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Sertraline Modulates Hippocampal Plasticity Via Sigma 1 Receptors, Cellular Stress And Neurosteroids, Yukitoshi Izumi, Angela M Reiersen, Eric J Lenze, Steven J Mennerick, Charles F Zorumski Nov 2024

Sertraline Modulates Hippocampal Plasticity Via Sigma 1 Receptors, Cellular Stress And Neurosteroids, Yukitoshi Izumi, Angela M Reiersen, Eric J Lenze, Steven J Mennerick, Charles F Zorumski

2020-Current year OA Pubs

In addition to modulating serotonin transport, selective serotonin reuptake inhibitors (SSRIs) have multiple other mechanisms that may contribute to clinical effects, and some of these latter actions prompt repurposing of SSRIs for non-psychiatric indications. In a recent study of the SSRIs fluvoxamine, fluoxetine and sertraline we found that, unlike the other two SSRIs, sertraline acutely inhibited LTP at a low micromolar concentration through inverse agonism of sigma 1 receptors (S1Rs). In the present studies, we pursued mechanisms contributing to sertraline modulation of LTP in rat hippocampal slices. We found that sertraline partially inhibits synaptic responses mediated by N-methyl-D-aspartate receptors (NMDARs) …


Samd7 Represses Short-Wavelength Cone Genes To Preserve Long-Wavelength Cone And Rod Photoreceptor Identity, Leo I Volkov, Yohey Ogawa, Ramiz Somjee, Hannah E Vedder, Hannah E Powell, Deepak Poria, Sam Meiselman, Vladimir J Kefalov, Joseph C Corbo Nov 2024

Samd7 Represses Short-Wavelength Cone Genes To Preserve Long-Wavelength Cone And Rod Photoreceptor Identity, Leo I Volkov, Yohey Ogawa, Ramiz Somjee, Hannah E Vedder, Hannah E Powell, Deepak Poria, Sam Meiselman, Vladimir J Kefalov, Joseph C Corbo

2020-Current year OA Pubs

The role of transcription factors in photoreceptor gene regulation is fairly well understood, but knowledge of the cell-type-specific function of transcriptional cofactors remains incomplete. Here, we show that the transcriptional corepressor


Disordered Proteins Interact With The Chemical Environment To Tune Their Protective Function During Drying, Shraddha Kc, Kenny H Nguyen, Vincent Nicholson, Annie Walgren, Tony Trent, Edith Gollub, Paulette Sofia Romero-Perez, Alex S Holehouse, Shahar Sukenik, Thomas C Boothby Nov 2024

Disordered Proteins Interact With The Chemical Environment To Tune Their Protective Function During Drying, Shraddha Kc, Kenny H Nguyen, Vincent Nicholson, Annie Walgren, Tony Trent, Edith Gollub, Paulette Sofia Romero-Perez, Alex S Holehouse, Shahar Sukenik, Thomas C Boothby

2020-Current year OA Pubs

The conformational ensemble and function of intrinsically disordered proteins (IDPs) are sensitive to their solution environment. The inherent malleability of disordered proteins, combined with the exposure of their residues, accounts for this sensitivity. One context in which IDPs play important roles that are concomitant with massive changes to the intracellular environment is during desiccation (extreme drying). The ability of organisms to survive desiccation has long been linked to the accumulation of high levels of cosolutes such as trehalose or sucrose as well as the enrichment of IDPs, such as late embryogenesis abundant (LEA) proteins or cytoplasmic abundant heat-soluble (CAHS) proteins. …


Electrical Impedance Tomography Monitoring In Adult Icu Patients: State-Of-The-Art, Recommendations For Standardized Acquisition, Processing, And Clinical Use, And Future Directions, Gaetano Scaramuzzo, Bhushan H Katira, Et Al. Nov 2024

Electrical Impedance Tomography Monitoring In Adult Icu Patients: State-Of-The-Art, Recommendations For Standardized Acquisition, Processing, And Clinical Use, And Future Directions, Gaetano Scaramuzzo, Bhushan H Katira, Et Al.

2020-Current year OA Pubs

Electrical impedance tomography (EIT) is an emerging technology for the non-invasive monitoring of regional distribution of ventilation and perfusion, offering real-time and continuous data that can greatly enhance our understanding and management of various respiratory conditions and lung perfusion. Its application may be especially beneficial for critically ill mechanically ventilated patients. Despite its potential, clear evidence of clinical benefits is still lacking, in part due to a lack of standardization and transparent reporting, which is essential for ensuring reproducible research and enhancing the use of EIT for personalized mechanical ventilation. This report is the result of a four-day expert meeting …


