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Articles 4141 - 4170 of 20289
Full-Text Articles in Entire DC Network
Characteristics Of Post Hoc Subgroup Analyses Of Oncology Clinical Trials: A Systematic Review, Jawad Alrawabdeh, Marah Alzu'bi, Muntaser Alzyoud, Nada Odeh, Yazan Hamadneh, Hira Mian, Ghulam Rehman Mohyuddin, Amar H Kelkar, Aaron M Goodman, Rajshekhar Chakraborty, David A Russler-Germain, Nikita Mehra, Diva Baggio, Edward R Scheffer Cliff, Samer Al Hadidi
Characteristics Of Post Hoc Subgroup Analyses Of Oncology Clinical Trials: A Systematic Review, Jawad Alrawabdeh, Marah Alzu'bi, Muntaser Alzyoud, Nada Odeh, Yazan Hamadneh, Hira Mian, Ghulam Rehman Mohyuddin, Amar H Kelkar, Aaron M Goodman, Rajshekhar Chakraborty, David A Russler-Germain, Nikita Mehra, Diva Baggio, Edward R Scheffer Cliff, Samer Al Hadidi
2020-Current year OA Pubs
BACKGROUND: Subgroup analyses in clinical trials assess intervention effects on specific patient subgroups, ensuring generalizability. However, they are usually only able to generate hypotheses rather than definitive conclusions. This study examined the prevalence and characteristics of post hoc subgroup analysis in oncology.
METHODS: We systematically reviewed published subgroup analyses from 2000 to 2022. We included articles presenting secondary, post hoc, or subgroup analyses of interventional clinical trials in oncology, cancer survivorship, or cancer screening, published separately from the original clinical trial publication. We collected cancer type, year of publication, where and how subgroup analyses were reported, and funding.
RESULTS: Out …
Mycobacterium Tuberculosis Carrying The Rifampicin Drug-Resistance-Conferring Rpob Mutation H445y Is Associated With Suppressed Immunity Through Type I Interferons, Suhas Bobba, Nicole C Howard, Shibali Das, Mushtaq Ahmed, Linrui Tang, Shyamala Thirunavukkarasu, Michelle H Larsen, Barun Mathema, Maziar Divangahi, Shabaana A Khader
Mycobacterium Tuberculosis Carrying The Rifampicin Drug-Resistance-Conferring Rpob Mutation H445y Is Associated With Suppressed Immunity Through Type I Interferons, Suhas Bobba, Nicole C Howard, Shibali Das, Mushtaq Ahmed, Linrui Tang, Shyamala Thirunavukkarasu, Michelle H Larsen, Barun Mathema, Maziar Divangahi, Shabaana A Khader
2020-Current year OA Pubs
This study highlights the impact of specific rifampicin-resistance-conferring mutations on the host immune response to
Application Of The Expert Recommendations For Implementing Change (Eric) Compilation Of Strategies To Health Intervention Implementation In Low- And Middle-Income Countries: A Systematic Review, Kathryn L Lovero, Christopher G Kemp, Bradley H Wagenaar, Ali Giusto, M Claire Greene, Byron J Powell, Enola K Proctor
Application Of The Expert Recommendations For Implementing Change (Eric) Compilation Of Strategies To Health Intervention Implementation In Low- And Middle-Income Countries: A Systematic Review, Kathryn L Lovero, Christopher G Kemp, Bradley H Wagenaar, Ali Giusto, M Claire Greene, Byron J Powell, Enola K Proctor
2020-Current year OA Pubs
BACKGROUND: The Expert Recommendations for Implementing Change (ERIC) project developed a compilation of implementation strategies that are intended to standardize reporting and evaluation. Little is known about the application of ERIC in low- and middle-income countries (LMICs). We systematically reviewed the literature on the use and specification of ERIC strategies for health intervention implementation in LMICs to identify gaps and inform future research.
