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Delayed Ipsilateral Intestinal Perforation After Endoscopic Gastrojejunostomy: A Perspective On Underlying Mechanisms, Juan Reyes Genere, Zoilo K Suarez, Vladimir Kushnir Apr 2023

Delayed Ipsilateral Intestinal Perforation After Endoscopic Gastrojejunostomy: A Perspective On Underlying Mechanisms, Juan Reyes Genere, Zoilo K Suarez, Vladimir Kushnir

2020-Current year OA Pubs

The endoscopic management for malignant gastric outlet obstruction has expanded with the advent of endoscopic ultrasound-guided gastrojejunostomy. Delayed perforation after endoscopic ultrasound-guided gastrojejunostomy is an important yet rarely reported adverse event, and it is unclear why some patients may suffer this complication. We present a case of intestinal perforation occurring one month after endoscopic ultrasound-guided gastrojejunostomy and discuss potential mechanisms which may contribute to this outcome.


Impact Of The Covid-19 Pandemic On Chronic Disease Management And Patient Reported Outcomes In Patients With Pulmonary Hypertension: The Pulmonary Hypertension Association Registry, Megan Mayer, Murali M Chakinala, Et Al. Apr 2023

Impact Of The Covid-19 Pandemic On Chronic Disease Management And Patient Reported Outcomes In Patients With Pulmonary Hypertension: The Pulmonary Hypertension Association Registry, Megan Mayer, Murali M Chakinala, Et Al.

2020-Current year OA Pubs

To better understand the impact of the COVID-19 pandemic on the care of patients with pulmonary hypertension, we conducted a retrospective cohort study evaluating health insurance status, healthcare access, disease severity, and patient reported outcomes in this population. Using the Pulmonary Hypertension Association Registry (PHAR), we defined and extracted a longitudinal cohort of pulmonary arterial hypertension (PAH) patients from the PHAR's inception in 2015 until March 2022. We used generalized estimating equations to model the impact of the COVID-19 pandemic on patient outcomes, adjusting for demographic confounders. We assessed whether insurance status modified these effects via covariate interactions. PAH patients …


Regulation Of Astrocyte Lipid Metabolism And Apoe Secretion By The Microglial Oxysterol, 25-Hydroxycholesterol, Anil G Cashikar, Danira Toral-Rios, David Timm, Johnathan Romero, Michael Strickland, Justin M Long, Xianlin Han, David M Holtzman, Steven M Paul Apr 2023

Regulation Of Astrocyte Lipid Metabolism And Apoe Secretion By The Microglial Oxysterol, 25-Hydroxycholesterol, Anil G Cashikar, Danira Toral-Rios, David Timm, Johnathan Romero, Michael Strickland, Justin M Long, Xianlin Han, David M Holtzman, Steven M Paul

2020-Current year OA Pubs

Neuroinflammation, a major hallmark of Alzheimer's disease and several other neurological and psychiatric disorders, is often associated with dysregulated cholesterol metabolism. Relative to homeostatic microglia, activated microglia express higher levels of Ch25h, an enzyme that hydroxylates cholesterol to produce 25-hydroxycholesterol (25HC). 25HC is an oxysterol with interesting immune roles stemming from its ability to regulate cholesterol metabolism. Since astrocytes synthesize cholesterol in the brain and transport it to other cells via ApoE-containing lipoproteins, we hypothesized that secreted 25HC from microglia may influence lipid metabolism as well as extracellular ApoE derived from astrocytes. Here, we show that astrocytes take up externally …


Expanding The Muscle Imaging Spectrum In Dysferlinopathy: Description Of An Outlier Population From The Classical Mri Pattern, Laura Llansó, Alan Pestronk, Et Al. Apr 2023

Expanding The Muscle Imaging Spectrum In Dysferlinopathy: Description Of An Outlier Population From The Classical Mri Pattern, Laura Llansó, Alan Pestronk, Et Al.

2020-Current year OA Pubs

Dysferlinopathy is a muscle disease characterized by a variable clinical presentation and is caused by mutations in the DYSF gene. The Jain Clinical Outcome Study for Dysferlinopathy (COS) followed the largest cohort of patients (n=187) with genetically confirmed dysferlinopathy throughout a three-year natural history study, in which the patients underwent muscle function tests and muscle magnetic resonance imaging (MRI). We previously described the pattern of muscle pathology in this population and established a series of imaging criteria for diagnosis. In this paper, we describe the muscle imaging and clinical features of a subgroup of COS participants whose muscle imaging results …


Race And Socioeconomic Status Interact With Hpv To Influence Survival Disparities In Oropharyngeal Squamous Cell Carcinoma, Emily Z Yan, Benjamin M Wahle, Sean T Massa, Paul Zolkind, Randal C Paniello, Patrik Pipkorn, Ryan S Jackson, Jason T Rich, Sidharth V Puram, Angela L Mazul Apr 2023

Race And Socioeconomic Status Interact With Hpv To Influence Survival Disparities In Oropharyngeal Squamous Cell Carcinoma, Emily Z Yan, Benjamin M Wahle, Sean T Massa, Paul Zolkind, Randal C Paniello, Patrik Pipkorn, Ryan S Jackson, Jason T Rich, Sidharth V Puram, Angela L Mazul

2020-Current year OA Pubs

BACKGROUND: HPV-related oropharyngeal squamous cell carcinoma (OPSCC) is associated with a favorable prognosis, yet patients of color and low socioeconomic status (SES) continue to experience inferior outcomes. We aim to understand how the emergence of HPV has impacted race and SES survival disparities in OPSCC.

