Medicine and Health Sciences Commons^™

A Deep Residual Model For Characterization Of 5d Spatiotemporal Network Dynamics Reveals Widespread Spatiodynamic Changes In Schizophrenia, Behnam Kazemivash, Theo G M Van Erp, Peter Kochunov, Vince D Calhoun

Faculty, Staff and Student Publications

Schizophrenia is a severe brain disorder with serious symptoms including delusions, disorganized speech, and hallucinations that can have a long-term detrimental impact on different aspects of a patient's life. It is still unclear what the main cause of schizophrenia is, but a combination of altered brain connectivity and structure may play a role. Neuroimaging data has been useful in characterizing schizophrenia, but there has been very little work focused on voxel-wise changes in multiple brain networks over time, despite evidence that functional networks exhibit complex spatiotemporal changes over time within individual subjects. Recent studies have primarily focused on static (average) …

Processing Speed – A Potential Candidate Cognitive Endophenotype For Bipolar Disorder, Mirona Letitia Dobri, Taya Prince, Alexandre Paim Diaz, Giovana B Zunta-Soares, Sudhakar Selvaraj, Rodrigo Machado-Vieira, Thomas D Meyer, Marsal Sanches, Jair C Soares

Faculty, Staff and Student Publications

BACKGROUND: Bipolar disorder (BD) is a chronic multifactorial disorder that presents with cognitive impairment as one of its main features, in patients as well as in their first-degree relatives. However, the profile of cognitive dysfunction in BD patients and their relatives is not yet well defined. Various neurocognitive deficits have been proposed as endophenotypes for BD. In the present study, we explored the susceptibility to neurocognitive deficits in BD patients and their siblings compared to healthy controls.

METHOD: A sample consisting of patients diagnosed with BD (

RESULTS: Compared to healthy controls, BD patients and their unaffected siblings showed deficits …

Non-Canonical Pathways In The Pathophysiology And Therapeutics Of Bipolar Disorder, Rodrigo Machado-Vieira, Alan C Courtes, Carlos A Zarate, Ioline D Henter, Husseini K Manji

Faculty, Staff and Student Publications

Bipolar disorder (BD) is characterized by extreme mood swings ranging from manic/hypomanic to depressive episodes. The severity, duration, and frequency of these episodes can vary widely between individuals, significantly impacting quality of life. Individuals with BD spend almost half their lives experiencing mood symptoms, especially depression, as well as associated clinical dimensions such as anhedonia, fatigue, suicidality, anxiety, and neurovegetative symptoms. Persistent mood symptoms have been associated with premature mortality, accelerated aging, and elevated prevalence of treatment-resistant depression. Recent efforts have expanded our understanding of the neurobiology of BD and the downstream targets that may help track clinical outcomes and …

Comorbidities And Risk Factors Associated With Insomnia In The Elderly Population, Neil Mookerjee, Nicole Schmalbach, Gianna Antinori, Subhadra Thampi, Dylan Windle-Puente, Amy Gilligan, Ha Huy, Megha Andrews, Angela Sun, Roshni Gandhi, William Benedict, Austin Chang, Ben Sanders, Justin Nguyen, Maanika Reddy Keesara, Janet Aliev, Aneri Patel, Isaiah Hughes, Ian Millstein, Krystal Hunter, Satyajeet Roy

Faculty, Staff and Student Publications

INTRODUCTION/OBJECTIVES: Sleep disorders affect around 50 to 70 million Americans, with chronic insomnia being the most common, especially in the elderly population. With an 11-fold increase in the US office visits due to insomnia, from 0.8 to 9.4 million, between 1993 and 2015, it is imperative to identify the modifiable risk factors. The aim of our study was to examine the association of risk factors and comorbid medical conditions with insomnia in patients 65 years, and older.

