Medical Sciences Commons^™

Neutrophil-To-Lymphocyte, Monocyte-To-Lymphocyte, And Platelet-To-Lymphocyte Ratio In Acute Hospitalized Patients With Schizophrenia, Apichan Dangrungroj, Mayteewat Chiddaycha

Chulalongkorn Medical Journal

Background: Schizophrenia has been increasingly linked to inflammation. The neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) have emerged as potential indicators of systemic inflammation.

Objectives: The objectives are to compare NLR, MLR, and PLR between patients with schizophrenia and healthy controls, and to investigate the factors associated with NLR. Methods: This retrospective study included 102 sex- and age-matched patients hospitalized with schizophrenia and control subjects. NLR, MLR, and PLR were calculated from the Complete Blood Count (CBC) results and compared between groups. Sociodemographic data and clinical characteristics were analyzed using multiple linear regression to identify …

Incidence Of Cytogenetic Abnormalities Detected By Fish Analysis In Multiple Myeloma Cases: A Seven-Year Study From A Cytogenetic Laboratory In King Chulalongkorn Memorial Hospital, Thailand (2018–2024), Montakarn Tansatit, Nutcharee Jongpornchai, Suwannee Songchart, Kittipornpan Krajokpap, Hudadini Da-Oh

Chulalongkorn Medical Journal

Background: Multiple myeloma (MM) is a genetically heterogeneous plasma cell malignancy with cytogenetic abnormalities influencing prognosis and treatment outcomes. Fluorescence in situ hybridization (FISH) is crucial for detecting clinically significant abnormalities, including IGH translocations and deletions (e.g., del(17p)), particularly in non-dividing plasma cells. However, cost and accessibility challenges limit comprehensive testing in resource-constrained settings like Thailand. Objectives: To investigate the incidence of cytogenetic abnormalities detected by FISH in MM cases over seven years in a Thai population, highlighting regional trends and barriers to comprehensive testing. Methods: A retrospective analysis was conducted on 360 bone marrow samples from MM patients between …

Biomarkers In Renal Cell Carcinoma: A Systematic Review And Immunohistochemical Validation Study, Brett Berezowski, Robert Boothe, Billy Chaplin, Sharon J Del Vecchio, Zakariya Fares, Tyrone L R Humphries, Keng Lim Ng, Taylor Noonan, Hemamali Samaratunga, Aaron Urquhart, David A Vesey, Simon T Wood, Glenda C Gobe, Robert J Ellis

Faculty, Staff and Student Publications

The worldwide incidence of renal cell carcinoma (RCC) rose by 22% between 2012 and 2022. In Australia, RCC accounted for 2.8% of all cancer diagnoses and contributing to 1.8% of cancer-related deaths. Identification of RCC biomarkers may aid in diagnosis and management. Methods: A systematic review of immunohistochemical markers of RCC studies published between 1990 and 2019 was undertaken to select candidate biomarkers of RCC. Immunohistochemical staining of 73 clear cell RCC tumors and paired normal tissue was undertaken using selected markers. Semi-quantitative and quantitative analysis of staining intensity between paired samples was undertaken to evaluate utility as potential …

Phenomenology Of Dissociation During (R/S)-Ketamine/(S)-Ketamine Therapy For Depression, Daniel William Cable

Doctoral Dissertations and Projects

The purpose of this study was to explore the dissociative experiences of patients who are receiving ketamine-assisted therapy for depression. This research was guided by the principles of phenomenological inquiry and focused on the subjective experiences of individuals and sought to explore the nuances of dissociative experiences and offer insight into its potential therapeutic implications.

