Individual and regional differences in the effects of school racial segregation on Black students' health.

Background: School racial segregation in the US has risen steadily since the 1990s, propelled by Supreme Court decisions rolling back the legacy of Brown v. Board. Quasi-experimental research has shown this resegregation harms Black students' health. However, whether individual or family characteristics (e.g., higher family incomes) are protective against segregation's health harms-or whether segregation is more damaging in regions of the US with fewer public sector investments-remains unclear. We leverage the quasi-random timing of school districts being released from Brown-era integration plans to examine heterogeneity in the association between resegregation and Black students' health. Methods & findings: We took an instrumental variables approach, using the timing of integration order releases as an instrument for school segregation and analyzing a pre-specified list of theoretically-motivated modifiers in the Panel Study of Income Dynamics. In sensitivity analyses, we fit OLS models that directly adjusted for relevant covariates. Results suggest resegregation may have been particularly harmful in the South, where districts resegregated more quickly after order releases. We find little evidence that the effects of school segregation differed across family income, gender, or age. Conclusion: The end of court-ordered integration threatens the health of Black communities-especially in the US South. Modestly higher incomes do not appear protective against school segregation's harms. Research using larger samples and alternative measures of school segregation-e.g., between districts, instead of within districts-may further our understanding of segregation's health effects, especially in Northern states.

Fabrication of atelocollagen-coated bioabsorbable suture and the evaluation of its regenerative efficacy in Achilles tendon healing using a rat experimental model.

Recently, the incidence of Achilles tendon ruptures (ATRs) has become more common, and repair surgery using a bioabsorbable suture is generally preferred, particularly in the case of healthy patients. Sutures composed of poly(lactic-co-glycolic acid) (PLGA) are commonly used in ATR surgeries. Nevertheless, owing to the inherent limitations of PLGA, novel bioabsorbable sutures that can accelerate Achilles tendon healing are sought. Recently, several studies have demonstrated the beneficial effects of atelocollagen on tendon healing. In this study, poly(3,4-dihydroxy-L-phenylalanine) (pDOPA), a hydrophilic biomimetic material, was used to modify the hydrophobic surface of a PLGA suture (Vicryl, VC) for the stable coating of atelocollagen on its surface. The main objective was to fabricate an atelocollagen-coated VC suture and evaluate its performance in the healing of Achilles tendon using a rat model of open repair for ATR. Structural analyses of the surface-modified suture indicated that the collagen was successfully coated on the VC/pDOPA suture. Postoperative in vivo biomechanical analysis, histological evaluation, ultrastructural/morphological analyses, and western blotting confirmed that the tendons in the VC/pDOPA/Col group exhibit superior healing than those in the VC and VC/pDOPA groups after 1 and 6 weeks following the surgery. The this study suggests that atelocollagen-coated PLGA/pDOPA sutures are preferable for future medical applications, especially in the repair of ATR.

Deciphering the Systemic Impact of Herbal Medicines on Allergic Rhinitis: A Network Pharmacological Approach.