METHODS: We performed a retrospective electronic medical record review of the patients aged 65 years and older, who visited our suburban internal medicine …

Reproductive Coercion Victimization And Associated Mental Health Outcomes Among Female-Identifying Young Adults, Emily A Muñoz, Ryan C Shorey, Jeff R Temple

Faculty, Staff and Student Publications

Reproductive coercion is a serious public health problem. Victimization has been associated with poor mental health outcomes, including symptoms of posttraumatic stress disorder (PTSD) and depression in clinical and college samples. We build on these findings by examining the association between reproductive coercion victimization and mental and behavioral health outcomes, including depression, PTSD symptoms, anxiety, and drinking behaviors in a diverse community-derived sample of female-identifying young adults (mean age = 20; SD=.72). Participants (n = 368) were originally recruited as part of a study on dating violence in seven Texas public high schools. Participants completed an online study that …

Editorial: Metabolic Regulation Under Oxidative Stress In Cancer, Elavarasan Subramani, Abishai Dominic, Pratip K Bhattacharya, Daniel E Frigo, Ilya Bederman, Ali Vaziri-Gohar

Faculty, Staff and Student Publications

Oxidative stress has emerged as a key component of cancer metabolism that impacts multiple facets of tumor biology (1). Recent studies have shed light on the complex interplay of cellular redox and its impact on molecular mechanisms that govern metabolic reprogramming under oxidative stress (2, 3). It is well established that altered glucose metabolism exhibited by tumor cells leads to an enormous oxidative burden through various metabolic routes (4, 5). What is less known but remains a great interest to the field is whether elevated oxidative stress has a causal role in …

“So Many Extra Safety Layers:” Virtual Service Provision And Implementing Social Distancing In Interpersonal Violence Service Agencies During Covid-19, Rachel J Voth Schrag, Sarah Leat, Bethany Backes, Saltanat Childress, Leila Wood

Faculty, Staff and Student Publications

The coronavirus pandemic necessitated rapid shifts in approach for service providers working with survivors of interpersonal violence. To reduce the spread of the virus, providers and agencies implemented a rapid and unplanned expansion of virtual services while also developing new protocols to support safe and socially distant in-person services. To understand how these shifts have impacted victim service professionals and the survivors they serve, to provide guidance for on-going efforts, and to inform planning for future public health emergencies, this study asks the question: What approaches did the interpersonal violence workforce use to address social distancing needs during COVID-19? Semi-structured …

Development And Internal Validation Of A Novel Nomogram For Predicting Lymph Node Invasion For Prostate Cancer Patients Undergoing Extended Pelvic Lymph Node Dissection, Zhen Li, Yixin Huang, Diwei Zhao, Xin Luo, Zeshen Wu, Xinyi Zheng, Ye Xie, Yixuan Liu, Jianwei Wu, Yulu Peng, Yonghong Li, Fangjian Zhou

Faculty, Staff and Student Publications

BACKGROUND: Few studies have focused on the performance of Briganti 2012, Briganti 2017 and MSKCC nomograms in the Chinese population in assessing the risk of lymph node invasion(LNI) in prostate cancer(PCa) patients and identifying patients suitable for extended pelvic lymph node dissection(ePLND). We aimed to develop and validate a novel nomogram based on Chinese PCa patients treated with radical prostatectomy(RP) and ePLND for predicting LNI.

METHODS: We retrospectively retrieved clinical data of 631 patients with localized PCa receiving RP and ePLND at a Chinese single tertiary referral center. All patients had detailed biopsy information from experienced uropathologist. Multivariate logistic-regression analyses …

Hyperviscosity Syndrome Induced Bilateral Visual And Auditory Impairment In Therapy Resistant Waldenström Macroglobulinemia With Myd88 And Cxcr4 Mutations, Marie M Plante, Erinmarie O Kimbrough, Amit K Agarwal, Liuyan Jiang, Kirk Bourgeois, Greta C Stamper, Michael W Stewart, Han W Tun

Faculty, Staff and Student Publications

Hyperviscosity syndrome (HVS) is an emergent complication of Waldenström macroglobulinemia (WM) characterized by visual, neurologic, and rarely auditory impairment. We report a 69-year-old female with MYD88 and CXCR4-mutant WM who developed HVS resulting in bilateral blindness and deafness associated with neurologic manifestations including confusion, severe generalized weakness, and imbalance. Ophthalmologic evaluation revealed bilateral central retinal vein occlusion (CRVO), diffuse retinal hemorrhages, macular edema, and serous macular detachments (SMD). Magnetic resonance imaging of the brain showed bleeding in the inner ears. Management was challenging as her WM was resistant to systemic therapies including bendamustine + rituximab (BR) and rituximab + bortezomib …

The Assembled Genome Of The Stroke-Prone Spontaneously Hypertensive Rat, Theodore S Kalbfleisch, Nahla A Hussien Abouel Ela, Kai Li, Wesley A Brashear, Kelli J Kochan, Andrew E Hillhouse, Yaming Zhu, Isha S Dhande, Eric J Kline, Elizabeth A Hudson, Terence D Murphy, Françoise Thibaud-Nissen, Melissa L Smith, Peter A Doris

Faculty, Staff and Student Publications

BACKGROUND: We report the creation and evaluation of a de novo assembly of the genome of the spontaneously hypertensive rat, the most widely used model of human cardiovascular disease.

