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Abstract Objective This study used real-world observational data to compare profiles of patients receiving different first-line treatment for hormone receptor positive (ER+), HER2 negative, metastatic breast cancer (MBC): CDK4/6 inhibitors (CDK4/6i) in combination with endocrine therapy (ET) versus ET alone. Method From a nationwide electronic health record-derived Flatiron Health de-identified database including 280 US cancer clinics, we identified patients with hormone receptor positive, HER2 negative, metastatic breast cancer receiving 1st -line therapy with ET alone or CDK4/6i plus ET between February 2015 and November 2021. Patient sociodemographic status, MBC treatment regimen and outcomes were the focus of this analysis. Patient characteristics were compared using t-tests and chi-square tests. Logistic regression analysis was performed to examine the association of patient characteristics with the likelihood of receiving 1st -line CDK4/6i plus ET vs. ET alone. Kaplan-Meier method and Cox proportional hazards were used to test the impact of 1st -line treatment regimen on real-world progression-free survival (PFS) and overall survival (OS). Baseline characteristics were balanced using inverse probability weighting (IPW). Results The study population included 3,917 patients receiving CDK4/6i plus ET (n = 2170) and ET alone (n = 1747) for their MBC. Compared to patients receiving ET alone, those receiving CDK4/6i plus ET were younger (mean age 66.8 vs. 68.6, p

Abstract Background High consumption of sugar-sweetened beverages (SSB) is a global health concern. Additionally, sugar-sweetened beverage (SSB) consumption is disproportionately high among adolescents and adults in rural Appalachia. The primary study objective is to determine the intervention effects of Kids SIPsmartER on students’ SSB consumption. Secondary objectives focus on caregivers’ SSB consumption and secondary student and caregiver outcomes [e.g, body mass index (BMI), quality of life (QOL)]. Methods This Type 1 hybrid, cluster randomized controlled trial includes 12 Appalachian middle schools (6 randomized to Kids SIPsmartER and 6 to control). Kids SIPsmartER is a 6-month, 12 lesson, multi-level, school-based, behavior and health literacy program aimed at reducing SSB among 7th grade middle school students. The program also incorporates a two-way text message strategy for caregivers. In this primary prevention intervention, all 7th grade students and their caregivers from participating schools were eligible to participate, regardless of baseline SSB consumption. Validated instruments were used to assess SSB behaviors and QOL. Height and weight were objectively measured in students and self-reported by caregivers. Analyses included modified two-part models with time fixed effects that controlled for relevant demographics and included school cluster robust standard errors. Results Of the 526 students and 220 caregivers, mean (SD) ages were 12.7 (0.5) and 40.6 (6.7) years, respectively. Students were 55% female. Caregivers were mostly female (95%) and White (93%); 25% had a high school education or less and 33% had an annual household income less than $50,000. Regardless of SSB intake at baseline and relative to control participants, SSB significantly decreased among students [-7.2 ounces/day (95% CI = -10.7, -3.7); p 24 SSB ounces/day at baseline (i.e., high consumers), the ES increased to 0.45 and 0.95, respectively. There were no significant effects for student or caregiver QOL indicators or objectively measured student BMI; however, caregiver self-reported BMI significantly decreased in the intervention versus control schools (p = 0.001). Conclusions Kids SIPsmartER was effective at reducing SSB consumption among students and their caregivers in the rural, medically underserved Appalachian region. Importantly, SSB effects were even stronger among students and caregivers who were high consumers at baseline. Trial registration Clincialtrials.gov: NCT03740113. Registered 14 November 2018– Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03740113 .

Abstract Background Adult smoking rates in the USA are highest in economically depressed rural Appalachia. Pharmacist-delivered tobacco cessation support that incorporates medication therapy management (such as the QuitAid intervention) is a promising approach to address this need. Methods Twenty-four adult smokers recruited between September and November 2021 through an independent pharmacy in rural Appalachia were randomized in a non-blinded 2 × 2 × 2 factorial design to (1) pharmacist delivered QuitAid intervention (yes vs. no); (2) combination nicotine replacement therapy (NRT) gum + NRT patch (vs. NRT patch); and/or (3) 8 weeks of NRT (vs. standard 4 weeks). Participants received 4 weeks of NRT patch in addition to the components to which they were assigned. Participants completed baseline and 3-month follow-up assessments. Primary outcomes were feasibility of recruitment and randomization, retention, treatment adherence, and fidelity. Results Participants were recruited in 7 weeks primarily through a referral process, commonly referred to as ask-advise-connect (61%). Participants were on average 52.4 years old, 29.2% were male and the majority were white (91.6%) and Non-Hispanic (91.7%). There was a high level of adherence to the interventions, with 85% of QuitAid sessions completed, 83.3% of the patch used, and 54.5% of gum used. Participants reported a high level of satisfaction with the program, and there was a high level of retention (92%). Conclusions This demonstration pilot randomized controlled study indicates that an ask-advise-connect model for connecting rural smokers to smoking cessation support and providing QuitAid for smoking cessation is feasible and acceptable among rural Appalachian smokers and independent pharmacists. Further investigation into the efficacy of a pharmacist-delivered approach for smoking cessation is needed. Trial registration The trial was retrospectively registered at ClinicalTrials.gov. Trial #: NCT05649241.