METHODS: A retrospective cohort of 18,362 OPSCC cases from 2010 to 2017 was assembled using the SEER (Surveillance, Epidemiology, and End Results) database. Cox proportional regression and Fine and Gray regression models were used to calculate hazard ratios (HRs) adjusting for race, SES, age, subsite, stage, and treatment.

RESULTS: Black patients had lower overall survival …


Design Of The Combination Effect Of Finerenone And Empagliflozin In Participants With Chronic Kidney Disease And Type 2 Diabetes Using A Uacr Endpoint Study (Confidence), Jennifer B Green, Amy K Mottl, George Bakris, Hiddo J L Heerspink, Johannes F E Mann, Janet B Mcgill, Masaomi Nangaku, Peter Rossing, Charlie Scott, Alain Gay, Rajiv Agarwal Mar 2023

Design Of The Combination Effect Of Finerenone And Empagliflozin In Participants With Chronic Kidney Disease And Type 2 Diabetes Using A Uacr Endpoint Study (Confidence), Jennifer B Green, Amy K Mottl, George Bakris, Hiddo J L Heerspink, Johannes F E Mann, Janet B Mcgill, Masaomi Nangaku, Peter Rossing, Charlie Scott, Alain Gay, Rajiv Agarwal

2020-Current year OA Pubs

BACKGROUND: Despite available interventions, people with type 2 diabetes (T2D) remain at risk of chronic kidney disease (CKD). Finerenone, a potent and selective nonsteroidal mineralocorticoid receptor antagonist, and sodium-glucose cotransporter 2 inhibitors (SGLT2is) can reduce both kidney and cardiovascular risks in people with CKD and T2D. Here we outline the design of a study to investigate whether dual therapy with finerenone and an SGLT2i is superior to either agent alone.

METHODS: CONFIDENCE (NCT05254002) is a randomized, controlled, double-blind, double-dummy, international, multicenter, three-armed, parallel-group, 7.5 - to 8.5-month, Phase 2 study in 807 adults with T2D, stage 2-3 CKD and a …


Nadph Oxidase 2 Limits Amplification Of Il-1Β-G-Csf Axis And An Immature Neutrophil Subset In Murine Lung Inflammation, Zhimin Song, Sourav Bhattacharya, Guangming Huang, Zev J Greenberg, Wei Yang, Juhi Bagaitkar, Laura G Schuettpelz, Mary C Dinauer Mar 2023

Nadph Oxidase 2 Limits Amplification Of Il-1Β-G-Csf Axis And An Immature Neutrophil Subset In Murine Lung Inflammation, Zhimin Song, Sourav Bhattacharya, Guangming Huang, Zev J Greenberg, Wei Yang, Juhi Bagaitkar, Laura G Schuettpelz, Mary C Dinauer

2020-Current year OA Pubs

The leukocyte NADPH oxidase 2 (NOX2) regulates inflammation independent of its antimicrobial activity. Inherited defects in NOX2 lead to chronic granulomatous disease (CGD), associated with recurrent bacterial and fungal infections, often with excessive neutrophilic inflammation that results in significant inflammatory burden and tissue damage. We previously showed that excessive leukotriene B4 (LTB4) production by NOX2-deficient mouse neutrophils was a key driver of elevated lung neutrophil infiltration in the initial response to pulmonary challenge with the model fungal particle zymosan. We now identify interleukin-1β (IL-1β) and downstream granulocyte colony-stimulating factor (G-CSF) as critical amplifying signals that augment and sustain neutrophil accrual …


Assessment Of Bladder Pressure And Discomfort Symptoms: How Do Overactive Bladder Differ From Interstitial Cystitis/Bladder Pain Syndrome Patients?, Angelíca Gousse, Joel Vetter, H Henry Lai Mar 2023

Assessment Of Bladder Pressure And Discomfort Symptoms: How Do Overactive Bladder Differ From Interstitial Cystitis/Bladder Pain Syndrome Patients?, Angelíca Gousse, Joel Vetter, H Henry Lai

2020-Current year OA Pubs

BACKGROUND: To better understand the sensation of bladder "pressure" and "discomfort", and how they are similar or distinct from the "pain" and "urgency" symptoms in IC/BPS and OAB.

METHODS: IC/BPS and OAB patients rated their bladder pain, pressure, discomfort, and urinary urgency on separate 0-10 numeric rating scales (NRS). Their NRS ratings were compared between IC/BPS and OAB, and Pearson correlations were performed.

