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A major limiting factor in the success of chimeric antigen receptor (CAR) T cell therapy for the treatment of solid tumors is targeting tumor antigens also found on normal tissues. CAR T cells against GD2 induced rapid, fatal neurotoxicity because of CAR recognition of GD2 + normal mouse brain tissue. To improve the selectivity of the CAR T cell, we engineered a synthetic Notch receptor that selectively expresses the CAR upon binding to P-selectin, a cell adhesion protein overexpressed in tumor neovasculature. These tumor microenvironment actuated T (MEAT) cells ameliorated T cell infiltration in the brain, preventing fatal neurotoxicity while maintaining antitumor efficacy. We found that conditional CAR expression improved the persistence of tumor-infiltrating lymphocytes because of enhanced metabolic fitness of MEAT cells and the infusion of a less differentiated product. This approach increases the repertoire of targetable solid tumor antigens by restricting CAR expression and subsequent killing to cancer cells only and provides a proof-of-concept model for other targets.

Dysbiosis may hinder effective tumor immunity and reduce the efficacy of therapies such as immune checkpoint blockade (ICB) in renal cell carcinoma (RCC). CBM588, a product containing live Clostridium butyricum, has shown promise in enhancing ICB effectiveness in metastatic RCC in terms of response rates and progression-free survival. Further research to confirm these findings should take factors such as diet and microbiome composition into account and include predictive biomarkers for patient selection., (Copyright © 2025 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Introduction: The Global Observatory for Physical Education (GoPE!) builds on the Global Observatory for Physical Activity (GoPA!) to address gaps in surveillance, policy, and research on physical education (PE) and activity (PA). GoPE! is a worldwide surveillance system of quality PE and school-based PA that informs policy and interventions and allows comparative analysis so that each country and region can check their status and progress. This paper presents GoPE!'s conceptual framework and describes the research protocol as a cross-continental and evidence-based surveillance system., Methods: Based on GoPA!'s framework and informed by the European Physical Education Observatory, as well as framed by the socioecological model of PE, United Nations Educational, Scientific, and Cultural Organization's quality PE, and the World Health Organization's whole-of-school approach, the GoPE! stands out by providing a comprehensive methodological approach. This approach relies on independently collected data about PE and PA at school policies, surveillance systems, and research. These data are critically reviewed by local representatives of the GoPE! network of experts. The GoPE! Country Card is the main product released every 5 years. It is a 1-page infographic summary of a country's key dimensions and indicators. The dimensions are: country and demographic data, PA participation, PE policy, PE surveillance, and PE and school-based PA intervention research., Conclusion: Through its vision and methodological framework, GoPE! aims to contribute to the establishment of a minimum common denominator of quality PE and school-based PA, ultimately informing promotion, advocacy, and agenda-setting efforts to achieve international goals and recommendations for more active, equitable, and healthy children and adolescents, schools, and societies.

The combination of transcranial magnetic stimulation and electroencephalography (TMS-EEG) is emerging as a valuable tool for investigating brain functions in health and disease. However, the detailed neural mechanisms underlying TMS-EEG responses, including TMS-evoked EEG potentials (TEPs) and TMS-induced EEG oscillations (TIOs), remain largely unknown. Combining TMS-EEG with pharmacological interventions provides a unique opportunity to elucidate the roles of specific receptor-mediated neurotransmissions in these responses. Here, we investigated the involvement of muscarinic acetylcholine receptor (mAChR)-mediated cholinergic neurotransmission in TMS-EEG responses by evaluating the effects of mAChR antagonists on TEPs and TIOs in twenty-four healthy participants using a randomized, placebo-controlled crossover design. TEPs and TIOs were measured before and after administering a single oral dose of scopolamine (a non-selective mAChR antagonist), biperiden (an M1 mAChR antagonist), or placebo, with TMS targeting the left medial prefrontal cortex (mPFC), angular gyrus (AG), and supplementary motor area (SMA). The results indicated that mAChR-mediated cholinergic neurotransmission played a role in TEPs, but not TIOs, in a target-specific manner. Specifically, scopolamine significantly increased the amplitude of a local TEP component between approximately 40 and 63 ms post-stimulus when TMS was applied to the SMA, but not the mPFC or AG. Biperiden produced a similar but less pronounced effect. Importantly, the effects of these mAChR antagonists on TEPs were independent of those on sensory-evoked EEG potentials caused by TMS-associated sensory stimulation. These findings expand our understanding of TMS-EEG physiology, providing insights for its application in physiological and clinical research., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: We demonstrated for the first time the safety and feasibility of escalating up to 55 Gy/11 Gy/fr/5fr in borderline (BRPC)/unresectable locally advanced pancreatic cancer (LAPC), using the standard LINAC platform. The aim of the present study is to assess for the first time the impact of this high-dose neoadjuvant stereotactic ablative radiotherapy (SABRT) protocol on tumor resectability and pathological responses., Materials/methods: From June 2017 to December 2022, patients with BRPC/LAPC were treated with neoadjuvant chemotherapy (ChT) and SABRT-escalated doses of SIB at 45 Gy, 50 Gy, and up to 55 Gy (BED ≥ 100). Radiological evaluation was conducted with a CT scan 6-8 weeks post-treatment to determine resectability status based on established criteria (SAR/APA2014). Surgical decisions were made by the multidisciplinary tumor board of the participating institutions. Pathological assessments post-surgery used criteria from the College of American Pathologists (CAP), categorizing resection status as R0 (negative margins), R1 (microscopic tumor margins), and R2 (macroscopic tumor margins). Tumor response was evaluated with the Tumor Response Scoring (TRS) system, as G0 (no viable cancer cells), G1 (single cells or rare small groups), G2 (residual cancer with evident regression), and G3 (extensive residual cancer)., Results: Thirty-three patients (p) were included: 39.4% (13p) BRPC/60.6% (20p) LAPC. After ChT-SABRT, 45.5% (15p) were considered resectable, with 11/13 (84.6%) BRPC and 4/20 (20%) LAPC ( p < 0.0001). One patient refused surgery and other patient died of COVID sepsis. Two more patients had disseminated disease at surgery. Among the 11 patients who underwent full surgery, all patients achieved either clean margins R0: 72.7% (8p) or microscopic affected margins R1: 27.3% (3p). TRS scores were G1: 27.3% (3p), G2: 54.5% (6p), and G3: 18.2% (2p). The present follow-up (FUP) was closed on 1 November 2024 (23.55 months, range: 6-71 months). The mean freedom from local progression as the first cause of disease failure was 43.30 ± 3.09 (37.23-49.38), and the median was not reached. The actuarial 1- and 2-year rates for freedom from local relapse as a first cause of disease failure were 92.3% (87.7-93.3%) and 79.7% (79.7-87.7%), respectively., Conclusions: Neoadjuvant ChT-SABRT in LAPC improves resectability rates and induces relevant tumor regression. These promising findings should be validated by larger sample sizes and extended follow-up.

Competing Interests: Competing interests: The authors declare no competing interests.

Brewers' spent grain (BSG), the major by-product of the brewery industry, has high nutritional value, making it suitable for upcycling into products such as healthy, and sustainable cookies. Nonetheless, the incorporation of BSG in cookies can impact their quality, given the increased fiber and protein content. This work explored the effect of replacing wheat flour with BSG at 50% and 75% in cookie formulations, focusing on physical, chemical, and sensory properties. The dietary fiber, lipid, and protein content of cookies improved considerably with the highest incorporation of BSG, increasing from 6.37% to 15.54%, 9.95% to 13.06%, and 9.59% to 12.29%, respectively. Conversely, moisture and water activity decreased from 11.03% to 3.37% and 0.742 to 0.506, respectively, forecasting a lower risk of microbial contamination and increased shelf-life. The incorporation of BSG in cookies resulted in decreased brightness and increased hardness, from 40 N to 97 N. Moreover, colorimetric shifts among the control cookies and the two BSG-rich formulations could be easily identified by an untrained observer. Sensory evaluation showed that cookies with 50% BSG retained acceptable sensory characteristics, suggesting potential for further development. Overall, BSG enhances the nutritional profile of cookies with no excessive detrimental impact on sensory features.