The research used a qualitative methodology involving participants who have experienced ketamine-assisted therapy for depression. The setting was a controlled clinical environment where the therapy sessions were conducted. To collect data, open-ended, semi-structured interviews as well as follow-up interviews were conducted with the participants in …

Dosimetric Evaluation Of Clearsight Bolus Versus Superflab Bolus For Vmat Head And Neck Treatment, Courtney M. Williams

Masters Projects

This study compares the dosimetric performance and fit accuracy of ClearSight and Superflab boluses in head and neck (HN) volumetric modulated arc therapy (VMAT) treatment plans, focusing on dose distribution and air gap volumes. A RANDO anthropomorphic phantom was used to simulate HN VMAT treatment for oral cavity cancer with positive lymph nodes, prescribed 70 Gy in 35 fractions. Four configurations were tested: ClearSight bolus over a thermoplastic mask (CSO), ClearSight under a mask (CSU), Superflab over a mask (SFO), and Superflab under a mask (SFU). Five computed tomography (CT) scans, one without bolus and four with bolus, were performed …

Pcsk9–Dyslipidemia Interplay In Children And Adolescents With Type 1 Diabetes: A Potential Modulator Of Vasculopathy, Eman Ramadan

Pharmacy

BACKGROUND: Proprotein convertase subtilisin/kexin type-9 (PCSK9) has recently emerged as an important vasculopathy modulator. However, limited data exist on its level and expression in children and adolescents with type 1 diabetes (T1D). AIM: To assess serum PCSK9 and gene expression among children and adolescents with T1D and correlate them with glycemia, dyslipidemia, and microvascular complications. METHODS: Fifty children and adolescents with T1D were compared to 50 matched healthy controls. Serum PCSK9 enzyme-linked immunosorbent assay (ELISA) and reverse transcription polymerase chain reaction (RT-PCR) gene expression, glycated-hemoglobin, fundus, urinary albumin-to-creatinine ratio (uACR) and fasting lipids were assessed with calculation of the estimated-glucose …

Immunomodulatory Effects Of Gold Nanoparticles: Impacts On Immune Cells And Mechanisms Of Action, Khadijeh Koushki, Prapannajeet Biswal, Geraldine Vidhya Vijay, Mahvash Sadeghi, Sajad Dehnavi, Ngoc Tuyet Tra, Sai Kumar Samala, Mahdieh Yousefi Taba, Arjun Balaji Vasan, Emily Han, Yuri Mackeyev, Sunil Krishnan

Faculty, Staff and Student Publications

Traditional anti-inflammatory medications-such as corticosteroids, biological agents, and non-steroidal anti-inflammatory drugs-are commonly employed to mitigate inflammation, despite their potential for debilitating side effects. There is a growing need for alternative next-generation therapies for symptomatic, unchecked, and/or detrimental inflammation with more favorable adverse effect profiles. The long history of use of gold salts as anti-inflammatory agents and the more recent exploration of gold nanoparticle (AuNP) formulations for clinical indications suggest that the targeted delivery of nanoparticles to inflammatory sites may be a promising approach worth investigating. Coupled with peptides that specifically target immune cells, AuNPs could potently counteract inflammation. Here, we …

Hydrogen Sulfide Deficiency And Therapeutic Targeting In Cardiometabolic Hfpef: Evidence For Synergistic Benefit With Glp-1/Glucagon Agonism, Jake E. Doiron, Mahmoud H. Elbatreek, Huijing Xia, Xiaoman Yu, Natalie D. Gehred, Tatiana Gromova, Jingshu Chen, Ian H. Driver, Naoto Muraoka, Martin Jensen, Smitha Shambhu, W. H.Wilson Tang, Kyle B. Lapenna, Thomas E. Sharp, Traci T. Goodchild, Ming Xian, Shi Xu, Heather Quiriarte, Timothy D. Allerton, Alexia Zagouras, Jennifer Wilcox, Sanjiv J. Shah, Josef Pfeilschifter, Karl Friedrich Beck, Thomas M. Vondriska, Zhen Li, David J. Lefer

School of Graduate Studies Faculty Publications

Heart failure with preserved ejection fraction (HFpEF) presents significant treatment challenges. We assessed hydrogen sulfide (H2S) bioavailability in HFpEF patients and 2 animal models: the "2-hit" L-NAME + high-fat diet mouse model and ZSF1 obese rats. H2S levels were significantly reduced in patients and both models, linked to decreased cystathionine-γ-lyase expression and increased sulfide quinone oxidoreductase. Cystathionine-γ-lyase knockout worsened HFpEF, whereas pharmacological supplementation with an H2S donor improved diastolic function and reduced cardiac fibrosis. H2S supplement synergized with GLP-1/glucagon agonist and ameliorated HFpEF. These findings suggest that enhancing H2S bioavailability may provide a novel therapeutic strategy for HFpEF.