Allergic rhinitis (AR) is a systemic allergic disease that has a considerable impact on patients' quality of life. Current treatments include antihistamines and nasal steroids; however, their long-term use often causes undesirable side effects. In this context, traditional Asian medicine (TAM), with its multi-compound, multi-target herbal medicines (medicinal plants), offers a promising alternative. However, the complexity of these multi-compound traits poses challenges in understanding the overall mechanisms and efficacy of herbal medicines. Here, we demonstrate the efficacy and underlying mechanisms of these multi-compound herbal medicines specifically used for AR at a systemic level. We utilized a modified term frequency-inverse document frequency method to select AR-specific herbs and constructed an herb-compound-target network using reliable databases and computational methods, such as the Quantitative Estimate of Drug-likeness for compound filtering, STITCH database for compound-target interaction prediction (with a high confidence score threshold of 0.7), and DisGeNET and CTD databases for disease-gene association analysis. Through this network, we conducted AR-related targets and pathway analyses, as well as clustering analysis based on target-level information of the herbs. Gene ontology enrichment analysis was conducted using a protein-protein interaction network. Our research identified 14 AR-specific herbs and analyzed whether AR-specific herbs are highly related to previously known AR-related genes and pathways. AR-specific herbs were found to target several genes related to inflammation and AR pathogenesis, such as PTGS2, HRH1, and TBXA2R. Pathway analysis revealed that AR-specific herbs were associated with multiple AR-related pathways, including cytokine signaling, immune response, and allergic inflammation. Additionally, clustering analysis based on target similarity identified three distinct subgroups of AR-specific herbs, corroborated by a protein-protein interaction network. Group 1 herbs were associated with the regulation of inflammatory responses to antigenic stimuli, while Group 2 herbs were related to the detection of chemical stimuli involved in the sensory perception of bitter taste. Group 3 herbs were distinctly associated with antigen processing and presentation and NIK/NF-kappa B signaling. This study decodes the principles of TAM herbal configurations for AR using a network pharmacological approach, providing a holistic understanding of drug effects beyond specific pathways.

The Impact of Physical Activity on Thyroid Health: Insights From Representative Data in Korea.

CONTEXT: Thyroid hormones are essential for energy metabolism related to thermogenesis and oxygen consumption. OBJECTIVE: This study evaluated the potential association of thyroid function including thyroid peroxidase antibodies (TPOAb) with physical activity in nationally representative data. DESIGN/SETTING/PARTICIPANTS: This retrospective cohort study used data from the Korean National Health and Nutrition Examination Survey between 2013 and 2015. Physical activity (PA) was assessed using metabolic equivalents based on the validated Korean version of the International Physical Activity Questionnaire Short Form. PA level was categorized into 3 groups of high, moderate, and low. Participants with abnormal thyroid function test, restricted activity, or previous history of thyroid disease were excluded in the study. RESULTS: A total of 5372 participants was finally selected. The free T4 level was lowest in the low PA group, while TSH was not significantly different among the groups. TPOAb titers increased in the following order: moderate PA, low PA, and high PA. After adjustment for confounding factors, moderate PA was associated with a high T4 level and a decrease in TSH and TPOAb with significance. However, there were no significant changes in free T4, TSH, or TPOAb titer in the high PA group. In a subanalysis, females with moderate PA showed a significant decrease in TSH and TPOAb. In both males and females, insulin sensitivity was increased with moderate PA. In obese participants, TSH negatively correlated with PA, and free T4 levels decreased in the low PA. The sensitivity to thyroid hormone did not differ in our study. CONCLUSION: The present study found an association between thyroid function and moderate PA. Therefore, moderate-intensity PA should be recommended to improve thyroid function.

Deep Learning Analysis with Gray Scale and Doppler Ultrasonography Images to Differentiate Graves' Disease.

CONTEXT: Thyrotoxicosis requires accurate and expeditious differentiation between Graves' disease (GD) and thyroiditis to ensure effective treatment decisions. OBJECTIVE: This study aimed to develop a machine learning algorithm using ultrasonography and Doppler images to differentiate thyrotoxicosis subtypes, with a focus on GD. METHODS: This study included patients who initially presented with thyrotoxicosis and underwent thyroid ultrasonography at a single tertiary hospital. A total of 7,719 ultrasonography images from 351 patients with GD and 2,980 images from 136 patients with thyroiditis were used. Data augmentation techniques were applied to enhance the algorithm's performance. Two deep learning models, Xception and EfficientNetB0_2, were employed. Performance metrics such as accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and F1 score were calculated for both models. Image pre-processing, neural network model generation, and neural network training results verification were performed using DEEP:PHI® platform. RESULTS: The Xception model achieved 84.94% accuracy, 89.26% sensitivity, 73.17% specificity, 90.06% PPV, 71.43% NPV, and an F1 score of 89.66 for the diagnosis of GD. The EfficientNetB0_2 model exhibited 85.31% accuracy, 90.28% sensitivity, 71.78% specificity, 89.71% PPV, 73.05% NPV, and an F1 score of 89.99. CONCLUSION: Machine learning models based on ultrasound and Doppler images showed promising results with high accuracy and sensitivity in differentiating GD from thyroiditis.

