Publications by Year: 2025

Periprosthetic joint infections (PJIs), particularly those caused by multidrug-resistant organisms (MDROs), remain a major therapeutic challenge. Antimicrobial blue light (ABL) offers a promising non-antibiotic approach, inducing bacterial killing through photoexcitation of endogenous chromophores and subsequent reactive oxygen species generation. However, conventional single-point illumination systems are limited by uneven light distribution and poor penetration, restricting their use to superficial infections. We evaluated a novel isotropic optical fiber designed to overcome these geometric and optical constraints. The fiber was tested against vancomycin-resistant Enterococcus faecium (VR-Ef) and carbapenemase-producing Klebsiella pneumoniae (CP-Kp) in time-to-kill assays under low-power (20.1 mW mm-1) and high-power (40.3 mW mm-1) conditions over 60 min. Bacterial counts (CFU per mL) were determined at 0, 10, 20, 30, and 60 min. A one-way analysis of variance (ANOVA) with Tukey's post hoc test assessed time-dependent reductions; a two-way ANOVA evaluated the combined effects of illumination power and exposure time. ABL exposure resulted in time- and intensity-dependent bacterial reduction in both strains. Significant CFU reductions occurred from 30 min onward under high-power ABL (HP-ABL) and after 60 min under low-power ABL (LP-ABL) for both VR-Ef and CP-Kp ( p < 0.001 ). The two-way ANOVA revealed significant main and interaction effects of illumination power and exposure time (all p < 0.001 ). Although bactericidal thresholds ( ≥ 3 log⁡ 10  reduction) were not reached, bacterial killing increased markedly with higher power and longer exposure. This novel isotropic optical fiber enables uniform intraluminal ABL delivery, potentially extending blue-light therapy from superficial to deep surgical infections such as PJIs. Further optimization of illumination parameters and potential integration with photosensitizers may enhance its antimicrobial efficacy and clinical applicability.

Neurological voice disorders, such as Parkinson's disease, laryngeal dystonia, and stroke-induced dysarthria, significantly impact speech production and communication. Traditional diagnostic methods rely on subjective assessment, whereas artificial intelligence (AI) offers objective, noninvasive, and scalable solutions for voice analysis. This review examines the applications, advancements, challenges, and future prospects of AI-driven methods in diagnosing, monitoring, and treating neurological voice disorders. We analyze recent advances in AI-based voice analysis, including machine learning, deep learning and signal processing techniques, and evaluate their effectiveness based on existing literature. AI models have demonstrated high accuracy in detecting subtle voice impairments, enabling early diagnosis of voice disorders, and predicting treatment response. Deep learning methods, particularly convolutional and transformer-based networks, have been effective in extracting meaningful biomarkers from acoustic or other modality data. Despite these promising advances, challenges remain, including limited high-quality data sets on some rare neurological voice disorders, ethical concerns regarding patient privacy, and the need for broad clinical validation. Further research should focus on developing standardized data sets, improving the ability of the AI model to learn representations, and enhancing its generalizability. With further development, AI-driven data analysis has the potential to transform the early detection and management of neurological voice disorders.

Vocal fold leukoplakia (VFL) is a descriptive term for a white plaque in the true vocal folds (TVF). It is estimated at 10.2 cases per 100,000 males and 2.1 per 100,000 females. The most critical aspect of managing a VLF is achieving an accurate pathological diagnosis, since a white plaque in the TVF can have numerous differential diagnoses. Patients with VFL usually complain of hoarseness and vocal strain. The common cause of VFL is premalignant lesions with primary risk factors of tobacco and alcohol consumption. Inflammatory aggressors such as laryngopharyngeal reflux disease are proven to affect directly the incidence of VFL. Infectious agents such as human papilloma virus and Helicobacter pylori may also play a role in the development of VFL. Frequent differential diagnosis includes laryngeal candidiasis, prolonged ulcerative laryngitis, previous head and neck radiotherapy, and, more rarely, lichen planus. The clinical investigation for a VLF includes laryngeal exam through a rigid or a flexible laryngoscope; videochromoendoscopy is a useful tool. Biopsy is mandatory so a pathological diagnosis is made. The most accepted classification for VFL and premalignant lesions is the fifth edition of the World Health Organization, and it uses a two-tiered system. The treatment for VFL and premalignant lesions can be done by cold knife surgery, KTP laser, or CO2 laser.

OBJECTIVE: To evaluate cognition at entry into the Gerofit program and its association with physical function.

DESIGN: Retrospective observational cross-sectional design.

SETTING: Gerofit outpatient clinical exercise programs at multiple Veterans Affairs Medical Centers from 2021 to 2023.

PARTICIPANTS: New enrollees (N=1172) completed measures of lower and upper extremity strength, balance, cardiovascular endurance, and measures of global cognition (telephone Montreal Cognitive Assessment, tMoCA) and cognitive set shifting (Oral Trail Making Test B). Dementia diagnosis in the medical record was exclusionary.

INTERVENTIONS: Not applicable.