Botulinum Toxin For The Treatment Of Motor Tics In Children: A Case Series, Ethan Edmondson, Mariam Hull, Sukru Aras, Mered Parnes

Faculty, Staff and Students Publications

Tic disorders, including Tourette syndrome, are characterized by brief, repetitive, and patterned movements or vocalizations. Botulinum neurotoxin (BoNT) has emerged as a therapeutic option for motor tics, particularly when oral medications are insufficient or poorly tolerated. This retrospective cohort study evaluated the safety and effectiveness of botulinum neurotoxin injections in 50 pediatric patients (aged 7-18 years) with motor tic disorders treated at a tertiary pediatric movement disorders clinic between May 2019 and January 2024. Botulinum neurotoxin injections were tailored to individual symptomatology. Overall, 64% of patients reported improvement in tic severity, 36% noted no change, and 6% worsened. Response did …

Mri-Based Radiomics For Outcome Stratification In Pediatric Osteosarcoma, Esther Ngan, Dolores Mullikin, Ashok J Theruvath, Ananth V Annapragada, Ketan B Ghaghada, Andras A Heczey, Zbigniew A Starosolski

Faculty, Staff and Students Publications

Background/Objectives: Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents; the survival rate is as low as 24%. Accurate prediction of clinical outcomes remains a challenge due to tumor heterogeneity and the complexity of pediatric cases. This study aims to improve predictions of progressive disease, therapy response, relapse, and survival in pediatric OS using MRI-based radiomics and machine learning methods. \

Methods: Pre-treatment contrast-enhanced coronal T1-weighted MR scans were collected from 63 pediatric OS patients, with an additional nine external cases used for validation. Three strategies were considered for target region segmentation (whole-tumor, tumor …

Drug Development Studies Supporting Zileuton As A Parenteral Adjuvant To Attenuate Antibiotic-Associated Nephrotoxicity, Cole S Hudson, James E Smith, Linh T Vuong, Nicholas S Teran, Nazanin Pouya, David Sheikh-Hamad, Xinli Liu, Shama Kajiji, Vincent H Tam

Faculty, Staff and Students Publications

Glycopeptide, polymyxin, and aminoglycoside antibiotics are among the most commonly used agents to treat drug-resistant bacterial infections; however, their clinical use is hindered by nephrotoxicity. We previously reported that zileuton has the potential to attenuate antibiotic-associated nephrotoxicity in an animal model. Here, we further report the development of a parenteral formulation and exploration of dosing strategies for zileuton. The solubility, stability, and multi-dose safety of two zileuton formulations were evaluated. Zileuton serum and renal tissue pharmacokinetics were evaluated after a single dose and compared to steady state after 10 days. Different dosing strategies of zileuton to attenuate vancomycin-, polymyxin B-, …

Hand Hygiene Knowledge, Attitudes, Practices, And Hand Dirtiness Of Primary School Students Before And After A Behavioral Change Intervention During The Covid-19 Pandemic, Belize 2022-2023, Anh N Ly, Christina Craig, Kelsey Mcdavid, Dian Maheia, Yolanda Gongora, Francis Morey, Russell Manzanero, Alexandra Medley, Allison Stewart, Allison Lino, Ramiro Quezada, Rosalva Blanco, Vickie Romero, Gerhaldine Morazan, Ella Hawes, Oluwadara Okeremi, Kanako Ishida, Matthew Lozier, Kristy O Murray