Consensus Definition Of A Radiologically Healed Fistula On Magnetic Resonance Imaging In Perianal Crohn's Disease: An International Delphi Study, Easan Anand, Jalpa Devi, Shivani Joshi, Anna Antoniou, Michelle Doering, Jaap Stoker, Phillip Lung, Ailsa L Hart, David H Ballard, Parakkal Deepak, Phil Tozer Nov 2024

Consensus Definition Of A Radiologically Healed Fistula On Magnetic Resonance Imaging In Perianal Crohn's Disease: An International Delphi Study, Easan Anand, Jalpa Devi, Shivani Joshi, Anna Antoniou, Michelle Doering, Jaap Stoker, Phillip Lung, Ailsa L Hart, David H Ballard, Parakkal Deepak, Phil Tozer

2020-Current year OA Pubs

INTRODUCTION: Perianal fistulising Crohn's disease (pfCD) is a distinct and debilitating phenotype seen in around one-third of patients with CD. Clinical trials in pfCD are increasingly using magnetic resonance imaging (MRI) criteria as a primary endpoint, but there is heterogeneity in the radiological definition of a healed perianal fistula that currently limits our ability to perform meaningful meta-analyses of studies. Our aim is to standardise outcomes through the generation of an international consensus definition of a radiologically healed fistula.

METHODS AND ANALYSIS: This international Delphi consensus study employs a two-part strategy.The first is a systematic review to identify a longlist …


Circulating Blood Circular Rna In Parkinson's Disease; From Involvement In Pathology To Diagnostic Tools In At-Risk Individuals, Aleksandra Beric, Yichen Sun, Santiago Sanchez, Charissa Martin, Tyler Powell, Ravindra Kumar, Jose Adrian Pardo, Gauri Darekar, Jessie Sanford, Devin Dikec, Bridget Phillips, Juan A Botia, Carlos Cruchaga, Laura Ibanez Nov 2024

Circulating Blood Circular Rna In Parkinson's Disease; From Involvement In Pathology To Diagnostic Tools In At-Risk Individuals, Aleksandra Beric, Yichen Sun, Santiago Sanchez, Charissa Martin, Tyler Powell, Ravindra Kumar, Jose Adrian Pardo, Gauri Darekar, Jessie Sanford, Devin Dikec, Bridget Phillips, Juan A Botia, Carlos Cruchaga, Laura Ibanez

2020-Current year OA Pubs

To identify circRNAs associated with Parkinson's disease (PD) we leveraged two of the largest publicly available studies with longitudinal clinical and blood transcriptomic data. We performed a cross-sectional study utilizing the last visit of each participant (N = 1848), and a longitudinal analysis that included 1166 participants with at least two time points. We identified 192 differentially expressed circRNAs, with effects that were sustained during disease, in mutation carriers, and diverse ancestry. The 192 circRNAs were leveraged to distinguish between PD and healthy participants with a ROC AUC of 0.797. Further, 71 circRNAs were sufficient to distinguish between genetic PD …


Comparative Neurofilament Light Chain Trajectories In Csf And Plasma In Autosomal Dominant Alzheimer's Disease, Anna Hofmann, Jorge J Llibre-Guerra, Richard J Perrin, Laura Ibanez, Randall J Bateman, Eric Mcdade, Brian A Gordon, Et Al. Nov 2024

Comparative Neurofilament Light Chain Trajectories In Csf And Plasma In Autosomal Dominant Alzheimer's Disease, Anna Hofmann, Jorge J Llibre-Guerra, Richard J Perrin, Laura Ibanez, Randall J Bateman, Eric Mcdade, Brian A Gordon, Et Al.

2020-Current year OA Pubs

Disease-modifying therapies for Alzheimer's disease (AD) are likely to be most beneficial when initiated in the presymptomatic phase. To track the benefit of such interventions, fluid biomarkers are of great importance, with neurofilament light chain protein (NfL) showing promise for monitoring neurodegeneration and predicting cognitive outcomes. Here, we update and complement previous findings from the Dominantly Inherited Alzheimer Network Observational Study by using matched cross-sectional and longitudinal cerebrospinal fluid (CSF) and plasma samples from 567 individuals, allowing timely comparative analyses of CSF and blood trajectories across the entire disease spectrum. CSF and plasma trajectories were similar at presymptomatic stages, discriminating …


Reconstitution Of Arp2/3-Nucleated Actin Assembly With Proteins Cp, V-1, And Carmil, Olivia L Mooren, Patrick Mcconnell, James D Debrecht, Anshuman Jaysingh, John A Cooper Nov 2024

Reconstitution Of Arp2/3-Nucleated Actin Assembly With Proteins Cp, V-1, And Carmil, Olivia L Mooren, Patrick Mcconnell, James D Debrecht, Anshuman Jaysingh, John A Cooper