MAIN OUTCOME MEASURES: Relationship between physical and cognitive function, self-rated memory change, and demographics were evaluated by linear regression.

RESULTS: Mean age was 75 years. 78% of participants were White and 20% Black; 88% were men. Mean tMoCA score was 17.39. tMoCA and Oral Trail Making Test B scores were significantly associated with lower extremity strength (P<.001), and tMoCA score was significantly associated with endurance. tMoCA score was significantly associated with self-rated memory.

CONCLUSIONS: Global cognitive functioning was below the cutoff for normal cognition in 61% of participants, suggesting mild cognitive impairment is common in older exercise program enrollees. Lower cognitive scores were related to both reduced strength and endurance.

OBJECTIVE: To examine the functional outcomes of a group of infants, children, and adolescents admitted to acute inpatient rehabilitation for neurologic impairments caused by a new childhood stroke.

DESIGN: Retrospective cross-sectional cohort study.

SETTING: A pediatric inpatient rehabilitation program in a stand-alone inpatient rehabilitation facility (IRF) located within an academic medical center.

PARTICIPANTS: A total of 91 patients (N=91) aged 6 months to 17.8 years were admitted to a pediatric inpatient rehabilitation program with a new diagnosis of childhood stroke.

INTERVENTIONS: Standard of care pediatric inpatient rehabilitation treatment.

MAIN OUTCOME MEASURES: Change in the functional independence measure in children (WeeFIM) score across inpatient rehabilitation treatment.

RESULTS: The 51 boys/39 girls/and 1 transgender patient were 9.6±5.7 years old with ischemic stroke (n=53) or hemorrhagic stroke (n=38). At admission, they had moderate-to-severe functional impairments (WeeFIM total score=46.5±25.5 points). Inpatient rehabilitation length of stay was 33.7±28.5 (range, 3-134) days. WeeFIM total score improved to 71.2±31.6 points at IRF discharge. Hemorrhagic (compared with ischemic) stroke was associated with higher rates of craniectomy (X2=4.6, P=.03) and older age at IRF admission (Z=1.98, P<.05). Older age was associated with higher age-corrected WeeFIM total scores at admission (F=7.9, P=.0007) and discharge (F=18.1, P<.001), but age did not affect change in WeeFIM score.

CONCLUSIONS: Pediatric inpatient rehabilitation results in functional improvements for new neurologic impairments caused by childhood stroke.

The mechanistic target of rapamycin (mTOR) complex 1 (mTORC1), a sensor of growth signals that control cell growth, has been studied mainly in proliferating cells. Primary cilia are sensory organelles present on most quiescent cells and are essential for receiving environmental and developmental signals. Given that ciliated cells are non-proliferative, we investigated whether mTORC1 signaling influences primary cilia growth. Here, we show that mTORC1 promotes cilia elongation without affecting ciliogenesis by suppressing autophagy. Inhibiting mTORC1 through pharmacological, nutritional, or genetic interventions shortened primary cilia, whereas activation of the pathway elongated them. Furthermore, pharmacological or genetic inhibition of autophagy-a key downstream process blocked by mTORC1-elongated primary cilia and rendered them resistant to mTORC1 inhibition. These mTORC1-mediated effects extend to mouse neurons ex vivo and in vivo. Thus, the mTORC1-mediated regulation of autophagy controls primary cilia length and may contribute to diseases in which ciliary function is altered, referred to as ciliopathies.

Sepsis is a life-threatening condition arising from a dysregulated host response to infection, characterized by a complex interplay between pro-inflammatory and anti-inflammatory immune mechanisms. B cells, that are key components of humoral immunity, are essential for antibody production, antigen presentation, and immune modulation. Sepsis is commonly associated with B cell lymphopenia, particularly in severe cases, as evidenced by a marked reduction in circulating B cells in both adult and pediatric patients. However, the mechanisms driving this depletion have not been completely understood, particularly in pediatric sepsis. In this study, we employed single-cell RNA sequencing (scRNA-seq) to profile peripheral blood leukocytes from pediatric patients with sepsis (three with mild and three with severe condition) alongside four healthy controls. Our analysis revealed a broad depletion of immune cells in sepsis, with B cells showing the most pronounced reduction and the strongest capacity to discriminate between mild and severe disease states. Subset-level analysis identified significant loss and transcriptional reprogramming of natural killer-like B cells (ΝΚΒ), MHC IIhighnaïve, and MHC IIlownaïve B cells in severe sepsis, accompanied by signatures indicative of intrinsic and extrinsic apoptosis, disrupted differentiation, and enhanced migratory potential. Importantly, we identified and validated the population of NKB cells in both pediatric and adult cohorts, broadening the known landscape of B cell phenotypes in human sepsis. We also explored intercellular communications, focusing on B cell-neutrophil interactions, given the notable neutrophilia observed, revealing potential crosstalk that may contribute to the overall immune dysregulation in sepsis. Collectively, these findings offer new insights into the cellular and molecular drivers of immune dysfunction in pediatric sepsis, shedding light on B cell depletion as a central feature of disease severity. This work lays the foundation for future diagnostic and therapeutic strategies targeting B cell-mediated immunity in septic children. The study was registered on ClinicalTrials.gov (NCT04103268), with registration date on 2019-09-23, before the first patient was enrolled.

