Category: Nevin Manimala

Neurology. 2025 May 13;104(9):e213498. doi: 10.1212/WNL.0000000000213498. Epub 2025 Apr 17.

ABSTRACT

BACKGROUND AND OBJECTIVES: Radioimmunoprecipitation assay (RIPA) is the gold standard for acetylcholine receptor (AChR)-immunoglobulin G (IgG) detection in patients with myasthenia gravis (MG), with a reported specificity of ≈99%. The risk of “false” AChR-IgG positivity in clinical practice is often considered negligible, although data on large, real-life populations are scarce. The objective of this study was to determine the positive predictive value (PPV) and risk of false AChR-IgG positivity with RIPA in a large cohort of patients with suspected MG.

METHODS: We retrospectively identified patients consecutively tested for AChR-IgG by RIPA at the University-Hospital of Sassari over 20 years (2003-2022) (n = 4,795). Medical records of AChR-IgG-positive patients (titer ≥0.5 nmol/L) were reviewed by 2 investigators to identify nonmyasthenic cases with false antibody positivity, defined as follows: (1) clinical phenotypes not consistent with MG and/or (2) symptoms better explained by alternative diagnoses. The characteristics of myasthenic and nonmyasthenic patients with AChR-IgG positivity were compared. A sample of nonmyasthenic patients was retested by fixed cell-based assay (CBA).

RESULTS: Among 445 of 4,795 patients testing positive for AChR-IgG during the study period, 83 were excluded (insufficient information). Of 362 AChR-IgG-positive patients included, 50 (13.8%) were designated as nonmyasthenic. The PPV and specificity were 86.2% (95% CI 82.2-89.6) and 98.9% (95% CI 98.5-99.2), respectively. Alternative diagnoses in nonmyasthenic patients included ophthalmologic diseases (n = 8), rheumatic diseases (n = 7), pseudoptosis (n = 5), myopathy (n = 4), functional disorders (n = 3), cranial nerve palsy (n = 2), parkinsonism (n = 2), demyelinating diseases (n = 2), and others (n = 17). Compared with patients with MG, nonmyasthenic patients were younger (median age 65 [range 7-91] vs 38 [range 5-80] years), more frequently female (155/312 [49.8%] vs 37/50 [74%]), had lower AChR-IgG titers (median 6 [range 0.5-28] vs 0.7 [range 0.5-5.5] nmol/L), and were more likely to become seronegative on subsequent tests (9/120 [8%] vs 6/11 [55%]). After stratification by titer ≥1 nmol/L, the PPV increased to 96.6% (95% CI 94-98.3). Serum of 7 nonmyasthenic patients was retested by CBA, giving negative results (n = 6) or selective positivity against the fetal AChR isoform (n = 1).

DISCUSSION: False AChR-IgG positivity may occur in clinical practice with RIPA and associates with low antibody titer. Caution is needed when titers between 0.5 and 0.9 nmol/L are detected in low-probability situations because failure to recognize false antibody positivity may lead to misdiagnosis and inappropriate treatments.

PMID:40245350 | DOI:10.1212/WNL.0000000000213498

J Esthet Restor Dent. 2025 Apr 17. doi: 10.1111/jerd.13467. Online ahead of print.

ABSTRACT

OBJECTIVE: To compare the long-term microtensile bond strength (μTBS) to coronal dentin using pre-endodontic dentin sealing (PEDS) and post-endodontic adhesion (PEA) techniques under various endodontic irrigation protocols.

MATERIALS AND METHODS: Ten study groups (n = 10) were established based on the timing of adhesive application (PEDS versus PEA) and irrigation protocol: distilled water (control), 3% sodium hypochlorite (NaOCl), 3% NaOCl followed by 17% ethylenediaminetetraacetic acid (EDTA), 3% NaOCl followed by 17% EDTA and 2% chlorhexidine, and a mixture of 3% NaOCl and 9% etidronic acid (HEDP). Specimens underwent μTBS testing after a six-month microspecimen aging period. Fracture patterns were analyzed, and adhesive interfaces were assessed using scanning electron microscopy (SEM). Statistical analysis employed a mixed linear regression model with a 5% significance level.