Abstract Background Cronkhite-Canada syndrome (CCS) is a rare, nonhereditary disease characterized by diffuse gastrointestinal polyposis and ectodermal abnormalities. Although it has been proposed to be a chronic inflammatory condition, direct evidence of its pathogenesis is lacking. This study aims to investigate the pathophysiology of CCS by analyzing transcriptomic changes in the colonic microenvironment. Methods Next-generation sequencing-based genome-wide transcriptional profiling was performed on colonic hamartomatous polyps from four CCS patients and normal colonic mucosa from four healthy volunteers. Analyses of differential expression and multiple enrichment analyses were conducted from the molecular level to the cellular level. Quantitative real-time PCR (qRT-PCR) was carried out to validate the sequencing accuracy in samples from six CCS patients and six healthy volunteers. Results A total of 543 differentially expressed genes were identified, including an abundance of CC- and CXC-chemokines. Innate immune response-related pathways and processes, such as leukocyte chemotaxis, cytokine production, IL-17, TNF, IL-1 and NF-kB signaling pathways, were prominently enhanced in CCS colonic polyps. Upregulation of wound healing, epithelial-mesenchymal transition, Wnt, and PI3K-Akt signaling pathways were also observed. Enrichment analyses at different levels identified extracellular structure disorganization, dysfunction of the gut mucosal barrier, and increased angiogenesis. Validation by qRT-PCR confirmed increased expression of the LCN2, IL1B, CXCL1, and CXCL3 genes in CCS colonic polyps. Conclusions This case-control whole transcriptome analysis of active CCS colonic hamartomatous polyps revealed intricate molecular pathways, emphasizing the role of the innate immune response, extracellular matrix disorganization, inflammatory cell infiltration, increased angiogenesis, and potential epithelial to mesenchymal transition. These findings supports CCS as a chronic inflammatory condition and sheds light on potential therapeutic targets, paving the way for more effective and personalized management of CCS in the future.

ObjectivesWe conducted a comprehensive meta-analysis to compare the effectiveness and safety of fluoroscopy-guided air enema reduction (FGAR) and ultrasound-guided hydrostatic enema reduction (UGHR) for the treatment of intussusception in pediatric patients.MethodsA systematic review and meta-analysis were conducted on retrospective studies obtained from various databases, including PUBMED, MEDLINE, Cochrane, Google Scholar, China National Knowledge Infrastructure (CNKI), WanFang, and VIP Database. The search included publications from January 1, 2003, to March 31, 2023, with the last search done on Jan 15, 2023.ResultsWe included 49 randomized controlled studies and retrospective cohort studies involving a total of 9,391 patients, with 4,841 in the UGHR and 4,550 in the FGAR. Specifically, UGHR exhibited a significantly shorter time to reduction (WMD = -4.183, 95% CI = (-5.402, -2.964), P < 0.001), a higher rate of successful reduction (RR = 1.128, 95% CI = (1.099, 1.157), P < 0.001), and a reduced length of hospital stay (WMD = -1.215, 95% CI = (-1.58, -0.85), P < 0.001). Furthermore, UGHR repositioning was associated with a diminished overall complication rate (RR = 0.296, 95% CI = (0.225, 0.389), P < 0.001) and a lowered incidence of perforation (RR = 0.405, 95% CI = (0.244, 0.670), P < 0.001).ConclusionUGHR offers the benefits of being non-radioactive, achieving a shorter reduction time, demonstrating a higher success rate in repositioning in particular, resulting in a reduced length of postoperative hospital stay, and yielding a lower overall incidence of postoperative complications, including a reduced risk of associated perforations.

