Medical Specialties Commons^™

Research Hot Spots And Trends In Endocrine-Related Adverse Events Caused By Immune Checkpoint Inhibitors: A Bibliometric Analysis And Visualization Research, Jun Zhao, Guangwei Liu, Xue Yang, Chuanzhou Zhang, Bing Han, Man Jiang

Faculty, Staff and Student Publications

Background: In recent years, with the widespread use of immune checkpoint inhibitors (ICIs) in cancer treatment, the toxicity associated with immunotherapy of ICIs has attracted more attention from scholars. Endocrine toxicity is the most likely immune-related adverse events (irAEs) and is often irreversible, posing a significant clinical treatment challenge.

Methods: In this study, bibliometric methods were used to analyze relevant literature in screening endocrine-related adverse events caused by ICIs in the Web of Science core collection database (WoSCC) and to summarize the status, research hot spots, and future trends in this field.

Results: 321 countries, 297 institutions, 365 authors, and …

Rapid Detection Of Mutations In Csf-Cftna With The Genexus Integrated Sequencer, Srividya Arjuna, Mauli Shah, Antonio Dono, Luis Nunez-Rubiano, Pavel S Pichardo-Rojas, Jay-Jiguang Zhu, Roy F Riascos, Rajyalakshmi Luthra, Sinchita Roy-Chowdhuri, Dzifa Duose, Daniel H Wang, Frederick F Lang, Yoshua Esquenazi, Leomar Y Ballester

Faculty, Staff and Student Publications

PURPOSE: Genomic alterations are fundamental for molecular-guided therapy in patients with breast and lung cancer. However, the turn-around time of standard next-generation sequencing assays is a limiting factor in the timely delivery of genomic information for clinical decision-making.

METHODS: In this study, we evaluated genomic alterations in 54 cerebrospinal fluid samples from 33 patients with metastatic lung cancer and metastatic breast cancer to the brain using the Oncomine Precision Assay on the Genexus sequencer. There were nine patients with samples collected at multiple time points.

RESULTS: Cell-free total nucleic acids (cfTNA) were extracted from CSF (0.1-11.2 ng/μl). Median base coverage …

Gut Microbiome And Hepatic Transcriptomic Determinants Of Hcc Development In Mice With Metabolic Dysfunction-Associated Steatohepatitis, Lillian I Dolapchiev, Kristyn A Gonzales, Lorenzo R Cruz, Mihai Gagea, Heather L Stevenson, Suet-Ying Kwan, Laura Beretta

Faculty, Staff and Student Publications

Purpose: Hepatocellular carcinoma (HCC) related to metabolic dysfunction-associated steatotic liver disease (MASLD) is often diagnosed at a late stage, and its incidence is increasing. Predictive biomarkers are therefore needed to identify individuals at high risk of HCC. We aimed to characterize the gut microbiome and hepatic transcriptome associated with HCC development in female mice with hepatocyte-deletion of Pten (HepPten -). These mice present with large variations in HCC development, making them a powerful model for biomarker discovery.

Methods & results: Sequencing of stool 16S and hepatic RNA was performed on a first set of mice. Among all liver histology …

Usp22 Overexpression Fails To Augment Tumor Formation In Mmtv-Erbb2 Mice But Loss Of Function Impacts Mmtv Promoter Activity, Xianghong Kuang, Andrew Salinger, Fernando Benavides, William J Muller, Sharon Y R Dent, Evangelia Koutelou

Faculty, Staff and Student Publications

The Ubiquitin Specific Peptidase 22 (USP22), a component of the Spt-Ada-Gcn5 Acetyltransferase (SAGA) histone modifying complex, is overexpressed in multiple human cancers, but how USP22 impacts tumorigenesis is not clear. We reported previously that Usp22 loss in mice impacts execution of several signaling pathways driven by growth factor receptors such as erythroblastic oncogene B b2 (ERBB2). To determine whether changes in USP22 expression affects ERBB2-driven tumorigenesis, we introduced conditional overexpression or deletion alleles of Usp22 into mice bearing the Mouse mammary tumor virus-Neu-Ires-Cre (MMTV-NIC) transgene, which drives both rat ERBB2/NEU expression and Cre recombinase activity from the MMTV promoter resulting …