Faculty, Staff and Students Publications

Hand hygiene (HH) can prevent the spread of infectious diseases and school absenteeism. However, limited data exist on HH practices at schools. Our study assesses the impact of a pilot HH intervention in 12 schools in Belize during the coronavirus disease 2019 (COVID-19) pandemic. After a national assessment of existing water, sanitation, and hygiene resources (December 2021-January 2022), 12 pilot schools were selected to evaluate an HH intervention, which included environmental nudges and HH education. Baseline assessments occurred in March 2022, the HH intervention was implemented during October 2022-May 2023, and follow-up assessments were conducted in June 2023. Student knowledge, …

Racial And Ethnic Disparities In Receipt Of Guideline-Concordant Pancreatic Cancer Care Among Older Adults In The United States, Joshua Herb, Kai-Ping Liao, John K Lin, Kever A Lewis, Sharon H Giordano, Matthew H G Katz, Rebecca A Snyder

Faculty, Staff and Student Publications

Purpose: Patients racialized as Black experience a higher mortality from pancreatic cancer (PC). Worse survival outcomes may relate to differences in delivered treatment. This study examined differences in receipt of guideline-concordant care (GCC) among older adults with PC according to race and ethnicity.

Methods: Patients 65 years and older with incident PC racialized as non-Hispanic White (NH-White) or racialized as NH-Black or of Hispanic ethnicity were identified in the SEER-Medicare database from 2004 to 2019. The primary outcome was receipt of stage-specific GCC. Multivariable logistic regression identified factors associated with GCC. Oaxaca-Blinder decomposition examined the contribution of measured and unmeasured …

Association Between Allostatic Load And Accelerated White Matter Brain Aging: Findings From The Uk Biobank, Li Feng, Zhenyao Ye, Zewen Du, Yezhi Pan, Travis Canida, Hongjie Ke, Song Liu, Shuo Chen, L Elliot Hong, Peter Kochunov, Jie Chen, David K Y Lei, Edmond Shenassa, Tianzhou Ma

Faculty, Staff and Student Publications

White matter (WM) brain age, a neuroimaging-derived biomarker indicating WM microstructural changes, helps predict dementia and neurodegenerative disorder risks. The cumulative effect of chronic stress on WM brain aging remains unknown. In this study, we assessed cumulative stress using a multi-system composite allostatic load (AL) index based on inflammatory, anthropometric, respiratory, lipidemia, and glucose metabolism measures, and investigated its association with WM brain age gap (BAG), computed from diffusion tensor imaging data using a machine learning model, among 22 951 European ancestries aged 40 to 69 (51.40% women) from UK Biobank. Linear regression, Mendelian randomization, along with inverse probability weighting, …

Leishmania In Texas: A Contemporary One Health Scoping Review Of Vectors, Reservoirs, And Human Health, Morgan H Jibowu, Richard Chung, Nina L Tang, Sarah Guo, Leigh-Anne Lawton, Brendan J Sullivan, Dawn M Wetzel, Sarah M Gunter

Faculty, Staff and Students Publications

Leishmaniasis, a vector-borne neglected tropical disease, affects over 6.2 million people globally. Case acquisition is increasingly recognized in the United States, and in Texas, most reported cases are locally acquired and speciated to Leishmania mexicana. We conducted a scoping literature review to systematically assess contemporary research on Leishmania in humans, animals, reservoir hosts, or vectors in Texas after 2000. Out of 22 eligible studies, the most prevalent themes were case reports, followed by studies on domestic animals, reservoirs, and vectors, with several studies bridging multiple disciplines. Climate change, urbanization, and habitat encroachment appear to be driving the northward expansion …

Survival To Hospital Discharge In The Fetus With Moderate To Severe Mitral Regurgitation Either In Isolation Or In Combination With Aortic Valve Stenosis Or Atresia, A Fetal Heart Society Collaborative Study, Betul Yilmaz Furtun, Kavitha Pundi, Anita Moon-Grady, Nicole Cresalia, Asela Nieuwsma, Sarah K Gelehrter, Bhawna Arya, Mary T Donofrio, Christopher Statile, Ann Kavanaugh-Mchugh, Lindsay Freud, Elijah Bolin, Megan Warner, Sowmya Balasubramanian, James Strainic, Carol Wittlieb-Weber, Nelangi M Pinto, Lisa Hornberger, Shaine A Morris

Faculty, Staff and Students Publications

Background: Case series report high mortality after fetal diagnosis of moderate to severe mitral regurgitation in combination with left atrial dilation, hydrops, or restrictive atrial septum. However, overall outcomes and specific high-risk features remain unclear.