2020-Current year OA Pubs

Actin polymerization is often associated with membrane proteins containing capping-protein-interacting (CPI) motifs, such as capping protein, Arp2/3, myosin I linker (CARMIL), CD2AP, and WASHCAP/Fam21. CPI motifs bind directly to actin-capping protein (CP), and this interaction weakens the binding of CP to barbed ends of actin filaments, lessening the ability of CP to functionally cap those ends. The protein V-1/myotrophin binds to the F-actin-binding site on CP and sterically blocks CP from binding barbed ends. CPI-motif proteins also weaken the binding between V-1 and CP, which decreases the inhibitory effects of V-1, thereby freeing CP to cap barbed ends. Here, we …


Mitochondrial Pyruvate Transport Regulates Presynaptic Metabolism And Neurotransmission, Anupama Tiwari, Jongyun Myeong, Arsalan Hashemiaghdam, Marion I Stunault, Hao Zhang, Xiangfeng Niu, Marissa A Laramie, Jasmin Sponagel, Leah P Shriver, Gary J Patti, Vitaly A Klyachko, Ghazaleh Ashrafi Nov 2024

Mitochondrial Pyruvate Transport Regulates Presynaptic Metabolism And Neurotransmission, Anupama Tiwari, Jongyun Myeong, Arsalan Hashemiaghdam, Marion I Stunault, Hao Zhang, Xiangfeng Niu, Marissa A Laramie, Jasmin Sponagel, Leah P Shriver, Gary J Patti, Vitaly A Klyachko, Ghazaleh Ashrafi

2020-Current year OA Pubs

Glucose has long been considered the primary fuel source for the brain. However, glucose levels fluctuate in the brain during sleep or circuit activity, posing major metabolic stress. Here, we demonstrate that the mammalian brain uses pyruvate as a fuel source, and pyruvate can support neuronal viability in the absence of glucose. Nerve terminals are sites of metabolic vulnerability, and we show that mitochondrial pyruvate uptake is a critical step in oxidative ATP production in hippocampal terminals. We find that the mitochondrial pyruvate carrier is post-translationally modified by lysine acetylation, which, in turn, modulates mitochondrial pyruvate uptake. Our data reveal …


A Phase I First-In-Human Study Of Abbv-011, A Seizure-Related Homolog Protein 6-Targeting Antibody-Drug Conjugate, In Patients With Small Cell Lung Cancer, Daniel Morgensztern, Et Al. Nov 2024

A Phase I First-In-Human Study Of Abbv-011, A Seizure-Related Homolog Protein 6-Targeting Antibody-Drug Conjugate, In Patients With Small Cell Lung Cancer, Daniel Morgensztern, Et Al.

2020-Current year OA Pubs

PURPOSE: Seizure-related homolog protein 6 (SEZ6) is a novel target expressed in small cell lung cancer (SCLC). ABBV-011, a SEZ6-targeted antibody conjugated to calicheamicin, was evaluated in a phase I study (NCT03639194) in patients with relapsed/refractory SCLC. We report initial outcomes of ABBV-011 monotherapy.

PATIENTS AND METHODS: ABBV-011 was administered intravenously once every 3 weeks during dose escalation (0.3-2 mg/kg) and expansion. Patients with SEZ6-positive tumors (≥25% of tumor cells with ≥1+ staining intensity by IHC) were preselected for expansion. Safety, tolerability, antitumor activity, and pharmacokinetics were evaluated.

RESULTS: As of August 2022, 99 patients received ABBV-011 monotherapy [dose escalation, …


High-Fat-Diet-Induced Hepatic Insulin Resistance Per Se Attenuates Murine De Novo Lipogenesis, Leigh Goedeke, Jordan W Strober, Rebecca Suh, Lauren M Paolella, Xiruo Li, Jillian C Rogers, Max C Petersen, Ali R Nasiri, Gregori Casals, Mario Kahn, Gary W Cline, Varman T Samuel, Gerald I Shulman, Daniel F Vatner Nov 2024

High-Fat-Diet-Induced Hepatic Insulin Resistance Per Se Attenuates Murine De Novo Lipogenesis, Leigh Goedeke, Jordan W Strober, Rebecca Suh, Lauren M Paolella, Xiruo Li, Jillian C Rogers, Max C Petersen, Ali R Nasiri, Gregori Casals, Mario Kahn, Gary W Cline, Varman T Samuel, Gerald I Shulman, Daniel F Vatner

2020-Current year OA Pubs

Hepatic insulin resistance (IR) is often said to be "pathway-selective" with preserved insulin stimulation of


Outcomes Of Patients With Acute Myeloid Leukemia And Bone Marrow Fibrosis, Samuel Urrutia, Et Al. Nov 2024

Outcomes Of Patients With Acute Myeloid Leukemia And Bone Marrow Fibrosis, Samuel Urrutia, Et Al.