Protection Against Fibrosis By A Bacterial Consortium In Metabolic Dysfunction-Associated Steatohepatitis And The Role Of Amino Acid Metabolism, Suet-Ying Kwan, Kristyn A Gonzales, Mohamed A Jamal, Heather L Stevenson, Lin Tan, Philip L Lorenzi, P Andrew Futreal, Ernest T Hawk, Joseph B Mccormick, Susan P Fisher-Hoch, Robert R Jenq, Laura Beretta

Faculty, Staff and Student Publications

The gut microbiota drives progression to liver fibrosis, the main determinant of mortality in metabolic dysfunction-associated steatohepatitis (MASH). In this study, we aimed to identify bacterial species associated with protection against liver fibrosis in a high-risk population, and test their potential to protect against liver fibrosis in vivo. Based on stool shotgun metagenomic sequencing of 340 subjects from a population cohort disproportionally affected by MASH, we identified bacterial species from the Bacteroidales and Clostridiales orders associated with reduced risk of liver fibrosis. A bacterial consortium was subsequently tested in a mouse model of MASH, which demonstrated protective effects against …

Usp22 Overexpression Fails To Augment Tumor Formation In Mmtv-Erbb2 Mice But Loss Of Function Impacts Mmtv Promoter Activity, Xianghong Kuang, Andrew Salinger, Fernando Benavides, William J Muller, Sharon Y R Dent, Evangelia Koutelou

Faculty, Staff and Student Publications

The Ubiquitin Specific Peptidase 22 (USP22), a component of the Spt-Ada-Gcn5 Acetyltransferase (SAGA) histone modifying complex, is overexpressed in multiple human cancers, but how USP22 impacts tumorigenesis is not clear. We reported previously that Usp22 loss in mice impacts execution of several signaling pathways driven by growth factor receptors such as erythroblastic oncogene B b2 (ERBB2). To determine whether changes in USP22 expression affects ERBB2-driven tumorigenesis, we introduced conditional overexpression or deletion alleles of Usp22 into mice bearing the Mouse mammary tumor virus-Neu-Ires-Cre (MMTV-NIC) transgene, which drives both rat ERBB2/NEU expression and Cre recombinase activity from the MMTV promoter resulting …

Early And Rapid Development Of Bronchiolitis Obliterans Syndrome After Allogeneic Hematopoietic Cell Transplantation, Jacqueline S Dickey, Burton F Dickey, Amin M Alousi, Richard E Champlin, Ajay Sheshadri

Faculty, Staff and Student Publications

Bronchiolitis obliterans (BO) is a form of graft-versus-host disease (GVHD) in the lung and manifests as moderate to severe airflow obstruction after hematopoietic stem cell transplantation (HCT). New-onset airflow obstruction on spirometry is considered diagnostic of bronchiolitis obliterans syndrome (BOS). BOS affects about 5% of all HCT recipients. In general, BO is thought of as a late complication of HCT, usually occurring after day 100 post-transplantation. However, the onset of airflow obstruction can be rapid and is most often irreversible even with treatment. We describe a patient who rapidly developed severe airflow obstruction less than one month after transplantation following …

Survivalcontour: Visualizing Predicted Survival Via Colored Contour Plots, Yushu Shi, Liangliang Zhang, Kim-Anh Do, Robert R Jenq, Christine B Peterson

Faculty, Staff and Student Publications

Advances in survival analysis have facilitated unprecedented flexibility in data modeling, yet there remains a lack of tools for illustrating the influence of continuous covariates on predicted survival outcomes. We propose the utilization of a colored contour plot to depict the predicted survival probabilities over time. Our approach is capable of supporting conventional models, including the Cox and Fine–Gray models. However, its capability shines when coupled with cutting-edge machine learning models such as random survival forests and deep neural networks.

Availability and implementation

We provide a Shiny app at https://biostatistics.mdanderson.org/shinyapps/survivalContour/ and an R package available at https://github.com/YushuShi/survivalContour as implementations of …

Interleukin-1beta And Inflammasome Expression In Spinal Cord Following Chronic Constriction Injury In Male And Female Rats, Suzanne M Green-Fulgham, Jayson B Ball, Andrew J Kwilasz, Michael E Harland, Matthew G Frank, Joseph M Dragavon, Peter M Grace, Linda R Watkins