RESULTS: Among IC/BPS patients (n = 27), their mean numeric ratings of pain, pressure, discomfort, and urinary urgency were almost identical (6.6 ± 2.1, 6.0 ± 2.5, 6.5 ± 2.2, and 6.0 ± 2.8 respectively). The three-way …


The Midwest Sarcoma Trials Partnership: Bridging Academic And Community Networks In A Collaborative Approach To Sarcoma, Natalie K Heater, Angela C Hirbe, Mia C Weiss, Brian Van Tine, Et Al. Mar 2023

The Midwest Sarcoma Trials Partnership: Bridging Academic And Community Networks In A Collaborative Approach To Sarcoma, Natalie K Heater, Angela C Hirbe, Mia C Weiss, Brian Van Tine, Et Al.

2020-Current year OA Pubs

The treatment of sarcoma necessitates a collaborative approach, given its rarity and complex management. At a single institution, multidisciplinary teams of specialists determine and execute treatment plans involving surgical, radiation, and medical management. Treatment guidelines for systemic therapies in advanced or nonresectable soft tissue sarcoma have advanced in recent years as new immunotherapies and targeted therapies become available. Collaboration between institutions is necessary to facilitate accrual to clinical trials. Here, we describe the success of the Midwest Sarcoma Trials Partnership (MWSTP) in creating a network encompassing large academic centers and local community sites. We propose a new model utilizing online …


Median Nerve Stimulation For Treatment Of Tics: A 4-Week Open Trial With Ecological Momentary Assessment, Ann M Iverson, Amanda L Arbuckle, David Y Song, Emily C Bihun, Kevin J. Black Mar 2023

Median Nerve Stimulation For Treatment Of Tics: A 4-Week Open Trial With Ecological Momentary Assessment, Ann M Iverson, Amanda L Arbuckle, David Y Song, Emily C Bihun, Kevin J. Black

2020-Current year OA Pubs

Median nerve stimulation (MNS) at 10-12 Hz was recently proposed as a treatment for Tourette syndrome and other chronic tic disorders (TS/CTD). We report on 31 participants ages 15-64 with TS/CTD in an open-label, comparative (within-group, several time points) study of MNS (ClinicalTrials.gov registration number NCT05016765). Participants were recruited from completers of a randomized controlled trial (RCT) of MNS and were given a transcutaneous electrical nerve stimulation (TENS) unit to use as desired for 12 Hz MNS for 4 weeks. Participants were instructed to complete surveys regarding tic symptoms and stimulation discomfort before and after stimulation, as well as twice …


Wdfy4 Deficiency In Nod Mice Ameliorates Autoimmune Diabetes And Insulitis, Stephen T Ferris, Tiantian Liu, Jing Chen, Ray A Ohara, Feiya Ou, Renee Wu, Sunkyung Kim, Theresa L Murphy, Kenneth M Murphy Mar 2023

Wdfy4 Deficiency In Nod Mice Ameliorates Autoimmune Diabetes And Insulitis, Stephen T Ferris, Tiantian Liu, Jing Chen, Ray A Ohara, Feiya Ou, Renee Wu, Sunkyung Kim, Theresa L Murphy, Kenneth M Murphy

2020-Current year OA Pubs

The events that initiate autoimmune diabetes in nonobese diabetic (NOD) mice remain poorly understood. CD4


Mfge8 Links Absorption Of Dietary Fatty Acids With Catabolism Of Enterocyte Lipid Stores Through Hnf4Γ-Dependent Transcription Of Ces Enzymes, Ritwik Datta, Mohammad A Gholampour, Christopher D Yang, Regan Volk, Sinan Lin, Michael J Podolsky, Thomas Arnold, Florian Rieder, Balyn W Zaro, Michael Verzi, Richard Lehner, Nada Abumrad, Carlos O Lizama, Kamran Atabai Mar 2023

Mfge8 Links Absorption Of Dietary Fatty Acids With Catabolism Of Enterocyte Lipid Stores Through Hnf4Γ-Dependent Transcription Of Ces Enzymes, Ritwik Datta, Mohammad A Gholampour, Christopher D Yang, Regan Volk, Sinan Lin, Michael J Podolsky, Thomas Arnold, Florian Rieder, Balyn W Zaro, Michael Verzi, Richard Lehner, Nada Abumrad, Carlos O Lizama, Kamran Atabai

2020-Current year OA Pubs

Enterocytes modulate the extent of postprandial lipemia by storing dietary fats in cytoplasmic lipid droplets (cLDs). We have previously shown that the integrin ligand MFGE8 links absorption of dietary fats with activation of triglyceride (TG) hydrolases that catabolize cLDs for chylomicron production. Here, we identify CES1D as the key hydrolase downstream of the MFGE8-αvβ5 integrin pathway that regulates catabolism of diet-derived cLDs. Mfge8 knockout (KO) enterocytes have reduced CES1D transcript and protein levels and reduced protein levels of the transcription factor HNF4γ. Both Ces1d and Hnf4γ KO mice have decreased enterocyte TG hydrolase activity coupled with retention of TG in …


Integrated Transcriptomics Contrasts Fatty Acid Metabolism With Hypoxia Response In Β-Cell Subpopulations Associated With Glycemic Control, Mario A Miranda, Juan F Macias-Velasco, Heather Schmidt, Heather A Lawson Mar 2023

Integrated Transcriptomics Contrasts Fatty Acid Metabolism With Hypoxia Response In Β-Cell Subpopulations Associated With Glycemic Control, Mario A Miranda, Juan F Macias-Velasco, Heather Schmidt, Heather A Lawson

2020-Current year OA Pubs

BACKGROUND: Understanding how heterogeneous β-cell function impacts diabetes is imperative for therapy development. Standard single-cell RNA sequencing analysis illuminates some factors driving heterogeneity, but new strategies are required to enhance information capture.