2020-Current year OA Pubs

The outcomes of patients with acute myeloid leukemia (AML) and bone marrow fibrosis (MF) are not well defined. The study objectives were to evaluate the degrees of MF in AML, and corresponding response rates and outcomes. We performed a retrospective review of 2302 patients with AML. We annotated the clinical and molecular characteristics, response to therapy, and survival outcomes of patients with bone marrow fibrosis. Overall, 492 patients (21.4%) had a reported microscopic evaluation of MF: 344 (69.9%) had MF grade 0-1 and 148 (30.1%) had MF grade 2-3. Patients with MF 2-3 had a higher proportion of complex cytogenetics …


The California Collaborative Network To Promote Data Driven Care And Improve Outcomes In Early Psychosis (Epi-Cal) Project: Rationale, Background, Design And Methodology, Valerie L Tryon, Adam B Wilcox, Et Al. Nov 2024

The California Collaborative Network To Promote Data Driven Care And Improve Outcomes In Early Psychosis (Epi-Cal) Project: Rationale, Background, Design And Methodology, Valerie L Tryon, Adam B Wilcox, Et Al.

2020-Current year OA Pubs

BACKGROUND: A prolonged first episode of psychosis (FEP) without adequate treatment is a predictor of poor clinical, functional, and health outcomes and significant economic burden. Team-based "coordinated specialty care" (CSC) for early psychosis (EP) has established effectiveness in promoting clinical and functional recovery. However, California's CSC program implementation has been unsystematic and could benefit from standardizing its processes and data collection infrastructure. To address this, we established a consortium of EP clinics across the state via a Learning Health Care Network (LHCN) framework to develop the Early Psychosis Intervention Network of California (EPI-CAL). EPI-CAL's LHCN developed a core battery of …


Neoantigen Dna Vaccines Are Safe, Feasible, And Induce Neoantigen-Specific Immune Responses In Triple-Negative Breast Cancer Patients, Xiuli Zhang, S Peter Goedegebuure, Michael Y Chen, Rashmi Mishra, Felicia Zhang, Yik Yeung Yu, Kartik Singhal, Lijin Li, Feng Gao, Nancy B Myers, Tammi Vickery, Jasreet Hundal, Michael D Mclellan, Mark A Sturmoski, Samuel W Kim, Ina Chen, Jesse T Davidson, Narendra V Sankpal, Stephanie Myles, Rama Suresh, Cynthia X Ma, Ademuyiwa Foluso, Andrea Wang-Gillam, Sherri Davies, Ian S Hagemann, Elaine R Mardis, Obi Griffith, Malachi Griffith, Christopher A Miller, Ted H Hansen, Timothy P Fleming, Robert D Schreiber, William E Gillanders Nov 2024

Neoantigen Dna Vaccines Are Safe, Feasible, And Induce Neoantigen-Specific Immune Responses In Triple-Negative Breast Cancer Patients, Xiuli Zhang, S Peter Goedegebuure, Michael Y Chen, Rashmi Mishra, Felicia Zhang, Yik Yeung Yu, Kartik Singhal, Lijin Li, Feng Gao, Nancy B Myers, Tammi Vickery, Jasreet Hundal, Michael D Mclellan, Mark A Sturmoski, Samuel W Kim, Ina Chen, Jesse T Davidson, Narendra V Sankpal, Stephanie Myles, Rama Suresh, Cynthia X Ma, Ademuyiwa Foluso, Andrea Wang-Gillam, Sherri Davies, Ian S Hagemann, Elaine R Mardis, Obi Griffith, Malachi Griffith, Christopher A Miller, Ted H Hansen, Timothy P Fleming, Robert D Schreiber, William E Gillanders

2020-Current year OA Pubs

BACKGROUND: Neoantigen vaccines can induce or enhance highly specific antitumor immune responses with minimal risk of autoimmunity. We have developed a neoantigen DNA vaccine platform capable of efficiently presenting both HLA class I and II epitopes and performed a phase 1 clinical trial in triple-negative breast cancer patients with persistent disease on surgical pathology following neoadjuvant chemotherapy, a patient population at high risk of disease recurrence.

METHODS: Expressed somatic mutations were identified by tumor/normal exome sequencing and tumor RNA sequencing. The pVACtools software suite of neoantigen prediction algorithms was used to identify and prioritize cancer neoantigens and facilitate vaccine design …


In Vivo Evaluation Of Complex Polyps With Endoscopic Optical Coherence Tomography And Deep Learning During Routine Colonoscopy: A Feasibility Study, Haolin Nie, Hongbo Luo, Vladimir Lamm, Shuying Li, Sanskar Thakur, Chao Zhou, Thomas Hollander, Daniel Cho, Erika Sloan, Jingxia Liu, Pooja Navale, Ahmad N Bazarbashi, Juan Pablo Reyes Genere, Vladimir M Kushnir, Quing Zhu Nov 2024