The present study aimed at describing and comparing the physical activity (PA) patterns of adolescents from a middle-income country over a 4-year period. This is a longitudinal observational study (four waves of data collection, 2014-2017) with 668 adolescents aged 10-13 years in 2014 (mean age of 11.8 ± 0.8 years), of both sexes (53.3% girls), from public schools in João Pessoa, Paraíba state, Brazil. PA was measured using a questionnaire and pattern operationally defined based on the following indicators: type, frequency, duration, and PA recommendations. The most practiced physical activities during the study period were active commuting, games, dancing, cycling, soccer, and futsal. There was a linear trend to a decline in the number of adolescents engaging in nearly all the physical activities, in the duration of activities and the proportion that met the PA recommendations (52.8% in 2014 to 32.2% in 2017). The adolescents engaged in different physical activities, but these declined over the years., (© 2024 The Author(s). European Journal of Sport Science published by Wiley‐VCH GmbH on behalf of European College of Sport Science.)

Babassu (Atallea sp.), a native palm tree from South America's Amazon produces bio-oil and biochar with significant potential for industrial applications. Babassu oil as a bio-based plasticizer is reported here for the first time to replace petrochemical alternatives in the production of conductive filaments for additive manufacturing purposes. The newly developed filament, consisting of 30 wt.% carbon black (CB), 60 wt.% polylactic acid (PLA), and 10 wt.% Babassu oil, demonstrates enhanced thermal stability, improved printability, and superior electrochemical performance. 3D-printed electrodes made from this Babassu-CB/PLA filament outperform those made from commercial CB/PLA filaments, exhibiting better voltammetric responses (e.g., lower peak-to-peak separation and higher current intensity) for inner-sphere redox probes. As a proof-of-concept, these bio-based electrodes were successfully used to detect cocaine in real-world street samples, with a limit of detection (LOD) of 1.2 µmol L -1 . The Babassu-CB/PLA electrodes provided reliable cocaine quantification without interference from common adulterants such as caffeine, paracetamol, and phenacetin and showed no matrix effects, as confirmed by recovery values ranging from 88 to 102%. Notably, the use of Babassu oil eliminates the need for laborious post-treatment protocols to achieve optimal electrochemical performance. In this study, only mechanical polishing on the electrode surface is required. This study highlights the potential of Babassu oil as a sustainable alternative in the fabrication of conductive filaments for electrochemical applications, advancing the field of environmentally friendly and efficient 3D-printed sensors., Competing Interests: Declarations. Ethical approval: Not applicable. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

The cumulative effects of human activities and natural pressures pose significant threats to ecosystem functioning and global biodiversity. Assessing the cumulative impact of multiple stressors-whether acting simultaneously or sequentially and directly or indirectly-is challenging due to their complex interactions. Consequently, these interactions may be unintentionally overlooked or disregarded in management decisions. While existing reviews have focused on coastal and freshwater ecosystems, analyses specifically targeting salmonids as a focal group are lacking. This research presents the first quantitative and qualitative assessment of stressor interactions affecting salmonid biology and physiology. A focused literature search identified 118 experimental trials with multiple stressors on salmonids. From these, 46 cases were considered suitable for the quantitative analysis. We calculated Hedges' g effect sizes to classify the interactions between multiple stressors as additive, synergistic, or antagonistic. Our findings revealed that additive effects were found most frequently (50% of interactions), followed by synergistic (30.5%) and antagonistic (19.5%) interactions. Additionally, we performed a network analysis including cases focusing on the influences of multiple stressors interactions (n = 38). Our qualitative analysis identified temperature, metals, and pesticides as the most paired stressors across the three types of interactions. The findings of this research highlight the potential vulnerabilities of salmonids and their habitats by identifying key interactions between multiple stressors, and priorities for future research. Understanding these interactions and cumulative effects, particularly in the context of climate change, can inform targeted conservation and management strategies, contributing to the preservation of these important fish species and their ecosystems, which are vital to local human communities., Competing Interests: Compliance with Ethical Standards. Conflict of Interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Enfortumab vedotin (EV) is used as monotherapy or combined with pembrolizumab in advanced urothelial carcinoma (aUC), but biomarker data associated with EV outcomes are limited. We identified 170 patients in the UNITE study who received EV monotherapy and had molecular biomarker data available. Outcomes for groups with and without a particular biomarker were compared using logistic regression (unadjusted) for the objective response rate (ORR), and a log-rank test and Cox proportional-hazard models (CPHMs) for progression-free survival (PFS) and overall survival (OS) from EV initiation. Molecular biomarkers were also evaluated in separate multivariable analyses using CPHMs that accounted for clinical characteristics. Median patient age was 70 yr; 78% of the cohort were male and 65% had pure UC histology. Median PFS was shorter for patients with CDKN2A alterations (4.6 vs 6 mo; p = 0.024) and for patients with CDKN2B alterations (4.4 vs 6 mo; p = 0.008). Median OS was longer for patients with high tumor mutational burden (13.6 vs 8.3 mo; p = 0.014). ORR was higher for patients with TSC1 alterations (87% vs 51%; p = 0.018). In multivariable analyses, CDKN2A and CDKN2B alterations were associated with inferior median PFS. This multi-institutional retrospective study of patients with aUC identified potential biomarkers associated with EV monotherapy outcomes that should be further investigated. PATIENT SUMMARY: We investigated genetic changes in urinary tract tumors that might be associated with response to enfortumab vedotin (EV) treatment in patients with advanced disease. Survival after EV treatment was longer for tumors with a higher number of mutations than for tumors with fewer mutations. However, mutations in two genes (CDKN2A and CDKN2B) were associated with worse outcomes after EV treatment. These findings will not affect current clinical practice, but should be investigated further in future studies., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Oral health represents a public health problem due to its remarkable social impact and medical costs. Crenotherapy with sulfur water is shown to be a complementary, less toxic, and traumatizing therapy, but the number of studies that evaluate the effect of natural mineral waters effect on oral health are scarce. The aim of this pilot study is to evaluate the impact of thermal water therapy on the oral health of the participants, assessing parameters such as plaque index, gingival bleeding index and periodontal probing depth as well on the perception of symptoms of oral mucosa diseases (OMD)., Methods: An observational, longitudinal and comparative study was designed, and 90 thermalists were randomly allocated to two treatment groups for 14 days: Thermal sulfuric natural mineral water of the Amarante Thermal baths group (TW&#95;TA group) (n = 45) or saline solution (control group) (n = 45), in May 2022. The study was based on clinical observation and application of a self-response questionnaire involving sociodemographic data and quality of life assessment. The evaluation was carried out in 2 different moments: before and at the end of treatment (14 days)., Results: The study involved 90 thermal practitioners, evenly split between the TW&#95;TA group and a control group. Most participants were women (70%), with a similar average age in both groups. Oral examination showed a high prevalence of filled and missing teeth, and around 25% of participants used removable prostheses, predominantly in the control group. Thermal treatment had a positive impact on oral health. In the TW&#95;TA group, gingival bleeding significantly decreased from 68.9% to 40%, while it remained unchanged in the control group. Periodontal health improved, with no participants in the TW&#95;TA group having pockets deeper than 5 mm by the end of the study, indicating reduced periodontal pathology. Also, plaque levels dropped in both groups after treatment, as assessed by the O'Leary index. Additionally, quality of life related to OMD improved, particularly in the TW&#95;TA group. The overall reduction in symptoms was significant, although the differences between groups were not statistically significant., Conclusions: This study demonstrates the positive effects of thermal water treatment on oral health, including reduced gingival bleeding and plaque levels, along with improved quality of life related to OMD. Further targeted research is needed to explore the benefits of thermal water effects and optimize oral health practices in Portugal using thermal waters., Competing Interests: Declarations. Ethics approval and consent to participate: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The research was approved by the Health Ethics Committee of the Universidade Católica Portuguesa (Approval report number 205). Written informed consent was obtained from all participants. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Indications for and implications of germline genetic testing (GGT) in patients with prostate cancer have expanded over the past decade, particularly related to precision therapies and management. GGT has become the standard of care for many cancers such as breast, ovarian, colorectal, pancreatic, and metastatic prostate cancer, and it is imperative that patients be offered timely and equitable access to testing as it can inform patient-physician shared decision making for management of the current cancer as well as anticipatory guidance for disease progression. Additionally, GGT guides screening for and prevention of secondary malignancies for the patient and cascade testing for at-risk family members. Here, we present data supporting the notion that clinicians should offer all patients with prostate cancer the opportunity to undergo comprehensive GGT for pathogenic germline variants known to be associated with familial cancer and/or known to have implications for treatment and management.

