Publications by Year: 2026

INTRODUCTION: Advances in nanotechnology and nanomedicine increasingly focus on the rational design of smart nanocarriers capable of site-specific and stimulus-triggered drug release to improve therapeutic efficacy and reduce systemic toxicity. Among them, cyclodextrins (CDs), particularly cyclodextrin nanosponges (CDNSs), have emerged as safe, biodegradable, and versatile platforms for drug delivery due to favorable biocompatibility and structural adaptability.

AREAS COVERED: CDNSs are three-dimensional, cross-linked polymeric networks formed through chemical reactions between cyclodextrins and suitable cross-linkers, generating porous architectures with high surface area and tunable physicochemical properties. These features enable efficient encapsulation of poorly water-soluble drugs and improvement of their solubility and bioavailability. Beyond conventional CD systems, stimulus-responsive CDNSs provide additional control by responding to internal or external triggers such as pH, temperature, light, and redox conditions. Particularly, glutathione-responsive CDNSs exploit intracellular redox gradients via disulfide bond cleavage, enabling selective drug release in cancerous and inflammatory tissues. Literature for this narrative review was identified through searches of PubMed, Web of Science, and Scopus, focusing on publications from 2000 to early 2025.

EXPERT OPINION: This review highlights glutathione-responsive cyclodextrin nanosponges as an advanced evolution of CD-based carriers, emphasizing emerging structure - property - responsiveness relationships rather than exhaustive coverage. By discussing nanosponge architecture and cross-linking density.

The Perturbation Complexity Index-State Transitions (PCIST) measures the complexity of the brain's response to transcranial magnetic stimulation (TMS) using electroencephalography (EEG) and is sensitive to consciousness, such as minimally conscious states. Individuals with early-stage Alzheimer's disease (AD) show dysfunction of conscious processes, such as attention, working memory, episodic memory, and executive function, with relatively spared unconscious processes, such as procedural memory, operant conditioning, and priming. We sought to test the hypothesis that PCIST would be reduced in AD compared to healthy aging. We assessed 28 participants with AD and 27 healthy controls (HC), measuring cognition with the Montreal Cognitive Assessment (MoCA) and disease severity with the Clinical Dementia Rating scale-Global (CDR-Global) and Sum of Boxes (CDR-SB). Results indicated lower PCIST in the AD group (M = 20.1) compared to controls (M = 28.2) across both the motor cortex (M1) and inferior parietal lobule (IPL) TMS stimulation sites, suggesting that PCIST may reflect the impaired conscious cognitive processes and functional capacity seen in AD. We therefore speculate that cortical dementias involve alterations in cortical complexity that may relate to deterioration of their conscious processes. This research opens the avenue for future studies in individuals with cortical dementia to examine the relationship between conscious processes, global measures of consciousness, and their underlying neuroanatomical correlates, in addition to enhancing our understanding of dementia and suggesting possible therapeutic strategies.

OBJECTIVE: To examine the associations of long term engagement in individual physical activities and physical activity variety with the risk of death.

DESIGN: Prospective cohort studies.

SETTING: Nurses' Health Study (1986-2018) and Health Professionals Follow-Up Study (1986-2020).

PARTICIPANTS: 70 725 women and 40 742 men who were free of diabetes, cardiovascular disease, cancer, respiratory disease, or neurological disease and had complete physical activity information at baseline (leisure time physical activity was biennially updated using validated questionnaires during follow-up; the variety of physical activity was measured as the total number of individual physical activities in which participants consistently engaged).

MAIN OUTCOME MEASURES: All cause and cause specific mortality.

RESULTS: During 2 431 318 person years of follow-up, 38 847 deaths were recorded, with 9901 from cardiovascular disease, 10 719 from cancer, and 3159 from respiratory disease. Total physical activity and most individual physical activities, except for swimming, were associated with lower mortality with non-linear dose-response relations. The pooled multivariable adjusted hazard ratios for all cause mortality in the highest categories of physical activity levels, compared with the lowest, were 0.83 (95% confidence interval 0.80 to 0.85) for walking, 0.89 (0.85 to 0.94) for jogging, 0.87 (0.80 to 0.93) for running, 0.96 (0.93 to 0.99) for bicycling, 1.01 (0.97 to 1.05) for swimming, 0.85 (0.80 to 0.89) for tennis or squash, 0.90 (0.87 to 0.93) for climbing stairs, 0.86 (0.84 to 0.89) for rowing or callisthenics, and 0.87 (0.82 to 0.91) for weight training or resistance exercises. Higher physical activity variety was associated with lower mortality. After adjustment for total physical activity levels, participants in the group with the highest physical activity variety score (group 5), compared with those in the lowest group (group 1), had a 19% lower all cause mortality and 13-41% lower mortality from cardiovascular disease, cancer, respiratory disease, and other causes (all P for trend <0.001).