Faculty, Staff and Student Publications

Females represent a majority of chronic pain patients and show greater inflammatory immune responses in human chronic pain patient populations as well as in animal models of neuropathic pain. Recent discoveries in chronic pain research have revealed sex differences in inflammatory signaling, a key component of sensory pathology in chronic neuropathic pain, inviting more research into the nuances of these sex differences. Here we use the chronic constriction injury (CCI) model to explore similarities and differences in expression and production of Inflammatory cytokine IL-1beta in the lumbar spinal cord, as well as its role in chronic pain. We have discovered …

The Contribution Of Dna Ligase 4 Polymorphisms To Colorectal Cancer, Yang Deng, Tao-Wei Ke, Te-Cheng Yueh, Yu-Ting Chin, Yun-Chi Wang, Yi-Chih Hung, Mei-Chin Mong, Ya-Chen Yang, Wen-Tzu Wu, Wen-Shin Chang, Jian Gu, Da-Tian Bau, Chia-Wen Tsai

Faculty, Staff and Student Publications

Background/aim: While numerous biomarkers associated with genetic susceptibility to colorectal cancer (CRC) have been identified and validated through epidemiological studies, the specific influence of DNA ligase 4 (Lig4) genotypes remains unexplored. This study aimed to elucidate the hitherto unexamined relationship between Lig4 genotypes and CRC risk.

Materials and methods: The genotypes of Lig4 rs1805388 were determined applying the polymerase chain reaction-restriction fragment length polymorphism methodology. The potential association between these genotypes and CRC risk was assessed in a Taiwanese population comprising 362 CRC cases and an equal number of age- and sex-matched controls.

Results: In the genotypic analysis, the distribution …

Non-Homologous End-Joining Genotype, Mrna Expression, And Dna Repair Capacity In Childhood Acute Lymphocytic Leukemia, Chao-Chun Chen, Wen-Shin Chang, Jen-Sheng Pei, Chien-Chung Kuo, Chung-Hsing Wang, Yun-Chi Wang, Pei-Chen Hsu, Jie-Long He, Jian Gu, Da-Tian Bau, Chia-Wen Tsai

Faculty, Staff and Student Publications

Background/aim: The capacity for non-homologous end-joining (NHEJ) repair plays a pivotal role in maintaining genome stability and in carcinogenesis. However, there is little literature on the involvement of NHEJ-related genes in childhood acute lymphocytic leukemia (ALL). Our study aimed to elucidate the impact of polymorphisms of X-ray repair cross-complementing group 4 (XRCC4) (rs6869366, rs2075685, rs2075686, rs28360071, rs3734091, rs28360317, rs1805377), XRCC5 (rs828907, rs11685387, rs9288518), XRCC6 (rs5751129, rs2267437, rs132770, rs132774), XRCC7 rs7003908, and DNA ligase IV (LIG4) rs1805388, on the odds of childhood ALL.

Materials and methods: Genotypes NHEJ-related genes of 266 cases and 266 controls were determined, and the genotype-phenotype correlation …

Differing Impacts Of The Covid-19 Pandemic On Farmers And Intermediaries: Insights Into The Ecuadorian Cocoa Value Chain, Guillermo Zambrano, Lina M Tennhardt, Moritz Egger, Karen Ramírez, Adriana Santos, Byron Moyano, Michael Curran

Faculty, Staff and Student Publications

The COVID-19 pandemic generated diverse impacts and responses in agricultural value chains worldwide. Cocoa is a key crop for Ecuadorian exports, and the analysis of effects the pandemic had on value chain actors contributes to the understanding of their individual capacities to coping with a major shock. The purpose of this study was to assess the number and severity of impacts and responses implemented by two links in the cocoa value chain to the pandemic, based on a survey of 158 cocoa farmers and 52 cocoa intermediaries from the main cocoa-producing provinces of the northern coast of Ecuador in 2021. …

Metarnn: Differentiating Rare Pathogenic And Rare Benign Missense Snvs And Indels Using Deep Learning, Fang Li, Zenan Sun, Ahmed Abdelhameed, Tiehang Duan, Laila Rasmy, Xinyue Hu, Jianping He, Yifang Dang, Jingna Feng, Jianfu Li, Yichen Wang, Tianchen Lyu, Naomi Braun, Si Pham, Michael Gharacholou, Delisa Fairweather, Degui Zhi, Jiang Bian, Cui Tao

Faculty, Staff and Student Publications

BACKGROUND: Effective management of dual antiplatelet therapy (DAPT) following drug-eluting stent (DES) implantation is crucial for preventing adverse events. Traditional prognostic tools, such as rule-based methods or Cox regression, despite their widespread use and ease, tend to yield moderate predictive accuracy within predetermined timeframes. This study introduces a new contrastive learning-based approach to enhance prediction efficacy over multiple time intervals.

