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Nevin Manimala Statistics

Discovery of a Novel Cyclopeptide as Tyrosinase Inhibitor for Skin Lightening

Skin Res Technol. 2025 Sep;31(9):e70207. doi: 10.1111/srt.70207.

ABSTRACT

BACKGROUND: Melanin synthesis plays a crucial role in skin pigmentation, and inhibiting tyrosinase, the key enzyme in melanin production, is a primary strategy for developing skin-lightening agents. This study investigates the tyrosinase inhibitory potential of CHP-9, a novel cyclopeptide, and evaluates its cytotoxicity and efficacy as a cosmetic depigmenting agent.

METHODS: CHP-9 was synthesized via a solid-phase peptide synthesis strategy. The tyrosinase inhibitory activity was assessed using an enzymatic assay, while its effects on melanin content were evaluated in cultured human melanocytes. The MTT assay was performed to assess cytotoxicity across a range of CHP-9 concentrations (0.0781-10 mg/mL). Molecular docking simulations were conducted to elucidate the interaction between CHP-9 and human tyrosinase (PDB ID: 5M8M). Statistical analysis was performed using GraphPad Prism Software, and significance was determined via one-way ANOVA.

RESULTS: CHP-9 exhibited significant tyrosinase inhibition (28.57% at 1% concentration) and reduced melanin content in treated melanocytes from 30.90 ± 1.13 to 23.51 ± 1.14 µg/mL. Cytotoxicity assays confirmed CHP-9’s high biocompatibility, with cell viability exceeding 90% at concentrations up to 2.5 mg/mL. Docking studies revealed strong binding affinity between CHP-9 and key tyrosinase residues via hydrogen bonding, supporting its inhibitory mechanism.

CONCLUSIONS: CHP-9 exhibited significant tyrosinase inhibition (28.57% at 1% concentration) and reduced melanin content in melanocytes, while maintaining over 90% cell viability at effective doses. These findings suggest that CHP-9 is a safe and effective candidate for cosmetic skin-lightening applications. Further research is needed to enhance formulation stability and evaluate long-term efficacy in vivo.

PMID:40939092 | DOI:10.1111/srt.70207

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Nevin Manimala Statistics

Longitudinal Associations of Social Isolation, Systemic Inflammation, and Cognitive Function Among Older Adults With Diabetes: Cross-Lagged Examination

Sci Diabetes Self Manag Care. 2025 Sep 12:26350106251371080. doi: 10.1177/26350106251371080. Online ahead of print.

ABSTRACT

PURPOSE: The purpose of the study was to examine the cross-lagged longitudinal associations between social isolation and cognitive function among older adults with diabetes and to investigate the mediating role of systemic inflammation in these associations.

METHODS: Secondary data from the Health and Retirement Study were utilized across 3 waves (2006, 2010, and 2014). To examine the longitudinal relationships between social isolation and cognitive function, a cross-lagged panel modeling approach was employed, with particular attention to the mediating role of C-reactive protein. A sequential predictor procedure was used; initially, only social isolation and cognitive function were analyzed; subsequently, sociodemographic covariates were controlled for; and finally, health-related covariates were added.

RESULTS: Data from 1336 older adults with diabetes in the United States were analyzed. In the partially adjusted model, reciprocal negative associations between social isolation and cognitive function were identified. However, these reciprocal negative associations were no longer statistically significant after accounting for health-related covariates. C-reactive protein did not serve as a mediator in the link between social isolation and cognitive function regardless of adjustments for covariates.

CONCLUSION: Given the reciprocal associations between social isolation and poorer cognitive function, a feedback loop may exist between these 2 factors. It is crucial to identify mediating mechanisms to disrupt this vicious cycle.

PMID:40939083 | DOI:10.1177/26350106251371080

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Just-in-Time Adaptive Interventions: Where Are We Now and What Is Next?

Annu Rev Psychol. 2025 Sep 12. doi: 10.1146/annurev-psych-121024-044244. Online ahead of print.

ABSTRACT

The past decade has seen a surge in developing just-in-time adaptive interventions (JITAIs)-an intervention approach that leverages advancements in digital technologies to address the rapidly changing needs of individuals in daily life. This article provides an overview of the state of science on JITAI development and highlights important directions for future research. We explain what a JITAI is (and what it is not) and review the scientific and practical rationales underlying this approach. We also call attention to three key challenges relating to the development of JITAIs. The first challenge is that individuals may not be able to engage with (i.e., invest energy in) an intervention when they need it most in daily life. The second concerns the generally suboptimal engagement of individuals in interventions that leverage digital technologies as currently implemented. The third concerns the paucity of research on ways to harness the power of social relationships in JITAIs. We conclude that much research effort is needed to build more sophisticated and effective JITAIs.