RESULTS: We integrate pancreatic islet single-cell and bulk RNA sequencing data to identify β-cell subpopulations based on gene expression and characterize genetic networks associated with β-cell function in obese SM/J mice. We identify β-cell subpopulations associated with basal insulin secretion, hypoxia response, cell polarity, and stress response. Network analysis associates fatty acid metabolism and basal insulin secretion with hyperglycemic-obesity, while expression of Pdyn and hypoxia response is associated …


Alzheimer's Disease Genetic Risk And Cognitive Reserve In Relationship To Long-Term Cognitive Trajectories Among Cognitively Normal Individuals, Corinne Pettigrew, John C Morris, Jason Hassenstab, Carlos Cruchaga, Et Al. Mar 2023

Alzheimer's Disease Genetic Risk And Cognitive Reserve In Relationship To Long-Term Cognitive Trajectories Among Cognitively Normal Individuals, Corinne Pettigrew, John C Morris, Jason Hassenstab, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

BACKGROUND: Both Alzheimer's disease (AD) genetic risk factors and indices of cognitive reserve (CR) influence risk of cognitive decline, but it remains unclear whether they interact. This study examined whether a CR index score modifies the relationship between AD genetic risk factors and long-term cognitive trajectories in a large sample of individuals with normal cognition.

METHODS: Analyses used data from the Preclinical AD Consortium, including harmonized data from 5 longitudinal cohort studies. Participants were cognitively normal at baseline (M baseline age = 64 years, 59% female) and underwent 10 years of follow-up, on average. AD genetic risk was measured by …


An Online Repository For Pre-Clinical Imaging Protocols (Pips), Seth T Gammon, Hongyu An, James D Quirk, Kooresh Shoghi, Et Al. Mar 2023

An Online Repository For Pre-Clinical Imaging Protocols (Pips), Seth T Gammon, Hongyu An, James D Quirk, Kooresh Shoghi, Et Al.

2020-Current year OA Pubs

Providing method descriptions that are more detailed than currently available in typical peer reviewed journals has been identified as an actionable area for improvement. In the biochemical and cell biology space, this need has been met through the creation of new journals focused on detailed protocols and materials sourcing. However, this format is not well suited for capturing instrument validation, detailed imaging protocols, and extensive statistical analysis. Furthermore, the need for additional information must be counterbalanced by the additional time burden placed upon researchers who may be already overtasked. To address these competing issues, this white paper describes protocol templates …


Structural And Functional Analysis Of Human Pannexin 2 Channel, Zhihui He, Yonghui Zhao, Michael J Rau, James A J Fitzpatrick, Rajan Sah, Hongzhen Hu, Peng Yuan Mar 2023

Structural And Functional Analysis Of Human Pannexin 2 Channel, Zhihui He, Yonghui Zhao, Michael J Rau, James A J Fitzpatrick, Rajan Sah, Hongzhen Hu, Peng Yuan

2020-Current year OA Pubs

The pannexin 2 channel (PANX2) participates in multiple physiological processes including skin homeostasis, neuronal development, and ischemia-induced brain injury. However, the molecular basis of PANX2 channel function remains largely unknown. Here, we present a cryo-electron microscopy structure of human PANX2, which reveals pore properties contrasting with those of the intensely studied paralog PANX1. The extracellular selectivity filter, defined by a ring of basic residues, more closely resembles that of the distantly related volume-regulated anion channel (VRAC) LRRC8A, rather than PANX1. Furthermore, we show that PANX2 displays a similar anion permeability sequence as VRAC, and that PANX2 channel activity is inhibited …


Epigenetic And Transcriptomic Characterization Reveals Progression Markers And Essential Pathways In Clear Cell Renal Cell Carcinoma, Yige Wu, Nadezhda V Terekhanova, Wagma Caravan, Nataly Naser Al Deen, Preet Lal, Siqi Chen, Chia-Kuei Mo, Song Cao, Yize Li, Alla Karpova, Ruiyang Liu, Yanyan Zhao, Andrew Shinkle, Ilya Strunilin, Cody Weimholt, Kazuhito Sato, Lijun Yao, Mamatha Serasanambati, Xiaolu Yang, Matthew Wyczalkowski, Houxiang Zhu, Daniel Cui Zhou, Reyka G Jayasinghe, Daniel Mendez, Michael C Wendl, Melissa A Reimers, Russell K Pachynski, Aadel A Chaudhuri, Milan G Chheda, Benjamin D Humphreys, James J Hsieh, Li Ding, Feng Chen, Et Al. Mar 2023