METHODS: We utilized retrospective, real-world data from the OneFlorida + Clinical Research Consortium. Our study focused on two primary endpoints: ischemic and bleeding events, with prediction windows of 1, 2, 3, 6, and 12 months post-DES implantation. Our approach first …

Polaris: A Phase 2 Trial Of Encorafenib Plus Binimetinib Evaluating High-Dose And Standard-Dose Regimens In Patients With Braf V600-Mutant Melanoma With Brain Metastasis, Alexander M Menzies, Georgina V Long, Amiee Kohn, Hussein Tawbi, Jeffrey Weber, Keith Flaherty, Grant A Mcarthur, Paolo A Ascierto, Yanina Pfluger, Karl Lewis, Katy K Tsai, Omid Hamid, Hans Prenen, Luis Fein, Erjian Wang, Carolin Guenzel, Fan Zhang, Joseph F Kleha, Alessandra Di Pietro, Michael A Davies

Faculty, Staff and Student Publications

Background: POLARIS (phase 2 [ph2]; NCT03911869) evaluated encorafenib (BRAF inhibitor) in combination with binimetinib (MEK1/2 inhibitor) in BRAF/MEK inhibitor-naïve patients with BRAF V600-mutant melanoma with asymptomatic brain metastases.

Methods: The safety lead-in (SLI) assessed tolerability for high-dose encorafenib 300 mg twice daily (BID) plus binimetinib 45 mg BID. If the high dose was tolerable in ph2, patients would be randomized to receive high or standard dose (encorafenib 450 mg once daily [QD] plus binimetinib 45 mg BID). Otherwise, standard dose was evaluated as the recommended ph2 dose (RP2D). Patients who tolerated standard dosing during Cycle 1 could be dose …

Association Of Preoperative Lung Function With Complications After Lobectomy Using Race-Neutral And Race-Specific Normative Equations, Ajay Sheshadri, Ravi Rajaram, Aaron Baugh, Mario Castro, Arlene M Correa, Felipe Soto, Carrie R Daniel, Liang Li, Scott E Evans, Burton F Dickey, Ara A Vaporciyan, David E Ost

Faculty, Staff and Student Publications

Rationale: Pulmonary function testing (PFT) is performed to aid patient selection before surgical resection for non-small cell lung cancer (NSCLC). The interpretation of PFT data relies on normative equations, which vary by race, but the relative strength of association of lung function using race-specific or race-neutral normative equations with postoperative pulmonary complications is unknown. Objectives: To compare the strength of association of lung function, using race-neutral or race-specific equations, with surgical complications after lobectomy for NSCLC.

Methods: We studied 3,311 patients who underwent lobectomy for NSCLC and underwent preoperative PFT from 2001 to 2021. We used Global Lung Function Initiative …

Usp22 Overexpression Fails To Augment Tumor Formatiaon In Mmtv-Erbb2 Mice But Loss Of Function Impacts Mmtv Promoter Activity, Xianghong Kuang, Andrew Salinger, Fernando Benavides, William J Muller, Sharon Y R Dent, Evangelia Koutelou

Faculty, Staff and Student Publications

The Ubiquitin Specific Peptidase 22 (USP22), a component of the Spt-Ada-Gcn5 Acetyltransferase (SAGA) histone modifying complex, is overexpressed in multiple human cancers, but how USP22 impacts tumorigenesis is not clear. We reported previously that Usp22 loss in mice impacts execution of several signaling pathways driven by growth factor receptors such as erythroblastic oncogene B b2 (ERBB2). To determine whether changes in USP22 expression affects ERBB2-driven tumorigenesis, we introduced conditional overexpression or deletion alleles of Usp22 into mice bearing the Mouse mammary tumor virus-Neu-Ires-Cre (MMTV-NIC) transgene, which drives both rat ERBB2/NEU expression and Cre recombinase activity from the MMTV promoter resulting …

Chronic Lymphocytic Leukemia: Novel Perspectives - How To Teach An Old Dog New Tricks, Tamar Tadmor, Jan Burger

Faculty, Staff and Student Publications

No abstract provided.