Objective To evaluate the cross-sectional association of physical activity during pregnancy with gestational weight gain and verify if associations are modified by levels of sleep duration and efficiency. Methods: Mothers who were participants of the 2015 Pelotas (Brazil) Birth Cohort study were analyzed. Physical activity (PA) and sleep were measured using the nondominant wrist accelerometer model wGT3X-BT (ActiGraph, Pensacola, FL). Moderate-to-vigorous activities were measured in bouts of 5 minutes (MVPA 5-min bout). Activities were characterized as sustained and overall physical activity was expressed in mg, and MVPA (non-bouted) activities were characterized as not sustained. Sleep was presented as minute bouts, sleep time window, total sleep time, and sleep efficiency. Gestational weight gain (GWG) was calculated by a woman's weight at the end of gestation minus the pre-pregnancy weight. Linear regression models were used to evaluate the association between PA and GWG. Stratification by sleep characteristics in tertiles was performed. Results: The analytical sample included 1,938 women with information for PA, sleep, and GWG. The mean GWG was 12,030 g (SD = 6658.8). After adjustments, for every 15 minutes of sustained physical activity (MVPA 5-min bout), the GWG decreased by 591.3 g [β= -591.3 (95%CI: -1,147.1; -35.5). A statistically significant association was observed between 15 minutes of sustained physical activity (MVPA 5-min bout) and GWG in the second and third tertiles of healthier sleep efficiency. Conclusion: MVPA with 5-min bouts is associated with lower GWG. The GWG reduction was greater in the higher sleep efficiency strata.

Purpose: To correlate speed and heat scores with anthropometric variables and lower-limb strength and power in professional surfers., Methods: A total of 19 men participated in simulated competitions on different days. All surfed waves were scored, and each athlete's best 2 were used for their total heat score. Speed values were extracted by global positioning system and adjusted by Z score. Squat jump, countermovement jump, and drop jump were executed. Anthropometric variables and 1-repetition maximum (1RM) in the half squat were measured. Pearson product-moment correlation was used to analyze the relationships., Results: Height had a significant (P < .05) inverse association with speed indicators (r = -.36 to - .68), and body mass index had a moderate association with maximum wave speed of the highest score. Significant correlations with moderate to large magnitudes were found between maximum speed and vertical jumps (r = .46 to .56), average speed and vertical jumps (r = .48 to .59), and both maximum and average speed with 1RM (r = .52-.53). Athletes' best score and total heat score showed moderate to large associations with vertical jumps and 1RM (r = .48-.64), whereas second scores were correlated with the reactive strength index of the drop jump (r = .48) and 1RM (r = .51)., Conclusions: Shorter surfers with lower center of gravity and those with superior lower-limb strength and power achieved greater speed and higher scores. Accordingly, surf coaches may consider prescribing dynamic strength and balance training based on an athlete's profile to improve performance.

Background and Objective: Advances in molecular diagnostics have ushered in a new era for patients with prostate, renal, and urothelial cancers, with novel radiographic and molecular modalities for the assessment of disease burden and minimal residual disease (MRD). Conventional imaging has a limited threshold for disease detection and is often unable to discern clinically occult disease with varying risks of false-negative or false-positive findings depending on the disease state and type of imaging., Methods: We provide an overview of emerging radiographic and molecular tools in development within the genitourinary (GU) disease space. A literature review of contemporary basic, translational, and clinical research studies was performed, covering the timeframe of 1980-2024 through the MEDLINE (via PubMed) and Scopus databases. We highlight select examples of emerging technologies and biomarker-informed clinical trials, which aim to quantify disease at lower thresholds and have the potential for integrating MRD in clinical practice for GU patients., Key Findings and Limitations: The development of novel radiotracers, such as prostate-specific membrane antigen or carbonic anhydrase IX, is being evaluated in both clinical practice and trial setting, aiming to change the management of these tumors. Molecular tools including circulating tumor cells and byproducts such as plasma and urine cell-free circulating tumor DNA provide the opportunity for MRD detection. MRD capture on single-cell or cellular byproducts can serve as a conduit for genomic and transcriptomic analyses, providing insight into the molecular underpinnings and clonal evolution of disease., Conclusions and Clinical Implications: While the full potential for MRD applications has yet to be realized, we are witnessing the emergence of novel techniques aimed at MRD detection and the rapid development of elegantly designed studies implementing iterative detection of MRD as means to provide biological rationale and tailor therapeutic options in GU tumors., (Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Pollution is a major global concern affecting biodiversity, particularly of freshwater species. Populations have developed mechanisms to deal with pollution, such as the chemical defensome, which is a set of genes involved in maintaining internal stability. Pollution significantly affects the Maipo River basin in Chile. This area is home to the endemic silverside fish Basilichthys microlepidotus, whose populations are affected by pollution to different degrees. We assessed gene expression in the liver and gill of this species, focusing on whole-transcriptome and chemical-defensome levels, to identify both independent and shared mechanisms in response to pollution. The results showed that 14-18 genes were consistently expressed differently among populations in polluted areas. These genes were primarily involved in liver cell mitosis and in responses to organic chemicals and carcinogenic processes. Genes expressed differently in the gill were more abundant in immune system biological processes. All populations consistently downregulated chemical-defensome genes in the liver. In differentially expressed chemical-defensome genes, shared biological processes included virus response, cellular redox homeostasis and transport, organic cyclic compound response and DNA-templated transcription regulation. Studying chemical-defensome genes can help reveal common ways that pollution builds up over time, and examining the whole transcriptome can elucidate the context in which this response develops., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Locally advanced rectal cancer (LARC) poses a significantly challenge in clinical management, requiring a multimodal treatment approach. Among innovative strategies, Total Neoadjuvant Therapy (TNT) has emerged, delivering all planned chemotherapy before surgery., Objective: Our aim was to evaluate the real-world application and efficacy of TNT and to compare it with the non-TNT standard strategy., Methods: This retrospective study compared locally advanced rectal adenocarcinoma patients treated with Total Neoadjuvant Therapy (TNT) in 2022 with those who underwent traditional chemoradiotherapy (CRT) in 2020-2021. The primary endpoints were the pathologic complete response rate and the sustained clinical complete response rate in patients under W&W., Results: Among 107 patients (54.2% male, mean age 62.48 years), non-TNT (67 patients) and TNT (40 patients) mean follow-ups were 26.7 and 8.2 months, respectively. No differences in gender(p = 0.163), staging (p = 0.707), or location (p = 0.727) were noted. TNT patients received more short-course radiotherapy (42.5% vs1.5%, p < 0.001). Clinical responses favored TNT (p = 0.030) with no significant differences in pathological responses, recurrence rates, or survival. TNT exhibited higher chemotherapy completion (p = 0.007) and lower adverse events (p < 0.001). Post-surgery events showed no significant differences (p = 0.470). Single center with retrospective design and carries limitations that may restrict the generalizability of the findings and the relatively short follow-up duration are our main limitations., Conclusion: Our data add to the body of literature favoring the TNT treatment strategy for locally advanced rectal cancer, aiming to achieve comparable complete response rates with less adverse events., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the local institutional Ethical Committee board (Comissão de Etica para a Saúde of Instituto Português de Oncologia de Lisboa Francisco Gentil, with the protocol code UIC/1649). Consent for publication: The manuscript does not contain any individual person’s data in any form, so inform consent is not necessary. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Competing Interests: Conflicts of Interest and Source of Funding: The authors declare no competing interest or source fundings.