In Vivo Evaluation Of Complex Polyps With Endoscopic Optical Coherence Tomography And Deep Learning During Routine Colonoscopy: A Feasibility Study, Haolin Nie, Hongbo Luo, Vladimir Lamm, Shuying Li, Sanskar Thakur, Chao Zhou, Thomas Hollander, Daniel Cho, Erika Sloan, Jingxia Liu, Pooja Navale, Ahmad N Bazarbashi, Juan Pablo Reyes Genere, Vladimir M Kushnir, Quing Zhu

2020-Current year OA Pubs

Standard-of-care (SoC) imaging for assessing colorectal polyps during colonoscopy, based on white-light colonoscopy (WLC) and narrow-band imaging (NBI), does not have sufficient accuracy to assess the invasion depth of complex polyps non-invasively during colonoscopy. We aimed to evaluate the feasibility of a custom endoscopic optical coherence tomography (OCT) probe for assessing colorectal polyps during routine colonoscopy. Patients referred for endoscopic treatment of large colorectal polyps were enrolled in this pilot clinical study, which used a side-viewing OCT catheter developed for use with an adult colonoscope. OCT images of polyps were captured during colonoscopy immediately before SoC treatment. A deep learning …


Pvacview: An Interactive Visualization Tool For Efficient Neoantigen Prioritization And Selection, Huiming Xia, My H Hoang, Evelyn Schmidt, Susanna Kiwala, Joshua Mcmichael, Zachary L Skidmore, Bryan Fisk, Jonathan J Song, Jasreet Hundal, Thomas Mooney, Jason R Walker, S Peter Goedegebuure, Christopher A Miller, William E Gillanders, Obi L Griffith, Malachi Griffith Nov 2024

Pvacview: An Interactive Visualization Tool For Efficient Neoantigen Prioritization And Selection, Huiming Xia, My H Hoang, Evelyn Schmidt, Susanna Kiwala, Joshua Mcmichael, Zachary L Skidmore, Bryan Fisk, Jonathan J Song, Jasreet Hundal, Thomas Mooney, Jason R Walker, S Peter Goedegebuure, Christopher A Miller, William E Gillanders, Obi L Griffith, Malachi Griffith

2020-Current year OA Pubs

BACKGROUND: Neoantigen-targeting therapies including personalized vaccines have shown promise in the treatment of cancers, particularly when used in combination with checkpoint blockade therapy. At least 100 clinical trials involving these therapies have been initiated globally. Accurate identification and prioritization of neoantigens is crucial for designing these trials, predicting treatment response, and understanding mechanisms of resistance. With the advent of massively parallel DNA and RNA sequencing technologies, it is now possible to computationally predict neoantigens based on patient-specific variant information. However, numerous factors must be considered when prioritizing neoantigens for use in personalized therapies. Complexities such as alternative transcript annotations, various …


Synthesis And Evaluation Of Photoaffinity Labeling Reagents For Identifying Binding Sites Of Sulfated Neurosteroids On Nmda And Gabaa Receptors, Mingxing Qian, Yuanjian Xu, Hong-Jin Shu, Zi-Wei Chen, Lei Wang, Charles F Zorumski, Alex S Evers, Steven Mennerick, Douglas F Covey Nov 2024

Synthesis And Evaluation Of Photoaffinity Labeling Reagents For Identifying Binding Sites Of Sulfated Neurosteroids On Nmda And Gabaa Receptors, Mingxing Qian, Yuanjian Xu, Hong-Jin Shu, Zi-Wei Chen, Lei Wang, Charles F Zorumski, Alex S Evers, Steven Mennerick, Douglas F Covey

2020-Current year OA Pubs

The endogenous neurosteroids dehydroepiandrosterone sulfate (DHEAS) and pregnenolone sulfate (PS) are allosteric modulators of γ-aminobutyric acid type A (GABA


Behavioral And Neural Mechanisms Of Face-Specific Attention During Goal-Directed Visual Search, Jie Zhang, Xiaocang Zhu, Huihui Zhou, Shuo Wang Nov 2024

Behavioral And Neural Mechanisms Of Face-Specific Attention During Goal-Directed Visual Search, Jie Zhang, Xiaocang Zhu, Huihui Zhou, Shuo Wang

2020-Current year OA Pubs

Goal-directed visual attention is a fundamental cognitive process that enables animals to selectively focus on specific regions of the visual field while filtering out irrelevant information. However, given the domain specificity of social behaviors, it remains unclear whether attention to faces versus nonfaces recruits different neurocognitive processes. In this study, we simultaneously recorded activity from temporal and frontal nodes of the attention network while macaques performed a goal-directed visual search task. V4 and inferotemporal (IT) visual category-selective units, selected during cue presentation, discriminated fixations on targets and distractors during the search but were differentially engaged by face and house targets. …