METHODS: The genome is assembled from long read sequencing (PacBio HiFi and continuous long read data [CLR]) and scaffolded with long-range structural information obtained from Bionano optical maps and proximity ligation sequencing proximity analysis of the genome. The genome assembly was polished with Illumina short reads. Completeness of the assembly was investigated using Benchmarking Universal Single Copy Orthologs analysis. The genome assembly was also evaluated with the rat reference gene set, …

Pain Experience And Sensory Changes In Astronauts During And After Short-Lasting Commercial Spaceflight: A Proof-Of-Concept Study, Andrea K Sauer, Marie Vigouroux, Patrick M Dougherty, Juan Pablo Cata, Pablo M Ingelmo

Faculty, Staff and Student Publications

Space travel has been associated with musculoskeletal pain, yet little is known about the nociceptive changes and pain experience during spaceflight. This preliminary study aims to investigate the pain experience and sensory alterations in astronauts following a 17-day mission to the International Space Station (ISS) on Axiom Space's AX-1 commercial space flight. Two participants were enrolled, and data were collected pre-flight, in-flight, post-flight, and three-month post-flight. Validated pain questionnaires assessed anxiety, catastrophizing, impact on physical and mental health, disability, and overall pain experience. Qualitative interviews were conducted post-landing and conditioned pain modulation (CPM) and quantitative sensory testing (QST) were performed. …

Frontostriatal And Limbic Contributions To Cognitive Decline In Parkinson’S Disease, Gregory Brown, Jonathan Hakun, Mechelle M Lewis, Sol De Jesus, Guangwei Du, Paul J Eslinger, Lan Kong, Xuemei Huang

Faculty, Staff and Student Publications

BACKGROUND AND PURPOSE: The circuitry underlying heterogenous cognitive profiles in Parkinson's disease (PD) remains unclear. The purpose of this study is to investigate whether structural changes in frontostriatal and limbic pathways contribute to different cognitive trajectories in PD.

METHODS: We obtained clinical and multimodal MRI data from 120 control and 122 PD subjects without dementia or severe motor disability. T1/T2-weighted images estimated volume, and diffusion imaging evaluated fractional anisotropy (FA) of frontostriatal (striatum and frontostriatal white matter [FSWM]) and limbic (hippocampus and fornix) structures. Montreal Cognitive Assessment (MoCA) gauged total and domain-specific (attention/executive and memory) cognitive function. Linear mixed-effects models …

Molecular Predictors Of Immunophenotypic Measurable Residual Disease Clearance In Acute Myeloid Leukemia, Maximilian Stahl, Andriy Derkach, Noushin Farnoud, Jan Philipp Bewersdorf, Troy Robinson, Christopher Famulare, Christina Cho, Sean Devlin, Kamal Menghrajani, Minal A Patel, Sheng F Cai, Linde A Miles, Robert L Bowman, Mark B Geyer, Andrew Dunbar, Zachary D Epstein-Peterson, Erin Mcgovern, Jessica Schulman, Jacob L Glass, Justin Taylor, Aaron D Viny, Eytan M Stein, Bartlomiej Getta, Maria E Arcila, Qi Gao, Juliet Barker, Brian C Shaffer, Esperanza B Papadopoulos, Boglarka Gyurkocza, Miguel-Angel Perales, Omar Abdel-Wahab, Ross L Levine, Sergio A Giralt, Yanming Zhang, Wenbin Xiao, Nidhi Pai, Elli Papaemmanuil, Martin S Tallman, Mikhail Roshal, Aaron D Goldberg

Faculty, Staff and Student Publications

Measurable residual disease (MRD) is a powerful prognostic factor in acute myeloid leukemia (AML). However, pre-treatment molecular predictors of immunophenotypic MRD clearance remain unclear. We analyzed a dataset of 211 patients with pre-treatment next-generation sequencing who received induction chemotherapy and had MRD assessed by serial immunophenotypic monitoring after induction, subsequent therapy, and allogeneic stem cell transplant (allo-SCT). Induction chemotherapy led to MRD- remission, MRD+ remission, and persistent disease in 35%, 27%, and 38% of patients, respectively. With subsequent therapy, 34% of patients with MRD+ and 26% of patients with persistent disease converted to MRD-. Mutations in CEBPA, NRAS, KRAS, and …