METHODS: We searched peer-reviewed articles published through March 2023 in any language that (1) were conducted in an LMIC and (2) cited seminal ERIC articles or (3) mentioned ERIC in the title or abstract. Two co-authors independently …
Functional Connectivity Between The Amygdala And Prefrontal Cortex Underlies Processing Of Emotion Ambiguity, Sai Sun, Hongbo Yu, Rongjun Yu, Shuo Wang
Functional Connectivity Between The Amygdala And Prefrontal Cortex Underlies Processing Of Emotion Ambiguity, Sai Sun, Hongbo Yu, Rongjun Yu, Shuo Wang
2020-Current year OA Pubs
Processing facial expressions of emotion draws on a distributed brain network. In particular, judging ambiguous facial emotions involves coordination between multiple brain areas. Here, we applied multimodal functional connectivity analysis to achieve network-level understanding of the neural mechanisms underlying perceptual ambiguity in facial expressions. We found directional effective connectivity between the amygdala, dorsomedial prefrontal cortex (dmPFC), and ventromedial PFC, supporting both bottom-up affective processes for ambiguity representation/perception and top-down cognitive processes for ambiguity resolution/decision. Direct recordings from the human neurosurgical patients showed that the responses of amygdala and dmPFC neurons were modulated by the level of emotion ambiguity, and amygdala …
Myofascial Urinary Frequency Syndrome Is A Novel Syndrome Of Bothersome Lower Urinary Tract Symptoms Associated With Myofascial Pelvic Floor Dysfunction, A Lenore Ackerman, Nicholas J Jackson, Ashley T Caron, Melissa R Kaufman, Jonathan C Routh, Jerry L Lowder
Myofascial Urinary Frequency Syndrome Is A Novel Syndrome Of Bothersome Lower Urinary Tract Symptoms Associated With Myofascial Pelvic Floor Dysfunction, A Lenore Ackerman, Nicholas J Jackson, Ashley T Caron, Melissa R Kaufman, Jonathan C Routh, Jerry L Lowder
2020-Current year OA Pubs
This study describes a novel, distinct phenotype of urinary symptoms named "myofascial urinary frequency syndrome" (MUFS) present in one-third of individuals presenting with urinary frequency. In addition to a characteristic symptom constellation suggestive of myofascial dysfunction, MUFS subjects exhibit "persistency": a persistent feeling of needing to urinate regardless of urine volume. On examination, 97% of MUFS patients demonstrated pelvic floor hypertonicity with either global tenderness or myofascial trigger points, and 92% displayed evidence of impaired muscular relaxation, hallmarks of myofascial dysfunction. To confirm this symptom pattern was attributable to the pelvic floor musculature, we confirmed the presence of "persistency" in …
Factors Associated With Humeral Avulsion Of Glenohumeral Ligament Lesions In Patients With Anterior Shoulder Instability: An Analysis Of The Moon Shoulder Instability Cohort, Ryan D Freshman, Robert H Brophy, Matthew V Smith, Et Al.
Factors Associated With Humeral Avulsion Of Glenohumeral Ligament Lesions In Patients With Anterior Shoulder Instability: An Analysis Of The Moon Shoulder Instability Cohort, Ryan D Freshman, Robert H Brophy, Matthew V Smith, Et Al.
2020-Current year OA Pubs
BACKGROUND: Humeral avulsion of the glenohumeral ligament (HAGL) lesions are an uncommon cause of anterior glenohumeral instability and may occur in isolation or combination with other pathologies. As HAGL lesions are difficult to detect via magnetic resonance imaging (MRI) and arthroscopy, they can remain unrecognized and result in continued glenohumeral instability.
PURPOSE: To compare patients with anterior shoulder instability from a large multicenter cohort with and without a diagnosis of a HAGL lesion and identify preoperative physical examination findings, patient-reported outcomes, imaging findings, and surgical management trends associated with HAGL lesions.
STUDY DESIGN: Cross-sectional study; Level of evidence, 3.
METHODS: …
High-Throughput, Fluorescent-Aptamer-Based Measurements Of Steady-State Transcription Rates For The Mycobacterium Tuberculosis Rna Polymerase, Drake Jensen, Ana Ruiz Manzano, Maxwell Rector, Eric J Tomko, M Thomas Record, Eric A Galburt
High-Throughput, Fluorescent-Aptamer-Based Measurements Of Steady-State Transcription Rates For The Mycobacterium Tuberculosis Rna Polymerase, Drake Jensen, Ana Ruiz Manzano, Maxwell Rector, Eric J Tomko, M Thomas Record, Eric A Galburt
2020-Current year OA Pubs
The first step in gene expression is the transcription of DNA sequences into RNA. Regulation at the level of transcription leads to changes in steady-state concentrations of RNA transcripts, affecting the flux of downstream functions and ultimately cellular phenotypes. Changes in transcript levels are routinely followed in cellular contexts via genome-wide sequencing techniques. However, in vitro mechanistic studies of transcription have lagged with respect to throughput. Here, we describe the use of a real-time, fluorescent-aptamer-based method to quantitate steady-state transcription rates of the Mycobacterium tuberculosis RNA polymerase. We present clear controls to show that the assay specifically reports on promoter-dependent, …
A Multi- And Mixed-Method Adaptation Study Of A Patient-Centered Perioperative Mental Health Intervention Bundle, Joanna Abraham, Alicia Meng, Ana Baumann, Katherine J Holzer, Emily Lenard, Kenneth E Freedland, Eric J Lenze, Michael S Avidan, Mary C Politi
A Multi- And Mixed-Method Adaptation Study Of A Patient-Centered Perioperative Mental Health Intervention Bundle, Joanna Abraham, Alicia Meng, Ana Baumann, Katherine J Holzer, Emily Lenard, Kenneth E Freedland, Eric J Lenze, Michael S Avidan, Mary C Politi
2020-Current year OA Pubs
BACKGROUND: Anxiety and depression are common among older adults and can intensify during perioperative periods, but few mental health interventions are designed for older surgical patients' unique needs. As part of the feasibility trial, we developed and adapted a perioperative mental health (PMH) bundle for older patients comprised of behavioral activation (BA) and medication optimization (MO) to ameliorate anxiety and depressive symptoms before, during, and after cardiac, orthopedic, and oncologic surgery.