Coronary Artery Calcium On Lung Cancer Radiation Planning Ct Aids Cardiovascular Risk Assessment, Matthew Lui, Noah Kim, Raja Zaghlol, Pouya Joolharzadeh, Elena Deych, Clifford Robinson, Shahed Badiyan, Pamela K Woodard, Joshua D Mitchell Nov 2024

Coronary Artery Calcium On Lung Cancer Radiation Planning Ct Aids Cardiovascular Risk Assessment, Matthew Lui, Noah Kim, Raja Zaghlol, Pouya Joolharzadeh, Elena Deych, Clifford Robinson, Shahed Badiyan, Pamela K Woodard, Joshua D Mitchell

2020-Current year OA Pubs

BACKGROUND: Patients with non-small cell lung cancer (NSCLC) undergoing thoracic radiation are at high cardiovascular risk. Semiquantitative assessment of coronary artery calcification (CAC) on baseline planning non-gated chest computed tomography (CT) scans may help further risk stratify patients.

OBJECTIVES: This study aimed to characterize the association between CAC and major adverse cardiovascular events (MACE; myocardial infarction or stroke) and assess the utility of semiquantitative assessment of CAC.

METHODS: Patients with NSCLC with non-contrast planning chest CT scans were evaluated for CAC. Planning scans were visually graded using the CAC-DRS method, stratifying patients into no, mild, moderate, and severe CAC groups. …


Dilated Cardiomyopathy-Associated Skeletal Muscle Actin (Acta1) Mutation R256h Disrupts Actin Structure And Function And Causes Cardiomyocyte Hypocontractility, Ankit Garg, Silvia Jansen, Lina Greenberg, Rui Zhang, Kory J Lavine, Michael J Greenberg Nov 2024

Dilated Cardiomyopathy-Associated Skeletal Muscle Actin (Acta1) Mutation R256h Disrupts Actin Structure And Function And Causes Cardiomyocyte Hypocontractility, Ankit Garg, Silvia Jansen, Lina Greenberg, Rui Zhang, Kory J Lavine, Michael J Greenberg

2020-Current year OA Pubs

Skeletal muscle actin (ACTA1) mutations are a prevalent cause of skeletal myopathies consistent with ACTA1's high expression in skeletal muscle. Rare de novo mutations in ACTA1 associated with combined cardiac and skeletal myopathies have been reported, but ACTA1 represents only ~20% of the total actin pool in cardiomyocytes, making its role in cardiomyopathy controversial. Here we demonstrate how a mutation in an actin isoform expressed at low levels in cardiomyocytes can cause cardiomyopathy by focusing on a unique ACTA1 variant, R256H. We previously identified this variant in a family with dilated cardiomyopathy, who had reduced systolic function without clinical skeletal …


Associations Between Dietary Patterns And Quality Of Life In A Longitudinal Cohort Of Colorectal Cancer Survivors, Kristen S Smith, Adetunji T Toriola, Et Al. Nov 2024

Associations Between Dietary Patterns And Quality Of Life In A Longitudinal Cohort Of Colorectal Cancer Survivors, Kristen S Smith, Adetunji T Toriola, Et Al.

2020-Current year OA Pubs

PURPOSE: To characterize dietary patterns and examine associations with cross-sectional and longitudinal changes in quality of life (QOL) over approximately one year after colorectal cancer (CRC) diagnosis.

METHODS: The ColoCare Study is an international, multi-center, prospective cohort study of newly diagnosed CRC survivors of any stage. A subset of participants with CRC in the United States completed patient-reported outcome measures at 6- and 12-months post-enrollment, including the Food Frequency Questionnaire (FFQ) and European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). Dietary patterns at 6 months (around the time of treatment completion) were identified …


Human Immunodeficiency Virus-1 Genome From Patient With Fever, Nepal, Eans Tara Tuladhar, Bimal Sharma Chalise, Binod Khadka, Mamta Tamang, Jenish Neupane, Shankar Poudel, Lindsay Droit, Kathie A Mihindukulasuriya, Annie Elong Ngono, Yuba Nidhi Basaula, Sujan Shresta, David Wang, Krishna Das Manandhar Nov 2024

Human Immunodeficiency Virus-1 Genome From Patient With Fever, Nepal, Eans Tara Tuladhar, Bimal Sharma Chalise, Binod Khadka, Mamta Tamang, Jenish Neupane, Shankar Poudel, Lindsay Droit, Kathie A Mihindukulasuriya, Annie Elong Ngono, Yuba Nidhi Basaula, Sujan Shresta, David Wang, Krishna Das Manandhar

2020-Current year OA Pubs

A patient with fever presented to the referral infectious disease hospital in Kathmandu, Nepal. Metagenomic sequencing of the patient's serum recovered a near-complete genome of human immunodeficiency virus-1 (HIV-1), distinct from previous HIV-1 genomes from Nepal in GenBank. It shared 92.48% nucleotide identity with an HIV-1 subtype C isolate from India.