Background: The US Food and Drug Administration (FDA) authorized over 690 machine learning (ML)-enabled medical devices between 1995 and 2023. In 2024, new guidance enabled the inclusion of Predetermined Change Control Plans (PCCPs), raising expectations for transparency, equity, and safety under the Good Machine Learning Practice (GMLP) framework. Objective: The objective was to assess regulatory pathways, predicate lineage, demographic transparency, performance reporting, and PCCP uptake among ML-enabled devices approved by the FDA in 2024. Methods: We conducted a cross-sectional analysis of all FDA-authorized ML-enabled devices in 2024. Data extracted from FDA summaries included regulatory pathway, predicate genealogy, performance metrics, demographic disclosures, PCCPs, and cybersecurity statements. Descriptive and nonparametric statistics were used. Results: The FDA authorized 168 ML-enabled Class II devices in 2024. Most (94.6%) were cleared via 510(k); 5.4% were cleared via De Novo. Radiology dominated (74.4%), followed by cardiovascular (6.5%) and neurology (6.0%). Non-US sponsors accounted for 57.7% of clearances. Among 159 510(k) devices, 97.5% cited an identifiable predicate; the median predicate age was 2.2 years (IQR 1.2-4.1), and 64.5% ML-enabled. Predicate reuse remained uncommon (9.9%). Median review time was 162 days (151 days for 510(k) vs. 372 days De Novo; p < 0.001). A total of 49 devices (29.2%) reported both sensitivity and specificity; 15.5% provided demographic data. PCCPs appeared in 16.7% of summaries, and cybersecurity considerations appeared in 54.2%. Conclusions: While 2024 marked a record year for ML-enabled device approvals and internationalization, uptake of PCCPs and transparent performance and demographic reporting remained limited. Policy efforts to standardize disclosures and strengthen post market oversight are critical for realizing the promises of GMLP.

Background/Objectives: Anterior cruciate ligament (ACL) injuries frequently lead to long-term quadriceps impairments despite surgical repair. There is growing evidence that these deficits are caused in part by alterations in the central nervous system. Thus, transcranial neuromodulation (TNM) could be valuable in ACL rehabilitation. To systematically review randomized controlled trials (RCTs) assessing the effects of TNM on neurophysiological, functional, and safety outcomes in patients with ACL injury or reconstruction. Methods: We conducted searches on PubMed, Scopus, Web of Science, and Cochrane. We considered all original studies evaluating TNM, including transcranial current stimulation (tCS) and transcranial magnetic stimulation (TMS), in patients with ACL reconstruction or injury. Measures of corticospinal excitability, safety, balance, and muscle strength were assessed. We employed the Cochrane RoB 2 method to assess the risk of bias. Results: Seven studies comprising 129 participants (64 TNM, 65 controls) were included. Most studies applied transcranial direct current stimulation (tDCS) over the primary motor cortex contralateral to the ACL injury in conjunction with physical rehabilitation. Single-session protocols demonstrated minimal effects, whereas repeated sessions resulted in improvements in corticospinal excitability, quadriceps strength, and balance. No serious adverse events were reported; minor effects included transient headache or scalp tingling. The risk of bias was assessed as low to moderate across the studies. Conclusions: TNM appears to be safe and may enhance functional recovery in individuals with ACL injuries when administered in multiple sessions alongside standard rehabilitation. Further high-quality trials are necessary to determine optimal protocols and long-term outcomes.

Multiple myeloma (MM) is a plasma cell malignancy that disrupts bone homeostasis by suppressing osteogenesis and promoting osteoclast activity. While most therapeutic interventions to date have focused on targeting tumor cells and reducing osteolysis, we investigate whether osteoinductive strategies can restore bone formation and counteract disease progression. Using a human bone marrow-like scaffold model that enables direct in vivo evaluation of tumor-stroma interactions and human bone formation, we demonstrate that MM-derived mesenchymal stromal cells (MSCs) retain osteogenic potential but are functionally suppressed by MM cells. Transcriptomic profiling of MM-primed MSCs revealed the downregulation of small leucine-rich proteoglycans (SLRPs), ASPN, OGN, and OMD, key mediators of bone morphogenetic protein (BMP) signaling, which governs osteoblast differentiation. Among the BMPs analyzed, BMP6 emerged as a potent inducer of osteogenesis and regulator of the expression of these SLRPs. Notably, BMP6 selectively promoted bone formation without enhancing osteoclastogenesis and attenuated inflammatory and tumor-supportive MSC phenotypes. BMP6 also directly inhibited MM cell proliferation and suppressed IL6-induced growth. These findings highlight BMP6 as a distinct multifunctional regulator warranting further investigation as a potential therapeutic approach, while establishing the humanized model as a valuable platform for dissecting tumor-bone interactions in MM.