Combining Mek And Src Inhibitors For Treatment Of Colorectal Cancer Demonstrate Increased Efficacy In Vitro But Not In Vivo, Fan Fan, Susmita Ghosh, Reid Powell, Jason Roszik, Yongsun Park, Mary Sobieski, Alexey Sorokin, Clifford Stephan, Scott Kopetz, Lee M Ellis, Rajat Bhattacharya

Faculty, Staff and Student Publications

Metastatic colorectal cancer (mCRC) is the second leading cause of cancer deaths in the United States. More than 50% of patients with mCRC harbor mutations of the oncogenic driver RAS (KRAS or NRAS). Because directly targeting most mutations of RAS is technically challenging, researchers have concentrated on targeting MEK, a downstream mediator of RAS. However, targeting MEK as single-agent therapy is ineffective in patients with mCRC. We hypothesize that combining a MEK inhibitor with other agents can enhance the efficacy of MEK targeting in mCRC. Unbiased high-throughput screening (HTS) was performed to identify drugs that enhance the efficacy of MEK …

Development And Validation Of Early Death Risk Score Model For Emergency Status Prediction In Very Severe Aplastic Anemia, Xu Liu, Wenrui Yang, Li Zhang, Liping Jing, Lei Ye, Kang Zhou, Yuan Li, Jianping Li, Huihui Fan, Yang Yang, Youzhen Xiong, Xin Zhao, Fengkui Zhang

Faculty, Staff and Student Publications

This study developed and validated the Early Death Risk Score Model for early identification of emergency patients with very severe aplastic anemia (VSAA). All 377 patients with VSAA receiving first-line immunosuppressive therapy (IST) were categorized into training (n=252) and validation (n=125) cohorts. In the training cohort, age >24 years, absolute neutrophil count ≤0.015×109/L, serum ferritin >900ng/mL and times of fever before IST >1 time were significantly associated with early death. Covariates were assigned scores and categorized as: low (score 0-4), medium (score 5-7) and high (score ≥8) risk. Early death rate was significantly different between risk groups and the validation …

Circulating Vitamin D And Breast Cancer Risk: An International Pooling Project Of 17 Cohorts, Kala Visvanathan, Alison M Mondul, Anne Zeleniuch-Jacquotte, Molin Wang, Mitchell H Gail, Shiaw-Shyuan Yaun, Stephanie J Weinstein, Marjorie L Mccullough, A Heather Eliassen, Nancy R Cook, Claudia Agnoli, Martin Almquist, Amanda Black, Julie E Buring, Chu Chen, Yu Chen, Tess Clendenen, Laure Dossus, Veronika Fedirko, Gretchen L Gierach, Edward L Giovannucci, Gary E Goodman, Marc T Goodman, Pascal Guénel, Göran Hallmans, Susan E Hankinson, Ronald L Horst, Tao Hou, Wen-Yi Huang, Michael E Jones, Corrine E Joshu, Rudolf Kaaks, Vittorio Krogh, Tilman Kühn, Marina Kvaskoff, I-Min Lee, Yahya Mahamat-Saleh, Johan Malm, Jonas Manjer, Gertraud Maskarinec, Amy E Millen, Toqir K Mukhtar, Marian L Neuhouser, Trude E Robsahm, Minouk J Schoemaker, Sabina Sieri, Malin Sund, Anthony J Swerdlow, Cynthia A Thomson, Giske Ursin, Jean Wactawski-Wende, Ying Wang, Lynne R Wilkens, Yujie Wu, Emilie Zoltick, Walter C Willett, Stephanie A Smith-Warner, Regina G Ziegler

Faculty, Staff and Student Publications

Laboratory and animal research support a protective role for vitamin D in breast carcinogenesis, but epidemiologic studies have been inconclusive. To examine comprehensively the relationship of circulating 25-hydroxyvitamin D [25(OH)D] to subsequent breast cancer incidence, we harmonized and pooled participant-level data from 10 U.S. and 7 European prospective cohorts. Included were 10,484 invasive breast cancer cases and 12,953 matched controls. Median age (interdecile range) was 57 (42-68) years at blood collection and 63 (49-75) years at breast cancer diagnosis. Prediagnostic circulating 25(OH)D was either newly measured using a widely accepted immunoassay and laboratory or, if previously measured by the cohort, …