CONCLUSIONS: Habitual engagement in most types of physical activity was associated with lower mortality. The variety of physical activity was inversely associated with mortality, independent of total physical activity levels. Overall, these data support the notion that long term engagement in multiple types of physical activity may help extend the lifespan.

OBJECTIVES: This study aims to compare nonunion rates between conventional plates versus specific systems for ulnar shortening osteotomy (USO).

MATERIALS AND METHODS: To identify relevant studies, we searched various databases, including MEDLINE via Ovid, Embase.com, Web of Science Core Collection, Cochrane CENTRAL via Wiley, and Google Scholar. The level of evidence was assessed independently by three evaluators. Preferred reporting items for systematic reviews (PRISMA) recommendations were followed during the study selection process, which involved applying inclusion and exclusion criteria. All studies that reported the postoperative nonunion rates and mentioned the manufacturer of the fixation device were included. A total of 42 studies were analyzed, with information retrieved on osteotomy type, fixation type, manufacturer, bone union period, and nonunion rate for each study.

RESULTS: A total of 42 relevant articles were included in this study, with a total sample size of 1617 cases. The nonunion rate with the conventional plates was 5% (41 nonunion out of 815 cases).The reported nonunion rate was 0% (0 out of 67 cases) for the Stryker Trauma plates, 1.9% (three nonunion out of 157 cases) for the Rayhack plates, 4% (11 nonunion out of 271 cases) for the Acumed plates, 10.3% (3 nonunion out of 29 cases) for the specialized AO plates and 5% (14 nonunion and out of 278 cases) for the TriMed plates.

CONCLUSION: Despite advances in plate designs for USO, the overall nonunion rate with USO-specific systems is almost comparable to that of conventional plates. So, it seems likely that the surgical technique and patient characteristics may play a more significant role than the type of device when planning for a USO. Cost and time savings should be weighed and considered when choosing between the less expensive conventional plates versus USO-specific systems.

LEVEL OF EVIDENCE: Prognostic level IV.

Comparative complete genome analyses were conducted on 173 field outbreak strains of foot-and-mouth disease virus (FMDV) serotype A, collected from various regions worldwide, including strains that have circulated in India in recent years. Phylogenetic analyses revealed that the majority of isolates included in this study belonged to the Asia (n = 108), followed by EURO-SA (n = 41) and Africa (n = 24) topotypes. The mean rate of evolutionary change in FMDV serotype A was estimated to be 2.369 × 10-3 substitutions/site/year for the Open Reading Frame (ORF). Faster substitution rates in the Asia topotype suggests heightened selective pressures, likely driven by pre-existing host immune responses due to prior infections or vaccination. The periodic emergence and subsequent dominance of notable genotypes or lineages within the Asia topotype such as genotype 18 (ASIA/VII), genotype 20 (Sea-97), and genotype 26 (Iran-05) underscore the ongoing diversification, adaptation, and selection of the virus in the field across Asia. Monophyletic clustering within the Asia and Africa topotypes suggests region-specific evolutionary trajectories, while the diversity observed within EURO-SA indicates an older and more genetically varied lineage pattern. The presence of amino acid insertions and deletions in some of the isolates points to potential hotspots for genetic change, particularly in regions such as L, VP1, and 3A, reflecting high genetic volatility. Positive selection across the protein-coding regions excluding VP4 and 2A highlights the virus's adaptive potential, likely contributing to immune evasion, host adaptation, and enhanced fitness for replication and transmission. Evidence of recombination events, particularly in five isolates with spatio-temporal overlaps, indicates dynamic viral evolution potentially favourable for emergence of new variants. These findings are crucial for understanding foot-and-mouth disease (FMD) epidemiology and may have implications for global FMD control strategies.

BACKGROUND: Previous studies have reported inconsistent findings regarding the relationship between socioeconomic status (SES) inequalities and comorbidities in patients with diabetes mellitus (DM). This systematic review and meta-analysis aims to evaluate, for the first time, the association between SES inequalities and comorbidities in individuals with DM.

METHODS: Two independent investigators searched the PubMed, Embase, Scopus, Web of Science and Google Scholar databases using MeSH terms to identify studies that investigated the association between SES and DM comorbidities up to 15 December 2025. This systematic review followed the PRISMA 2020 checklist. Heterogeneity among studies was assessed using Cochran's Q and I2 statistics. Meta-regression was used to control for heterogeneity; Egger's test assessed publication bias.

RESULTS: Thirteen studies involving 757,599 DM patients were included. A pooled estimate of 13 studies showed that low SES, compared with moderate or high SES, was significantly associated with an increased probability of DM comorbidities (OR: 1.43; 95% CI: 1.30, 1.59; I2: 92.7, p: 0.01). Subgroup analysis of 12 studies showed that the probability of DM comorbidities was different in men (OR: 1.30; 95% CI: 1.28, 1.32) and women (OR: 1.39; 95% CI: 1.36, 1.42).

