Digital Commons Network^™

Wnt7a, Naomi M Calhoun, Richard R Behringer

Faculty, Staff and Student Publications

WNT7A regulates numerous developmental processes. It can activate canonical and non-canonical signaling depending on context. It is expressed in the developing central nervous system, limb buds, reproductive organs, and other tissues. Spontaneous and targeted Wnt7a mutations in mouse models resulted in abnormal limbs, defects in male and female reproductive tract organs, infertility, and defects in cerebellar axon remodeling. In zebrafish, wnt7aa mutants exhibited neurogenesis and angiogenesis defects in the central nervous system. In humans, recessive WNT7A missense and nonsense mutations resulted in severe limb and pelvic bone defects. Alterations in WNT7A expression correlated with multiple types of cancer.

Bismuth-Infused Perivascular Wrap Facilitates Delivery Of Mesenchymal Stem Cells And Attenuation Of Neointimal Hyperplasia In Rat Arteriovenous Fistulas, Allan John R Barcena, Joy Vanessa D Perez, Marvin R Bernardino, Jossana A Damasco, Erin Marie D San Valentin, Carleigh Klusman, Benjamin Martin, Gino Martin Canlas, Francisco M Heralde, Natalie Fowlkes, Richard R Bouchard, Jizhong Cheng, Steven Y Huang, Marites P Melancon

Faculty, Staff and Student Publications

BACKGROUND: Mesenchymal stem cells (MSCs) have emerged as novel therapies for supporting arteriovenous fistula (AVF) maturation, and bioresorbable polymeric scaffolds have enabled sustained MSC delivery into maturing AVFs. However, the radiolucency of biopolymeric wraps prevents in vivo monitoring of their integrity and location, hindering long-term preclinical investigations.

METHODS: We infused bismuth nanoparticles (BiNPs) into polycaprolactone (PCL) to fabricate an electrospun perivascular wrap capable of MSC delivery and conducive to longitudinal monitoring using conventional imaging. We tested the wraps' effects on the attenuation of markers of neointimal hyperplasia (i.e., endothelial dysfunction, hypoxia, and inflammation), the leading cause of AVF failure, in …

An Unusual Case Of Gastrointestinal Bleeding In A Recent Roux-En-Y Patient, Christopher J Carnabatu, Tanyaradzwa M Kajese, Erik B Wilson

Faculty, Staff and Student Publications

The incidence of obesity nationwide has led to an increase in both medicinal and surgical interventions, with recent studies indicating a drop in obesity prevalence for the first time in over a decade. Laparoscopic Roux-en-Y gastric bypass remains one of the most commonly performed bariatric procedures in the United States, accounting for about 22% of all bariatric surgeries in 2022. While considered a safe procedure, gastric bypass results in an anatomic configuration that poses a unique challenge from both a surveillance and interventional standpoint. The gastric remnant, biliopancreatic (BP) limb, and extrahepatic biliary tree are not readily accessible vis-à-vis esophagogastroduodenoscopy …

Palliative Care In Acute Care Surgery: Research Challenges And Opportunities, Amelia W Maiga, Vanessa Ho, Rachel S Morris, Lisa M Kodadek, Thaddeus J Puzio, Gail T Tominaga, Masami Tabata-Kelly, Zara Cooper

Faculty, Staff and Student Publications

Palliative care includes effective communication, relief of suffering and symptom management with an underlying goal of improving the quality of life for patients with serious illness and their families. Best practice palliative care is delivered in parallel with life-sustaining or life-prolonging care. Palliative care affirms life and regards death as a normal process, intends neither to hasten death nor to postpone death and includes but is not limited to end-of-life care. Palliative care encompasses both primary palliative care (which can and should be incorporated into the practice of acute care surgery) and specialty palliative care (consultation with a fellowship-trained palliative …

Latent Classes Of Adolescent Trauma Exposure, Posttraumatic Stress Disorder Symptoms, And Substance Use Predict Clinical Diagnoses At 12-Month Follow-Up, John Leri, Josh M Cisler, Shaunna L Clark, Cody G Dodd, Saman Siddiqui, Leslie Taylor, Alexa Ayala, Sunita Stewart, Robyn Richmond, Jeffrey D Shahidullah, Justin F Rousseau, John M Hettema, D Jeffrey Newport, Karen D Wagner, Charles B Nemeroff

Faculty, Staff and Student Publications

BACKGROUND: Trauma exposure, posttraumatic stress disorder (PTSD), and substance use commonly co-occur among youth. Identifying specific subgroups of youth based on unique constellations across these domains may provide a novel way to identify and target youth at prospective risk for specific types of negative clinical outcomes.