METHODS: We used mixed-methods including workshop studios with patients, caregivers, clinicians, researchers, and interventionists; intervention refinement and reflection meetings; patient case review meetings; intervention session audio-recordings and documentation forms; …
Pain And Itch Coding Mechanisms Of Polymodal Sensory Neurons, Changxiong Guo, Haowu Jiang, Cheng-Chiu Huang, Fengxian Li, William Olson, Weishan Yang, Michael Fleming, Guang Yu, George Hoekel, Wenqin Luo, Qin Liu
Pain And Itch Coding Mechanisms Of Polymodal Sensory Neurons, Changxiong Guo, Haowu Jiang, Cheng-Chiu Huang, Fengxian Li, William Olson, Weishan Yang, Michael Fleming, Guang Yu, George Hoekel, Wenqin Luo, Qin Liu
2020-Current year OA Pubs
Pain and itch coding mechanisms in polymodal sensory neurons remain elusive. MrgprD
A Disordered Region Controls Cbaf Activity Via Condensation And Partner Recruitment, Ajinkya Patil, Amy R Strom, Joao A Paulo, Clayton K Collings, Kiersten M Ruff, Min Kyung Shinn, Akshay Sankar, Kasey S Cervantes, Tobias Wauer, Jessica D St Laurent, Grace Xu, Lindsay A Becker, Steven P Gygi, Rohit V Pappu, Clifford P Brangwynne, Cigall Kadoch
A Disordered Region Controls Cbaf Activity Via Condensation And Partner Recruitment, Ajinkya Patil, Amy R Strom, Joao A Paulo, Clayton K Collings, Kiersten M Ruff, Min Kyung Shinn, Akshay Sankar, Kasey S Cervantes, Tobias Wauer, Jessica D St Laurent, Grace Xu, Lindsay A Becker, Steven P Gygi, Rohit V Pappu, Clifford P Brangwynne, Cigall Kadoch
2020-Current year OA Pubs
Intrinsically disordered regions (IDRs) represent a large percentage of overall nuclear protein content. The prevailing dogma is that IDRs engage in non-specific interactions because they are poorly constrained by evolutionary selection. Here, we demonstrate that condensate formation and heterotypic interactions are distinct and separable features of an IDR within the ARID1A/B subunits of the mSWI/SNF chromatin remodeler, cBAF, and establish distinct "sequence grammars" underlying each contribution. Condensation is driven by uniformly distributed tyrosine residues, and partner interactions are mediated by non-random blocks rich in alanine, glycine, and glutamine residues. These features concentrate a specific cBAF protein-protein interaction network and are …
Infants Exposed In Utero To Hurricane Maria Have Gut Microbiomes With Reduced Diversity And Altered Metabolic Capacity, Ai Zhang, David De Ángel Solá, Midnela Acevedo Flores, Lijuan Cao, Leran Wang, Josh G Kim, Phillip I Tarr, Barbara B Warner, Nicolás Rosario Matos, Leyao Wang
Infants Exposed In Utero To Hurricane Maria Have Gut Microbiomes With Reduced Diversity And Altered Metabolic Capacity, Ai Zhang, David De Ángel Solá, Midnela Acevedo Flores, Lijuan Cao, Leran Wang, Josh G Kim, Phillip I Tarr, Barbara B Warner, Nicolás Rosario Matos, Leyao Wang
2020-Current year OA Pubs
The gut microbiome is a potentially important mechanism that links prenatal disaster exposures with increased disease risks. However, whether prenatal disaster exposures are associated with alterations in the infant's gut microbiome remains unknown. We established a birth cohort study named Hurricane as the Origin of Later Alterations in Microbiome (HOLA) after Hurricane Maria struck Puerto Rico in 2017. We enrolled vaginally born Latino term infants aged 2 to 6 months, including