First-In-Human Phase 1 Study Of The Arginase Inhibitor Incb001158 Alone Or Combined With Pembrolizumab In Patients With Advanced Or Metastatic Solid Tumours, Aung Naing, Kyriakos P Papadopoulos, Michael J Pishvaian, Osama Rahma, Glenn J Hanna, Elena Garralda, Omar Saavedra, Sven Gogov, Howard Kallender, Lulu Cheng, Michael Smith, Xuejun Chen, Emil Kuriakose, Todd Bauer

Faculty, Staff and Student Publications

Objective: The arginase inhibitor INCB001158 was evaluated for safety (primary endpoint) in locally advanced or metastatic solid tumours; pharmacokinetics, pharmacodynamics and efficacy were also assessed.

Methods and analysis: In this non-randomised, open-label, three-part phase 1 study, INCB001158 was orally administered two times per day as monotherapy or in combination with intravenous pembrolizumab 200 mg every 3 weeks. Dose expansion was conducted in tumour-type cohorts (with or without prior anti-PD-1/PD-L1 (programmed death protein 1/programmed death ligand 1) therapy).

Results: A total of 107 patients received INCB001158 50-150 mg two times per day as monotherapy, and 153 patients, including 6 with moderate …

Tumor Treating Fields (Ttfields) For Spinal Metastasis–The Case For Bone Removal And Spinal Implants As Waveguides To Enhance Field Strength At The Target, Claudio E Tatsui, Kristen W Carlson, Chirag B Patel

Faculty, Staff and Student Publications

No abstract provided.

Hypoxia-Adenosine Axis As Therapeutic Targets For Acute Respiratory Distress Syndrome, Katherine Figarella, Jieun Kim, Wei Ruan, Tingting Mills, Holger Klaus Eltzschig, Xiaoyi Yuan

Faculty, Staff and Student Publications

The human respiratory and circulatory systems collaborate intricately to ensure oxygen delivery to all cells, which is vital for ATP production and maintaining physiological functions and structures. During limited oxygen availability, hypoxia-inducible factors (HIFs) are stabilized and play a fundamental role in maintaining cellular processes for hypoxia adaptation. First discovered during investigations of erythropoietin production regulation, HIFs influence physiological and pathological processes, including development, inflammation, wound healing, and cancer. HIFs promote extracellular adenosine signaling by enhancing adenosine generation and receptor signaling, representing an endogenous feedback mechanism that curbs excessive inflammation, supports injury resolution, and enhances hypoxia tolerance. This is especially …

Development And Initial Validation Of A Hospital Stress Questionnaire, Daniel M Ford, Rebecca Lawton, Elizabeth Travis, Elizabeth A Teale, Daryl B O'Connor

Faculty, Staff and Student Publications

BACKGROUND: Hospitalisation can be a traumatic experience, where inpatients are exposed to an abundance of physical and psychological stressors. Evidence suggests that these hospital-related stressors negatively impact health: a phenomenon known as post-hospital syndrome. The current study aimed to identify hospital-related stressors, and to develop and provide initial validation for a new measure of in-hospital stress.

METHODS: Measure development occurred in three stages: (i) semi-structured interviews, (ii) item generation, and (iii) pilot testing. Twenty-one patients were interviewed regarding their recent hospital experiences, and a list of hospital-related stressors was produced. These stressors were compiled into a questionnaire and piloted on …

Outcomes And Toxicities In Patients With Diffuse-Large B Cell Lymphoma Involving The Gastrointestinal Tract And Digestive Organs, Gohar S Manzar, Elaine E Cha, Kelsey L Corrigan, Alison K Yoder, Benjamin R Schrank, Lewis F Nasr, Dai Chihara, Luis Malpica Castillo, Ranjit Nair, Preetesh Jain, Sattva S Neelapu, Maria A Rodriguez, Paolo Strati, Loretta J Nastoupil, Jillian R Gunther, Bouthaina S Dabaja, Chelsea C Pinnix, Susan Y Wu, Penny Q Fang

Faculty, Staff and Student Publications

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) involving the gastrointestinal (GI) organs is rare, and real-world outcomes after combined modality therapy (CMT) with systemic therapy (ST) and radiotherapy (RT) are not well-characterized, particularly in the contemporary era. We characterized outcomes in a large cohort of GI-DLBCL patients treated with ST alone or CMT.