METHODS: Trauma exposed youth completed structured clinical assessments as part of a longitudinal study (

RESULTS: Four latent classes were identified which differentiated participants based on the type of trauma exposure, the number of PTSD symptoms endorsed, and the propensity to be engaged in polysubstance use. Latent classes which were characterized by exposure to …

The Urgent Need For Well-Being Programs In Medical Residencies In Brazil, Marcelo Bruno Generoso, Pedro Shiozawa, Ricardo Uchida, Marsal Sanches

Faculty, Staff and Student Publications

No abstract provided.

A Prior-Knowledge-Guided Feature Selection Method And Its Application To Biomarker Identification Of Schizophrenia, Ying Xing, Godfrey D Pearlson, Peter Kochunov, Vince D Calhoun, Yuhui Du

Faculty, Staff and Student Publications

Despite considerable efforts to uncover the neural basis of psychiatric disorders using neuroimaging, few methods utilize intrinsic brain-derived knowledge, leading to limited specificity and discriminability in biomarker identification. To leverage the inherent characteristics within the brain, we propose a prior-knowledge-guided feature selection method to flexibly unveil discriminative and target-oriented biomarkers of psychiatric disorders. Specifically, we construct a constrained sparse regularization allowing for the flexible integration of diverse prior knowledge to identify sparse neuroimaging features linked to specific psychopathology. Additionally, we simultaneously integrate graph-based regularization and redundancy-removal regularization to further ensure the discriminability and independence among the selected features. Different priors …

Brazilian Psychiatric Association Guidelines For The Treatment Of Social Anxiety Disorder, Leonardo Baldaçara, Thales Marcon Almeida, Diogo Cesar Dos Santos, Ana Beatriz Paschoal, Aldo Felipe Pinto, Luiz Antonio Vesco Gaiotto, Diogo De Lacerda Veiga, Fabiano Franca Loureiro, Leandro Fernandes Malloy-Diniz, Roseli Lage De Oliveira, Quirino Cordeiro, Marsal Sanches, Antônio E Nardi, Antônio Geraldo Da Silva, Ricardo R Uchida

Faculty, Staff and Student Publications

Social anxiety disorder (SAD), one of the most prevalent anxiety disorders, is not well recognized. In most cases, SAD follows an unremitted and chronic course, affecting individual functioning in relationships, education, and work. Due to the disorder’s relevance in Brazil, guideline-based treatments adapted to the Brazilian social and economic context are needed. We conducted a systematic review assessing several treatment modalities for SAD. PubMed, Cochrane, SciELO, and ClinicalTrials.gov were searched using the Medical Subject Headings social anxiety disorder and social phobia. Of the 438 selected articles, 20 were selected. Selective serotonin reuptake inhibitors are considered a first-line treatment for SAD …

Examining The Relationship Between Cardiometabolic Risk Factors And Telomere Length In Women: A Systematic Review, Jeni Page, Catherine Stephens, Melissa A Richard, Elizabeth Lyons, Elizabeth Baumler, M Terese Verklan, Elizabeth Lorenzo

Faculty, Staff and Student Publications

Background and objectives: Cardiometabolic syndrome (CMS) poses a significant public health challenge due to its rising prevalence in aging and significant healthcare costs. Recent studies have suggested telomere length (TL), a marker of cellular aging, may be impacted by CMS among women, but comprehensive evidence remains limited. This study aimed to examine the association between CMS risk factors (increased waist circumference [WC], elevated blood pressure, impaired fasting blood glucose, elevated triglycerides, decreased high-density lipoproteins) and TL in women, with consideration of age and race or ethnicity.