Lysosomes are important cellular structures for human health as centers for recycling, signaling, metabolism and stress adaptation. However, the potential role of lysosomes in stress‐related emotions has long been overlooked. Here, it is found that lysosomal morphology in astrocytes is altered in the medial prefrontal cortex (mPFC) of susceptible mice after chronic social defeat stress. A screen of lysosome‐related genes revealed that the expression of the mucolipin 1 gene (Mcoln1; protein: mucolipin TRP channel 1) is decreased in susceptible mice and depressed patients. Astrocyte‐specific knockout of mucolipin TRP channel 1 (TRPML1) induced depressive‐like behaviors by inhibiting lysosomal exocytosis‐mediated adenosine 5′‐triphosphate (ATP) release. Furthermore, this stress response of astrocytic lysosomes is mediated by the transcription factor EB (TFEB), and overexpression of TRPML1 rescued depressive‐like behaviors induced by astrocyte‐specific knockout of TFEB. Collectively, these findings reveal a lysosomal stress‐sensing signaling pathway contributing to the development of depression and identify the lysosome as a potential target organelle for antidepressants. [ABSTRACT FROM AUTHOR]

As computer graphics technology continues to advance, Collision Detection (CD) has emerged as a critical element in fields such as virtual reality, computer graphics, and interactive simulations. CD is indispensable for ensuring the fidelity of physical interactions and the realism of virtual environments, particularly within complex scenarios like virtual assembly, where both high precision and real-time responsiveness are imperative. Despite ongoing developments, current CD techniques often fall short in meeting these stringent requirements, resulting in inefficiencies and inaccuracies that impede the overall performance of virtual assembly systems. To address these limitations, this study introduces a novel algorithm that leverages the capabilities of a Backpropagation Neural Network (BPNN) to optimize the structural composition of the Hybrid Bounding Volume Tree (HBVT). Through this optimization, the research proposes a refined Hybrid Hierarchical Bounding Box (HHBB) framework, which is specifically designed to enhance the computational efficiency and precision of CD processes. The HHBB framework strategically reduces the complexity of collision detection computations, thereby enabling more rapid and accurate responses to collision events. Extensive experimental validation within virtual assembly environments reveals that the proposed algorithm markedly improves the performance of CD, particularly in handling complex models. The optimized HBVT architecture not only accelerates the speed of collision detection but also significantly diminishes error rates, presenting a robust and scalable solution for real-time applications in intricate virtual systems. These findings suggest that the proposed approach offers a substantial advancement in CD technology, with broad implications for its application in virtual reality, computer graphics, and related fields. [ABSTRACT FROM AUTHOR]

Background: Cognitive function (CF) deterioration is a pressing concern in geriatric research. This study aimed to explore the relationship between physical activity (PA) and CF in older adults. Methods: This study adopted a dual approach, employing both observational and genetic approaches through data from the National Health and Nutrition Examination Survey (NHANES) 2011-2014 and Mendelian Randomization (MR) analysis. For the NHANES component, PA levels were evaluated using the Global Physical Activity Questionnaire, and CF was assessed via standardized tests. Multivariate regression, threshold effect analysis, smoothing curve fitting, and subgroup analyses were conducted to examine the association between PA and CF. In parallel, MR methods, using genetic variants as instrumental variables, assessed the causal impact of PA on CF and related conditions such as Alzheimer's disease and dementia. Results: Observational findings from NHANES demonstrated a positive correlation between PA and CF, notably among female participants. The detailed analysis identified specific thresholds of PA that correlate with cognitive enhancements. However, MR results did not support a significant causal relationship between PA and CF or dementia-related outcomes, indicating an absence of a direct genetic basis for the observational associations. Conclusion: Although observational data from NHANES suggest that PA is positively associated with CF in older adults, particularly among women, MR analysis did not confirm these findings as causally related. The discrepancy highlights the complexity of the PA-CF relationship and underscores the need for further research. These results emphasize the potential of PA as a modifiable risk factor for CF, though causal effects remain to be definitively established. [ABSTRACT FROM AUTHOR]