METHODS: Patients with GI-DLBCL treated at a single institution were retrospectively reviewed. Kaplan-Meier and Cox regression models estimated survival. Multivariable analyses were conducted using the Cox proportional hazards model.

RESULTS: Of 204 patients, gastric involvement was most common (63%). Most presented with early-stage disease (61%). All patients received …

Efficacy And Safety Of Trastuzumab Deruxtecan In Patients With Her2-Expressing Solid Tumors: Primary Results From The Destiny-Pantumor02 Phase Ii Trial, Funda Meric-Bernstam, Vicky Makker, Ana Oaknin, Do-Youn Oh, Susana Banerjee, Antonio González-Martín, Kyung Hae Jung, Iwona Ługowska, Luis Manso, Aránzazu Manzano, Bohuslav Melichar, Salvatore Siena, Daniil Stroyakovskiy, Anitra Fielding, Yan Ma, Soham Puvvada, Norah Shire, Jung-Yun Lee

Faculty, Staff and Student Publications

PURPOSE: Trastuzumab deruxtecan (T-DXd) is a human epidermal growth factor 2 (HER2)-directed antibody-drug conjugate approved in HER2-expressing breast and gastric cancers and HER2-mutant non-small-cell lung cancer. Treatments are limited for other HER2-expressing solid tumors.

METHODS: This open-label phase II study evaluated T-DXd (5.4 mg/kg once every 3 weeks) for HER2-expressing (immunohistochemistry [IHC] 3+/2+ by local or central testing) locally advanced or metastatic disease after ≥1 systemic treatment or without alternative treatments. The primary end point was investigator-assessed confirmed objective response rate (ORR). Secondary end points included safety, duration of response, progression-free survival (PFS), and overall survival (OS).

RESULTS: At primary …

First Evidence Of Microplastic Inhalation Among Free-Ranging Small Cetaceans, Miranda K Dziobak, Andreas Fahlman, Randall S Wells, Ryan Takeshita, Cynthia Smith, Austin Gray, John Weinstein, Leslie B Hart

Faculty, Staff and Student Publications

Plastic is a ubiquitous environmental contaminant, resulting in widespread exposure across terrestrial and marine spaces. In the environment, plastics can degrade into microparticles where exposure has been documented in a variety of fauna at all trophic levels. Human epidemiological studies have found relationships between inhaled microplastics and oxidative stress and inflammation. Previous studies of bottlenose dolphins (Tursiops truncatus) have reported prevalent exposure to plasticizing chemicals (e.g., phthalates) as well as particle loads in gastrointestinal tracts, but exposure from inhalation has not yet been studied. The objective of this study was to determine if inhalation is a viable route of microplastic …

Awareness And Interest In Cannabis Use For Cancer Management Among Cancer Survivors, Ikponmwosa Osaghae, Rajesh Talluri, Onyema Greg Chido-Amajuoyi, Kimberson Tanco, Dimpy P Shah, Mala Pande, Sanjay Shete

Faculty, Staff and Student Publications

BACKGROUND: We examined the awareness, interest, and information sources relating to cannabis use for cancer management (including management of cancer symptoms and treatment-related side effects) and determined factors associated with cancer survivors' awareness and interest in learning about cannabis use for cancer management.

METHODS: This was a cross-sectional study of adult cancer survivors (N = 1886) receiving treatment at a comprehensive cancer center. Weighted prevalence and multivariable logistic regression analyses were conducted.

RESULTS: Among cancer survivors, 88% were aware and 60% were interested in learning about cannabis use for cancer management. Common sources of information to learn about cannabis use …

Multiple Unfolded Protein Response Pathways Cooperate To Link Cytosolic Dsdna Release To Stimulator Of Interferon Gene Activation, Tiancheng Hu, Yiping Liu, Jeremy Fleck, Cason King, Elaine Schalk, Zhenyu Zhang, Andrew Mehle, Judith A Smith

Faculty, Staff and Student Publications

The double-stranded DNA (dsDNA) sensor STING has been increasingly implicated in responses to "sterile" endogenous threats and pathogens without nominal DNA or cyclic di-nucleotide stimuli. Previous work showed an endoplasmic reticulum (ER) stress response, known as the unfolded protein response (UPR), activates STING. Herein, we sought to determine if ER stress generated a STING ligand, and to identify the UPR pathways involved. Induction of IFN-β expression following stimulation with the UPR inducer thapsigargin (TPG) or oxygen glucose deprivation required both STING and the dsDNA-sensing cyclic GMP-AMP synthase (cGAS). Furthermore, TPG increased cytosolic mitochondrial DNA, and immunofluorescence visualized dsDNA punctae in …