Research design and methods: A systematic review was conducted following PRISMA guidelines, with searches …

Mental Health Outcomes Of Latino Emerging Adults With Autism Spectrum Disorder In A Community-Based, Transition To Adulthood Program, Antonio F Pagán, Ana C Ramirez, Katherine A Loveland, Cecilia Montiel-Nava, Ron Acierno

Faculty, Staff and Student Publications

Latino individuals with autism spectrum disorder (ASD) face unique challenges during their transition to adulthood. This study evaluates ¡Iniciando! la Adultez, a culturally adapted behavioral health program aimed at addressing the co-occurring mental health needs of Latino young adults with ASD and their families. The program integrates culturally relevant elements to enhance engagement and effectiveness. Results indicated that the behavioral health intervention was associated with significant reductions in anxiety and depressive symptoms, highlighting the urgent need for tailored behavioral health services in this population. Additionally, the involvement of parents in group therapy demonstrated a positive impact on both parental and …

Consistent Frontal-Limbic-Occipital Connections In Distinguishing Treatment-Resistant And Non-Treatment-Resistant Schizophrenia, Yijie Zhang, Shuzhan Gao, Chuang Liang, Juan Bustillo, Peter Kochunov, Jessica A Turner, Vince D Calhoun, Lei Wu, Zening Fu, Rongtao Jiang, Daoqiang Zhang, Jing Jiang, Fan Wu, Ting Peng, Xijia Xu, Shile Qi

Faculty, Staff and Student Publications

Background and hypothesis: Treatment-resistant schizophrenia (TR-SZ) and non-treatment-resistant schizophrenia (NTR-SZ) lack specific biomarkers to distinguish from each other. This investigation aims to identify consistent dysfunctional brain connections with different atlases, multiple feature selection strategies, and several classifiers in distinguishing TR-SZ and NTR-SZ.

Study design: 55 TR-SZs, 239 NTR-SZs, and 87 healthy controls (HCs) were recruited from the Affiliated Brain Hospital of Nanjing Medical University. Resting-state functional connection (FC) matrices were constructed from automated anatomical labeling (AAL), Yeo-Networks (YEO) and Brainnetome (BNA) atlases. Two feature selection methods (Select From Model and Recursive Feature Elimination) and four classifiers (Adaptive Boost, Bernoulli Naïve …

Detection Of Erg11 Gene Mutation In Coding And Non-Coding Regions Of Clinical Candida Glabrata (Nakaseomyces Glabratus) Isolates From Pakistan, Saba Memon, Najia Karim Ghanchi, Urooj Zafar, Joveria Farooqi, Sadaf Zaka, Kauser Jabeen

Faculty, Staff and Student Publications

Azoles inhibit the cytochrome P450-dependent enzyme lanosterol 14α-demethylase (CYP51) that is encoded by the ERG11 gene. Azole resistance in Candida species arises through different mechanisms, like mutations in the ERG11 gene, ERG11 overexpression, CDR1,2 (Candida drug resistance) overexpression that actively efflux azole drugs, reducing their intracellular concentration and therapeutic effectiveness, and biofilm formation. We sequenced the ERG11 gene to determine mutations in the coding and non-coding regions of ERG11 in clinical isolates of Candida glabrata (Nakaseomyces glabratus) from Pakistan. Eight C. glabrata (N. glabratus) strains from our fungal strain bank (five fluconazole-resistant and …

Peer Support During In Vivo Exposure Homework Increases Likelihood Of Prolonged Exposure Therapy Completion, Melba A Hernandez-Tejada, Madeline J Bruce, Wendy Muzzy, Anna Birks, Giovanni Macedo E Cordeiro, Stephanie M Hart, Stephanie Hamski, Ron Acierno

Faculty, Staff and Student Publications

Exposure-based treatments such as prolonged exposure therapy (PE) are effective for veterans with PTSD. However, dropout rates as high as 50% are common. The Department of Veterans Affairs employs peers to increase mental health treatment engagement, however peers are not routinely used to help patients complete PE homework assignments. The present study included 109 veterans who decided to drop out from exposure-based treatment after completing seven or fewer sessions and used a randomized controlled design to compare PE treatment completion rates in response to 2 forms of peer support: (1) standard weekly telephone-based peer support vs. (2) peer-assisted in vivo …

Therapeutic Alliance In A Culturally Tailored Transition Program For Latino Young Adults With Autism And Their Families, Antonio F Pagán, Katherine A Loveland, Ron Acierno