Acupuncture for tinnitus: a scoping review of clinical studies.

BACKGROUND: Acupuncture treatment for tinnitus has received attention owing to its potential as an alternative to conventional treatment modalities. We conducted a scoping review to identify detailed information on acupuncture treatment methods used in clinical studies and to provide useful information for practitioners, patients, and researchers. METHODS: 　Medline, Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, Oriental Medicine Advanced Searching Integrated System (OASIS), Korean Research Information Sharing Service (RISS), DataBase Periodical Information Academic (DBPIA), and the China National Knowledge Infrastructure (CNKI) were searched from their inception to December 2023. This review included single-arm trials, open-label randomized controlled trials (RCTs), and double-blind RCTs using needle-type acupuncture to treat tinnitus in English, Chinese, and Korean. We investigated basic and detailed information on the acupuncture treatment methods, assessment methods, and study outcomes. Network analysis was also conducted to evaluate the centrality between acupoints in the double-blind RCTs. RESULTS: We included 106 articles. There were 11 single-arm trials, 90 open-label RCTs, and 5 double-blind RCTs. Most (89.6%) of these studies were conducted in China. Manual acupuncture was the most common type of acupuncture in treatment group. A total of 119 acupuncture points were used 1,138 times. The most frequently used acupoints were local points around the ear (TE17, GB2, SI19, and TE21). Both local and distant acupoints were used simultaneously in these studies. The treatment duration of 20 to 39 days, 10 to 19 sessions of treatment, the mean acupuncture duration of 30 minutes, needle diameter of 0.30 mm x 40 mm, and needling depth over 30 mm and less than 50 mm were confirmed as the most common. CONCLUSION: This study outcomes will enable future acupuncture studies on tinnitus to perform more effective and standardized acupuncture treatments in selecting acupoints and procedures. Furthermore, the study has implications for informing clinicians and students about more impactful acupuncture strategies for addressing tinnitus.

Stiffness assisted cell-matrix remodeling trigger 3D mechanotransduction regulatory programs.

Engineered matrices provide a valuable platform to understand the impact of biophysical factors on cellular behavior such as migration, proliferation, differentiation, and tissue remodeling, through mechanotransduction. While recent studies have identified some mechanisms of 3D mechanotransduction, there is still a critical knowledge gap in comprehending the interplay between 3D confinement, ECM properties, and cellular behavior. Specifically, the role of matrix stiffness in directing cellular fate in 3D microenvironment, independent of viscoelasticity, microstructure, and ligand density remains poorly understood. To address this gap, we designed a nanoparticle crosslinker to reinforce collagen-based hydrogels without altering their chemical composition, microstructure, viscoelasticity, and density of cell-adhesion ligand and utilized it to understand cellular dynamics. This crosslinking mechanism utilizes nanoparticles as crosslink epicenter, resulting in 10-fold increase in mechanical stiffness, without other changes. Human mesenchymal stem cells (hMSCs) encapsulated in 3D responded to mechanical stiffness by displaying circular morphology on soft hydrogels (5 kPa) and elongated morphology on stiff hydrogels (30 kPa). Stiff hydrogels facilitated the production and remodeling of nascent extracellular matrix (ECM) and activated mechanotransduction cascade. These changes were driven through intracellular PI3AKT signaling, regulation of epigenetic modifiers and activation of YAP/TAZ signaling. Overall, our study introduces a unique biomaterials platform to understand cell-ECM mechanotransduction in 3D for regenerative medicine as well as disease modelling.

Material assembly from collective action of shape-changing polymers.