Epigenetic And Transcriptomic Characterization Reveals Progression Markers And Essential Pathways In Clear Cell Renal Cell Carcinoma, Yige Wu, Nadezhda V Terekhanova, Wagma Caravan, Nataly Naser Al Deen, Preet Lal, Siqi Chen, Chia-Kuei Mo, Song Cao, Yize Li, Alla Karpova, Ruiyang Liu, Yanyan Zhao, Andrew Shinkle, Ilya Strunilin, Cody Weimholt, Kazuhito Sato, Lijun Yao, Mamatha Serasanambati, Xiaolu Yang, Matthew Wyczalkowski, Houxiang Zhu, Daniel Cui Zhou, Reyka G Jayasinghe, Daniel Mendez, Michael C Wendl, Melissa A Reimers, Russell K Pachynski, Aadel A Chaudhuri, Milan G Chheda, Benjamin D Humphreys, James J Hsieh, Li Ding, Feng Chen, Et Al.

2020-Current year OA Pubs

Identifying tumor-cell-specific markers and elucidating their epigenetic regulation and spatial heterogeneity provides mechanistic insights into cancer etiology. Here, we perform snRNA-seq and snATAC-seq in 34 and 28 human clear cell renal cell carcinoma (ccRCC) specimens, respectively, with matched bulk proteogenomics data. By identifying 20 tumor-specific markers through a multi-omics tiered approach, we reveal an association between higher ceruloplasmin (CP) expression and reduced survival. CP knockdown, combined with spatial transcriptomics, suggests a role for CP in regulating hyalinized stroma and tumor-stroma interactions in ccRCC. Intratumoral heterogeneity analysis portrays tumor cell-intrinsic inflammation and epithelial-mesenchymal transition (EMT) as two distinguishing features of tumor …


Validation Of A Farsi Version Of The Eating Pathology Symptoms Inventory (F-Epsi) Among Iranian Adolescents, Reza N Sahlan, Jessica F Saunders, Ellen E Fitzsimmons-Craft Mar 2023

Validation Of A Farsi Version Of The Eating Pathology Symptoms Inventory (F-Epsi) Among Iranian Adolescents, Reza N Sahlan, Jessica F Saunders, Ellen E Fitzsimmons-Craft

2020-Current year OA Pubs

PURPOSE: Limited research has validated eating pathology assessments in Iranian adolescent boys and girls. In particular, the measures that have been validated do not capture both boys' and girls' eating behaviors in adolescence. The purpose of the current study was to validate a Farsi version of the Eating Pathology Symptoms Inventory (F-EPSI) for use in Iranian adolescents.

METHODS: Participants (N = 913; 85.3% girls) were adolescents who completed a battery of questionnaires including the F-EPSI. In addition, F-EPSI data for Iranian adolescents were compared with those of previously published data of adult Iranian college students.

RESULTS: Confirmatory Factor Analysis (CFA) …


Median Nerve Stimulation For Treatment Of Tics: Randomized, Controlled, Crossover Trial, Ann M Iverson, Amanda L Arbuckle, Keisuke Ueda, David Y Song, Emily C Bihun, Jonathan M Koller, Michael Wallendorf, Kevin J. Black Mar 2023

Median Nerve Stimulation For Treatment Of Tics: Randomized, Controlled, Crossover Trial, Ann M Iverson, Amanda L Arbuckle, Keisuke Ueda, David Y Song, Emily C Bihun, Jonathan M Koller, Michael Wallendorf, Kevin J. Black

2020-Current year OA Pubs

A prior study showed that rhythmic, but not arrhythmic, 12 Hz stimulation of the median nerve (MNS) entrained the sensorimotor cortex EEG signal and found that 10 Hz MNS improved tics in Tourette syndrome (TS). However, no control condition was tested, and stimulation blocks lasted only 1 min. We set out to replicate the TS results and to test whether tic improvement occurs by the proposed cortical entrainment mechanism. Preregistration was completed at ClinicalTrials.gov, under number NCT04731714. Thirty-two people with TS, age 15-64, completed two study visits with repeated MNS on and off blocks in random order, one visit for …


Incidence Of Pneumocystis Pneumonia In Immunocompromised Patients Without Human Immunodeficiency Virus On Intravenous Pentamidine Prophylaxis: A Systematic Review And Meta-Analysis, Chia-Yu Chiu, Patrick R Ching Mar 2023

Incidence Of Pneumocystis Pneumonia In Immunocompromised Patients Without Human Immunodeficiency Virus On Intravenous Pentamidine Prophylaxis: A Systematic Review And Meta-Analysis, Chia-Yu Chiu, Patrick R Ching

2020-Current year OA Pubs

BACKGROUND: Trimethoprim-sulfamethoxazole (TMP-SMX) is a first-line

METHOD: We performed a systematic review and meta-analysis to estimate breakthrough PCP incidence and adverse reactions in HIV-uninfected immunocompromised patients receiving IVP. MEDLINE, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov were searched from their inception until 15 December 2022.