Purpose: To compare objective and subjective intraocular pressure measurements immediately after cataract surgery and intraocular pressure measurements between less experienced surgeons (Group 1) and experienced surgeons (Group 2)., Methods: Surgeons were asked to estimate the IOP after corneal sealing after surgery based on their tactile perception of eye tension (subjective intraocular pressure) Objective intraocular pressure was measured using a Perkins tonometer while patients were still in the surgical field. Objective intraocular pressure was compared to subjective intraocular pressure. Results from less experienced surgeons were compared to more experienced surgeons., Results: The study comprised 81 surgeries (81 eyes) performed by 27 surgeons. The mean objective intraocular pressure (9.14 mmHg; SD=5.86) was statistically significantly lower (p<0.001) than the mean subjective intraocular pressure (19.21 mmHg; SD=4.82). Hypotony (intraocular pressure <6mmHg) was observed in 25 eyes (30.86%). The mean subjective intraocular pressure was 18.8 mmHg (SD=5.19) for less experienced surgeons and 19.5 mmHg (SD=4.46) for more experienced, without statistically significant difference (p=0.541). No statistically significant difference (p=0.71) was observed when comparing objective intraocular pressure in Group 1 (10.32 mmHg; SD=6.65) and Group 2 (7.97 mmHg; SD=4.7)., Conclusion: Objective intraocular pressure was significantly lower than subjective intraocular pressure, regardless of surgeons' experience. This study showed that the subjective method is unreliable compared to the gold standard (Perkins tonometer) and does not improve with surgeons' experience. Establishing standard training methods is paramount to developing surgeons' skills.

Resting tremor (RT) is a Parkinson's disease (PD) symptom with an unclear relationship to the dopaminergic system. We analysed data from 432 subjects from the Parkinson's Progression Markers Initiative, 57 additional PD patients and controls and 86 subjects referred for dopamine transporter single-photon emission computed tomography (DaT-SPECT). Caudate binding ratio (CBR), but not putamen binding ratio, was higher in RT patients. Furthermore, higher baseline CBR was linked to RT development. In the smaller cohorts, a 4-6 Hz oscillation-based metric from inertial sensors correlated with RT amplitude, distinguished controls from patients with reduced DaT binding and correlated with CBR in the latter group. In silico modelling uncovered that higher CBR in RT patients explained correlations between RT and DaT-SPECT found in several datasets, supporting a spurious origin for ipsilateral correlations between CBR and RT. These results suggest that caudate dopaminergic terminals integrity is a feature of RT with potential pathophysiological implications., Competing Interests: Competing interests M.M. has received in the past 3 years, payment, honoraria or other support from Bial, Phamacademy, Evidenze and AbbVie. A.J.O.-M. was a national coordinator for Portugal of a non-interventional study (EDMS-ERI-143085581, 4.0) to characterize a treatment-resistant depression cohort in Europe, sponsored by Janssen-Cilag, Ltd. (2019–2020), a trial of psilocybin therapy for treatment-resistant depression, sponsored by Compass Pathways, Ltd. (EudraCT number 2017-003288-36), and a trial of esketamine for treatment-resistant depression, sponsored by Janssen-Cilag, Ltd. (EudraCT NUMBER: 2019-002992-33). He is a recipient of a grant from Schuhfried GmBH for norming and validation of cognitive tests. In the past 3 years, he received payment, honoraria or other support from Angelini, Janssen, MSD, Neurolite AG, and the European Monitoring Centre for Drugs and Drug Addiction. He is vice-president of the Portuguese Society for Psychiatry and Mental Health and Head of the Psychiatry Working Group for the National Board of Medical Examination (GPNA) at the Portuguese Medical Association and Portuguese Ministry of Health. None of the aforementioned agencies had a role in the preparation, review, or approval of the manuscript or in the decision to submit the manuscript for publication. Other authors report no conflict of interest. M.D.M. and P.F. contributed equally to this work. M.D.M. and J.A.d.S. should be listed as corresponding authors., (© 2024. The Author(s).)

Objective: To examine the acute and chronic effects of reducing prolonged sedentary time (ST) with physical activity (PA) on cognitive and brain health., Design: Systematic review and meta-analysis., Data Sources: PubMed, Scopus, CINAHL, PsycINFO, SPORTDiscus, Web of Science, and ProQuest Dissertation and Theses., Eligibility Criteria: Randomised controlled trials (RCTs) published from inception to 17 June 2024, with healthy participants without cognitive impairment or neurological conditions that affect cognitive functioning, aged ≥4 years, testing acute and chronic effects of reducing ST and/or prolonged ST by reallocating ST to PA on cognitive function, brain function, and structure., Results: We included 25 RCTs (n=1289) investigating acute (21 studies) and chronic (4 studies) effects on cognitive function (acute: n=20, chronic: n=4) and brain function (acute: n=7, chronic: n=1); there were no studies on brain structure. Acutely interrupting continuous ST with either multiple or a single PA bout improved cognitive function measured from 3 hours to three consecutive days based on 91 effect sizes ( g =0.17, 95% CI: 0.05 to 0.29, p=0.005, I 2 =45.5%). When comparing single versus multiple PA bouts, only multiple PA bouts yielded a positive effect on cognitive function based on 72 effect sizes ( g =0.20, 95% CI: 0.06 to 0.35, p=0.006; I 2 =48.8%). Chronic studies reported null findings on cognitive function (n=4), with some evidence of improved neural efficiency of the hippocampus (n=1)., Conclusion: Interrupting ST with PA acutely improves cognitive function. The evidence from chronic studies remains inconclusive., Systematic Review Registration: PROSPERO CRD42020200998., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Physical activity is crucial for maintaining health and preventing chronic diseases. However, climate conditions can impact physical activity patterns, and conversely, physical activity can impact climate change. This umbrella review aims to summarize the existing evidence regarding the relationships between physical activity and climate change, as revealed in previous reviews., Methods: Systematic reviews and meta-analyses were analyzed. Searches were conducted across GreenFILE, PubMed, and Web of Science databases for peer-reviewed articles published in English. A 2-stage independent screening process was conducted, and methodological quality was assessed using the JBI framework. Standardized data extraction methods were then applied., Results: Out of 1292 articles retrieved, 7 met all eligibility criteria and were included in the review. Three articles examined physical activity as a primary exposure, 3 focused on the impacts of climate change, and one considered both physical activity and climate change as primary exposures., Conclusions: Findings reveal an interplay between climate change and physical activity. While rising temperatures may prompt outdoor activities up to a certain temperature threshold, air pollution and extreme heat can have harmful effects. Active transportation and improved logistics around large-scale sporting events can mitigate climate change by reducing greenhouse gas emissions, but transportation systems linked to sports venues may increase emissions. Research on the reciprocal relationship between climate change and physical activity domains, and integrating the community into climate discussions, is crucial for equity, especially for marginalized communities. Incorporating climate adaptation and mitigation strategies in physical activity infrastructure to minimize environmental impacts is critical.