Some animals form transient, responsive and solid-like ensembles through dynamic structural interactions. These ensembles demonstrate emergent responses such as spontaneous self-assembly, which are difficult to achieve in synthetic soft matter. Here we use shape-morphing units comprising responsive polymers to create solids that self-assemble, modulate their volume and disassemble on demand. The ensemble is composed of a responsive hydrogel, liquid crystal elastomer or semicrystalline polymer ribbons that reversibly bend or twist. The dispersions of these ribbons mechanically interlock, inducing reversible aggregation. The aggregated liquid crystal elastomer ribbons have a 12-fold increase in the yield stress compared with cooled dispersion and contract by 34% on heating. Ribbon type, concentration and shape dictate the aggregation and govern the global mechanical properties of the solid that forms. Coating liquid crystal elastomer ribbons with a liquid metal begets photoresponsive and electrically conductive aggregates, whereas seeding cells on hydrogel ribbons enables self-assembling three-dimensional scaffolds, providing a versatile platform for the design of dynamic materials.

Gastroparesis might not be uncommon in patients with diabetes mellitus in a real-world clinical setting: a cohort study.

BACKGROUND: This study investigated the frequency of diabetic gastroparesis and associated risk factors in a real-world clinical setting. METHODS: This retrospective cross-sectional study included patients who underwent assessments of solid gastric emptying time (GET) by technetium-99 m scintigraphy between May 2019 and December 2020. We categorized patients into three groups according to gastric retention of technetium-99 m: rapid (< 65% at 1 h or < 20% at 2 h), normal (≤60% at 2 h and/or ≤ 10% at 4 h), and delayed (> 60% at 2 h and/or > 10% at 4 h). RESULTS: Patients with diabetes mellitus (DM) were more likely to show abnormal GET than those without DM (119 [70.8%] vs. 16 [44.4%]). The mean glycated A1c was 10.3% in DM patients. DM patients with normal GET were significantly younger (57.2 years, P = 0.044) than those with delayed (65.0 years) or rapid GET (60.2 years). Fasting glucose levels were the lowest in the normal GET group and the highest in the rapid GET group (delayed: 176.3 mg/dL, normal: 151.2 mg/dL, rapid: 181.0 mg/dL, P = 0.030). However, glycated A1c was not significantly different among the delayed, normal, and rapid GET groups in patients with DM. Patients with delayed and rapid GET showed a higher frequency of retinopathy (6.0 vs. 15.5%, P = 0.001) and peripheral neuropathy (11.3 vs. 24.4%, P = 0.001) than those with normal GET. In the multinomial logistic regression analysis, retinopathy demonstrated a positive association with delayed GET, while nephropathy showed a significant negative correlation. CONCLUSION: DM gastroparesis in the clinical setting was not uncommon. Abnormal GET, including delayed and rapid GET, was associated with DM retinopathy or peripheral neuropathy.

Associations of Everyday and Lifetime Experiences of Discrimination With Willingness to Undergo Alzheimer Disease Predictive Testing.

BACKGROUND AND OBJECTIVES: Rapid developments in Alzheimer disease (AD) biomarker research suggest that predictive testing may become widely available. To ensure equal access to AD predictive testing, it is important to understand factors that affect testing interest. Discrimination may influence attitudes toward AD testing, particularly among racially and ethnically minoritized populations, because of structural racism in health care systems. This study examined whether everyday or lifetime discrimination experiences shape interest in AD predictive testing. METHODS: In the 2010 and 2012 biennial Health and Retirement Study waves, respondents were randomly selected to complete questions on interest in receiving free testing that could determine whether they would develop AD in the future. The exposures were everyday discrimination (6 items) and lifetime discrimination (7 items); both were transformed into a binary variable. Logistic regression models predicting interest in AD testing were controlled for deciles of propensity scores for each discrimination measure. Odds ratios were re-expressed as risk differences (RDs). RESULTS: Our analytic sample included 1,499 respondents. The mean age was 67 (SD = 10.2) years, 57.4% were women, 65.7% were White, and 80% endorsed interest in AD predictive testing. Most of the participants (54.7%) experienced everyday discrimination in at least one domain; 24.1% experienced major lifetime discrimination in at least one domain. Those interested in predictive testing were younger (66 vs 70 years) and more likely to be Black (20% vs 15%) or Latinx (14% vs 8%) than participants uninterested in testing. The probability of wanting an AD test was not associated with discrimination for Black (RD everyday discrimination = -0.026; 95% CI [-0.081 to 0.029]; RD lifetime discrimination = -0.012; 95% CI [-0.085 to 0.063]) or Latinx (RD everyday discrimination = -0.023, 95% CI [-0.082 to 0.039]; RD lifetime discrimination = -0.011; 95% CI [-0.087 to 0.064]) participants. DISCUSSION: Despite historical and contemporary experiences of discrimination, Black and Latinx individuals express interest in AD testing. However, Black and Latinx individuals remain underrepresented in AD research, including research on AD testing. Interest in personalized information about dementia risk may be a pathway to enhance their inclusion in research and clinical trials.