Volatile Profiling Distinguishes Streptococcus Pyogenes From Other Respiratory Streptococcal Species, Amalia Z Berna, Joseph A Merriman, Leah Mellett, Danealle K Parchment, Michael G Caparon, Audrey R Odom John
Volatile Profiling Distinguishes Streptococcus Pyogenes From Other Respiratory Streptococcal Species, Amalia Z Berna, Joseph A Merriman, Leah Mellett, Danealle K Parchment, Michael G Caparon, Audrey R Odom John
2020-Current year OA Pubs
Sore throat is one of the most common complaints encountered in the ambulatory clinical setting. Rapid, culture-independent diagnostic techniques that do not rely on pharyngeal swabs would be highly valuable as a point-of-care strategy to guide outpatient antibiotic treatment. Despite the promise of this approach, efforts to detect volatiles during oropharyngeal infection have yet been limited. In our research study, we sought to evaluate for specific bacterial volatile organic compounds (VOC) biomarkers in isolated cultures
Exchanging Words: Engaging The Challenges Of Sharing Qualitative Research Data, James M Dubois, Jessica Mozersky, Meredith Parsons, Heidi A Walsh, Annie Friedrich, Amy Pienta
Exchanging Words: Engaging The Challenges Of Sharing Qualitative Research Data, James M Dubois, Jessica Mozersky, Meredith Parsons, Heidi A Walsh, Annie Friedrich, Amy Pienta
2020-Current year OA Pubs
In January 2023, a new NIH policy on data sharing went into effect. The policy applies to both quantitative and qualitative research (QR) data such as data from interviews or focus groups. QR data are often sensitive and difficult to deidentify, and thus have rarely been shared in the United States. Over the past 5 y, our research team has engaged stakeholders on QR data sharing, developed software to support data deidentification, produced guidance, and collaborated with the ICPSR data repository to pilot the deposit of 30 QR datasets. In this perspective article, we share important lessons learned by addressing …
Cognitive Impact Of Multidomain Intervention And Omega 3 According To Blood Aβ42/40 Ratio: A Subgroup Analysis From The Randomized Mapt Trial, Julien Delrieu, Bruno Vellas, Sophie Guyonnet, Christelle Cantet, Vitaliy Ovod, Yan Li, James Bollinger, Randall Bateman, Sandrine Andrieu, Mapt/Dsa Group
Cognitive Impact Of Multidomain Intervention And Omega 3 According To Blood Aβ42/40 Ratio: A Subgroup Analysis From The Randomized Mapt Trial, Julien Delrieu, Bruno Vellas, Sophie Guyonnet, Christelle Cantet, Vitaliy Ovod, Yan Li, James Bollinger, Randall Bateman, Sandrine Andrieu, Mapt/Dsa Group
2020-Current year OA Pubs
BACKGROUND: In MAPT (Multidomain Alzheimer Preventive Trial), a cognitive effect of multidomain intervention (MI) was showed in non-demented subjects with positive amyloid PET. However, screening eligible patients for multidomain intervention by PET is difficult to generalize in real-world settings.