Methods: We performed a multicenter retrospective cohort study of fetuses with ≥moderate mitral regurgitation and normal cardiac connections evaluated January 1, 2005 to January 31, 2016. Fetuses undergoing fetal cardiac intervention (FCI) were described separately. We assessed associations between fetal echocardiographic features and discharge mortality using mixed logistic regression and classification and regression tree modeling, stratified by studies performed < 28 and ≥28 weeks gestational age (GA).

Results: Of 67 fetuses, 96% had …

Increased Fungal Burden In The Gastrointestinal Tract Of Brain-Dead Organ Donors, Erika J Nachman, Colleen K Ardis, A Kyle B Ardis, Javier Nieto, Madeline M Bresson, Clare M Robertson, Maggie N Seale, Nora M Villafuerte, Zhe Lyu, Eva C Preisner, Heather A Danhof, Sara C Di Rienzi, Yolanda T Becker, Robert A Britton

Faculty, Staff and Students Publications

Approximately 3% of organ transplant recipients will be diagnosed with an invasive fungal infection (IFI), with 10%-47% being fatal. The source of IFI is typically not known, but Candida spp. cause the majority of IFI cases. We obtained intestines from two types of organ donors, brain-dead (BD) (n = 7) and donation after circulatory death (DCD) (n = 5), to sample microbes from the mucosal surface and the lumen. BD donors were parenterally fed and treated with corticosteroids in the days before procurement, whereas DCD donors were enterally fed and not given corticosteroids. We found fungi present in …

Rescue Of Male Infertility By Human Prss55 In Transgenic Mice Establishes A Contraceptive Research Model, Courtney M Sutton, Kohei Umezu, Daisuke Mashiko, Masahito Ikawa, Irina V Larina, Thomas X Garcia, Martin M Matzuk

Faculty, Staff and Students Publications

The development of non-hormonal male contraceptives requires validated preclinical models. This study investigated whether human orthologs of two mouse testis-specific serine proteases, PRSS55 and TMPRSS12, both essential for male fertility in mice, could functionally rescue the infertility phenotypes of their respective knockout mouse lines. We generated transgenic mouse lines expressing human PRSS55 with either an extracellularly or intracellularly positioned C-terminal 3xFLAG tag (RES GPI or RES TM), and a line expressing human TMPRSS12 with a C-terminal 3xFLAG tag (T12 RES), all on their respective mouse null backgrounds. Fertility was assessed through continuous mating trials, and sperm parameters were evaluated. Both …

Grade Concept Paper 9: Rationale And Process For Creating A Grade Ontology, Paul Whaley, Brian Alper, Joanne Dehnbostel, Carlos Alva-Diaz, Stavros Antoniou, Antonio Bognanni, Javier Bracchiglione, Therese Kristine Dalsbø, Sean Grant, Jennifer Hunter, Alfonso Iorio, Malgorzata Lagisz, Harold Lehmann, Sheyu Li, Joerg Meerpohl, Saphia Mokrane, Cauê Monaco, Ignacio Neumann, Kevin Pottie, Shahab Sayfi, Nigar Sekercioglu, Jasvinder Singh, Bernardo Sousa-Pinto, Janice Tufte, Lenny Thinagaran Vasanthan, Li Wang, Jun Xia, Xiaomei Yao, Holger Schünemann

Faculty, Staff and Students Publications

Context: As the rate of research production accelerates, the ability to efficiently and unambiguously communicate judgments relating to the synthesis, evaluation, and use of scientific information becomes paramount.