A Nationwide Population-Based Study for the Recurrence and Comorbidities in Sudden Sensorineural Hearing Loss.

OBJECTIVES: The aims of this study were to investigate the cumulative recurrence rate of SSNHL and to determine association between comorbidities and recurrence of SSNHL by comparing patients with and without recurrence. METHODS: Using the National Health Insurance Claims Database (NHICD) from 2009 to 2020, we conducted a population-based study. We only enrolled patients whose records showed a prescription for steroid and audiometry findings as well as an appropriate diagnostic code. Recurrence of SSNHL was defined as an episode of SSNHL greater than or equal to 3 months after the first episode of SSNHL. We compared the recurrence rate of SSNHL according to age and number of SSNHL recurrences. We also explored comorbidities including autoimmune, metabolic, chronic renal diseases, cancer, and migraine associated with recurrent SSNHL. RESULTS: A total of 257,123 patients were identified. We found that 6.7% (17,270/257,123) of the patients had at least one recurrence of SSNHL. The recurrence rate increases with the number of recurrences and over time. The incidence per 100,000 people tended to increase with age, and the recurrence rate appeared to decrease with age. We found an increase in the incidence of ankylosing spondylitis (AS) and a decrease in the incidence of type 2 diabetes mellitus (T2DM), myocardial infarction (MI), and hemorrhagic stroke in patients with recurrence. CONCLUSION: For patients with recurrence or AS, considerable efforts should be made to prevent recurrence. As SSNHL is an emergent otologic condition, when symptoms occur, they should receive immediate treatment. Additional well-designed population-based studies are required to generalize our results. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:1417-1425, 2024.

Effects of organizational and individual factors on nurses' practice of central line-associated bloodstream infection prevention.

BACKGROUND: This study explored rarely investigated organizational factors (resource support and organizational culture) in conjunction with well-established individual factors (demographic characteristics, knowledge, and awareness) that impact nurses' practice of central line-associated bloodstream infection (CLABSI) prevention. METHODS: Self-reported questionnaire data were collected from 173 nurses recruited from departments that use central venous catheters (ie, intensive care units, emergency rooms, hemodialysis rooms, and oncology wards) in tertiary hospitals in South Korea. Multiple regression analyses were performed to examine the effects of individual and organizational factors. RESULTS: Organizational culture (ß = 0.350) had the greatest association with CLABSI prevention practice, followed by awareness (ß = 0.328) and department (ß = -0.217; all ps < 0.01). These variables explained 41.1% of the variance in CLABSI prevention practice (F = 20.996, P < .001). Higher self-reported CLABSI prevention practice was associated with a favorable organizational culture and higher awareness. Emergency room nurses' CLABSI prevention practice was notably inferior as compared to nurses in other departments. DISCUSSION: Organizational culture is the most significant factor affecting nurses' practice of CLABSI prevention. CONCLUSIONS: An organizational culture with environmental improvements and resource support as well as infection prevention education and awareness-building programs should be fostered.

