivatizations and in the total synthesis of Sulindac, a nonsteroidal anti-inflammatory drug, demonstrating the versatility and practicality of the developed methodology for synthetic applications.