Identification And Characterization Of The Lipoprotein N-Acyltransferase In Bacteroides, Krista M Armbruster, Jiawen Jiang, Mariana G Sartorio, Nichollas E Scott, Jenna M Peterson, Jonathan Z Sexton, Mario F Feldman, Nicole M Koropatkin Nov 2024

Identification And Characterization Of The Lipoprotein N-Acyltransferase In Bacteroides, Krista M Armbruster, Jiawen Jiang, Mariana G Sartorio, Nichollas E Scott, Jenna M Peterson, Jonathan Z Sexton, Mario F Feldman, Nicole M Koropatkin

2020-Current year OA Pubs

Members of the Bacteroidota compose a large portion of the human gut microbiota, contributing to overall gut health via the degradation of various polysaccharides. This process is facilitated by lipoproteins, globular proteins anchored to the cell surface by a lipidated N-terminal cysteine. Despite their importance, lipoprotein synthesis by these bacteria is understudied. In


Evaluation Of Prognostic Factors In Patients With High-Risk Classical Hodgkin Lymphoma Undergoing Autologous Transplantation, Narendranath Epperla, Amanda F Cashen, Et Al. Nov 2024

Evaluation Of Prognostic Factors In Patients With High-Risk Classical Hodgkin Lymphoma Undergoing Autologous Transplantation, Narendranath Epperla, Amanda F Cashen, Et Al.

2020-Current year OA Pubs

There are limited data assessing the risk scores for primary treatment failure (PTF) in patients with classical Hodgkin lymphoma (cHL; PTF-cHL) undergoing autologous hematopoietic cell transplantation (auto-HCT). ECLIPSE (Evaluation of Classical Hodgkin Lymphoma patients wIth Primary treatment failure and analySis of outcomEs) is a multicenter retrospective cohort of patients with PTF-cHL (aged ≥15 years) diagnosed on or after 1 January 2005, at 15 US medical centers. PTF was defined as 1 of the following patterns of failure: (1) progressive disease by imaging during or within 6 weeks of completion of frontline chemotherapy (primary progression [PP]); (2) partial response (PR) or …


Impact Of Socioeconomic Deprivation On Care Quality And Surgical Outcomes For Early-Stage Non-Small Cell Lung Cancer In United States Veterans, Steven Tohmasi, Brendan T Heiden, Nikki E Rossetti, Ana A Baumann, Theodore S Thomas, Su-Hsin Chang, Nahom Seyoum, Yan Yan, Whitney S Brandt, Bryan F Meyers, Benjamin D Kozower, Varun Puri, Et Al. Nov 2024

Impact Of Socioeconomic Deprivation On Care Quality And Surgical Outcomes For Early-Stage Non-Small Cell Lung Cancer In United States Veterans, Steven Tohmasi, Brendan T Heiden, Nikki E Rossetti, Ana A Baumann, Theodore S Thomas, Su-Hsin Chang, Nahom Seyoum, Yan Yan, Whitney S Brandt, Bryan F Meyers, Benjamin D Kozower, Varun Puri, Et Al.

2020-Current year OA Pubs

No abstract provided.


Immunofluorescence Use And Techniques In Glomerular Diseases: A Review, Nidia Messias Nov 2024

Immunofluorescence Use And Techniques In Glomerular Diseases: A Review, Nidia Messias

2020-Current year OA Pubs

BACKGROUND: Immunofluorescence (IF) studies play an essential role in the evaluation of medical renal biopsies. Particularly, in the study of renal glomerular diseases, where it provides fundamental data for the diagnosis, classification, and etiology of the glomerular pathologies. Diverse techniques may be used to optimize the utilization of IF studies, from variations on the test methodologies to expertise on the interpretation of the results and knowledge of potential pitfalls.

SUMMARY: This manuscript presents a brief review on the history of IF and its utilization in kidney pathology, followed by a description of the IF methods, including the use of IF …


Regulatory T Cells Require Peripheral Ccl2-Ccr2 Signaling To Facilitate The Resolution Of Medication Overuse Headache-Related Behavioral Sensitization, Sun Ryu, Jintao Zhang, Roli Simoes, Xuemei Liu, Zhaohua Guo, Li Feng, Jacqueline Unsinger, Richard S Hotchkiss, Yu-Qing Cao Nov 2024

Regulatory T Cells Require Peripheral Ccl2-Ccr2 Signaling To Facilitate The Resolution Of Medication Overuse Headache-Related Behavioral Sensitization, Sun Ryu, Jintao Zhang, Roli Simoes, Xuemei Liu, Zhaohua Guo, Li Feng, Jacqueline Unsinger, Richard S Hotchkiss, Yu-Qing Cao

