Krish Shah

All Publications

• A bioactive intramedullary implant enables accelerated bone regeneration and early load-bearing in distraction osteogenesis. Acta biomaterialia Uno, T., Lee, T. C., Shah, K., Chen, A. A., Lui, E., Alizadeh, H. V., Li, J., Muniz, R., Zhao, P., Pérez, A. S., Maekawa, H., Kim, S., Cherief, M., Regan, D. P., Takakubo, Y., Takagi, M., James, A., Young, J. L., Gardner, M. J., Mohler, D. G., Maloney, W. J., Yang, Y. P. 2026

  Abstract

  Distraction osteogenesis (DO) remains limited by prolonged consolidation and delayed bone union. This study evaluated whether a biodegradable, bone morphogenetic protein-2 (BMP-2)-releasing intramedullary implant (IMI) could enhance bone regenerate formation in a rat monofocal femoral lengthening model. We developed a Hybrid Tissue Engineering Construct (HyTEC) comprising a 3D-printed polycaprolactone-β-tricalcium phosphate IMI coated with a BMP-2-loaded hydrogel. Rats underwent standardized lengthening in three groups: control (DO only), IMI (implant without BMP-2), and IMI-BMP2 (BMP-2-releasing implant), with evaluation at postoperative days 31 and 52. The IMI-BMP2 group demonstrated significantly superior osteogenesis, achieving a bone volume fraction of 80 ± 22% at day 31, compared to 35 ± 19% (IMI) and 54 ± 25% (control), indicating accelerated regenerate formation. Radiographic and histological analyses confirmed early, uniform callus formation, while immunohistochemistry revealed elevated osteocalcin expression. Mechanical testing demonstrated restoration of approximately 50% of normal bone strength by day 52. Transcriptomic profiling revealed an exploratory BMP-2-associated regenerative gene signature, suggesting coordinated early-phase regulation of remodeling and metabolic reprogramming. This bioactive implant accelerated bone union, facilitated improved early ambulation consistent with partial mechanical competence restoration, and significantly shortened consolidation time, representing a promising clinically translatable strategy to overcome conventional DO limitations and improve patient outcomes. STATEMENT OF SIGNIFICANCE: Distraction osteogenesis is an effective strategy for managing large bone defects, but its clinical use is limited by prolonged consolidation and delayed functional recovery. This study presents a biodegradable intramedullary implant that provides sustained bone morphogenetic protein-2 (BMP-2) delivery and markedly accelerates regenerate formation, improves early mechanical strength, and enables earlier weight-bearing in a rat femoral lengthening model. In addition to demonstrating therapeutic efficacy, the work identifies a BMP-2-associated regenerative transcriptional signature linked to remodeling, osteoclast activity, and metabolic reprogramming. These findings establish a clinically translatable biomaterial-based approach to shorten treatment time and improve outcomes in distraction osteogenesis.

  View details for DOI 10.1016/j.actbio.2026.07.047

  View details for PubMedID 42526824

• INSIGHT: Ingest and Standardize Glucose Harmonization Tool. Journal of diabetes science and technology Ehlert, B., Shah, K., Katarya, D., Wu, Y., Wang, T., Snyder, M. P. 2026: 19322968261467778

  Abstract

  Publicly available continuous glucose monitoring (CGM) datasets are fragmented across schemas, limiting reuse, pooling, and machine learning development. Although large biobanks provide harmonized resources, many smaller CGM studies remain difficult to access because ingestion and standardization require substantial manual effort.We developed INSIGHT (Ingest and Standardize Glucose Harmonization Tool), an open-source large language model (LLM)-assisted harmonization pipeline that standardizes public CGM datasets into a minimal common schema: Subject_ID, Timestamp, and Glucose. INSIGHT combines deterministic rules with structured LLM assistance to identify CGM files, classify file roles, generate schema-specific read plans, normalize timestamps and glucose units, resolve subject identifiers, detect overlapping exports, merge outputs, and retain auditable JSON artifacts. We evaluated INSIGHT on 14 public CGM datasets with curated reference outputs using pre-specified training and held-out testing partitions. Performance was assessed using file-level precision/recall, subject recovery, temporal alignment, glucose fidelity, scalar CGM feature accuracy, and composite INSIGHT scores.INSIGHT is open-source at https://github.com/benehlert/CGMHarmonization. Across 90 model-dataset evaluations spanning 9 model variants and 10 datasets, top configurations achieved near-perfect held-out harmonization fidelity. GPT-5.4 and Gemini 3.1 Pro Preview achieved mean INSIGHT scores of 0.990, with glucose mean absolute error (MAE) below 0.03 mg/dL and within 5 mg/dL agreement of 0.9996. Errors primarily reflected complex subject-timestamp recovery rather than glucose conversion, with failures concentrated in deeply nested datasets containing overlapping or co-located non-CGM exports.INSIGHT demonstrates that LLM-assisted code generation can generalize CGM harmonization across heterogeneous datasets while producing auditable loaders. By reducing reuse costs, INSIGHT complements curated repositories and supports large-scale pooled analyses and foundation model development for glycemic physiology.

  View details for DOI 10.1177/19322968261467778

  View details for PubMedID 42509666

• Associations of Cerebrospinal Fluid Orexin-A, Alzheimer Disease Biomarkers, and Cognitive Performance. Annals of clinical and translational neurology Lu, R., Shah, K., Toedebusch, C. D., Hess, A., Richardson, R., Mignot, E., Schindler, S. E., Benzinger, T. L., Flores, S., Hassenstab, J., Xiong, C., Morris, J. C., Holtzman, D. M., Lucey, B. P. 2025

  Abstract

  Cerebrospinal fluid (CSF) orexin-A has been suggested to be a biomarker of Alzheimer disease (AD). In both cognitively unimpaired healthy older adults and individuals with symptomatic AD, CSF orexin-A is positively associated with CSF Aβ42, p-tau181, and total tau (t-tau) concentrations. However, a recent systematic review and meta-analysis did not support differences in orexin-A between AD and controls. In this study, we tested the association between CSF orexin-A concentrations, AD biomarkers, and cognitive performance in older adults with and without symptomatic AD.Two hundred and seventy community-dwelling older adults underwent standardized cognitive assessments, sleep monitoring with a single-channel electroencephalography test, one night of home sleep apnea testing, biofluid and imaging AD biomarker measurement within 1 year of sleep monitoring, and APOE genotyping. Plasma and CSF AD biomarkers were measured by immunoassay or mass spectrometry. CSF orexin-A was measured by radioimmunoassay.CSF orexin-A levels did not differ by amyloid positivity, cognitive status, or AD stage. However, CSF AD biomarkers (Aβ40, Aβ42, and t-tau) were positively associated with CSF orexin-A levels even after correction for multiple comparisons. CSF orexin-A was not associated with any measure of cognitive performance.This study showed that CSF orexin-A is associated with multiple CSF AD biomarkers, but not with AD pathology or cognitive performance. We hypothesize that this is due to similar mechanisms of production/release of these proteins with sleep-wake activity. Future studies measuring other forms of orexin peptides, such as orexin-B, may provide evidence for orexin as a marker for AD.

  View details for DOI 10.1002/acn3.70009

  View details for PubMedID 39957622