Faculty, Staff and Student Publications

Latino young adults with autism spectrum disorder (ASD) often face barriers to accessing culturally appropriate interventions that support adaptive functioning and family dynamics. Therapeutic alliance, the collaborative and trusting relationship between participants and providers, is a critical component of intervention success, yet its role in culturally tailored programs for Latino families remains underexplored. The present study examined therapeutic alliance in ¡Iniciando! la Adultez, a 12-week, culturally adapted intervention for Latino young adults with ASD and their Spanish-speaking parents. The program integrates Latino cultural values and language and consists of parent group therapy, young adult group therapy, and individual therapy sessions. …

Small Molecule-Based Regulation Of Gene Expression In Human Astrocytes Switching On And Off The G-Quadruplex Control Systems, Vijay Kumar M J, Jérémie Mitteaux, Zi Wang, Ellery Wheeler, Nitin Tandon, Sung Yun Jung, Robert H E Hudson, David Monchaud, Andrey S Tsvetkov

Faculty, Staff and Student Publications

A great deal of attention is being paid to strategies seeking to uncover the biology of the four-stranded nucleic acid structure G-quadruplex (G4) via their stabilization in cells with G4-specific ligands. The conventional definition of chemical biology implies that a complete assessment of G4 biology can only be achieved by implementing a complementary approach involving the destabilization of cellular G4s by ad hoc molecular effectors. We report here on an unprecedented comparison of the cellular consequences of G4 chemical stabilization by pyridostatin (PDS) and destabilization by phenylpyrrolocytosine (PhpC) at both transcriptome- and proteome-wide scales in patient-derived primary human astrocytes. Our …

Single-Cell Multiome Characterizing Intercellular Communication And Intracellular Regulation Of Epithelium And Mesenchymal During Secondary Palate Development In Mice, Usama Hussein, Yulin Dai, Andi Liu, Toshiyuki Itai, Fangfang Yan, Lukas M Simon, Zhongming Zhao

Faculty, Staff and Student Publications

Cell-cell communication between adjacent tissues is fundamental to orchestrating organ morphogenesis. During secondary palate development, interactions between epithelial and mesenchymal cells regulate epithelial-mesenchymal signaling, thereby controlling cell proliferation, differentiation, and tissue patterning. However, the precise molecular mechanisms underlying these interactions remain largely unexplored. In this study, we employed single-cell multiome sequencing to simultaneously profile chromatin accessibility and gene expression in 35,150 individual cells isolated from the developing mouse secondary palate at embryonic days E12.5, E13.5, E14.0, and E14.5. Our analysis revealed that intercellular signaling plays a pivotal role in directing secondary palate morphogenesis, with WNT, BMP, and PDGF pathways emerging …

Clinician Attitudes Toward Palliative Care To Enhance The Quality Of Life For Patients With Sickle Cell Disease, Eberechi Nwogu-Onyemkpa, Amber B Amspoker, Nimrah Saleem, Aanand D Naik, Elizabeth Kvale, Ifeyinwa Osunkwo

Faculty, Staff and Student Publications

Objectives: Palliative care (PC) is rare for patients with sickle cell disease (SCD). This study evaluated clinician attitudes toward PC for SCD.

Methods: A cross-sectional survey was conducted between October 2022 and February 2023. Clinicians were recruited from institutions across the United States.

Results: Eighty-six participants completed the survey. Most were physicians (90%), female (72%), had >10 years of experience (63%), and lacked prior PC training (57%). Most participants agreed (83%) that patients with SCD would benefit from PC, disagreed (99%) that PC is only for dying patients, and expressed interest (91%) in learning about PC interventions. Clinicians with prior …

The Human Spinothalamic Tract: Lessons From Cordotomy, Anthony K Allam, Michael Benjamin Larkin, Ishan A Patel, Mohammed Hasen, David Mears, Patrick Dougherty, Ashwin Viswanathan

Faculty, Staff and Student Publications

The spinothalamic tract has long been known as a primary conductor of nociceptive information, with its anatomical and physiological understanding evolving over centuries of research. This comprehensive review traces the history of the spinothalamic tract beginning with Brown-Sequard’s 1860 report of contralateral analgesia following a hemisection of the spinal cord. As clinical and surgical interventions, such as cordotomies have advanced, so did our understanding of the spinothalamic tract’s function and anatomy. The spinothalamic tract’s role as a crossed pathway conducting pain and temperature sensations was solidified by the mid-20th century. However, intricate details of its somatotopic arrangement, anatomical distributions and …

The Impact Of Insurance On Adolescent Transition To Adult Care, Diane V Murrell, Cassandra J Enzler, Lauren Bretz, Beth H Garland, Albert C Hergenroeder, Christine Markham, Constance M Wiemann

Faculty, Staff and Student Publications

Background: This study sought to examine how adolescents and young adults with special health care needs (AYA) prepare for managing medical insurance (private and public) as an adult and the role of insurance in locating an adult provider and engaging in care.