RESULTS: PEDS consistently preserved high bond strength across all irrigation protocols (57.4-59.5 MPa), while PEA groups treated with endodontic irrigants resulted in significantly lower values (33.3-40.8 MPa; p < 0.001). No significant differences were observed within the PEDS groups (p > 0.05). SEM analysis revealed consistent hybrid layers in PEDS and PEA/Control groups, while PEA groups treated with endodontic irrigation solutions showed significant resin-dentin interface variations and interfacial gaps.

CONCLUSIONS: The PEDS technique preserved high and consistent μTBS regardless of the irrigation protocol, whereas endodontically irrigated PEA groups exhibited significantly reduced bond strength. PEDS offers a predictable approach to optimizing adhesive performance in endodontic-restorative treatments.

CLINICAL SIGNIFICANCE: Integrating PEDS into routine endodontic-restorative workflow is recommended to enhance long-term bond strength to coronal dentin. The PEDS technique ensures consistent adhesive performance regardless of the endodontic irrigation protocol, enhancing restorative predictability and treatment success while preserving tooth structure.

PMID:40245338 | DOI:10.1111/jerd.13467

J Craniofac Surg. 2025 Apr 17. doi: 10.1097/SCS.0000000000011399. Online ahead of print.

ABSTRACT

Advancements in natural language processing (NLP) have led to the emergence of large language models (LLMs) as potential tools for patient consultations. This study investigates the ability of reasoning-capable models to provide diagnostic and treatment recommendations for orofacial clefts. A cross-sectional comparative study was conducted using 20 questions based on Google Trends and expert experience, with both models providing responses to these queries. Readability was assessed using the Flesch-Kincaid Reading Ease (FRES), Flesch-Kincaid Grade Level (FKGL), sentence count, number of sentences, and percentage of complex words. No statistically significant differences were found in the readability metrics for FKGL (P = 0.064) and FRES (P = 0.56) between the responses of the 2 models. Physician evaluation using a 4-point Likert scale assessed accuracy, clarity, relevance, and trustworthiness, with Deepseek-R1 achieving significantly higher ratings overall (P = 0.041). However, GPT o1-preview exhibited notable empathy in certain clinical scenarios. Both models displayed complementary strengths, indicating potential for clinical consultation applications. Future research should focus on integrating these strengths within medical-specific LLMs to generate more reliable, empathetic, and personalized treatment recommendations.

PMID:40245329 | DOI:10.1097/SCS.0000000000011399

Proc Natl Acad Sci U S A. 2025 Apr 22;122(16):e2407626122. doi: 10.1073/pnas.2407626122. Epub 2025 Apr 17.

ABSTRACT

In order to forage for food, many animals regulate not only specific limb movements but the statistics of locomotor behavior, switching between long-range dispersal and local search depending on resource availability. How premotor circuits regulate locomotor statistics is not clear. Here, we analyze and model locomotor statistics and their modulation by attractive food odor in walking Drosophila. Food odor evokes three motor regimes in flies: baseline walking, upwind running during odor, and search behavior following odor loss. During search, we find that flies adopt higher angular velocities and slower ground speeds and turn for longer periods in the same direction. We further find that flies adopt periods of different mean ground speed and that these state changes influence the length of odor-evoked runs. We next developed a simple model of neural locomotor control that suggests that contralateral inhibition plays a key role in regulating the statistical features of locomotion. As the fly connectome predicts decussating inhibitory neurons in the premotor lateral accessory lobe (LAL), we gained genetic access to a subset of these neurons and tested their effects on behavior. We identified one population whose activation induces all three signature of local search and that regulates angular velocity at odor offset. We identified a second population, including a single LAL neuron pair, that bidirectionally regulates ground speed. Together, our work develops a biologically plausible computational architecture that captures the statistical features of fly locomotion across behavioral states and identifies neural substrates of these computations.

PMID:40244663 | DOI:10.1073/pnas.2407626122

JMIR Infodemiology. 2025 Apr 17;5:e59076. doi: 10.2196/59076.

ABSTRACT

BACKGROUND: The COVID-19 pandemic intensified the challenges associated with mental health and substance use (SU), with societal and economic upheavals leading to heightened stress and increased reliance on drugs as a coping mechanism. Centers for Disease Control and Prevention data from June 2020 showed that 13% of Americans used substances more frequently due to pandemic-related stress, accompanied by an 18% rise in drug overdoses early in the year. Simultaneously, a significant increase in social media engagement provided unique insights into these trends. Our study analyzed social media data from January 2019 to December 2021 to identify changes in SU patterns across the pandemic timeline, aiming to inform effective public health interventions.