Validation Of An Automated Contouring And Treatment Planning Tool For Pediatric Craniospinal Radiation Therapy, Soleil Hernandez, Hester Burger, Callistus Nguyen, Arnold C Paulino, John T Lucas, Austin M Faught, Jack Duryea, Tucker Netherton, Dong Joo Rhee, Carlos Cardenas, Rebecca Howell, David Fuentes, Julianne Pollard-Larkin, Laurence Court, Jeannette Parkes

Faculty, Staff and Student Publications

PURPOSE: Treatment planning for craniospinal irradiation (CSI) is complex and time-consuming, especially for resource-constrained centers. To alleviate demanding workflows, we successfully automated the pediatric CSI planning pipeline in previous work. In this work, we validated our CSI autosegmentation and autoplanning tool on a large dataset from St. Jude Children's Research Hospital.

METHODS: Sixty-three CSI patient CT scans were involved in the study. Pre-planning scripts were used to automatically verify anatomical compatibility with the autoplanning tool. The autoplanning pipeline generated 15 contours and a composite CSI treatment plan for each of the compatible test patients (n=51). Plan quality was evaluated quantitatively …

The Development Of Tumour Vascular Networks, Cassandra B Iroz, Willemijn L A Schäfer, Julie K Johnson, Meagan S Ager, Reiping Huang, Salva N Balbale, Jonah J Stulberg

Faculty, Staff and Student Publications

BACKGROUND: Opioids prescribed to treat postsurgical pain have contributed to the ongoing opioid epidemic. While opioid prescribing practices have improved, most patients do not use all their pills and do not safely dispose of leftovers, which creates a risk for unsafe use and diversion. We aimed to generate consensus on the content of a "safe opioid use agreement" for the perioperative settings to improve patients' safe use, storage, and disposal of opioids.

METHODS: We conducted a modified three-round Delphi study with clinicians across surgical specialties, quality improvement (QI) experts, and patients. In Round 1, participants completed a survey rating the …

Hiatal Hernia Repair With Transoral Incisionless Fundoplication Versus Nissen Fundoplication For Gastroesophageal Reflux Disease: A Retrospective Study, Veeravich K Jaruvongvanich, Reem Matar, Janani Reisenauer, Peter Janu, Peter Mavrelis, Glenn Ihde, Michael Murray, Sneha Singh, Jennifer Kolb, Ninh T Nguyen, Nirav Thosani, Erik B Wilson, Rasa Zarnegar, Kenneth Chang, Marcia I Canto, Barham K Abu Dayyeh

Faculty, Staff and Student Publications

Background and study aims  Concomitant hiatal hernia (HH) repair with transoral incisionless fundoplication (TIF) is a therapeutic option for patients with HH > 2 cm and gastroesophageal reflux disease (GERD). Data comparing this approach with laparoscopic Nissen fundoplication (LNF) are lacking. We performed an exploratory analysis to compare these two approaches' adverse events (AEs) and clinical outcomes.

Patients and methods  This was a multicenter retrospective cohort study of HH repair followed by LNF versus HH repair followed by TIF in patients with GERD and moderate HH (2–5 cm). AEs were assessed using the Clavien-Dindo classification. Symptoms (heartburn/regurgitation, bloating, and dysphagia) were …

Association Between Surgical Technical Skills And Clinical Outcomes: A Systematic Literature Review And Meta-Analysis, Michael S Woods, Joshua N Liberman, Pinyao Rui, Emily Wiggins, Joan White, Bruce Ramshaw, Jonah J Stulberg

Faculty, Staff and Student Publications

BACKGROUND: A systematic literature review and meta-analysis was conducted to assess the association between intraoperative surgical skill and clinical outcomes.

METHODS: Peer-reviewed, original research articles published through August 31, 2021 were identified from PubMed and Embase. From the 1,513 potential articles, seven met eligibility requirements, reporting on 151 surgeons and 17,932 procedures. All included retrospective assessment of operative videos. Associations between surgical skill and outcomes were assessed by pooling odds ratios (OR) using random-effects models with the inverse variance method. Eligible studies included pancreaticoduodenectomy, gastric bypass, laparoscopic gastrectomy, prostatectomy, colorectal, and hemicolectomy procedures.