PMID:40939059 | DOI:10.1146/annurev-psych-121024-044244

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Nevin Manimala Statistics

Malnutrition Mortality Among Older Adults by County and Race and/or Ethnicity in the United States, 2000-2019

J Am Geriatr Soc. 2025 Sep 12. doi: 10.1111/jgs.70042. Online ahead of print.

ABSTRACT

BACKGROUND: Older adults are at an increased risk of malnutrition due to chronic diseases and social vulnerabilities. This study estimates protein-energy malnutrition mortality rates among adults aged 65-74 and ≥ 75 by race and ethnic population group and county.

METHODS: We analyzed death data from the National Vital Statistics System and population data from the National Center for Health Statistics from 2000 to 2019. We calculated county-level mortality rates using small-area estimation methods, adjusting for misclassifications in death certificates. The primary outcome was deaths attributed to malnutrition. The exposures were to populations (American Indian/Alaskan Native [AIAN], Asian, Black, Hispanic/Latino, and White) and the county.

RESULTS: From 2000 to 2019, malnutrition mortality rates increased in individuals aged ≥ 75 from 19.5 (95% uncertainty interval [UI]: 18.8-20.1) to 49.2 (48.4-50.0) deaths per 100,000, and in those aged 65-74 from 2.2 (2.0-2.3) to 4.6 (4.4-4.7). In 2019, Black individuals had the highest national mortality rates: 60.8 (58.2-63.3) for ≥ 75 years and 7.7 (7.3-8.2) for 65-74 years. In 2019, a county in Georgia had the highest rate for White individuals aged ≥ 75 at 334.9 (236.6-464.8), and a county in Montana had the highest for AIAN individuals aged 65-74 at 34.9 (13.1-72.0). Counties in the New York metro had the lowest mortality rates across all population groups and ages.

CONCLUSION: Malnutrition mortality rates have increased among older adults, varying by geography and population group, underscoring the need for targeted nutritional interventions.

PMID:40939057 | DOI:10.1111/jgs.70042

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Personal Care Aides in Adult Day Services Centers and Residential Care Communities: United States, 2022

Natl Health Stat Report. 2025 Jul 29;(217):1. doi: 10.15620/cdc/174600.

ABSTRACT

INTRODUCTION: Personal care aides (aides) are a key part of the long-term care infrastructure and provide hands-on care and support with essential activities of daily living to older and disabled Americans. This report presents the number of aides employed in adult day services centers (ADSC) and residential care communities (RCC), the hours they spend with their service users, and their training and benefits.

METHODS: Data are from the ADSC and RCC provider components of the 2022 National Post-acute and Long-term Care Study, conducted biennially by the National Center for Health Statistics. The study includes several questions on staffing, including about the number of registered nurses (RNs), licensed practical nurses (LPNs) or licensed vocational nurses (LVNs), and aides employed directly by ADSCs and RCCs. Full-time equivalent (FTE) staff is based on the number of full-time and part-time employees. A measure of hours per user (participant or resident) per day was used to compare staffing levels in the two settings relative to the number of users. Responses to questions on number of hours of training required and types of training and benefits offered to aides were used to compare in and across ADSC and RCC settings.

RESULTS: Of the 15,600 nursing (RN, LPN or LVN, and aide) FTEs employed in ADSCs and 452,000 employed in RCCs, the majority were aides (63.2% and 76.0%, respectively). Both settings often employed at least one aide (56.2% and 75.6%). The average total of all nursing staffing hours per participant or resident per day was 1 hour and 34 minutes for ADSCs and 4 hours and 25 minutes for RCCs. A lower percentage of ADSCs than RCCs offered training in dementia care (50.8% and 72.3%) and end-of-life issues (19.7% and 58.4%).

PMID:40939053 | DOI:10.15620/cdc/174600

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The Efficacy and Safety of Transcranial Photobiomodulation for Mild Cognitive Impairment Due to Alzheimer’s Disease: A Randomized, Double-Blind, Sham-Controlled Study

Photobiomodul Photomed Laser Surg. 2025 Sep;43(9):411-416. doi: 10.1177/15578550251369575.