OBJECTIVE: This study aims to analyze SU from large-scale social media data during the COVID-19 pandemic, including the prepandemic and postpandemic periods as baseline and consequence periods. The objective was to examine the patterns related to a broader spectrum of drug types with underlying themes, aiming to provide a more comprehensive understanding of SU trends during the COVID-19 pandemic.

METHODS: We leveraged a deep learning model, Robustly Optimized Bidirectional Encoder Representations from Transformers Pretraining Approach (RoBERTa), to analyze 1.13 billion Twitter (subsequently rebranded X) posts from January 2019 to December 2021, aiming to identify SU posts. The model’s performance was enhanced by a human-in-the-loop strategy that subsequently enriched the annotated data used during the fine-tuning phase. To gain insights into SU trends over the study period, we applied a range of statistical techniques, including trend analysis, k-means clustering, topic modeling, and thematic analysis. In addition, we integrated the system into a real-time application designed for monitoring and preventing SU within specific geographic locations.

RESULTS: Our research identified 9 million SU posts in the studied period. Compared to 2019 and 2021, the most substantial display of SU-related posts occurred in 2020, with a sharp 21% increase within 3 days of the global COVID-19 pandemic declaration. Alcohol and cannabinoids remained the most discussed substances throughout the research period. The pandemic particularly influenced the rise in nonillicit substances, such as alcohol, prescription medication, and cannabinoids. In addition, thematic analysis highlighted COVID-19, mental health, and economic stress as the leading issues that contributed to the influx of substance-related posts during the study period.

CONCLUSIONS: This study demonstrates the potential of leveraging social media data for real-time detection of SU trends during global crises. By uncovering how factors such as mental health and economic stress drive SU spikes, particularly in alcohol and prescription medication, we offer crucial insights for public health strategies. Our approach paves the way for proactive, data-driven interventions that will help mitigate the impact of future crises on vulnerable populations.

PMID:40244656 | DOI:10.2196/59076

Elife. 2025 Apr 17;13:RP102166. doi: 10.7554/eLife.102166.

ABSTRACT

Mammalian gut microbiomes are highly dynamic communities that shape and are shaped by host aging, including age-related changes to host immunity, metabolism, and behavior. As such, gut microbial composition may provide valuable information on host biological age. Here, we test this idea by creating a microbiome-based age predictor using 13,563 gut microbial profiles from 479 wild baboons collected over 14 years. The resulting ‘microbiome clock’ predicts host chronological age. Deviations from the clock’s predictions are linked to some demographic and socio-environmental factors that predict baboon health and survival: animals who appear old-for-age tend to be male, sampled in the dry season (for females), and have high social status (both sexes). However, an individual’s ‘microbiome age’ does not predict the attainment of developmental milestones or lifespan. Hence, in our host population, gut microbiome age largely reflects current, as opposed to past, social and environmental conditions, and does not predict the pace of host development or host mortality risk. We add to a growing understanding of how age is reflected in different host phenotypes and what forces modify biological age in primates.

PMID:40244653 | DOI:10.7554/eLife.102166

Invest Ophthalmol Vis Sci. 2025 Apr 1;66(4):44. doi: 10.1167/iovs.66.4.44.

ABSTRACT

PURPOSE: The lacrimal gland (LG) is the major source of aqueous tears, and insufficient LG secretion leads to aqueous-deficient dry eye (ADDE) disease. To provide a foundational description of LG’s protein expression patterns, we prepared protein extracts of LGs from a wild-type and an ADDE mouse model and analyzed the proteome by quantitative mass spectrometry.

METHODS: LGs were isolated from an ADDE mouse model, male non-obese diabetic (NOD) mice and control wild-type BALB/c mice (n = 6 each). Protein samples were prepared in urea-based lysis buffer and protein concentrations determined by the BCA method. The equivalent of 200 µg protein were tryptically digested and analyzed by nanoflow liquid chromatography tandem mass spectrometry (LC-MS/MS). Proteins were identified and quantified using the PEAKS X bioinformatics suite. Downstream differential protein expression analysis was performed using the MS-DAP R package. Selected significantly differentially expressed and detected proteins were subjected to spatial expression analysis using immunohistochemistry.