Introduction: Deep learning (DL) models predicting biomarker expression in images of hematoxylin and eosin (H&E)-stained tissues can improve access to multi-marker immunophenotyping, crucial for therapeutic monitoring, biomarker discovery, and personalized treatment development. Conventionally, these models are trained on ground truth cell labels derived from IHC-stained tissue sections adjacent to H&Estained ones, which might be less accurate than labels from the same section. Although many such DL models have been developed, the impact of ground truth cell label derivation methods on their performance has not been studied. Methodology: In this study, we assess the impact of cell label derivation on H&E model performance, with CD3+ T-cells in lung cancer tissues as a proof-ofconcept. We compare two Pix2Pix generative adversarial network (P2P-GAN)- based virtual staining models: one trained with cell labels obtained from the same tissue section as the H&E-stained section (the 'same-section' model) and one trained on cell labels from an adjacent tissue section (the 'serial-section' model). Results: We show that the same-section model exhibited significantly improved prediction performance compared to the 'serial-section' model. Furthermore, the same-section model outperformed the serial-section model in stratifying lung cancer patients within a public lung cancer cohort based on survival outcomes, demonstrating its potential clinical utility. Discussion: Collectively, our findings suggest that employing ground truth cell labels obtained through the same-section approach boosts immunophenotyping DL solutions. [ABSTRACT FROM AUTHOR]

Chemodynamic therapy (CDT) has received increasing attention in recent years due to its effectiveness and specificity. However, the limited endogenous hydrogen peroxide (H2O2) concentration and resistance to reactive oxygen species in cancer cells hinder the further application of CDT. Here, an H2O2 self‐supplied nanosystem FCaO2@ZIF‐67‐2‐DG‐FA (FZDF) is synthesized to achieve efficient CDT improvement by Ca2+ overload and starvation therapy. Under folic acid‐mediated tumor targeting and endocytosis, the ZIF‐67 layer of FZDF is cleaved in the mildly acidic environment, releasing Co2+ and 2‐deoxy‐D‐glucose (2‐DG). The decomposition of exposed FCaO2 generates sufficient H2O2, which further produces abundant •OH via the Fenton‐like reaction of Co2+. Simultaneously, Ca2+ overload‐triggered mitochondrial dysfunction couples with glycolysis inhibition via 2‐DG‐induced starvation, which disrupts intracellular adenosine triphosphate (ATP) synthesis and amplifies the efficacy of CDT. Silicon nanoparticles released from FCaO2 are applied as in vitro fluorescent probes to image tumor cells overexpressing folate receptors. The results have presented that FZDF can actively accumulate in tumor cells, causing the mitochondrial membrane potential abnormality and a decrease in intracellular ATP content, thereby enhancing the self‐supplied CDT with less effect on normal cells and tissues. This work provides a novel strategy for constructing effective CDT nanosystems by hindering intracellular energy supply. [ABSTRACT FROM AUTHOR]

IntroductionDeep learning (DL) models predicting biomarker expression in images of hematoxylin and eosin (H&E)-stained tissues can improve access to multi-marker immunophenotyping, crucial for therapeutic monitoring, biomarker discovery, and personalized treatment development. Conventionally, these models are trained on ground truth cell labels derived from IHC-stained tissue sections adjacent to H&E-stained ones, which might be less accurate than labels from the same section. Although many such DL models have been developed, the impact of ground truth cell label derivation methods on their performance has not been studied.MethodologyIn this study, we assess the impact of cell label derivation on H&E model performance, with CD3+ T-cells in lung cancer tissues as a proof-of-concept. We compare two Pix2Pix generative adversarial network (P2P-GAN)-based virtual staining models: one trained with cell labels obtained from the same tissue section as the H&E-stained section (the ‘same-section’ model) and one trained on cell labels from an adjacent tissue section (the ‘serial-section’ model).ResultsWe show that the same-section model exhibited significantly improved prediction performance compared to the ‘serial-section’ model. Furthermore, the same-section model outperformed the serial-section model in stratifying lung cancer patients within a public lung cancer cohort based on survival outcomes, demonstrating its potential clinical utility.DiscussionCollectively, our findings suggest that employing ground truth cell labels obtained through the same-section approach boosts immunophenotyping DL solutions.

Nitrite (NO 2 - ) is widely present in the natural environment and human daily life. Excessive NO 2 - can cause harm to the environment and human health. Herein, silicon nanoparticles (SiNPs) with a fluorescence quantum yield of up to 70 % were synthesised using a one-pot hydrothermal method and combined with the common and inexpensive o-phenylenediamine (OPD) to achieve the detection of NO 2 - . Upon the addition of NO 2 - , the blue fluorescence of the SiNPs was quenched due to static quenching and Förster resonance energy transfer (FRET), while the yellow fluorescence of benzotriazole, the reaction product of OPD and NO 2 - , was enhanced, resulting in the fluorescence color change from blue to yellow. Based on these phenomena, a ratiometric fluorescence sensor integrated with smartphone imaging technology was developed. This sensor is notable for its portability, cost-effectiveness, and satisfactory detection limits (0.016 μM for ratiometric fluorescence and 1.64 μM for smartphone imaging). Importantly, it demonstrates high reliability and practicability in detecting NO 2 - in real water and food samples. This broadens the application of SiNPs in the sensing field and introduces new possibilities for NO 2 - detection in complex sample matrices., 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 Elsevier B.V. All rights reserved.)