Methods: Twenty-eight AYA aged 18-24 years with renal, inflammatory bowel, or rheumatologic diseases completed individual semi-structured interviews designed to evaluate the impact of insurance (private vs. public) on their health care transition experiences. An interdisciplinary team of coders analyzed transcripts using The Framework Method.

Results: Three themes emerged: continuum of accepting health insurance responsibility; the impact of insurance …

Overview Of The Head And Neck Tumor Segmentation For Magnetic Resonance Guided Applications (Hnts-Mrg) 2024 Challenge, Kareem A Wahid, Cem Dede, Dina M El-Habashy, Serageldin Kamel, Michael K Rooney, Yomna Khamis, Moamen R A Abdelaal, Sara Ahmed, Kelsey L Corrigan, Enoch Chang, Stephanie O Dudzinski, Travis C Salzillo, Brigid A Mcdonald, Samuel L Mulder, Lucas Mccullum, Qusai Alakayleh, Carlos Sjogreen, Renjie He, Abdallah S R Mohamed, Stephen Y Lai, John P Christodouleas, Andrew J Schaefer, Mohamed A Naser, Clifton D Fuller

Faculty, Staff and Student Publications

Magnetic resonance (MR)-guided radiation therapy (RT) is enhancing head and neck cancer (HNC) treatment through superior soft tissue contrast and longitudinal imaging capabilities. However, manual tumor segmentation remains a significant challenge, spurring interest in artificial intelligence (AI)-driven automation. To accelerate innovation in this field, we present the Head and Neck Tumor Segmentation for MR-Guided Applications (HNTS-MRG) 2024 Challenge, a satellite event of the 27th International Conference on Medical Image Computing and Computer Assisted Intervention. This challenge addresses the scarcity of large, publicly available AI-ready adaptive RT datasets in HNC and explores the potential of incorporating multi-timepoint data to enhance RT …

Head-To-Head Comparison Of Aptamer- And Antibody-Based Proteomic Platforms In Human Cerebrospinal Fluid Samples From A Real-World Memory Clinic Cohort, Raquel Puerta, Amanda Cano, Pablo García-González, Fernando García-Gutiérrez, Maria Capdevila, Itziar De Rojas, Clàudia Olivé, Josep Blázquez-Folch, Oscar Sotolongo-Grau, Andrea Miguel, Laura Montrreal, Pamela Martino-Adami, Asif Khan, Adelina Orellana, Yun Ju Sung, Ruth Frikke-Schmidt, Natalie Marchant, Jean Charles Lambert, Maitée Rosende-Roca, Montserrat Alegret, Maria Victoria Fernández, Marta Marquié, Sergi Valero, Lluís Tárraga, Carlos Cruchaga, Alfredo Ramírez, Mercè Boada, Bart Smets, Alfredo Cabrera-Socorro, Agustín Ruiz

Faculty, Staff and Student Publications

High-throughput proteomic platforms are crucial to identify novel Alzheimer’s disease (AD) biomarkers and pathways. In this study, we evaluated the reproducibility and reliability of aptamer-based (SomaScan® 7k) and antibody-based (Olink® Explore 3k) proteomic platforms in cerebrospinal fluid (CSF) samples from the Ace Alzheimer Center Barcelona real-world cohort. Intra- and inter-platform reproducibility were evaluated through correlations between two independent SomaScan® assays analyzing the same samples, and between SomaScan® and Olink® results. Association analyses were performed between proteomic measures, CSF biological traits, sample demographics, and AD endophenotypes. Our 12-category metric of reproducibility combining correlation analyses identified 2428 highly reproducible SomaScan CSF measures, …