RESULTS: Meta-analytic pooling identified significant associations between …

Utilizing 10khz Stimulation To Salvage A Failed Low Frequency Spinal Cord Stimulation Trial, Jamal Hasoon, Christopher Robinson, Ivan Urits, Omar Viswanath, Alan D Kaye

Faculty, Staff and Student Publications

Spinal cord stimulation (SCS) is a viable treatment option for chronic pain. One of the primary indications for SCS implantation is persistent pain after spinal surgery. Studies have demonstrated that these patients have a better response to SCS over conservative management or repeat surgery. Traditional SCS therapy uses parasthesias to overlap a patient's pain pattern and provide relief, though some patients find this uncomfortable. To avoid the use of paresthesias, a 10kHz waveform can be utilized to provide a subthreshold level of high frequency stimulation to provide superior pain relief without paresthesias. Additionally, 10kHz stimulation may be used to salvage …

Review: Discogenic Back Pain: Update On Treatment, Edgar Remotti, Chinoso Nduaguba, Parker A Woolley, Ryan Ricciardelli, Anh Phung, Rosa Kim, Ivan Urits, Alan David Kaye, Jamal Hasoon, Thomas Simopoulos, Cyrus Yazdi, Christopher L Robinson

Faculty, Staff and Student Publications

Purpose of review: Lower back pain (LBP) has a lifetime prevalence of 80% in the United States population. Discogenic back pain (DBP), a subcategory of LBP, occurs as a result of the interverbal disc degeneration without disc herniation. Diagnosis relies on history, physical exam, and imaging such as MRI, provocative discography, or CT discography.

Recent findings: Treatment of DBP involves a multifaceted approach with an emphasis on conservative measures including behavioral modification, pharmacologic management, and other non-pharmacologic interventions with invasive therapy reserved for select patients. Due to the paucity of data on the treatment of DBP, treatment also relies on …

Burning Mouth Syndrome Treated With Mandibular And Maxillary Nerve Blocks, Jamal Hasoon, Christopher Robinson, Ivan Urits, Omar Viswanath, Alan D Kaye

Faculty, Staff and Student Publications

Burning mouth syndrome is a condition characterized by a painful burning sensation in the oral mucosa lasting at least 3-6 months with no definitive etiology. The pathophysiology is not well understood, though there appears to be a connection with other neuropsychiatric conditions such as depression, anxiety, and mood disorders. We briefly discuss our experience with a patient who suffered from this conidtion and how it was treated with mandibular and maxillary nerve blocks after failing more conservative pharmacological options.

Effects Of Heterozygous Deletion Of Autism-Related Gene Cullin-3 In Mice, Qiang-Qiang Xia, Angela K Walker, Chenghui Song, Jing Wang, Anju Singh, James A Mobley, Zhong X Xuan, Jeffrey D Singer, Craig M Powell

Faculty, Staff and Student Publications

Autism Spectrum Disorder (ASD) is a developmental disorder in which children display repetitive behavior, restricted range of interests, and atypical social interaction and communication. CUL3, coding for a Cullin family scaffold protein mediating assembly of ubiquitin ligase complexes through BTB domain substrate-recruiting adaptors, has been identified as a high-risk gene for autism. Although complete knockout of Cul3 results in embryonic lethality, Cul3 heterozygous mice have reduced CUL3 protein, demonstrate comparable body weight, and display minimal behavioral differences including decreased spatial object recognition memory. In measures of reciprocal social interaction, Cul3 heterozygous mice behaved similarly to their wild-type littermates. In area …

Editorial: Ovarian Cancer-Targeted Medication: Parp Inhibitors, Anti-Angiogenic Drugs, Immunotherapy, And More, Zhi-Bin Wang, Dan Liu, Guang Lei, Zhao-Qian Liu, Nayiyuan Wu, Jing Wang

Faculty, Staff and Student Publications

No abstract provided.