RESULTS: Cumulatively, the LC-MS/MS-based proteomics analyses of the murine LG samples identified a total of 31,932 peptide sequences resulting in 2617 protein identifications at a 1% false discovery rate at the peptide and protein level. Principal component analysis (PCA) and hierarchical cluster analysis revealed a separation of NOD and BALB/c samples. Overall, protein diversity was consistently higher in NOD samples. After applying global peptide filter criteria and peptide-to-protein rollup, 1750 remaining proteins were subjected to differential expression analysis using the MSqRob algorithm, which identified 580 proteins with statistically significant expression differences. Data are available via ProteomeXchange with identifier PXD060937. At the cellular level, the up- and downregulation of select proteins were confirmed by immunohistochemistry.

CONCLUSIONS: Our data suggest that chronic inflammation leads to significant alterations in the LG proteome. Ongoing studies aim to identify potentially unique, inflammation-induced proteins that could be amenable to pharmacological modulation.

PMID:40244610 | DOI:10.1167/iovs.66.4.44

Invest Ophthalmol Vis Sci. 2025 Apr 1;66(4):48. doi: 10.1167/iovs.66.4.48.

ABSTRACT

PURPOSE: The purpose of this study was to evaluate the neuroprotective effects of delivering nerve growth factor (NGF) to retinal ganglion cells (RGCs) through adeno-associated virus serotype 2 (AAV2) carrying a neuronal-specific human synapsin (hSyn) promoter.

METHODS: AAV2-hSyn-NGF was injected intravitreally in three glaucoma models: optic nerve crush (ONC), microbead-induced ocular hypertension (MB), and genetic glaucoma model (DBA). Quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA) determined the optimal injection concentration of AAV vector. Flow cytometry monitored immune responses. Transduction efficiency was quantified using green fluorescent protein (GFP) co-localization with RGC-specific marker RNA-binding protein with multiple splicing (RBPMS). The RGCs’ density, retinal nerve fiber density, ganglion cell complex thickness, and positive scotopic threshold response (pSTR) were measured to assess structural and functional outcomes of the RGCs. Non-parametric Mann-Whitney U tests or Kruskal-Wallis tests were utilized to ascertain the statistical significance (P < 0.05).

RESULTS: The optimal concentration of AAV vector for intravitreal injection was determined to be 1 × 1010 vector particles (VPs) per eye. The use of the hSyn promoter significantly enhanced targeting specificity to RGCs, resulting in a transduction efficiency of 46.64% ± 2.18%. Administration of AAV2-hSyn-NGF effectively preserved the RGCs’ density, nerve fiber layer integrity, and the thickness of ganglion cell complex, while maintaining the RGCs’ function across three glaucoma models. Furthermore, this gene delivery system did not elicit detectable immune responses or structural damage to the retina.

CONCLUSIONS: The AAV2-hSyn-NGF gene therapy offers a safe and effective neuroprotective strategy for RGCs across multiple glaucoma models, making it a promising candidate for future clinical trials in patients with glaucoma.

PMID:40244606 | DOI:10.1167/iovs.66.4.48

Dent Med Probl. 2025 Apr 17. doi: 10.17219/dmp/192096. Online ahead of print.

ABSTRACT

The hyoid bone exhibits potential sex-based variations and is implicated in the severity of obstructive sleep apnea (OSA). Sex-specific comparisons are lacking. The present meta-analysis aimed to address this gap.The Embase, MEDLINE and Web of Science databases were searched. The inclusion criteria were as follows: studies that reported the measurements of the hyoid bone-mandibular plane distance (HMP), demonstrated in cephalometric imaging (CEPH) in patients with OSA of both sexes, involving a polysomnography (PSG) examination with the apnea-hypopnea index (AHI), as well as information on the body mass index (BMI) and age. The exclusion criteria comprised reviews, meta-analyses and case reports. The risk of bias was assessed with the use of the Scottish Intercollegiate Guidelines Network (SIGN) checklist. Statistical analysis was conducted using Comprehensive Meta-Analysis software (CMA) and IBM SPSS Statistics for Windows.Seven observational studies with 718 adult patients (515 males and 203 females) met the inclusion criteria. The mean HMP value was 20.5 ±3.8 mm, with a significant difference observed between males (21.6 ±3.3 mm) and females (17.8 ±3.7 mm) (p < 0.00001). The correlation between HMP and AHI was significantly stronger in females – 2.5 times higher than in males (r = 0.423 vs. r = 0.167, respectively).Although a standard range of the hyoid bone position for healthy adults and elderly individuals is currently lacking, sex significantly affects the anatomical variation of the hyoid mandibular position in patients with OSA. It is crucial to identify distinct OSA endotypes by sex to ensure accurate diagnosis and treatment planning, which could lead to sex-specific therapeutic strategies.