Background: Ubiquitous car ownership may affect children's activity and health. We assessed the cross-sectional and longitudinal associations between household car ownership and children's daily time spent sedentary (SED) and in moderate to vigorous physical activity (MVPA)., Methods: Pooled cohort data were from the International Children's Accelerometry Database. Outcome measures were average daily accelerometer-measured SED and MVPA (in minutes per day). Exposures were household car ownership (none, 1, and ≥2) and change in car ownership. Associations were examined using multivariable mixed-effects linear regression., Results: Mean age of participants (N = 4193) was 10.4 years (SD = 2.0), 53.4% were girls, and mean follow-up duration (N = 1333) was 3.3 years (SD = 1.1). Cross-sectionally, household car ownership was associated with higher SED (vs none: 1 car: β = 14.1 min/d, 95% CI, 6.7-21.5; ≥2 cars: 12.8, 95% CI, 5.3-20.4) and lower MVPA (vs none: 1 car: β = -8.8, 95% CI, -11.9 to -5.7; ≥2 cars: β = -8.8, 95% CI, -12.0 to -5.7). Associations were stronger in boys than girls and in children from lower socioeconomic backgrounds (SED only). Prospectively, there were no associations with increased car ownership. Reductions in household car ownership (of which 93.1% had ≥ 2 cars at baseline) were associated with a greater reduction in MVPA (vs no change: β = -8.4, 95% CI, -13.9 to -3.0) but not SED., Conclusions: Children in households with car access were more SED and less active than those without. Losing access to a second car was associated with greater decreases in MVPA, potentially related to losing access to activity-enabling environments. Reducing car access and use are important public health targets (eg, reducing air pollution), but their potential impact on children's activity opportunities should be mitigated.

Introduction: Although propofol is widely preferred as a sedative agent in gastrointestinal endoscopy, its use is commonly associated with hemodynamic adverse events. New sedatives, such as ciprofol, are emerging with promising results. Thus, we aimed to perform a systematic review and meta-analysis to compare efficacy-, safety-, and satisfaction-related outcomes between ciprofol and propofol for adult sedation in gastrointestinal endoscopy., Evidence Acquisition: We systematically searched MEDLINE, Embase, and Cochrane databases for randomized controlled trials comparing sedation with ciprofol vs. propofol in adult patients undergoing gastrointestinal endoscopy. Risk ratios (RRs) and mean differences (MDs) with their 95% confidence intervals (95% CIs) were employed for dichotomous and continuous outcomes, respectively, using a random-effects model. We conducted all statistical analyses using R software (version 4.2.1)., Evidence Synthesis: We included six trials (1225 patients). The ciprofol group had a significantly lower risk of respiratory depression (RR 0.47; 95% CI 0.31, 0.71) and injection pain (RR 0.09; 95% CI 0.04, 0.20) compared with the propofol group, while there were no significant differences in other adverse events between both drugs. There were no significant differences between both groups in time-related outcomes, as well as in the probability of procedure success (RR 1.01; 95% CI 0.99, 1.03). Additionally, ciprofol provided a significantly higher patient satisfaction compared with propofol (MD 0.19; 95% CI 0.08, 0.31)., Conclusions: This systematic review and meta-analysis demonstrated similar clinical efficacy and better safety profile of ciprofol compared with propofol for adult sedation in gastrointestinal endoscopies. Furthermore, patient satisfaction scores were higher with ciprofol.

Background: During the COVID-19 pandemic, changes were seen in city mobility patterns around the world, including in active transportation (walking, cycling, micromobility, and public transit use), creating a unique opportunity for global public health lessons and action. We aimed to analyse a global natural experiment exploring city mobility patterns during the pandemic and how they related to the implementation of COVID-19-related policies., Methods: We obtained data from Apple's Mobility Trends Reports on city mobility indexes for 296 cities from Jan 13, 2020 to Feb 4, 2022. Mobility indexes represented the frequency of Apple Maps queries for driving, walking, and public transit journeys relative to a baseline value of 100 for the pre-pandemic period (defined as Jan 13, 2020). City mobility index trajectories were plotted with stratification by country income level, transportation-related city type, population density, and COVID-19 pandemic severity (SARS-CoV-2 infection rate). We also synthesised global pandemic policies and recovery actions that promoted or restricted city mobility and active transportation (walking, cycling and micromobility, and public transit) using the Shifting Streets dataset. Additionally, a natural experiment on a global scale evaluated the effects of new active transportation policies on walking and public transit use in cities around the world. We used multivariable regression with a difference-in-difference (DID) analysis to explore whether the implementation of walking or public transit promotion policies affected mobility indexes, comparing cities with and without implementation of these policies in the pre-intervention period (Jan 27 to April 12, 2020) and post-intervention period (April 13 to June 28, 2020)., Findings: Based on city mobility index trajectories, we observed an overall decline in mobility indexes for walking, driving, and public transit at the beginning of the pandemic, but these values began to increase in April, 2020. Cities with lower population densities generally had higher driving and walking indexes than cities with higher population density, while cities with higher population densities had higher public transit indexes. Cities with higher pandemic severity generally had higher driving and walking indexes than cities with lower pandemic severity, while cities with lower pandemic severity had higher public transit indexes than other cities. We identified 587 policies in the dataset that had known implementation dates and were relevant to active transportation, which included 305 policies on walking, 321 on cycling and micromobility, and 143 on public transit, across 230 cities within 33 countries (19 high-income, 11 middle-income, and three low-income countries). In the global natural experiment (including 39 cities), implementation of policy interventions promoting walking was significantly associated with a higher absolute value of the walking index (DID coefficient 20·675 [95% CI 8·778-32·572]), whereas no such effect was seen for public transit-promoting policies (0·600 [-13·293 to 14·494])., Interpretation: Our results suggest that the policies implemented to mitigate the COVID-19 pandemic were effective in changing city mobility patterns, especially increasing active transportation. Given the known benefits of active transportation, such policies could be maintained, expanded, and evaluated post pandemic. The discrepancy in the interventions between countries of different incomes highlights that changes to the infrastructure to prioritise safe walking, cycling, and easy access to public transit use could help with the future-proofing of cities in low-income and middle-income countries., Funding: None., Competing Interests: Declaration of interests JT reports grant payments from the National Health and Medical Research Council (NHMRC) and the Australian Research Council (ARC) for projects unrelated to the current manuscript. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: The purpose of this paper is to examine the evolution of physical activity research and the comprehensiveness of national physical activity policies and surveillance systems in Canada., Methods: A systematic review was conducted by the Global Observatory for Physical Activity (GoPA! ) on physical activity and health publications between 1950 and 2019. Findings from Canada were extracted and included in the present analysis. The number of articles published, female researcher involvement in authorship, author institution affiliations, and publication themes were examined. Policies were evaluated by determining if there was a standalone physical activity plan and if national guidelines existed. Surveillance systems were assessed for periodicity, instruments used, and age inclusivity., Results: Out of 23,000 + publications analyzed worldwide; 1,962 included data collected in Canada. Physical activity research in Canada increased considerably from the 2000s to 2010s (543 articles vs. 1,288 articles), but an apparent stabilization has been observed more recently. Most physical activity publications in Canada focused on surveillance (37%), with fewer articles on policy (8%) and interventions (7%). The proportion of female first authors increased from 38% in the 1980s to 60% in the last decade. However, females remain the minority for senior authors. With respect to policy, "A Common Vision" is Canada's national plan, which has a singular policy focus on physical activity. National surveillance data is collected regularly with both the Canadian Health Measures Survey (CHMS) and the Canadian Community Health Survey. In addition to self-report, the CHMS also collects accelerometer data from participants., Conclusion: Through collaborative and coordinated action, Canada remains well equipped to tackle physical inactivity. Continued efforts are needed to enhance sustained awareness of existing physical activity promotion resources to increase physical activity., (© 2024. The Author(s).)