ABSTRACT

Background: Transcranial photobiomodulation (tPBM) is a promising noninvasive neuromodulation modality with potential therapeutic benefits for neurodegenerative diseases. Infrared light delivered by a tPBM device penetrates the cortex, stimulating neuronal activity by increasing mitochondrial adenosine triphosphate production and enhancing regional cerebral blood flow. Objective: This study investigated the efficacy and safety of a self-administered, at-home, wearable tPBM device for improving cognitive function in individuals with mild cognitive impairment (MCI) due to Alzheimer’s disease (AD). Methods: Individuals with MCI due to AD, diagnosed according to the National Institute on Aging and Alzheimer’s Association criteria, with a Korean version of Mini-Mental State Examination-2 (K-MMSE2) score of 23-27 and a global Clinical Dementia Rating (CDR) score of 0.5-1.0 were enrolled. Subjects self-administered tPBM six times per week for 12 weeks. Assessments were conducted at weeks 7 and 13 using the Korean version of the Montreal Cognitive Assessment (K-MoCA), K-MMSE2, the Korean version of the Consortium to Establish a Registry for Alzheimer’s Disease, and the Geriatric Depression Scale. Results: A total of 26 participants were enrolled. The treatment group showed a statistically significant improvement in K-MoCA scores at week 13 (p < 0.05) compared with the sham group. Although K-MMSE2 scores improved in the treatment group, the difference was not statistically significant. No serious adverse events were reported. Conclusion: Findings suggest that tPBM is an effective and safe home-use intervention for individuals with MCI, with promising therapeutic and preventative roles in Alzheimer’s dementia.

PMID:40939031 | DOI:10.1177/15578550251369575

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Accelerating Systematic Reviews: A Novel One-Week Screening Protocol Using Rule-Based Automation with AI-Assisted Python Coding

Am J Physiol Heart Circ Physiol. 2025 Sep 12. doi: 10.1152/ajpheart.00374.2025. Online ahead of print.

ABSTRACT

The exponential growth in academic publishing – exceeding 2 million papers annually 2023 – has rendered traditional systematic review methods unsustainable1-3. These conventional approaches typically require 6-24 months for completion4-6, creating critical delays between evidence availability and clinical implementation. While existing automation tools demonstrate workload reductions of 30-72.5%, their machine learning dependencies create barriers to immediate implementation7-10. Additionally, direct AI screening methods involve substantial computational costs, lack real-time adaptability, suffer from inconsistent performance across different research domains, and provide no clear audit trail for regulatory compliance. We present a one-week systematic review acceleration protocol using rule-based automation where artificial intelligence (AI) assists with code generation. Researchers define screening criteria, then use AI language models (Claude, ChatGPT) as coding assistants. This protocol employs a two-phase screening process: (1) rule-based title/abstract screening and (2) rule-based full-text analysis, while adhering to established systematic review guidelines such as Cochrane methodology and PRISMA reporting5, 6. The rule-based system provides immediate implementation with complete transparency, while validation framework guides researchers in systematically testing screening sensitivity to minimize false negatives and ensure comprehensive study capture; meta-analysis and statistical synthesis remain manual processes requiring human expertise. We demonstrate the protocol’s application through a case study examining cardiac fatty acid oxidation in heart failure with preserved ejection fraction (HFpEF)11, and validated through a separate review examining e-cigarette versus traditional cigarette cardiopulmonary effects, which successfully processed 3,791 records12. This protocol represents a substantial advancement in systematic review methodology, making high-quality evidence synthesis more accessible across a broad range of scientific disciplines.

PMID:40939020 | DOI:10.1152/ajpheart.00374.2025

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Impact of Levetiracetam Cost on Epilepsy in a Resource-limited Country

Clin Neuropharmacol. 2025 Sep 11. doi: 10.1097/WNF.0000000000000656. Online ahead of print.

ABSTRACT

OBJECTIVES: High treatment costs remain a major barrier for people with epilepsy (PWE), leading to significant treatment gaps. At the University of Malaya Medical Centre (UMMC), levetiracetam (LEV) is sold at a retail price (self-paying), but some patients receive subsidization. This study aimed to study the impact of medication costs on adherence, dosing, and quality of life among self-paying versus subsidized patients.

METHODS: This cross-sectional study was conducted at a tertiary care center in Kuala Lumpur, Malaysia. A structured questionnaire was used to assess the medication adherence, dosing, and quality of life among patients prescribed LEV, incorporating the Malaysian Medication Adherence Scale (MALMAS) and the Quality of Life in Epilepsy Inventory (QOLIE-31).