Background: Psychological intervention nursing (PIN) has been considered to have a curative effect on cesarean section (CS) postoperative recovery. However, the therapeutic mechanisms remain obscure., Aim: To explore the effects of PIN combined with acupressure massage on CS postoperative recovery., Methods: A retrospective study was conducted on 150 pregnant women admitted to an obstetrics department between January 2020 and January 2023. The control group (CG) received acupressure therapy ( n = 73), and the intervention group (IG) received acupressure therapy and PIN therapy ( n = 77). Postoperative recovery time was assessed by anal-exhausting, defecation, bed activity, breastfeeding, and hospital stay times. Adverse effects, including infection, bleeding, limb numbness, intrauterine hematoma, urinary retention, and venous thromboembolism, were recorded. the pain visual analogue scale (VAS) was used to evaluate the degree of pain. Anxiety and depression status were qualitatively assessed using the self-rating anxiety scale (SAS), self-rating depression scale (SDS), and Edinburgh postpartum depression scale (EPDS). The Pittsburgh sleep quality index (PSQI) was used to compare sleep quality between the groups., Results: The baseline data and SAS, SDS, EPDS, and PSQI scores did not significantly differ before CS ( P > 0.05) and neither did complication rates between the two groups after CS ( P > 0.05). However, anal-exhausting, defecation, waking up, breastfeeding, and hospitalization times were significantly shorter for participants in the IG than those for participants in the CG ( P < 0.05). The VAS, SAS, SDS, EPDS, and PSQI scores of the IG were significantly lower than those of the CG ( P < 0.05)., Conclusion: PIN, combined with acupressure massage, effectively promotes maternal recovery, reduces post-CS pain, and improves postoperative negative emotions and sleeping quality., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Cognitive function ( CF ) deterioration is a pressing concern in geriatric research. This study aimed to explore the relationship between physical activity (PA) and CF in older adults., Methods: This study adopted a dual approach, employing both observational and genetic approaches through data from the National Health and Nutrition Examination Survey (NHANES) 2011-2014 and Mendelian Randomization (MR) analysis. For the NHANES component, PA levels were evaluated using the Global Physical Activity Questionnaire, and CF was assessed via standardized tests. Multivariate regression, threshold effect analysis, smoothing curve fitting, and subgroup analyses were conducted to examine the association between PA and CF. In parallel, MR methods, using genetic variants as instrumental variables, assessed the causal impact of PA on CF and related conditions such as Alzheimer's disease and dementia., Results: Observational findings from NHANES demonstrated a positive correlation between PA and CF , notably among female participants. The detailed analysis identified specific thresholds of PA that correlate with cognitive enhancements. However, MR results did not support a significant causal relationship between PA and CF or dementia-related outcomes, indicating an absence of a direct genetic basis for the observational associations., Conclusion: Although observational data from NHANES suggest that PA is positively associated with CF in older adults, particularly among women, MR analysis did not confirm these findings as causally related. The discrepancy highlights the complexity of the PA- CF relationship and underscores the need for further research. These results emphasize the potential of PA as a modifiable risk factor for CF , though causal effects remain to be definitively established., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Zhang and Zhang.)

In this paper, we consider decomposing an image into its cartoon and texture components. Traditional methods, which mainly rely on the gradient amplitude of images to distinguish between these components, often show limitations in decomposing small-scale, high-contrast texture patterns and large-scale, low-contrast structural components. Specifically, these methods tend to decompose the former to the cartoon image and the latter to the texture image, neglecting the scale features inherent in both components. To overcome these challenges, we introduce a new variational model which incorporates an L 0 -based total variation norm for the cartoon component and an L 2 norm for the scale space representation of the texture component. We show that the texture component has a small L 2 norm in the scale space representation. We apply a quadratic penalty function to handle the non-separable L 0 norm minimization problem. Numerical experiments are given to illustrate the efficiency and effectiveness of our approach.