Objectives: This study aims to evaluate the gender inequalities in accelerometer-based physical activity (PA) across different age groups using data from 5 Pelotas (Brazil) cohorts., Methods: The data come from 4 birth cohort studies, covering all live births in the urban area of Pelotas for each respective year (1982, 1993, 2004, and 2015), and the Como vai? cohort study focusing on 60 years and above. Raw accelerometry data were collected on the nondominant wrist using GENEActive/ActiGraph devices and processed with the GGIR package. Overall PA was calculated at ages 1, 2, 4, 6, 11, 15, 18, 23, 30, and 60+ years, while moderate to vigorous PA was calculated from 6 years onward. Absolute (difference) and relative (ratio) gender inequalities were calculated and intersectionality between gender and wealth was also evaluated., Results: The sample sizes per cohort ranged from 965 to 3462 participants. The mean absolute gender gap was 19.3 minutes (95% confidence interval, 12.7-25.9), with the widest gap at 18 years (32.9 min; 95% confidence interval, 30.1-35.7) for moderate to vigorous PA. The highest relative inequality was found in older adults (ratio 2.0; 95% confidence interval, 1.92-2.08). Our intersectionality results showed that the poorest men being the most active group, accumulating around 60 minutes more moderate to vigorous PA per day compared with the wealthiest women at age 18., Conclusions: Men were more physically active than women in all ages evaluated. PA gender inequalities start at an early age and intensify in transition periods of life. Relative inequalities were marked among older adults.

Background : The use of radiation is important in different medical procedures, and to ensure a high level of good medical practice, radiation protection (RP) should be seen as a very important subject. This review shows information about the knowledge in the scope of radiation protection among healthcare professionals exposed to ionizing radiation. There are not many studies that evaluate the radiation exposure of healthcare professionals. Methods : A systematic search was performed, using PRISMA guidelines, in Pubmed and Scopus databases and manually to identify relevant articles to answer the PICOS question, "Is there an adequate level of literacy in the scope of radiation protection among healthcare professionals exposed to ionizing radiation?". This systematic review included cross-sectional studies with the following inclusion criteria: (i) in Portuguese, Spanish, or English; (ii) about literacy in the scope of radiation protection; (iii) published between 2017 and 2024; and (iv) participants must be dentists, radiographers, doctors, and nurses. The JBI critical assessment tool was used to assess the risk of bias. Results : The search identified 566 potentially relevant references, which, after applying inclusion/exclusion criteria, resulted in 12 articles. Studies found that the overall knowledge of these healthcare workers was unsatisfactory, and a lack of knowledge in radiation protection negatively affects health services' quality. Training is essential and must emphasize how radiation exposure can be minimized, safeguarding health professionals' trust and sense of security. Results showed that more years of experience make workers more attentive to protection measures, suggesting that training strategies focused on basic radiological risks and radiation safety are needed. Conclusions : Key findings recommend implementing a standardized national training program on the basic principles and safety of ionizing radiation for all healthcare professionals.

Background: There is limited evidence on the priorities and opportunities associated with promoting population physical activity (PA) participation for the post-COVID-19-pandemic future., Purpose: This study assessed government-led PA promotion efforts before and during the COVID-19 pandemic, along with post-COVID-19-pandemic priorities and recommendations., Methods: Two separate cross-sectional surveys conducted in 2023. Survey 1 was targeted at the Global Observatory for Physical Activity (GoPA!) Country Contacts. Survey 2 also included key international informants representing influential stakeholders in PA policy implementation., Results: There were 68 respondents to Survey 1, collectively representing 61 countries. An additional 37 people, including representatives from 14 key international stakeholders responded to Survey 2. Eighty-two percent of countries had national PA policies. COVID-19 widely disrupted PA policy implementation. Less than 40% of countries integrated PA into their COVID-19 response plan and more than 75% reported policies that restricted PA participation. Although most respondents indicated that government PA priorities did not change due to the COVID-19 pandemic, one in five countries reported that cross-sectoral partnership had become more important during this period. Less than a third of postpandemic governments reported as highly engaged despite the widespread proliferation of PA policies and plans prior to the pandemic. There were variations according to country, region, and income., Conclusions: Elevating PA promotion on the public health agenda is crucial for the post-COVID-19-pandemic era. At a policy level, it is critical to focus on adequate resourcing, cross-sectoral partnerships, integrated interventions, and inequities in participation. These factors have become increasingly important in the postpandemic PA policy landscape.

Objective: To evaluate the clinical significance of subtyping (type 1 vs 2) of papillary renal cell carcinoma (PRCC) in patients treated with targeted therapy, as well as the concordance, sensitivity and positive predictive value (PPV) of local review pathology review., Methods: Patients with advanced refractory PRCC were randomised to receive sunitinib or cabozantinib, crizotinib or savolitinib, stratified by PRCC subtype (type 1, type 2, or not otherwise specified [NOS]/mixed) by local review. Central review was retrospectively conducted by three expert genitourinary pathologists who independently reviewed cases. The sensitivity and PPV of local review were estimated and outcomes [objective response rate (ORR), progression-free survival (PFS)] were summarised for treatment groups stratified by subtypes by central review., Results: Amongst the 147 patients reviewed, the prevalence of individual subtypes varied by local or central review (type 1: 17.7% vs 29.3%; type 2: 53.1% vs 45.6%; NOS/mixed: 29.3% vs 25.2%), respectively. Individual cases were frequently reclassified and local pathology review demonstrated low sensitivity (type 1: 48%, 95% confidence interval [CI] 33, 65; type 2: 67%, 95% CI 55, 78; NOS/mixed: 43%, 95% CI 27, 61). The PPVs of local review were 80%, 57.7% and 37% for type 1, 2 and NOS/mixed, respectively. Compared to sunitinib, cabozantinib demonstrated improved PFS for both type 1 and type 2 PRCC subgroups (7.4 vs 9.0 and 2.9 vs 5.6 months, respectfully) as well as higher ORR., Conclusions: The PRCC subtype assignment did not identify a subset of patients with greater clinical benefit from cabozantinib, with significant discordance between local and central review. Our findings confirm the limited clinical value of pathological subtyping of metastatic PRCC, in line with the recent World Health Organisation 2022 guidelines., Patient Summary: In this study, categorising papillary renal cell carcinoma into type 1 or 2 subtypes showed limited concordance between central and local pathological review and did not enrich for patients more likely to benefit from cabozantinib in the S1500 PAPMET trial., (© 2024 BJU International.)