Perspective: Scientific information can be viewed as a "layered infrastructure" of data, evidence, knowledge, and use. The GRADE approach serves as a de facto data standard for this infrastructure, supporting movement between layers by reducing ambiguity in claims to knowledge (in the form of judgements of certainty in the evidence when answering research questions) and level of commitment to possible solutions to problems (in the form of strength of recommendations for interventions). …

Three Things We Can Do Now To Reduce The Risk Of Avian Influenza Spillovers, Kenneth B Yeh, William P Bahnfleth, Elaine Bradford, Carol Cardona, Kristen K Coleman, Peter J Hudson, Bernadeta Dadonaite, Rebecca J Hutchins, Anthony Maresso, C Raina Macintyre, Matthew Scotch

Faculty, Staff and Students Publications

No abstract provided.

Development And Validation Of Venous Thromboembolism-Bidirectional Encoder Representations From Transformers (Vte-Bert) Natural Language Processing Model, Omid Jafari, Shengling Ma, Barbara D Lam, Jun Y Jiang, Emily Zhou, Mrinal Ranjan, Justine Ryu, Raka Bandyo, Arash Maghsoudi, Bo Peng, Christopher I Amos, Abiodun Oluyomi, Nathanael R Fillmore, Jennifer La, Ang Li

Faculty, Staff and Students Publications

Background: Accurate and rapid phenotyping of venous thromboembolism (VTE) in longitudinal studies is important. A natural language processing (NLP) tool externally validated in representative patients is lacking.

Objectives: To train and validate an efficient NLP model to detect incident VTE event.

Methods: We designed a novel NLP platform, NLPMed, to assist thrombosis researchers with data preprocessing, phenotype annotation, language model finetuning, and NLP application. Using clinical notes, discharge summaries, and radiology reports from patients with cancer at 2 healthcare institutions, we finetuned Bio_Clinical Bidirectional Encoder Representations from Transformers (BERT) to develop VTE-BERT. The new model was trained to detect acute …

The Neurosurgeon's Role In The Brain Economy: How Strategic Investment In Neurosurgical Care And Innovation Will Improve Global Outcomes, Daniela A Perez-Chadid, Riya M Dange, Harris A Eyre, Graham Fieggen, Kerry A Vaughan, Sameer A Sheth, Jafri Malin Abdullah, Bello B Shehu, Daniel Donoho, Samuel Browd, Agustin Ibanez, Saksham Gupta, Frederick Lang, Anil Nanda, Gail Rosseau

Faculty, Staff and Student Publications

No abstract provided.

Phase 2 Study Of Zilovertamab Vedotin In Participants With Metastatic Solid Tumors, Funda Meric-Bernstam, Martin Gutierrez, Enrique Sanz-Garcia, Diego Villa, Jun Zhang, Jennifer Friedmann, Fengting Yan, Mark A Socinski, John Sarantopoulos, Luis E Raez, Quincy S Chu, Maxime Chénard-Poirier, Manash Chatterjee, Hong Ren, Qi Liu, Douglas A Levine, Komal L Jhaveri

Faculty, Staff and Student Publications

Purpose: Zilovertamab vedotin, an antibody‒drug conjugate targeting receptor tyrosine kinase‒like orphan receptor 1 (ROR1), had manageable safety and promising antitumor activity in participants with relapsed or refractory non-Hodgkin lymphomas. We evaluated zilovertamab vedotin in participants with previously-treated metastatic solid tumors.

Methods: This phase 2, open-label, nonrandomized study (NCT04504916) enrolled participants with metastatic triple-negative breast cancer, hormone receptor‒positive (HR+) breast cancer, nonsquamous non‒small-cell lung cancer, platinum-resistant ovarian cancer, or pancreatic cancer. Participants received zilovertamab vedotin ≤2.5 mg/kg once every 3 weeks (Q1/3W) or < 1.75 mg/kg twice every 3 weeks (Q2/3W). Primary endpoint was objective response rate (ORR) per RECIST v1.1 by blinded independent central review. ROR1 protein expression was correlated with clinical outcomes.