RESULTS: Among the 172 respondents, those under the subsidization scheme (86, 50%) had a higher mean maximum dose (2055.2 mg vs. 1688.4 mg, P=0.013) and were less likely to reduce LEV intake due to cost concerns (7.7% vs. 23.7%, P=0.021). In the self-paying group, more patients had low adherence (23.3% vs. 17.6%), the seizure-free rate was lower (22.1% vs. 29.1%), and the mean QOLIE-31 score was lower (60.5 vs. 62.4) than the subsidized group, but the differences were not statistically significant.

CONCLUSIONS: Financial support is crucial in optimizing LEV dosing and adherence, with subsidized patients receiving higher doses and being less likely to reduce intake due to cost.

PMID:40939014 | DOI:10.1097/WNF.0000000000000656

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Competition and cooperation of assembly sequences in recurrent neural networks

PLoS Comput Biol. 2025 Sep 12;21(9):e1013403. doi: 10.1371/journal.pcbi.1013403. Online ahead of print.

ABSTRACT

Neural activity sequences are ubiquitous in the brain and play pivotal roles in functions such as long-term memory formation and motor control. While conditions for storing and reactivating individual sequences have been thoroughly characterized, it remains unclear how multiple sequences may interact when activated simultaneously in recurrent neural networks. This question is especially relevant for weak sequences, comprised of fewer neurons, competing against strong sequences. Using a non-linear rate -based and a spiking model with discrete, pre-configured assemblies, we demonstrate that weak sequences can compensate for their competitive disadvantage either by increasing excitatory connections between subsequent assemblies or by cooperating with other co-active sequences. Further, our models suggest that such cooperation can negatively affect sequence speed unless subsequently active assemblies are paired. Our analysis characterizes the conditions for successful sequence progression in isolated, competing, and cooperating assembly sequences, and identifies the distinct contributions of recurrent and feed-forward projections. This proof-of-principle study shows how even disadvantaged sequences can be prioritized for reactivation, a process which has recently been implicated in hippocampal memory processing.

PMID:40939008 | DOI:10.1371/journal.pcbi.1013403

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Maternal-infant rotavirus-specific antibody kinetics to inform timing of vaccine boosting in Malawi: An observational study

PLoS Med. 2025 Sep 12;22(9):e1004734. doi: 10.1371/journal.pmed.1004734. Online ahead of print.

ABSTRACT

METHODS AND FINDINGS: We collected longitudinal serum samples from 84 infants at five time points between January 2021 and October 2023, and cross-sectional samples from 798 healthy individuals aged 0-86 years between December 2022 and June 2024. For participants under 18 years of age, a written consent was obtained from parents or guardians, with assent from the child where appropriate, individuals aged 18 years and above provided written informed consent directly. Rotavirus-specific IgG and IgA concentrations were measured using a gold standard enzyme-linked immunosorbent assay (ELISA). Rotavirus gastroenteritis case data were extracted from ongoing surveillance during the same period. All participants were recruited from the Southern region of Malawi, a rotavirus high-burden setting. We applied linear mixed-effects and generalised linear models with natural splines to assess age-dependent trends in antibody levels. Prior to scheduled Rotarix rotavirus vaccine dose 1, the median maternally derived rotavirus-specific IgG levels were significantly lower in infants who were seropositive following vaccination compared with those who remained seronegative (5,745.0 IU/ml versus 9,689.8 IU/ml; Wilcoxon-test, p = 0.015). Infants with the lowest maternal IgG levels were over five times more likely to seroconvert (odds ratio [OR] = 5.8, 95% confidence interval (CI): 1.6-24.2; Chi-square test, p = 0.012). An exponential decay model estimated that the median IgG concentration in non-seroconverters crossed the seroconversion-probability threshold at 6.2 months. Population-level analyses revealed IgG concentrations reached their nadir at 8.4 months, coinciding with a peak in severe rotavirus gastroenteritis cases at 9 months. Serum IgA levels peaked at 9 months and were associated with a decline in disease incidence between 9 and 17 months. Key limitations include the small number of non-seroconverting infants (n = 27) who were unexposed during follow-up and the observational study design. These factors may influence interpretation, but the findings nonetheless provide important insights into rotavirus antibody dynamics.

CONCLUSIONS: These findings suggest that administering a booster dose between 6 and 8 months of age, when maternal antibody titer is low and severe rotavirus gastroenteritis risk is high, may enhance the immunogenicity and effectiveness of the rotavirus vaccine in LMICs.

PMID:40938968 | DOI:10.1371/journal.pmed.1004734