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MSTPublications: December 2023

Posted by on Monday, December 18, 2023 in New Publications .

Developing and evaluating pediatric phecodes (Peds-Phecodes) for high-throughput phenotyping using electronic health records.
Grabowska ME, Van Driest SL, Robinson JR, Patrick AE, Guardo C, Gangireddy S, Ong HH, Feng Q, Carroll R, Kannankeril PJ, Wei WQ.
J Am Med Inform Assoc. 2023 Dec 1:ocad233. doi: 10.1093/jamia/ocad233. Online ahead of print.

Objective: Pediatric patients have different diseases and outcomes than adults; however, existing phecodes do not capture the distinctive pediatric spectrum of disease. We aim to develop specialized pediatric phecodes (Peds-Phecodes) to enable efficient, large-scale phenotypic analyses of pediatric patients.
Materials and methods: We adopted a hybrid data- and knowledge-driven approach leveraging electronic health records (EHRs) and genetic data from Vanderbilt University Medical Center to modify the most recent version of phecodes to better capture pediatric phenotypes. First, we compared the prevalence of patient diagnoses in pediatric and adult populations to identify disease phenotypes differentially affecting children and adults. We then used clinical domain knowledge to remove phecodes representing phenotypes unlikely to affect pediatric patients and create new phecodes for phenotypes relevant to the pediatric population. We further compared phenome-wide association study (PheWAS) outcomes replicating known pediatric genotype-phenotype associations between Peds-Phecodes and phecodes.
Results: The Peds-Phecodes aggregate 15 533 ICD-9-CM codes and 82 949 ICD-10-CM codes into 2051 distinct phecodes. Peds-Phecodes replicated more known pediatric genotype-phenotype associations than phecodes (248 vs 192 out of 687 SNPs, P < .001).
Discussion: We introduce Peds-Phecodes, a high-throughput EHR phenotyping tool tailored for use in pediatric populations. We successfully validated the Peds-Phecodes using genetic replication studies. Our findings also reveal the potential use of Peds-Phecodes in detecting novel genotype-phenotype associations for pediatric conditions. We expect that Peds-Phecodes will facilitate large-scale phenomic and genomic analyses in pediatric populations.
Conclusion: Peds-Phecodes capture higher-quality pediatric phenotypes and deliver superior PheWAS outcomes compared to phecodes.


Survey of the infant male urobiome and genomic analysis of Actinotignum spp.
Reasoner SA, Flores V, Van Horn G, Morales G, Peard LM, Abelson B, Manuel C, Lee J, Baker B, Williams T, Schmitz JE, Clayton DB, Hadjifrangiskou M.
NPJ Biofilms Microbiomes. 2023 Dec 1;9(1):91. doi: 10.1038/s41522-023-00457-6.

The urinary bladder harbors a community of microbes termed the urobiome, which remains understudied. In this study, we present the urobiome of healthy infant males from samples collected by transurethral catheterization. Using a combination of enhanced culture and amplicon sequencing, we identify several common bacterial genera that can be further investigated for their effects on urinary health across the lifespan. Many genera were shared between all samples suggesting a consistent urobiome composition among this cohort. We note that, for this cohort, early life exposures including mode of birth (vaginal vs. Cesarean section), or prior antibiotic exposure did not influence urobiome composition. In addition, we report the isolation of culturable bacteria from the bladders of these infant males, including Actinotignum spp., a bacterial genus that has been associated with urinary tract infections in older male adults. Herein, we isolate and sequence 9 distinct strains of Actinotignum spp. enhancing the genomic knowledge surrounding this genus and opening avenues for delineating the microbiology of this urobiome constituent. Furthermore, we present a framework for using the combination of culture-dependent and sequencing methodologies for uncovering mechanisms in the urobiome.


Community-guided, autism-adapted group cognitive behavioral therapy for depression in autistic youth (CBT-DAY): Preliminary feasibility, acceptability, and efficacy.
Schwartzman JM, Roth MC, Paterson AV, Jacobs AX, Williams ZJ.
Autism. 2023 Nov 27:13623613231213543. doi: 10.1177/13623613231213543. Online ahead of print.