Results: 102 participants were enrolled (Q1/3W, n=70; Q2/3W, n=32). ORR was 1% (95% CI, 0%‒8%) with …

Nuak Kinases: Signaling Mechanisms And Therapeutic Applications, Nicole M. Cullen, Peter Rosston, Bakhtawar Tufail, Anne E. D'Armond, Ayushi Patel, Dara H. Khosravi, Bridgette M. Collins-Burow, Van T. Hoang, Elizabeth C. Martin, David H. Drewry, Matthew E. Burow, Suresh K. Alahari

School of Medicine Faculty Publications

The novel (nua) kinases 1 and 2 are two of 12 AMP-activated protein–related kinases whose signaling pathways are involved in cancer progression, as well as neurologic, fibrotic, and inflammatory diseases. Currently, there are 80 Food and Drug Administration-approved kinase inhibitors which target roughly 24 of the 500+ known human kinases, leaving most kinases underexplored, including NUAK1 and NUAK2. Thus, there is a critical need for selective inhibition of NUAK1 and NUAK2 signaling. Here, we review the protein structure, known upstream regulators and downstream targets, and expression profiles of NUAK1 and NUAK2 in cancerous compared to noncancerous tissue. We also delineate …

Information Theory Optimization Of Signals From Small-Angle Scattering Measurements, Robert P Rambo, John A Tainer

Faculty, Staff and Student Publications

Small-angle X-ray scattering (SAXS) of particles in solution informs on the conformational states and assemblies of biological macromolecules (bioSAXS) outside of cryo- and solid-state conditions. In bioSAXS, the SAXS measurement under dilute conditions is resolution limited, and through an inverse Fourier transform, the measured SAXS intensities directly relate to the physical space occupied by the particles via the P(r)-distribution. Yet, this inverse transform of SAXS data has been historically cast as an ill-posed, ill-conditioned problem requiring an indirect approach. Here, we show that through the applications of matrix and information theories, the inverse transform of SAXS intensity data is a …

Interactive 3d Segmentation For Primary Gross Tumor Volume In Oropharyngeal Cancer, Mikko Saukkoriipi, Jaakko Sahlsten, Joel Jaskari, Lotta Orsmaa, Jari Kangas, Nastaran Rasouli, Roope Raisamo, Jussi Hirvonen, Helena Mehtonen, Jorma Järnstedt, Antti Mäkitie, Mohamed Naser, Clifton Fuller, Benjamin Kann, Kimmo Kaski

Faculty, Staff and Student Publications

Radiotherapy is the main treatment modality of oropharyngeal cancer (OPC), in which an accurate segmentation of primary gross tumor volume (GTVt) is essential but also challenging due to significant interobserver variability and the time consumed in manual tumor delineation. For such a challenge an interactive deep learning (DL) based approach offers the advantage of automatic high-performance segmentation with the flexibility for user correction when necessary. In this study, we investigate an interactive DL for GTVt segmentation in OPC by introducing a novel two-stage Interactive Click Refinement (2S-ICR) framework and implementing state-of-the-art algorithms. Using the 2021 HEad and neCK TumOR dataset …

Rare Variants In Bmal1 Are Associated With A Neurodevelopmental Syndrome, Vishnu Anand Cuddapah, Dechun Chen, Bumsik Cho, Rebecca Moore, Mohnish Suri, Hana Safraou, Frederic Tran-Mau-Them, Ashley Wilson, Jacqueline Odgis, Atteeq U Rehman, Carol Saunders, Shiva Ganesan, Vaidehi Jobanputra, Stephen W Scherer, Ingo Helbig, Amita Sehgal

Duncan NRI Faculty and Staff Publications

Children with neurodevelopmental disorders exhibit highly penetrant sleep and circadian dysfunction, but the underlying mechanisms are unclear. We asked whether a subset of individuals with neurodevelopmental disorders might have genetic variants in genes known to drive circadian rhythms. Through international collaboration, we identified ten individuals with very rare genetic variants in BMAL1, a core component of the molecular clock. These individuals exhibited overlapping signs and symptoms including developmental delay, autism spectrum disorder, and variably penetrant marfanoid features. We functionally tested the identified BMAL1 variants in cell culture and in vivo and found disrupted BMAL1 function. These findings demonstrate that …