Linking Transcriptome And Morphology In Bone Cells At Cellular Resolution With Generative Ai, Lu Lu, Noriaki Ono, Joshua D Welch

Faculty, Staff and Student Publications

Recent advancements in deep learning (DL) have revolutionized the capability of artificial intelligence (AI) by enabling the analysis of large-scale, complex datasets that are difficult for humans to interpret. However, large amounts of high-quality data are required to train such generative AI models successfully. With the rapid commercialization of single-cell sequencing and spatial transcriptomics platforms, the field is increasingly producing large-scale datasets such as histological images, single-cell molecular data, and spatial transcriptomic data. These molecular and morphological datasets parallel the multimodal text and image data used to train highly successful generative AI models for natural language processing and computer vision. …

Dynamic And Concordance-Assisted Learning For Risk Stratification With Application To Alzheimer’S Disease, Wen Li, Ruosha Li, Ziding Feng, Jing Ning

Faculty, Staff and Student Publications

Dynamic prediction models capable of retaining accuracy by evolving over time could play a significant role for monitoring disease progression in clinical practice. In biomedical studies with long-term follow up, participants are often monitored through periodic clinical visits with repeat measurements until an occurrence of the event of interest (e.g. disease onset) or the study end. Acknowledging the dynamic nature of disease risk and clinical information contained in the longitudinal markers, we propose an innovative concordance-assisted learning algorithm to derive a real-time risk stratification score. The proposed approach bypasses the need to fit regression models, such as joint models of …

A Bayesian Pharmacokinetics Integrated Phase I-Ii Design To Optimize Dose-Schedule Regimes, Mengyi Lu, Ying Yuan, Suyu Liu

Faculty, Staff and Student Publications

The schedule of administering a drug has profound impact on the toxicity and efficacy profiles of the drug through changing its pharmacokinetics (PK). PK is an innate and indispensable component of the dose-schedule optimization. Motivated by this, we propose a Bayesian PK integrated dose-schedule finding (PKIDS) design to identify the optimal dose-schedule regime by integrating PK, toxicity, and efficacy data. Based on the causal pathway that dose and schedule affect PK, which in turn affects efficacy and toxicity, we jointly model the three endpoints by first specifying a Bayesian hierarchical model for the marginal distribution of the longitudinal dose-concentration process. …

Neurofilament Light Chain In Serum Of Cancer Patients With Acute Neurological Complications, Amulya Gottiparthy, Keng Lam, Suprateek Kundu, Zixi Yang, Ivo Tremont-Lukats, Sudhakar Tummala

Faculty, Staff and Student Publications

Aim: Neurofilament light chain (NfL) is a nonspecific sensitive biomarker of axonal damage.

Methods: This case series identified cancer patients with neurological complications who had serum NfL measurements and paired these results to outcomes.

Results: NfL serum levels were available in 15 patients with hematological malignancies or solid tumors. The neurological complications studied were immune effector cell-associated neurotoxicity syndrome, immune checkpoint inhibitor-related encephalopathy, anoxic brain injury, Guillain-Barre syndrome, hemophagocytic lymphohistiocytosis, transverse myelitis, paraneoplastic syndrome, central nervous system demyelinating disorder and chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids. All patients but one with serum NfL >900 pg/ml died …

Predicting Kidney Graft Function And Failure Among Kidney Transplant Recipients, Yi Yao, Brad C Astor, Wei Yang, Tom Greene, Liang Li

Faculty, Staff and Student Publications

Background: Graft loss is a major health concern for kidney transplant (KTx) recipients. It is of clinical interest to develop a prognostic model for both graft function, quantified by estimated glomerular filtration rate (eGFR), and the risk of graft failure. Additionally, the model should be dynamic in the sense that it adapts to accumulating longitudinal information, including time-varying at-risk population, predictor-outcome association, and clinical history. Finally, the model should also properly account for the competing risk by death with a functioning graft. A model with the features above is not yet available in the literature and is the focus of …

Implications Of Myocardial Strain In Primary Mitral Regurgitation-A Cardiovascular Magnetic Resonance Study, Simone Romano, Danai Kitkungvan, Duc T Nguyen, Carlos El-Tallawi, Edward A Graviss, Afshin Farzaneh-Far, Dipan J Shah

Faculty, Staff and Student Publications

Aims: Chronic primary mitral regurgitation (MR) results in progressive left ventricular (LV) remodelling. Abnormal myocardial deformation (strain) can be present despite preserved ejection fraction (EF). Cardiovascular magnetic resonance (CMR) feature-tracking techniques allow assessment of global longitudinal strain (GLS) from routine cine images. The aim of this study is to evaluate the prognostic value of CMR feature tracking-derived GLS in patients with primary MR.