CONCLUSION: The chance of developing type 2 diabetes comorbidities in patients with T2DM of low SES, especially in women, may be higher than in patients with middle and high SES. Improvements in healthcare systems and interventions to reduce inequalities in SES in patients with type 2 diabetes, especially in patients with low SES, are recommended.

INTRODUCTION: The COVID-19 pandemic significantly disrupted daily routines, including Contact Lens (CL) usage patterns. This study examines the factors influencing adherence to CL guidelines among residents in the northern West Bank, both before and during the pandemic.

METHODS: A cross-sectional analysis was conducted using a questionnaire completed by 379 CL users aged 18-35 between April 25 and May 1, 2022. The survey covered demographic data, CL history, behavioral changes, and adherence practices. A validated seven-item Likert-scale tool (Cronbach's α = 0.9025) was used to assess adherence levels. Multivariable logistic regression was performed to identify predictors of adherence change.

RESULTS: CL usage significantly declined during the pandemic from 5.2 to 3.4 days per week (p < 0.01). Approximately 35% of participants reported reduced adherence to CL safety guidelines. Guidance from optometrists or ophthalmologists was associated with improved adherence (aOR = 0.54, 95% CI: 0.33- 0.88, p = 0.013). While city residents showed better adherence compared to those in villages or camps, this was not statistically significant (aOR = 1.14, 95% CI: 0.72-1.80, p = 0.585).

DISCUSSION: Lifestyle shifts during lockdowns contributed to decreased adherence, with professional eye care guidance emerging as a key protective factor.

CONCLUSION: The pandemic negatively impacted CL hygiene behaviors, but professional support mitigated this effect. Strengthening patient education may improve adherence during future public health crises.

BACKGROUND: Surveillance activities are emerging as exemplar use cases for large language models (LLMs) in health care. The aim of this study was to evaluate the potential for LLMs to support the expansion of surveillance activities to include cardiovascular implantable electronic device (CIED) procedures.

METHODS: A validated machine learning-based infection flagging tool was applied to a cohort of VA CIED procedures from 7/1/2021 to 9/30/2023; cases with ≥10% probability of CIED infection underwent manual review. Then, a weighted random sample of 50 infected and 50 uninfected cases was reviewed with generative artificial intelligence (GenAI) assistance. GenAI prompts were iteratively refined to extract and classify all components of infection-related variables from clinical notes. Data extracted by GenAI were compared with manual chart reviews to assess infection status and extraction consistency.

RESULTS: Among 12,927 CIED procedures, 334 (2.58%) had ≥10% probability of CIED infection. Among 100 sampled cases, 50 of 50 uninfected cases were correctly categorized. Among 50 infection cases, GenAI identified all CIED infections, but the timing of events and the attribution to a preceding procedure were incorrect in 7 of 50 cases. The overall specificity of the GenAI-assisted process was 100% and the sensitivity for accurately classifying timing and attribution of CIED infection events was 82%. Errors in timing improved with iterative prompt updates. Manual chart reviews averaged 25 minutes per chart; the GenAI-assisted process averaged 5-7 minutes per chart.

CONCLUSIONS: LLMs can help streamline the review process for healthcare-associated infection surveillance, but manual adjudication of output is needed to ensure the correct timeline of events and attribution.

Given the absence of curative treatments for neurodegenerative diseases, early detection and therapeutic intervention are critical to slowing disease progression. Extracellular vesicles (EVs) have emerged as promising biomarkers for neurodegeneration, owing to their accessibility in bodily fluids and dynamic molecular cargo, including microRNAs (miRNAs). The last decade has seen accumulating evidence for miRNA dysregulation in circulating EVs from people with neurodegenerative diseases; however, assessing reproducibility between studies remains challenging, largely due to clinical and methodological heterogeneity. In this systematic review, we comprehensively searched the MEDLINE database for studies investigating miRNA expression in biofluids from people with neurodegenerative diseases. We extracted miRNA expression data from 185 peer-reviewed publications, published until June of 2025, reporting altered miRNA levels in fluid-derived EVs from people with neurodegenerative diseases. We consolidated results between studies to identify the most frequently dysregulated miRNAs across diseases, with a focus on Alzheimer's disease, Parkinson's disease, mild cognitive impairment, multiple sclerosis, amyotrophic lateral sclerosis, frontotemporal dementia, stroke, traumatic brain injury, and schizophrenia. Evaluating tissue specificity of frequently dysregulated miRNAs revealed enrichment of select miRNAs in the nervous system relative to blood and immune compartments. Summarizing miRNA regulation across biofluids emphasized consistencies between cerebrospinal fluid and plasma, but not serum. We highlight circulating miRNAs that may be reflective of neuropathology, including miR-143-3p, miR-127-3p, miR-9-5p, miR-15a-5p, and miR-125b-5p. Finally, we provide a repository of miRNA expression data from over 30 neurodegenerative conditions which can be exploited to further investigate miRNA regulation in diseases of interest.