Hemispherotomy For Drug-Resistant Epilepsy In Bilateral Sturge-Weber Syndrome: Illustrative Cases, Eveline Teresa Hidalgo, Eric A Grin, Yosef Dastagirzada, Nealen Laxpati, Judith Bluvstein, Julia R Schneider, Daniel Miles, Michal Tzadok, James Riviello, Howard L Weiner

Faculty, Staff and Students Publications

Background: Sturge-Weber syndrome (SWS) is a congenital neurocutaneous disorder characterized by angiomas of the face, choroid, and leptomeninges. Seizures in these children often present within the first 2 years of life. SWS is typically unilateral, but bilateral SWS occurs in approximately 15% of cases. Bilateral SWS is associated with earlier seizure onset and poorer cognitive, developmental, and functional outcomes. More than half of children with SWS develop drug-resistant epilepsy requiring surgical intervention. Hemispherotomy has been established as a successful treatment for unilateral SWS, but resective surgery has traditionally not been considered a treatment option for patients with bilateral disease.

Observations: …

Upregulating Ankhd1 In Ps19 Mice Reduces Tau Phosphorylation And Mitigates Tau Toxicity-Induced Cognitive Deficits, Xiaolin Tian, Nathan Le, Yuhai Zhao, Dina Alawamleh, Andrew Schwartz, Lauren Meyer, Elizabeth Helm, Chunlai Wu

School of Graduate Studies Faculty Publications

Using the fly eye as a model system, we previously demonstrated that upregulation of the fly gene mask protects against FUS- and Tau-induced photoreceptor degeneration. Building upon this finding, we investigated whether the protective role of mask is conserved in mammals. To this end, we generated a transgenic mouse line carrying Cre-inducible ANKHD1, the human homolog of mask. Utilizing the TauP301S-PS19 mouse model for Tau-related dementia, we found that expressing ANKHD1 driven by CamK2a-Cre reduced hyperphosphorylated human Tau in 6-month-old mice. Additionally, ANKHD1 expression was associated with a trend toward reduced gliosis and preservation of the presynaptic marker Synaptophysin, suggesting …

Integrating Ctdna Analysis And Radiomics For Dynamic Risk Assessment In Localized Lung Cancer, Everett J Moding, Mohammad Shahrokh Esfahani, Cheng Jin, Angela B Hui, Barzin Y Nabet, Yufei Liu, Jacob J Chabon, Michael S Binkley, David M Kurtz, Emily G Hamilton, Aadel A Chaudhuri, Chih Long Liu, Zhe Li, Rene F Bonilla, Alice L Jiang, Brianna C Lau, Pablo Lopez, Jianzhong He, Yawei Qiao, Ting Xu, Luyang Yao, Saumil Gandhi, Zhongxing Liao, Millie Das, Kavitha J Ramchandran, Sukhmani K Padda, Joel W Neal, Heather A Wakelee, Michael F Gensheimer, Billy W Loo, Ruijiang Li, Steven H Lin, Ash A Alizadeh, Maximilian Diehn

Faculty, Staff and Student Publications

The complementarity and clinical utility of combining liquid biopsies and radiomic image analysis has not been demonstrated. Circulating tumor DNA (ctDNA) minimal residual disease after chemoradiotherapy (CRT) for non-small cell lung cancer (NSCLC) is highly prognostic, but on-treatment biomarkers are needed to enable response-adapted therapies. Here, we analyzed 418 patients with NSCLC undergoing CRT to develop and validate a novel dynamic risk model that accurately predicts ultimate progression-free survival during treatment. We optimize tissue-free variant calling from plasma samples to facilitate ctDNA monitoring and demonstrate the importance of accounting for persistent clonal hematopoiesis variants. We show that mid-CRT ctDNA concentration …