RESULTS: The pooled incidence of breakthrough PCP with IVP was 0.7% (95% CI, 0.3-1.4%, 16 studies, 3025 patients) and was similar when used as first-line prophylaxis (0.5%; 95% CI, 0.2-1.4%, 7 studies, 752 patients). The pooled incidence of adverse reactions was 11.3% (95% CI, 6.7-18.6%, 14 studies, 2068 patients). The pooled adverse event-related discontinuation …


Calpain Activity Is Negatively Regulated By A Kctd7-Cullin-3 Complex Via Non-Degradative Ubiquitination, Jaiprakash Sharma, Shalaka Mulherkar, Uan-I Chen, Yan Xiong, Lakshya Bajaj, Byoung-Kyu Cho, Young Ah Goo, Hon-Chiu Eastwood Leung, Kimberley F Tolias, Marco Sardiello Mar 2023

Calpain Activity Is Negatively Regulated By A Kctd7-Cullin-3 Complex Via Non-Degradative Ubiquitination, Jaiprakash Sharma, Shalaka Mulherkar, Uan-I Chen, Yan Xiong, Lakshya Bajaj, Byoung-Kyu Cho, Young Ah Goo, Hon-Chiu Eastwood Leung, Kimberley F Tolias, Marco Sardiello

2020-Current year OA Pubs

Calpains are a class of non-lysosomal cysteine proteases that exert their regulatory functions via limited proteolysis of their substrates. Similar to the lysosomal and proteasomal systems, calpain dysregulation is implicated in the pathogenesis of neurodegenerative disease and cancer. Despite intensive efforts placed on the identification of mechanisms that regulate calpains, however, calpain protein modifications that regulate calpain activity are incompletely understood. Here we show that calpains are regulated by KCTD7, a cytosolic protein of previously uncharacterized function whose pathogenic mutations result in epilepsy, progressive ataxia, and severe neurocognitive deterioration. We show that KCTD7 works in complex with Cullin-3 and Rbx1 …


Rapamycin Perfluorocarbon Nanoparticle Mitigates Cisplatin-Induced Acute Kidney Injury, Qingyu Zhou, James D Quirk, Ying Hu, Huimin Yan, Joseph P Gaut, Christine T N Pham, Samuel A Wickline, Hua Pan Mar 2023

Rapamycin Perfluorocarbon Nanoparticle Mitigates Cisplatin-Induced Acute Kidney Injury, Qingyu Zhou, James D Quirk, Ying Hu, Huimin Yan, Joseph P Gaut, Christine T N Pham, Samuel A Wickline, Hua Pan

2020-Current year OA Pubs

For nearly five decades, cisplatin has played an important role as a standard chemotherapeutic agent and been prescribed to 10-20% of all cancer patients. Although nephrotoxicity associated with platinum-based agents is well recognized, treatment of cisplatin-induced acute kidney injury is mainly supportive and no specific mechanism-based prophylactic approach is available to date. Here, we postulated that systemically delivered rapamycin perfluorocarbon nanoparticles (PFC NP) could reach the injured kidneys at sufficient and sustained concentrations to mitigate cisplatin-induced acute kidney injury and preserve renal function. Using fluorescence microscopic imaging and fluorine magnetic resonance imaging/spectroscopy, we illustrated that rapamycin-loaded PFC NP permeated and …


Antidepressant Augmentation Versus Switch In Treatment-Resistant Geriatric Depression, Eric J Lenze, Pilar Cristancho, Torie R Gettinger, Emily Lenard, J Philip Miller, Ginger E Nicol, Vy T Pham, Lei Yang, Et Al. Mar 2023

Antidepressant Augmentation Versus Switch In Treatment-Resistant Geriatric Depression, Eric J Lenze, Pilar Cristancho, Torie R Gettinger, Emily Lenard, J Philip Miller, Ginger E Nicol, Vy T Pham, Lei Yang, Et Al.

2020-Current year OA Pubs

BACKGROUND: The benefits and risks of augmenting or switching antidepressants in older adults with treatment-resistant depression have not been extensively studied.

METHODS: We conducted a two-step, open-label trial involving adults 60 years of age or older with treatment-resistant depression. In step 1, patients were randomly assigned in a 1:1:1 ratio to augmentation of existing antidepressant medication with aripiprazole, augmentation with bupropion, or a switch from existing antidepressant medication to bupropion. Patients who did not benefit from or were ineligible for step 1 were randomly assigned in step 2 in a 1:1 ratio to augmentation with lithium or a switch to …


Imc-Denoise: A Content Aware Denoising Pipeline To Enhance Imaging Mass Cytometry, Peng Lu, Karolyn A Oetjen, Diane E Bender, Marianna B Ruzinova, Daniel A C Fisher, Kevin G Shim, Russell K Pachynski, W Nathaniel Brennen, Stephen T Oh, Daniel C Link, Daniel L J Thorek Mar 2023

Imc-Denoise: A Content Aware Denoising Pipeline To Enhance Imaging Mass Cytometry, Peng Lu, Karolyn A Oetjen, Diane E Bender, Marianna B Ruzinova, Daniel A C Fisher, Kevin G Shim, Russell K Pachynski, W Nathaniel Brennen, Stephen T Oh, Daniel C Link, Daniel L J Thorek