PMID:40244603 | DOI:10.17219/dmp/192096

JAMA Netw Open. 2025 Apr 1;8(4):e255359. doi: 10.1001/jamanetworkopen.2025.5359.

ABSTRACT

IMPORTANCE: Digital health care services expanded with the COVID-19 pandemic. Disparities in telehealth, telemedicine, and telemonitoring use remain understudied.

OBJECTIVE: To examine associations between individual-level characteristics and digital health care use and if these associations differ by county-level social vulnerability.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study was an online survey that included a nonprobability sample of US adults aged 18 years or older who resided in 871 counties in the least or most vulnerable quartiles of the Minority Health Social Vulnerability Index (MHSVI), an indicator of county-level social vulnerability. The study was conducted between February and August 2022, and data were analyzed from August 2023 to August 2024.

EXPOSURES: Participant characteristics and MHSVI county-level social vulnerability.

MAIN OUTCOMES AND MEASURES: Self-reported use of telehealth, telemedicine, and telemonitoring. Multivariable logistic regression models were fit to examine associations between sociodemographic, health, and technology factors and each service use, overall and stratified by MHSVI.

RESULTS: Of the 5444 participants who were included in this study, 2927 were female (53.77%), 798 were non-Hispanic Black or African American (14.66%), 838 were Hispanic or Latino (15.39%), 3542 were non-Hispanic White (65.06%); the mean (SE) age was 45.4 (0.2) years. Overall, 2754 participants used telehealth (50.59%), 1609 used telemedicine (29.56%), and 854 used telemonitoring (15.69%). Being English nonproficient (adjusted odds ratio [aOR], 1.54; 95% CI, 1.23-1.92) and having had in-person health care visits (aOR, 4.71; 95% CI, 3.93-5.63) were associated with higher odds of using telehealth, whereas not having a primary care clinician was associated with lower odds (aOR, 0.68; 95% CI, 0.59-0.78). Similar findings were documented for telemedicine and telemonitoring use. Education was associated with higher odds of digital health care use in MHSVI most vulnerable counties (telehealth: aOR, 1.18; 95% CI, 1.06-1.32; telemedicine: aOR, 1.18; 95% CI, 1.05-1.33), whereas individuals who did not self-identify as heterosexual (telehealth: aOR, 1.47; 95% CI, 1.10-1.97; telemedicine: aOR, 1.57; 95% CI, 1.16-2.11; telemonitoring: aOR, 1.54; 95% CI, 1.02-2.31) and those who self-reported fair or poor mental health (telehealth: aOR, 1.29; 95% CI, 1.03-1.61) had higher odds of digital service use in the least vulnerable counties. Self-identifying as Black or African American or Hispanic was associated with high odds of telehealth (Black or African American: aOR, 1.41; 95% CI, 1.17-1.70; Hispanic or Latino: aOR, 1.41; 95% CI, 1.17-1.70), telemedicine (Black or African American: aOR, 1.44; 95% CI, 1.18-1.76; Hispanic or Latino: aOR, 1.27; 95% CI, 1.04-1.54), and telemonitoring (Black or African American: aOR, 1.40; 95% CI, 1.11-1.78; Hispanic or Latino: aOR, 1.46; 95%CI, 1.16-1.84) use overall, but these associations varied across MHSVI strata.

CONCLUSIONS AND RELEVANCE: In this cross-sectional study of US adults from MHSVI most and least vulnerable counties, digital health care use varied by participant characteristics. Some traditionally underserved groups self-reported higher use of digital health care. Differing associations between individual-level characteristics and digital health care use by county-level social vulnerability reflect the importance of place-based disadvantage indicators. Eliminating digital health care use disparities is important as it represents a complementary avenue to access health care for underserved populations.

PMID:40244585 | DOI:10.1001/jamanetworkopen.2025.5359