Introduction: Platinum-based chemotherapy (CTX) has historically been the primary treatment for advanced urothelial cancer (aUC), with limited alternative options. The therapeutic landscape experienced a paradigm shift following the results of the EV-302 and Checkmate-901 trials, which led to the approval of Enfortumab vedotin plus pembrolizumab (EV-P) as the preferred first-line treatment, and nivolumab plus CTX for those unable to receive the preferred regimen. Currently, further investigations are underway to explore PD-1 and PD-L1 inhibitors in the initial treatment of aUC., Patients and Methods: We conducted a systematic search across PubMed, Embase, and the Cochrane Library for randomized controlled trials (RCTs) comparing immune checkpoint inhibitors (ICI)-CTX combinations versus CTX alone as first-line treatment for advanced UC. Employing a random-effects model, we pooled hazard ratios (HR) with 95% confidence intervals (CI)., Results: Our analysis encompassed 3 RCTs, involving 2162 participants, with 51.16% randomized to combination therapy with platinum-based CTX. Compared to CTX alone, immune-chemotherapy significantly improved overall survival (HR 0.84; 95% CI 0.75-0.93; P < .01), progression-free survival (HR 0.78; 95% CI 0.70-0.86; P < .01), and objective response rate (RR 1.20; 95% CI 1.06-1.36; P < .01), while elevating the risk of immune-related adverse events (P-value = .02)., Conclusion: In this meta-analysis of RCTs, ICI plus CTX demonstrated a significant association with improved survival at the expense of an increased risk of immune-related adverse events. Therefore, our findings suggest that this combination should be considered as an initial treatment for aUC in platinum-eligible patients who cannot receive EV-P., Competing Interests: Disclosure None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Hydrochlorothiazide is an extremely important diuretic that regulates body functions, which can prevent several diseases. However, the abuse of this diuretic is concerning since it does not require a medical prescription, particularly for aesthetic purposes such as weight loss, which can lead to various health problems, including ventricular arrhythmia. The present work aims to use a glassy carbon electrode modified with Super P carbon black (SPCB/GCE) to quantify hydrochlorothiazide through Linear Sweep Adsorptive Stripping Voltammetry (LSAdSV). The modification of the GCE with SPCB significantly improved the response of hydrochlorothiazide. Furthermore, due to the adsorptive nature of charge transport, applying preconcentration time enhanced sensitivity. The optimized system provided a linear range of 0.5 to 30.0 μmol L -1 with a detection limit of 0.083 μmol L -1 . Pharmaceutical tablet analyses indicated approximately 25 mg per tablet, which was confirmed by the UV-vis and in agreement with that indicated by the manufacturer. Furthermore, analyses of the tea, synthetic urine, tap water and lake water samples indicated recovery values close to 100%, demonstrating that there was no matrix effect. Therefore, it is possible to infer that the proposed method together with the sensor modified with carbon black nanoparticles presented excellent results, demonstrating that it can be an alternative method of monitoring this drug in different samples.

Background: Cyclin-dependent kinases (CDK) 4/6 inhibitors have significantly improved outcomes for patients with ER+/HER2- breast cancer. Nevertheless, they differ from each other in terms of chemical, biological, and pharmacological features, as well as toxicity profiles. We aim to determine whether QTc prolongation is caused by CDK4/6i in general or if it is associated with ribociclib only., Methods: We systematically searched PubMed, Embase, and Cochrane Library for randomized controlled trials (RCTs) comparing the prevalence of QTc prolongation as an adverse event in HR+ breast cancer patients treated with CDK4/6i vs those without CDK4/6i. We pooled relative risk (RR) and mean difference (MD) with 95% confidence interval (CI) for the binary endpoint of QT prolongation., Results: We included 14 RCTs comprising 16 196 patients, of whom 8576 underwent therapy with CDK4/6i. An increased risk of QTc prolongation was associated with the use of CDK4/6i (RR = 2.35, 95% CI = 1.67 to 3.29, P < .001; I2 = 44%). Subgroup analyses revealed a significant increase in the QTc interval for the ribociclib and palbociclib cohorts. The ribociclib subgroup showed a relative risk of 3.12 (95% CI = 2.09 to 4.65, P < .001; I2 = 12%), whereas the palbociclib subgroup had a relative risk of 1.51 (95% CI = 1.05 to 2.15, P = .025; I2 = 0%)., Conclusion: Palbociclib was associated with QTc prolongation; however, the relative risk for any grade QTc was quantitively twice with ribociclib. Furthermore, grade 3 QTc prolongations were observed exclusively with ribociclib. These results are important for guiding clinical decision-making and provide reassurance regarding the overall safety profile of this drug class., (© The Author(s) 2024. Published by Oxford University Press.)

Purpose: Laparoscopic pancreatoduodenectomy (LPD) has emerged as an alternative to open technique in treating periampullary tumors. However, the safety and efficacy of LPD compared to open pancreatoduodenectomy (OPD) remain unclear. Thus, we conducted an updated meta-analysis to evaluate the efficacy and safety of LPD versus OPD in patients with periampullary tumors, with a particular focus on the pancreatic ductal adenocarcinoma patient subgroup., Methods: According to PRISMA guidelines, we searched PubMed, Embase, and Cochrane Library in December 2023 for randomized controlled trials (RCTs) that directly compare LPD versus OPD in patients with periampullary tumors. Endpoints and sensitive analysis were conducted for short-term endpoints. All statistical analysis was performed using R software version 4.3.1 with a random-effects model., Results: Five RCTs yielding 1018 patients with periampullary tumors were included, of whom 511 (50.2%) were randomized to the LPD group. Total follow-up time was 90 days. LPD was associated with a longer operation time (MD 66.75; 95% CI 26.59 to 106.92; p = 0.001; I 2  = 87%; Fig. 1A), lower intraoperative blood loss (MD - 124.05; 95% CI - 178.56 to - 69.53; p < 0.001; I 2  = 86%; Fig. 1B), and shorter length of stay (MD - 1.37; 95% IC - 2.31 to - 0.43; p = 0.004; I 2  = 14%; Fig. 1C) as compared with OPD. In terms of 90-day mortality rates and number of lymph nodes yield, no significant differences were found between both groups., Conclusion: Our meta-analysis of RCTs suggests that LPD is an effective and safe alternative for patients with periampullary tumors, with lower intraoperative blood loss and shorter length of stay., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Electroencephalogram (EEG) recorded as response to transcranial magnetic stimulation (TMS) can be highly informative of cortical reactivity and connectivity. Reliable EEG interpretation requires artifact removal as the TMS-evoked EEG can contain high-amplitude artifacts. Several methods have been proposed to uncover clean neuronal EEG responses. In practice, determining which method to select for different types of artifacts is often difficult. Here, we used a unified data cleaning framework based on beamforming to improve the algorithm selection and adaptation to the recorded signals. Beamforming properties are well understood, so they can be used to yield customized methods for EEG cleaning based on prior knowledge of the artifacts and the data. The beamforming implementations also cover, but are not limited to, the popular TMS-EEG cleaning methods: independent component analysis (ICA), signal-space projection (SSP), signal-space-projection-source-informed-reconstruction method (SSP-SIR), the source-estimate-utilizing noise-discarding algorithm (SOUND), data-driven Wiener filter (DDWiener), and the multiple-source approach. In addition to these established methods, beamforming provides a flexible way to derive novel artifact suppression algorithms by considering the properties of the recorded data. With simulated and measured TMS-EEG data, we show how to adapt the beamforming-based cleaning to different data and artifact types, namely TMS-evoked muscle artifacts, ocular artifacts, TMS-related peripheral responses, and channel noise. Importantly, beamforming implementations are fast to execute: We demonstrate how the SOUND algorithm becomes orders of magnitudes faster via beamforming. Overall, the beamforming-based spatial filtering framework can greatly enhance the selection, adaptability, and speed of EEG artifact removal., (© 2024. The Author(s).)

Competing Interests: We declare no competing interests.