2020-Current year OA Pubs

BACKGROUND: Medication overuse headache (MOH) is the most common secondary headache disorder, resulting from chronic and excessive use of medication to treat headaches, for example, sumatriptan. In a recent study, we have shown that the peripheral C-C motif ligand 2 (CCL2), C-C motif chemokine receptor 2 (CCR2) and calcitonin-gene-related peptide (CGRP) signaling pathways interact with each other and play critical roles in the development of chronic migraine-related behavioral and cellular sensitization. In the present study, we investigated whether CCL2-CCR2 and CGRP signaling pathways play a role in the development of sumatriptan overuse-induced sensitization, and whether they are involved in its …


Length Of Hospital And Intensive Care Unit Stay In Patients With Invasive Candidiasis And/Or Candidemia Treated With Rezafungin: A Pooled Analysis Of Two Randomised Controlled Trials, Patrick M Honoré, Matteo Bassetti, Oliver A Cornely, Herve Dupont, Jesús Fortún, Marin H Kollef, Peter Pappas, John Pullman, Jose Vazquez, Inga Bielicka, Sara Dickerson, Nick Manamley, Taylor Sandison, George R Thompson Nov 2024

Length Of Hospital And Intensive Care Unit Stay In Patients With Invasive Candidiasis And/Or Candidemia Treated With Rezafungin: A Pooled Analysis Of Two Randomised Controlled Trials, Patrick M Honoré, Matteo Bassetti, Oliver A Cornely, Herve Dupont, Jesús Fortún, Marin H Kollef, Peter Pappas, John Pullman, Jose Vazquez, Inga Bielicka, Sara Dickerson, Nick Manamley, Taylor Sandison, George R Thompson

2020-Current year OA Pubs

BACKGROUND: Invasive candidiasis/candidemia (IC/C) is associated with a substantial health economic burden driven primarily by prolonged hospital stay. The once-weekly IV echinocandin, rezafungin acetate, has demonstrated non-inferiority to caspofungin in the treatment of IC/C. This paper reports a post hoc pooled exploratory analysis of length of stay (LoS) for hospital and intensive care unit (ICU) stays in two previously published clinical trials (ReSTORE [NCT03667690] and STRIVE [NCT02734862], that compared rezafungin with daily IV caspofungin (stable patients in the caspofungin group who met relevant criteria could step down to fluconazole after 3 days or more).

METHODS: LoS outcomes were analysed descriptively …


Collaboration Strategies Affecting Implementation Of A Cross-Systems Intervention For Child Welfare And Substance Use Treatment: A Mixed Methods Analysis, Emmeline Chuang, Byron J Powell, Et Al. Nov 2024

Collaboration Strategies Affecting Implementation Of A Cross-Systems Intervention For Child Welfare And Substance Use Treatment: A Mixed Methods Analysis, Emmeline Chuang, Byron J Powell, Et Al.

2020-Current year OA Pubs

BACKGROUND: Collaboration strategies refer to policies and practices used to align operations and services across organizations or systems. These strategies can influence implementation of cross-system interventions focused on improving integration of care, but remain under-specified and under-examined. This study identifies collaboration strategies and the conditions under which they affected implementation of Sobriety Treatment and Recovery Teams (START), an evidence-based intervention focused on integrating child welfare and behavioral health services for families involved with both systems.

METHODS: Our study sample included 17 county child welfare agencies that implemented START. Data on collaboration strategies and organizational context were obtained from key informant …


Sacituzumab-Govitecan-Induced Severe Acute Tubulointerstitial Nephritis Requiring Hemodialysis, Geneva Guarin, Audrey Netzel, Karen Marie Flores, Arun Cumpelik, Ron Bose Nov 2024

Sacituzumab-Govitecan-Induced Severe Acute Tubulointerstitial Nephritis Requiring Hemodialysis, Geneva Guarin, Audrey Netzel, Karen Marie Flores, Arun Cumpelik, Ron Bose

2020-Current year OA Pubs

BACKGROUND: Sacituzumab govitecan is an antibody-drug conjugate that is FDA approved for refractory metastatic triple-negative breast cancer. It targets the human trophoblastic cell-surface antigen 2 (Trop-2) with SN-38, a topoisomerase I inhibitor, attached to the antibody [1]. SN-38 breaks DNA strands and induces tumor apoptosis [2]. Acute kidney injury (AKI) is one of its adverse effects mainly prerenal due to gastrointestinal toxicity, but it has not been reported to cause acute tubulointerstitial nephritis (ATIN).

CASE PRESENTATION: This report describes a rare adverse effect of sacituzumab govitecan, the approach to diagnosing the etiology of the patient's AKI, and the mechanism by …