Methods and results: Consecutive patients undergoing CMR for chronic MR from January 2012 to June 2018 were enrolled. Patients with LVEF < 50% were excluded. The composite primary outcome aiming to detect decompensation related to MR comprised (i) referral for mitral surgery owing to symptoms or LV systolic dysfunction or (ii) cardiovascular death. The secondary outcome was all-cause death. A total of 422 patients were followed for a median of 2.7 years, and the primary endpoint was met in 93 patients (34 patients reported symptoms at baseline). At multivariable analysis, GLS≥ -16.6% was associated with primary outcome [hazard ratio (HR) 1.90, P = 0.01]. In moderate MR cohort, patients with GLS≥ -16.6% had worse event-free survival, whereas there was no significant difference in mild or severe MR groups. GLS≥ -16.0% remained associated with all-cause death after adjusting for other covariates including the MR severity (HR 2.24, P = 0.02).

Conclusion: In patients with primary MR with preserved systolic function, GLS was associated with our composite …

Transcriptomic Profile Analysis Of Brain Tissue In The Absence Of Functional Trpm8 Calcium Channel, Erick B Saldes, Alexandra Erdmier, Jai Velpula, Timothy E Koeltzow, Michael X Zhu, Swapna Asuthkar

Faculty, Staff and Student Publications

Background/Objectives: Transient Receptor Potential Melastatin 8 (TRPM8) is a non-selective, Ca2+-permeable cation channel involved in thermoregulation and other physiological processes, such as basal tear secretion, cell differentiation, and insulin homeostasis. The activation and deactivation of TRPM8 occur through genetic modifications, channel interactions, and signaling cascades. Recent evidence suggests a significant role of TRPM8 in the hypothalamus and amygdala related to pain sensation and sexual behavior. Notably, TRPM8 has been implicated in neuropathic pain, migraines, and neurodegenerative diseases such as Parkinson's disease. Our laboratory has identified testosterone as a high-affinity ligand of TRPM8. TRPM8 deficiency appears to influence behavioral traits in …

Disruption Of Distal Appendage Protein Cep164 Causes Skeletal Malformation In Mice, Hiroyuki Yamaguchi, Megumi Kitami, Margaret Li, Sowmya Swaminathan, Radbod Darabi, Ken-Ichi Takemaru, Yoshihiro Komatsu

Faculty, Staff and Student Publications

The primary cilium is a cellular antenna to orchestrate cell growth and differentiation. Deficient or dysfunctional cilia are frequently linked to skeletal abnormalities. Previous research demonstrated that ciliary proteins regulating axoneme elongation are essential for skeletogenesis. However, the role of the ciliary proteins responsible for initiating cilium assembly in skeletal development remains unknown. Here, we investigate the function of centrosomal protein of 164 kDa (CEP164), a key ciliogenesis regulator that localizes at the distal appendages of the mother centriole, during skeletal development in mice. Interestingly, the mesodermal cell-specific Cep164 deletion resulted in severe bone defects and osteoblast-specific deletion of Cep164 …

The Win Ratio Approach In Bayesian Monitoring For Two-Arm Phase Ii Clinical Trial Designs With Multiple Time-To-Event Endpoints, Xinran Huang, Jian Wang, Jing Ning

Faculty, Staff and Student Publications

To assess the preliminary therapeutic impact of a novel treatment, futility monitoring is commonly employed in Phase II clinical trials to facilitate informed decisions regarding the early termination of trials. Given the rapid evolution in cancer treatment development, particularly with new agents like immunotherapeutic agents, the focus has often shifted from objective response to time-to-event endpoints. In trials involving multiple time-to-event endpoints, existing monitoring designs typically select one as the primary endpoint or employ a composite endpoint as the time to the first occurrence of any event. However, relying on a single efficacy endpoint may not adequately evaluate an experimental …