Importance: Clinical trial data on adjuvant therapy in patients with non-clear cell renal cell carcinoma (RCC) are scant., Objective: To evaluate the effect of adjuvant everolimus after nephrectomy on recurrence-free survival (RFS) and overall survival (OS) in patients with localized papillary and chromophobe RCC., Design, Setting, and Participants: This prespecified subgroup analysis of a phase 3 randomized clinical trial, EVEREST, included patients enrolled between April 1, 2011, and September 15, 2016. Eligible patients had fully resected RCC at intermediate-high risk (pT1 grade 3-4, N0 to pT3a grade 1-2, N0) or very-high risk (pT3a grade 3-4 to pT4 any grade or N+) for recurrence who had received radical or partial nephrectomy. Final analyses was completed in March 2022., Intervention: The intervention group received 54 weeks of everolimus (10 mg orally daily); the control group received a matching placebo., Main Outcomes and Measures: The main outcomes were RFS, OS, and rates of adverse events. For testing the hazard ratio (HR) for treatment effect, a Cox regression model was used for both OS and RFS., Results: Of 1545 adult patients with treatment-naive, nonmetastatic, fully resected RCC in EVEREST, 109 had papillary RCC (median [range] age, 60 [19-81] years; 82 [75%] male; 50 patients [46%] with very high-risk disease) and 99 had chromophobe RCC (median [range] age 51 [18-71] years; 53 [54%] male; 34 patients [34%] with very high-risk disease). Among 57 patients with papillary RCC in the intervention group, 26 (46%) completed 54 weeks of treatment, and among 53 patients with chromophobe RCC in the intervention group, 26 (49%) completed 54 weeks of treatment. With a median (IQR) follow-up of 76 (61-96) months, adjuvant everolimus did not improve RFS compared with placebo in either papillary RCC (5-year RFS: 62% vs 70%; HR, 1.19; 95% CI, 0.61-2.33; P = .61) or chromophobe RCC (5-year RFS: 79% vs 77%; HR, 0.89; 95% CI, 0.37-2.13; P = .79). In the combined non-clear RCC cohort, grade 3 or higher adverse events occurred in 48% of patients who received everolimus and 9% of patients who received placebo., Conclusions and Relevance: In this clinical trial assessing the use of adjuvant everolimus, postoperative everolimus did not show evidence of improved RFS among patients with papillary or chromophobe RCC, and results from the study do not support adjuvant everolimus for this cohort. However, since the lower bounds of the 95% CIs were 0.61 and 0.89, respectively, potential treatment benefit in these subgroups cannot be ruled out., Trial Registration: ClinicalTrials.gov Identifier: NCT01120249.

The growing concerns on environmental pollution and sustainability have raised the interest on the development of functional biobased materials for different applications, including food packaging, as an alternative to the fossil resources-based counterparts, currently available in the market. In this work, functional wood inspired biopolymeric nanocomposite films were prepared by solvent casting of suspensions containing commercial beechwood xylans, cellulose nanofibers (CNF) and lignosulfonates (magnesium or sodium), in a proportion of 2:5:3 wt%, respectively. All films presented good homogeneity, translucency, and thermal stability up to 153 °C. The incorporation of CNF into the xylan/lignosulfonates matrix provided good mechanical properties to the films (Young's modulus between 1.08 and 3.79 GPa and tensile strength between 12.75 and 14.02 MPa). The presence of lignosulfonates imparted the films with antioxidant capacity (DPPH radical scavenging activity from 71.6 to 82.4 %) and UV barrier properties (transmittance ≤19.1 % (200-400 nm)). Moreover, the films obtained are able to successfully delay the browning of packaged fruit stored over 7 days at 4 °C. Overall, the obtained results show the potential of using low-cost and eco-friendly resources for the development of sustainable active food packaging materials., Competing Interests: Declaration of competing interest The authors proclaim that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this manuscript., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: We assessed the utility of red blood cell (RBC) CD105 and side scatter (SSC) parameters by flow cytometry for the detection of low-grade myelodysplastic neoplasms (MDS) in bone marrow specimens., Methods: Ten RBC parameters incorporating CD105 or SSC combined with the Meyerson-Alayed scoring system (MASS) metrics were retrospectively evaluated by flow cytometry for utility in detecting low-grade MDS (n = 56) compared with cytopenic controls (n = 86)., Results: Myelodysplastic neoplasms were associated with 7 of the RBC parameters in univariate analysis. Multivariate analysis using cutoff values based on optimal and 95% specificity levels of the RBC metrics and the MASS parameters revealed the SSC ratio of CD105-positive and CD105-negative RBC fractions (CD105+/- SSC); the percentage and coefficient of variation of the CD105-positive fraction of RBCs (CD105%, CD105+CV) emerged as significant RBC variables. Two simple scoring schemes using these RBC values along with MASS parameters were identified: 1 using CD105+/- SSC, CD105%, and CD105+CV combined with the percentage of CD177-positive granulocytes (CD177%), myeloblast percentage (CD34%), and granulocyte SSC (GranSSC), and the other incorporating CD105+/- SSC, CD105+CV, CD177%, CD34%, GranSSC, and B-cell progenitor percentage. Both demonstrated a sensitivity of approximately 80%, with a specificity of roughly 90% for the detection of MDS compared with cytopenic controls., Conclusions: The red blood cell parameter, CD105+/- SSC, appears to be beneficial in the evaluation of low-grade MDS by flow cytometry., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Studies have reported the occurrence of gastrointestinal (GI) symptoms, primarily diarrhea, in COVID-19. However, the pathobiology regarding COVID-19 in the GI tract remains limited. This work aimed to evaluate SARS-CoV-2 Spike protein interaction with gut lumen in different experimental approaches. Here, we present a novel experimental model with the inoculation of viral protein in the murine jejunal lumen, in vitro approach with human enterocytes, and molecular docking analysis. Spike protein led to increased intestinal fluid accompanied by Cl - secretion, followed by intestinal edema, leukocyte infiltration, reduced glutathione levels, and increased cytokine levels [interleukin (IL)-6, tumor necrosis factor-α, IL-1β, IL-10], indicating inflammation. Additionally, the viral epitope caused disruption in the mucosal histoarchitecture with impairment in Paneth and goblet cells, including decreased lysozyme and mucin, respectively. Upregulation of toll-like receptor 2 and toll-like receptor 4 gene expression suggested potential activation of local innate immunity. Moreover, this experimental model exhibited reduced contractile responses in jejunal smooth muscle. In barrier function, there was a decrease in transepithelial electrical resistance and alterations in the expression of tight junction proteins in the murine jejunal epithelium. Additionally, paracellular intestinal permeability increased in human enterocytes. Finally, in silico data revealed that the Spike protein interacts with cystic fibrosis transmembrane conductance regulator (CFTR) and calcium-activated chloride conductance (CaCC), inferring its role in the secretory effect. Taken together, all the events observed point to gut impairment, affecting the mucosal barrier to the innermost layers, establishing a successful experimental model for studying COVID-19 in the GI context., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: Outcomes data for DNA-damaging therapeutics for men with prostate cancer (PC) and non- BRCA1/2 homologous recombination repair (HRR) mutations are limited. We evaluated outcomes by HRR alteration in men with PC treated with poly(ADP-ribose)polymerase inhibitors (PARPi) and/or platinum chemotherapy., Methods: Retrospective data from the PROMISE consortium were used. Clinical outcomes differences were assessed between patients with BRCA1 / 2 mutations (cohort A) and those with HRR mutations without direct BRCA complex interaction (cohort B: ATM , CDK12 , CHEK1 , CHEK2 , and FANCL ). Outcomes in patients with HRR mutations with direct BRCA complex interaction were also explored (cohort C: RAD51B/C/D , RAD54L2 , BARD1 , GEN1 , PALB2 , FANCA , and BRIP1 )., Results: One hundred and forty-six patients received PARPi (cohort A: 94, cohort B: 45, cohort C: 7) and 104 received platinum chemotherapy (cohort A: 48, cohort B: 44, cohort C: 10). PSA50 response rate to PARPi was higher in cohort A (61%) than cohort B (5%), P < .001. Median clinical/radiographic progression-free survival (crPFS) with PARPi in cohort A was significantly longer than in cohort B: 15.9 versus 8.7 months, P = .005. PSA50 response rate to platinum therapy was higher in cohort A (62%) than in cohort B (32%), P = .024, although crPFS was not significantly different. PSA50 response rate to PARPi and platinum was 40% and 32%, respectively, in cohort C. In multivariable analysis, cohort A had significantly improved overall survival and crPFS compared with cohort B with PARPi but not platinum chemotherapy., Conclusion: Patients with BRCA1/2 -mutated PC had significantly improved outcomes to PARPi but not platinum chemotherapy compared with those with HRR mutations without direct BRCA complex interaction.