Plantar warts successfully treated with bee venom: A case report.

BACKGROUND: Plantar warts, or verruca plantaris, are common cutaneous lesions of the plantar surface caused by the human papilloma virus (HPV) infection. Current treatments include salicylic acid, cryotherapy, bleomycin, and immunotherapy; however, they have limitations of low-cure rates or side effects. Plantar warts treated with bee venom (BV) have not been reported. Here we present a case of a patient who showed complete remission of multiple plantar warts after BV treatment. CASE PRESENTATION: A 13-year-old boy experienced total of 16 plantar warts and visited department of dermatology of Korean Medicine. BV was injected into wart sites. Warts were completely removed at the end of the 8-week treatment with no adverse event recorded. There was improvement during the follow-up after 4 weeks. CONCLUSION: This is the first case of plantar warts that improved with BV injection. This study suggests that BV may be a therapeutic option for individuals who cannot receive cryotherapy due to pain during and after treatment or who have refractory or relapsed warts.

Exploring the Association between Thyroid Function and Frailty: Insights from Representative Korean Data.

BACKGRUOUND: This study investigates the association between thyroid function and frailty in the old patients using representative data. METHODS: The study was conducted using data from the Korea National Health and Nutrition Examination Survey conducted from 2013 to 2015. The study population included 2,416 participants aged 50 years and older with available thyroid function test data. Frailty assessment was performed using the Fried frailty phenotype. The prevalence of frailty was analyzed across different thyroid diseases and thyroid function parameters. RESULTS: The significant association between thyroid dysfunction and frailty was observed in overt hyperthyroidism and subclinical hyperthyroidism. After adjusting for various factors, the association between thyroid dysfunction and frailty remained significant. On the other hand, overt hypothyroidism did not show a significant association with frailty in the adjusted analysis. For individuals with overt hyperthyroidism and subclinical hyperthyroidism, higher levels of free thyroxine (FT4) were significantly associated with an increased risk of frailty (aOR >999; 95% CI, >999 to 999). Among individuals with overt hypothyroidism, lower level of FT4 levels and high thyrotropin (TSH) levels showed a significant association with frailty risk (FT4: aOR, <0.01; TSH: aOR, 999). In participants with subclinical hypothyroidism, there were no significant associations between parameters for thyroid and frailty risk. CONCLUSION: These findings suggest that thyroid dysfunction, particularly overt hyperthyroidism and subclinical hyperthyroidism, may be associated with an increased risk of frailty in the old patients.

Associations between body composition and the risk of fracture according to bone mineral density in postmenopausal women: a population-based database cohort study.

OBJECTIVE: We aimed to investigate the associations of body composition and the risk of fracture in postmenopausal women, stratified based on bone mineral density. METHODS: A population-based cohort study using the database of the National Screening Program for Transitional Ages with women aged 66 years was performed. Bone mineral density was categorized as normal, osteopenia, and osteoporosis. The following body mass index (BMI) categories for general obesity were used: underweight (<18.5), normal (18.5-22.9), overweight (23-24.9), obese (25-29.9), and severely obese (≥30 kg/m2). Waist circumference (WC) used for central obesity assessment was categorized into 5 groups. Newly diagnosed fracture during the follow-up period defined based on ICD-10 codes was the primary outcome. RESULTS: During 7.7 ± 1.4 years of follow-up, 41 672 (17.9%) participants experienced any fracture, 20 326 (8.7%) experienced vertebral fractures (VFs), and 2883 (1.2%) experienced hip fractures (HFs). The adjusted hazard ratios (aHRs) for any fracture showed a progressive increase with higher BMI and WC categories in individual with osteopenia and osteoporosis. Regarding VF, aHR was highest in severely obese individuals with osteoporosis (aHR [95% CI], 3.45 [2.99-3.97]) and in individuals with WC ≥ 95 cm with osteoporosis (4.79 [4.09-5.60]). The aHR [95% CI] for HF was highest in the underweight group with osteopenia (1.94 [1.16-3.27]) and osteoporosis (2.96 [2.15-4.10]). In central obesity individuals with WC ≥ 95 cm, aHR [95% CI] for HF was 2.80 [1.91-4.91]. CONCLUSIONS: General obesity and central obesity are not protective against any fracture, VF and HF in postmenopausal women with osteopenia or osteoporosis.