Depression in youth is a significant public health problem worldwide, particularly for autistic youth who are over twice as likely to experience depression than their non-autistic peers. Although pathways to depression are complex, emotional reactivity and negative self-esteem are two risk factors for depression in autistic and non-autistic youth. Although autistic youth are more likely to experience depression than their non-autistic peers, psychotherapy options for autistic youth are very limited; community guidance in the development and testing of psychotherapy programs is a promising approach in autism. Therefore, in this study, we designed an autism-adapted CBT-DAY, in collaboration with autistic community members. Specifically, CBT-DAY combined neurodiversity-affirming and cognitive behavioral approaches to target emotional reactivity and self-esteem in youth to improve depressive symptom severity in a group setting across 12 weeks. We examined the preliminary feasibility, acceptability, and efficacy of CBT-DAY in a pilot non-randomized trial. In addition, we implemented a rigorous protocol for assessing, monitoring, and addressing potential harms in this intervention. Results from 24 autistic youth (11-17 years old) suggest that CBT-DAY may be feasible to use in an outpatient clinical setting and generally acceptable to youth and their caregivers. Participation in CBT-DAY may be associated with significant improvements in youth emotional reactivity and self-esteem, as well as depressive symptom severity per self-report only. Exploratory analyses showed that participation in CBT-DAY may also be associated with significant improvements in internalizing symptoms. Findings demonstrate the potential promise of neurodiversity-affirming and cognitive behavioral approaches to treating depressive symptoms in some autistic youth.


DeepN4: Learning N4ITK Bias Field Correction for T1-weighted Images.
Kanakaraj P, Yao T, Cai LY, Lee HH, Newlin NR, Kim ME, Gao C, Pechman KR, Archer D, Hohman T, Jefferson A, Beason-Held LL, Resnick SM; Alzheimer’s Disease Neuroimaging Initiative (ADNI); BIOCARD Study Team; Garyfallidis E, Anderson A, Schilling KG, Landman BA, Moyer D.
Res Sq. 2023 Nov doi: 10.21203/ Preprint.

Genetic risk converges on regulatory networks mediating early type 2 diabetes.
Walker JT, Saunders DC, Rai V, Chen HH, Orchard P, Dai C, Pettway YD, Hopkirk AL, Reihsmann CV, Tao Y, Fan S, Shrestha S, Varshney A, Petty LE, Wright JJ, Ventresca C, Agarwala S, Aramandla R, Poffenberger G, Jenkins R, Mei S, Hart NJ, Phillips S, Kang H, Greiner DL, Shultz LD, Bottino R, Liu J, Below JE; HPAP Consortium; Parker SCJ, Powers AC, Brissova M.
Nature. 2023 Dec 4. doi: 10.1038/s41586-023-06693-2. Online ahead of print

Raising the alarm: fosfomycin resistance associated with non-susceptible inner colonies imparts no fitness cost to the primary bacterial uropathogen.
Bermudez TA, Brannon JR, Dudipala N, Reasoner S, Morales G, Wiebe M, Cecala M, DaCosta M, Beebout C, Amir O, Hadjifrangiskou M.
Antimicrob Agents Chemother. 2023 Dec 11:e0080323. doi: 10.1128/aac.00803-23. Online ahead of print.

Tumor-Reactive CD8+ T Cells Enter a TCF1+PD-1- Dysfunctional State.
Roetman JJ, Erwin MM, Rudloff MW, Favret NR, Detrés Román CR, Apostolova MKI, Murray KA, Lee TF, Lee YA, Philip M.
Cancer Immunol Res. 2023 Dec 1;11(12):1630-1641. doi: 10.1158/2326-6066.CIR-22-0939.

Detecting macromolecular differences of the CSF in low disability multiple sclerosis using quantitative MT MRI at 3T.
Lawless RD, McKnight CD, O’Grady KP, Combes AJ, Rogers BP, Witt AA, Visagie M, Houston DC, Prock LE, Bagnato FR, Smith SA.
Mult Scler J Exp Transl Clin. 2023 Nov 13;9(4):20552173231211396. doi: 10.1177/20552173231211396. eCollection 2023 Oct-Dec.

Imaging and Stereotactic Electroencephalography Functional Networks to Guide Epilepsy Surgery.
Doss DJ, Johnson GW, Englot DJ.
Neurosurg Clin N Am. 2024 Jan;35(1):61-72. doi: 10.1016/ Epub 2023 Sep 23. Review.