2020-Current year OA Pubs

Imaging Mass Cytometry (IMC) is an emerging multiplexed imaging technology for analyzing complex microenvironments using more than 40 molecularly-specific channels. However, this modality has unique data processing requirements, particularly for patient tissue specimens where signal-to-noise ratios for markers can be low, despite optimization, and pixel intensity artifacts can deteriorate image quality and downstream analysis. Here we demonstrate an automated content-aware pipeline, IMC-Denoise, to restore IMC images deploying a differential intensity map-based restoration (DIMR) algorithm for removing hot pixels and a self-supervised deep learning algorithm for shot noise image filtering (DeepSNiF). IMC-Denoise outperforms existing methods for adaptive hot pixel and background …


Radiological Society Of North America (Rsna) 3d Printing Special Interest Group (Sig) Clinical Situations For Which 3d Printing Is Considered An Appropriate Representation Or Extension Of Data Contained In A Medical Imaging Examination: Breast Conditions, Elsa M Arribas, Tatiana Kelil, Lumarie Santiago, Arafat Ali, Seetharam C Chadalavada, Leonid Chepelev, Anish Ghodadra, Ciprian N Ionita, Joonhyuk Lee, Prashanth Ravi, Justin R Ryan, Adnan M Sheikh, Frank J Rybicki, David H Ballard, Rsna Special Interest 3d Printing Breast Conditions Voting Group Mar 2023

Radiological Society Of North America (Rsna) 3d Printing Special Interest Group (Sig) Clinical Situations For Which 3d Printing Is Considered An Appropriate Representation Or Extension Of Data Contained In A Medical Imaging Examination: Breast Conditions, Elsa M Arribas, Tatiana Kelil, Lumarie Santiago, Arafat Ali, Seetharam C Chadalavada, Leonid Chepelev, Anish Ghodadra, Ciprian N Ionita, Joonhyuk Lee, Prashanth Ravi, Justin R Ryan, Adnan M Sheikh, Frank J Rybicki, David H Ballard, Rsna Special Interest 3d Printing Breast Conditions Voting Group

2020-Current year OA Pubs

The use of medical 3D printing has expanded dramatically for breast diseases. A writing group composed of the Radiological Society of North America (RSNA) Special Interest Group on 3D Printing (SIG) provides updated appropriateness criteria for breast 3D printing in various clinical scenarios. Evidence-based appropriateness criteria are provided for the following clinical scenarios: benign breast lesions and high-risk breast lesions, breast cancer, breast reconstruction, and breast radiation (treatment planning and radiation delivery).


Advance Care Planning And Health-Related Quality Of Life In Huntington Disease: Results From A Multicenter National Study, Leonard L Sokol, Jonathan P Troost, Danny Bega, Benzi M Kluger, Holly G Prigerson, Martha Nance, Samuel Frank, Joel S Perlmutter, Praveen Dayalu, David Cella, Noelle E Carlozzi Mar 2023

Advance Care Planning And Health-Related Quality Of Life In Huntington Disease: Results From A Multicenter National Study, Leonard L Sokol, Jonathan P Troost, Danny Bega, Benzi M Kluger, Holly G Prigerson, Martha Nance, Samuel Frank, Joel S Perlmutter, Praveen Dayalu, David Cella, Noelle E Carlozzi

2020-Current year OA Pubs

OBJECTIVE: With Huntington disease (HD), a fatal neurodegenerative disease where the prevalence of suicidal thoughts and behavior (STB) remains elevated as compared to other neurological disorders, it is unknown whether STB and health-related quality of life (HRQoL) affect plans for the end of life or more broadly, advance care planning (ACP). Conversely, it is unknown whether ACP would provoke future changes to STB and HRQoL. Therefore, we sought to evaluate whether STB and HRQoL patient-reported outcomes (PROs) contribute to ACP and whether ACP relates to changes in STB and HRQoL at 24 months.

METHODS: HD-validated clinician- and patient-assessments (i.e., HRQoL …


Acceptability And User Experiences Of A Patient-Held Smart Card For Antenatal Services In Nigeria: A Qualitative Study, Ijeoma Uchenna Itanyi, Juliet Iwelunmor, John Olajide Olawepo, Semiu Gbadamosi, Alexandra Ezeonu, Adaeze Okoli, Amaka Grace Ogidi, Donaldson Conserve, Byron Powell, Chima Ariel Onoka, Echezona Edozie Ezeanolue Mar 2023

Acceptability And User Experiences Of A Patient-Held Smart Card For Antenatal Services In Nigeria: A Qualitative Study, Ijeoma Uchenna Itanyi, Juliet Iwelunmor, John Olajide Olawepo, Semiu Gbadamosi, Alexandra Ezeonu, Adaeze Okoli, Amaka Grace Ogidi, Donaldson Conserve, Byron Powell, Chima Ariel Onoka, Echezona Edozie Ezeanolue

2020-Current year OA Pubs

BACKGROUND: Poor maternal, newborn and child health outcomes remain a major public health challenge in Nigeria. Mobile health (mHealth) interventions such as patient-held smart cards have been proposed as effective solutions to improve maternal health outcomes. Our objectives were to assess the acceptability and experiences of pregnant women with the use of a patient-held smartcard for antenatal services in Nigeria.