Post-Covid-19 Cognitive Symptoms In Patients Assisted By A Teleassistance Service: A Retrospective Cohort Study, Lívia Paula Freire Bonfim, Thais Rotsen Correa, Bruno Cabaleiro Cortizo Freire, Thais Marques Pedroso, Daniella Nunes Pereira, Thalita Baptisteli Fernandes, Luciane Kopittke, Clara Rodrigues Alves De Oliveira, Antonio Lucio Teixeira, Milena Soriano Marcolino

Faculty, Staff and Student Publications

INTRODUCTION: Four years after the onset of the COVID-19 pandemic, the frequency of long-term post-COVID-19 cognitive symptoms is a matter of concern given the impact it may have on the work and quality of life of affected people.

OBJECTIVE: To evaluate the incidence of post-acute COVID-19 cognitive symptoms, as well as the associated risk factors.

METHODS: Retrospective cohort, including outpatients with laboratory-confirmed COVID-19 and who were assisted by a public telehealth service provided by the Telehealth Network of Minas Gerais (TNMG), during the acute phase of the disease, between December/2020 and March/2022. Data were collected through a structured questionnaire, applied …

Healthcare Resource Utilization, Costs And Treatment Associated With Myasthenia Gravis Exacerbations Among Patients With Myasthenia Gravis In The Usa: A Retrospective Analysis Of Claims Data, Julia Pisc, Angela Ting, Michelle Skornicki, Omar Sinno, Edward Lee

Faculty, Staff and Student Publications

Aim: There are limited data on the clinical and economic burden of exacerbations in patients with myasthenia gravis (MG). We assessed patient clinical characteristics, treatments and healthcare resource utilization (HCRU) associated with MG exacerbation. Patients & methods: This was a retrospective analysis of adult patients with MG identified by commercial, Medicare or Medicaid insurance claims from the IBM® MarketScan® database. Eligible patients had two or more MG diagnosis codes, without evidence of exacerbation or crisis in the baseline period (12 months prior to index [first eligible MG diagnosis]). Clinical characteristics were evaluated at baseline and 12 weeks before each exacerbation. …

Voluntary Wheel Running Prevents Formation Of Membrane Attack Complexes And Myelin Degradation After Peripheral Nerve Injury, Suzanne M Green-Fulgham, Michael J Lacagnina, Kendal F Willcox, Jiahe Li, Michael E Harland, Adriano Polican Ciena, Igor R Correia Rocha, Jayson B Ball, Renee A Dreher, Younus A Zuberi, Joseph M Dragavon, Marucia Chacur, Steven F Maier, Linda R Watkins, Peter M Grace

Faculty, Staff and Student Publications

Regular aerobic activity is associated with a reduced risk of chronic pain in humans and rodents. Our previous studies in rodents have shown that prior voluntary wheel running can normalize redox signaling at the site of peripheral nerve injury, attenuating subsequent neuropathic pain. However, the full extent of neuroprotection offered by voluntary wheel running after peripheral nerve injury is unknown. Here, we show that six weeks of voluntary wheel running prior to chronic constriction injury (CCI) reduced the terminal complement membrane attack complex (MAC) at the sciatic nerve injury site. This was associated with increased expression of the MAC inhibitor …

Case Report: Early Acute Kidney Failure In An 11-Year-Old Boy With Dent Disease Type 1, Nicolette Murphey, Craig Authement, Paul Hillman, Samhar I Al-Akash, Kate Richardson

Faculty, Staff and Student Publications

Dent disease type 1 (Dent 1) is a rare X-linked genetic condition which impacts kidney function and is caused by pathogenic variants in CLCN5. Affected males typically develop low molecular weight proteinuria, hypercalciuria, nephrocalcinosis, nephrolithiasis, and other symptoms. Kidney failure often occurs between the third to fifth decade of life. Here, we report an 11-year-old boy with Dent 1 and a severe kidney disease phenotype. The patient presented with flank pain, nocturnal enuresis, foamy urine, and increased urinary frequency. He was found to have nephrotic-range proteinuria, without hypoalbuminemia, and a significantly decreased estimated glomerular filtration rate at presentation. Further, he …