Chromogranin B (Chgb) Is Dimorphic And Responsible For Dominant Anion Channels Delivered To Cell Surface Via Regulated Secretion, Gaya P Yadav, Haiyuan Wang, Joke Ouwendijk, Stephen Cross, Qiaochu Wang, Feng Qin, Paul Verkade, Michael X Zhu, Qiu-Xing Jiang

Faculty, Staff and Student Publications

Regulated secretion is conserved in all eukaryotes. In vertebrates granin family proteins function in all key steps of regulated secretion. Phase separation and amyloid-based storage of proteins and small molecules in secretory granules require ion homeostasis to maintain their steady states, and thus need ion conductances in granule membranes. But granular ion channels are still elusive. Here we show that granule exocytosis in neuroendocrine cells delivers to cell surface dominant anion channels, to which chromogranin B (CHGB) is critical. Biochemical fractionation shows that native CHGB distributes nearly equally in soluble and membrane-bound forms, and both reconstitute highly selective anion channels …

Molecular Mechanisms Of Osteosarcoma Metastasis And Possible Treatment Opportunities, Xinhui Du, Hua Wei, Boya Zhang, Bangmin Wang, Zhehuang Li, Lon Kai Pang, Ruiying Zhao, Weitao Yao

Faculty, Staff and Student Publications

In osteosarcoma patients, metastasis of the primary cancer is the leading cause of death. At present, management options to prevent metastasis are limited and non-curative. In this study, we review the current state of knowledge on the molecular mechanisms of metastasis and discuss promising new therapies to combat osteosarcoma metastasis. Genomic and epigenomic changes, metabolic reprogramming, transcription factors, dysregulation of physiologic pathways, and alterations to the tumor microenvironment are some of the changes reportedly involved in the regulation of osteosarcoma metastasis. Key factors within the tumor microenvironment include infiltrating lymphocytes, macrophages, cancer-associated fibroblasts, platelets, and extracellular components such as vesicles, …

Unveiling The Prognostic Implications Of Rplp1 Upregulation In Osteosarcoma, Xinhui Du, Hua Wei, Boya Zhang, Lon Kai Pang, Ruiying Zhao, Xu Dong Zhang, Weitao Yao

Faculty, Staff and Student Publications

Osteosarcoma, a malignant bone tumor characterized by a high rate of metastasis and poor survival, presents a critical need for identifying novel biomarkers associated with metastasis. In this study, we conducted an extensive analysis utilizing transcriptional and clinical data sourced from databases such as GEO, TCGA, CCLE, R2, and Xena. And we discovered that Ribosomal protein LP1 (RPLP1) ranked among the top upregulated genes in relation to osteosarcoma metastasis. Notably, RPLP1 exhibited significant expression in both osteosarcoma cell lines and patient samples. Moreover, multiple osteosarcoma studies revealed a strong correlation between RPLP1 overexpression and worse metastasis-free survival as well as …

Pseudohypoadrenalism, A Subclinical Cortisol Metabolism Disorder In Hyperuricemia, Ruixia Bao, Beibei Chen, Jujie Pan, Alexander Wang, Haiyang Yu, Qian Chen, Yi Zhang, Tao Wang

Faculty, Staff and Student Publications

Background: Hyperuricemia is a known risk factor of lipid metabolism disorder. However, the mechanisms have not been fully understood.

Methods: The serum samples from hyperuricemia subjects were used to analyze the correlation between serum uric acid and clinical characteristics. Hyperuricemia mice induced by potassium oxonate (PO) and adenine were used to explore glucocorticoid metabolism.

Results: In hyperuricemia patients, the levels of serum uric acid were positively correlated with the levels of γ-glutamyltransferase, associated with a cortisol metabolism disorder. In hyperuricemia state, the adrenal glands failed to respond to adrenocorticotropic hormone properly, leading to low cortisol, but not corticosterone production, and …

Frequentist Model Averaging For Analysis Of Dose-Response In Epidemiologic Studies With Complex Exposure Uncertainty, Deukwoo Kwon, Steven L Simon, F Owen Hoffman, Ruth M Pfeiffer

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In epidemiologic studies, association estimates of an exposure with disease outcomes are often biased when the uncertainties of exposure are ignored. Consequently, corresponding confidence intervals (CIs) will not have correct coverage. This issue is particularly problematic when exposures must be reconstructed from physical measurements, for example, for environmental or occupational radiation doses that were received by a study population for which radiation doses cannot be measured directly. To incorporate complex uncertainties in reconstructed exposures, the two-dimensional Monte Carlo (2DMC) dose estimation method has been proposed and used in various dose reconstruction efforts. The 2DMC method generates multiple exposure realizations from …