METHODS: Using focus group discussions, qualitative data were obtained from 35 pregnant women attending antenatal services in four Local Government Areas (LGAs) in Benue State, Nigeria. The audio-recorded data were transcribed and analyzed using framework analysis techniques such as the …


Integrated Analysis Of Genomic And Transcriptomic Data For The Discovery Of Splice-Associated Variants In Cancer, Kelsy C Cotto, Yang-Yang Feng, Avinash Ramu, Megan Richters, Sharon L Freshour, Zachary L Skidmore, Huiming Xia, Joshua F Mcmichael, Jason Kunisaki, Katie M Campbell, Timothy Hung-Po Chen, Emily B Rozycki, Douglas Adkins, Siddhartha Devarakonda, Sumithra Sankararaman, Yiing Lin, William C Chapman, Christopher A Maher, Vivek Arora, Ramaswamy Govindan, Obi L Griffith, Malachi Griffith, Et Al. Mar 2023

Integrated Analysis Of Genomic And Transcriptomic Data For The Discovery Of Splice-Associated Variants In Cancer, Kelsy C Cotto, Yang-Yang Feng, Avinash Ramu, Megan Richters, Sharon L Freshour, Zachary L Skidmore, Huiming Xia, Joshua F Mcmichael, Jason Kunisaki, Katie M Campbell, Timothy Hung-Po Chen, Emily B Rozycki, Douglas Adkins, Siddhartha Devarakonda, Sumithra Sankararaman, Yiing Lin, William C Chapman, Christopher A Maher, Vivek Arora, Ramaswamy Govindan, Obi L Griffith, Malachi Griffith, Et Al.

2020-Current year OA Pubs

Somatic mutations within non-coding regions and even exons may have unidentified regulatory consequences that are often overlooked in analysis workflows. Here we present RegTools ( www.regtools.org ), a computationally efficient, free, and open-source software package designed to integrate somatic variants from genomic data with splice junctions from bulk or single cell transcriptomic data to identify variants that may cause aberrant splicing. We apply RegTools to over 9000 tumor samples with both tumor DNA and RNA sequence data. RegTools discovers 235,778 events where a splice-associated variant significantly increases the splicing of a particular junction, across 158,200 unique variants and 131,212 unique …


Macrophages Promote Repair Of Inner Hair Cell Ribbon Synapses Following Noise-Induced Cochlear Synaptopathy, Vijayprakash Manickam, Dinesh Y Gawande, Andrew R Stothert, Anna C Clayman, Lyudmila Batalkina, Mark E Warchol, Kevin K Ohlemiller, Tejbeer Kaur Mar 2023

Macrophages Promote Repair Of Inner Hair Cell Ribbon Synapses Following Noise-Induced Cochlear Synaptopathy, Vijayprakash Manickam, Dinesh Y Gawande, Andrew R Stothert, Anna C Clayman, Lyudmila Batalkina, Mark E Warchol, Kevin K Ohlemiller, Tejbeer Kaur

2020-Current year OA Pubs

Resident cochlear macrophages rapidly migrate into the inner hair cell synaptic region and directly contact the damaged synaptic connections after noise-induced synaptopathy. Eventually, such damaged synapses are spontaneously repaired, but the precise role of macrophages in synaptic degeneration and repair remains unknown. To address this, cochlear macrophages were eliminated using colony stimulating factor 1 receptor (CSF1R) inhibitor, PLX5622. Sustained treatment with PLX5622 in


Exercise Training To Improve Brain Health In Older People Living With Hiv: Study Protocol For A Randomized Controlled Trial, Sarah Cooley, Brittany M Nelson, Alexander Rosenow, Elizabeth Westerhaus, W Todd Cade, Dominic N Reeds, Florin Vaida, Kevin E Yarasheski, Robert H Paul, Beau M Ances Mar 2023

Exercise Training To Improve Brain Health In Older People Living With Hiv: Study Protocol For A Randomized Controlled Trial, Sarah Cooley, Brittany M Nelson, Alexander Rosenow, Elizabeth Westerhaus, W Todd Cade, Dominic N Reeds, Florin Vaida, Kevin E Yarasheski, Robert H Paul, Beau M Ances

2020-Current year OA Pubs

BACKGROUND: With the advent of antiretrovirals, people living with HIV are living near-normal lifespans. However, people living with HIV are at greater risk of experiencing cognitive impairment and reduced brain integrity despite well-controlled viremia. A robust literature supports exercise interventions as a method of improving cognition and structural brain integrity in older individuals without HIV. The effects of exercise on cardiometabolic, neurocognitive, and neural structures in middle-aged to older people living with HIV are less well known, with few prospective studies examining these measures.

OBJECTIVE: This prospective randomized clinical trial will examine the effects of a 6-month exercise training intervention …