Ceramide synthase 4 overexpression exerts oncogenic properties in breast cancer.

BACKGROUND: Ceramide, a bioactive signaling sphingolipid, has long been implicated in cancer. Members of the ceramide synthase (CerS) family determine the acyl chain lengths of ceramides, with ceramide synthase 4 (CerS4) primarily generating C18-C20-ceramide. Although CerS4 is known to be overexpressed in breast cancer, its role in breast cancer pathogenesis is not well established. METHODS: To investigate the role of CerS4 in breast cancer, public datasets, including The Cancer Genome Atlas (TCGA) and two Gene Expression Omnibus (GEO) datasets (GSE115577 and GSE96058) were analyzed. Furthermore, MCF-7 cells stably overexpressing CerS4 (MCF-7/CerS4) as a model for luminal subtype A (LumA) breast cancer were produced, and doxorubicin (also known as Adriamycin [AD])-resistant MCF-7/ADR cells were generated after prolonged treatment of MCF-7 cells with doxorubicin. Kaplan-Meier survival analysis assessed the clinical significance of CERS4 expression, while Student's t-tests or Analysis of Variance (ANOVA) compared gene expression and cell viability in different MCF-7 cell lines. RESULTS: Analysis of the public datasets revealed elevated CERS4 expression in breast cancer, especially in the most common breast cancer subtype, LumA. Persistent CerS4 overexpression in MCF-7 cells activated multiple cancer-associated pathways, including pathways involving sterol regulatory element-binding protein, nuclear factor kappa B (NF-κB), Akt/mammalian target of rapamycin (mTOR), and ß-catenin. Furthermore, MCF-7/CerS4 cells acquired doxorubicin, paclitaxel, and tamoxifen resistance, with concomitant upregulation of ATP-binding cassette (ABC) transporter genes, such as ABCB1, ABCC1, ABCC2, ABCC4, and ABCG2. MCF-7/CerS4 cells were characterized by increased cell migration and epithelial-mesenchymal transition (EMT). Finally, CERS4 knockdown in doxorubicin-resistant MCF-7/ADR cells resulted in reduced activation of cancer-associated pathways (NF-κB, Akt/mTOR, ß-catenin, and EMT) and diminished chemoresistance, accompanied by ABCB1 and ABCC1 downregulation. CONCLUSIONS: Chronic CerS4 overexpression may exert oncogenic effects in breast cancer via alterations in signaling, EMT, and chemoresistance. Therefore, CerS4 may represent an attractive target for anticancer therapy, especially in LumA breast cancer.

Neighborhood resources and risk of cognitive decline among a community-dwelling long-term care population in the U.S.

Objective: To examine the associations between neighborhood resources (i.e., number of restaurants, recreation centers, or social services for seniors and persons with disability per land area) and cognitive decline among a community-dwelling long-term care population and whether they differ by baseline cognition status. Study design: Prospective longitudinal cohort study. Methods: We used a longitudinal dataset that assessed over a two-year period older adults receiving state-funded home- and community-based services in Michigan Metropolitan areas (N = 9,802) and applied nonlinear mixed models with a random intercept with Poisson distribution. Results: Cognitively intact older adults were less likely to experience cognitive decline when they resided in resource-rich neighborhoods, compared to those cognitively intact but living in neighborhoods that lacked resources. But their cognitively impaired or dementia-diagnosed counterparts did not similarly benefit from living in neighborhoods with rich resources. Conclusions: Neighborhood resources may be an important aspect of intervention to mitigate cognitive decline before older adults become cognitively impaired.