METHODS: MAPT study was a 3-year, randomized, placebo-controlled trial followed by a 2-year observational and optional extension. All participants were non-demented and randomly assigned (1:1:1:1) to the MI plus omega 3, MI plus placebo, omega 3 alone, or placebo alone group. The objectives were to assess the cognitive effect of MAPT interventions (omega 3 supplementation, MI, combined intervention) in non-demented subjects …
Inhibition Of Retinoic Acid Signaling In Proximal Tubular Epithelial Cells Protects Against Acute Kidney Injury, Min Yang, Lauren N. Lopez, Maya Brewer, Rachel Delgado, Anna Menshikh, Kelly Clouthier, Yuantee Zhu, Thitinee Vanichapol, Haichun Yang, Raymond C. Harris, Leslie Gewin, Craig R. Brooks, Alan J. Davidson, Mark De Caestecker
Inhibition Of Retinoic Acid Signaling In Proximal Tubular Epithelial Cells Protects Against Acute Kidney Injury, Min Yang, Lauren N. Lopez, Maya Brewer, Rachel Delgado, Anna Menshikh, Kelly Clouthier, Yuantee Zhu, Thitinee Vanichapol, Haichun Yang, Raymond C. Harris, Leslie Gewin, Craig R. Brooks, Alan J. Davidson, Mark De Caestecker
2020-Current year OA Pubs
Retinoic acid receptor (RAR) signaling is essential for mammalian kidney development but, in the adult kidney, is restricted to occasional collecting duct epithelial cells. We now show that there is widespread reactivation of RAR signaling in proximal tubular epithelial cells (PTECs) in human sepsis-associated acute kidney injury (AKI) and in mouse models of AKI. Genetic inhibition of RAR signaling in PTECs protected against experimental AKI but was unexpectedly associated with increased expression of the PTEC injury marker Kim1. However, the protective effects of inhibiting PTEC RAR signaling were associated with increased Kim1-dependent apoptotic cell clearance, or efferocytosis, and this was …
Development Of Novel Composite Data Quality Scores To Evaluate Facility-Level Data Quality In Electronic Data In Kenya: A Nationwide Retrospective Cohort Study, Beryne M Odeny, Anne Njoroge, Steve Gloyd, James P Hughes, Bradley H Wagenaar, Jacob Odhiambo, Lilly M Nyagah, Ayub Manya, Ooga Wesley Oghera, Nancy Puttkammer
Development Of Novel Composite Data Quality Scores To Evaluate Facility-Level Data Quality In Electronic Data In Kenya: A Nationwide Retrospective Cohort Study, Beryne M Odeny, Anne Njoroge, Steve Gloyd, James P Hughes, Bradley H Wagenaar, Jacob Odhiambo, Lilly M Nyagah, Ayub Manya, Ooga Wesley Oghera, Nancy Puttkammer
2020-Current year OA Pubs
BACKGROUND: In this evaluation, we aim to strengthen Routine Health Information Systems (RHIS) through the digitization of data quality assessment (DQA) processes. We leverage electronic data from the Kenya Health Information System (KHIS) which is based on the District Health Information System version 2 (DHIS2) to perform DQAs at scale. We provide a systematic guide to developing composite data quality scores and use these scores to assess data quality in Kenya.
METHODS: We evaluated 187 HIV care facilities with electronic medical records across Kenya. Using quarterly, longitudinal KHIS data from January 2011 to June 2018 (total N = 30 quarters), …
The Herbicide Glyphosate Inhibits Hippocampal Long-Term Potentiation And Learning Through Activation Of Pro-Inflammatory Signaling, Yukitoshi Izumi, Kazuko A O'Dell, Charles F Zorumski
The Herbicide Glyphosate Inhibits Hippocampal Long-Term Potentiation And Learning Through Activation Of Pro-Inflammatory Signaling, Yukitoshi Izumi, Kazuko A O'Dell, Charles F Zorumski
2020-Current year OA Pubs
Glyphosate, a herbicide marketed as Roundup, is widely used but there are concerns this exposure could impair cognitive function. In the CA1 region of rat hippocampal slices, we investigated whether glyphosate alters synaptic transmission and long-term potentiation (LTP), a cellular model of learning and memory. Our hypothesis is that glyphosate alters neuronal function and impairs LTP induction via activation of pro-inflammatory processes. Roundup depressed excitatory synaptic potentials(EPSPs) in a dose-dependent manner with complete suppression at 2000 mg/L. At concentrations ≤ 20 mg/L Roundup did not affect basal transmission, but 4 mg/L Roundup administered for 30 min inhibited LTP induction. Acute …
Early Resveratrol Treatment Mitigates Joint Degeneration And Dampens Pain In A Mouse Model Of Pseudoachondroplasia (Psach), Jacqueline T Hecht, Alka C Veerisetty, Debabrata Patra, Mohammad G Hossain, Frankie Chiu, Claire Mobed, Francis H Gannon, Karen L Posey
Early Resveratrol Treatment Mitigates Joint Degeneration And Dampens Pain In A Mouse Model Of Pseudoachondroplasia (Psach), Jacqueline T Hecht, Alka C Veerisetty, Debabrata Patra, Mohammad G Hossain, Frankie Chiu, Claire Mobed, Francis H Gannon, Karen L Posey
2020-Current year OA Pubs
Pseudoachondroplasia (PSACH), a severe dwarfing condition associated with early-onset joint degeneration and lifelong joint pain, is caused by mutations in cartilage oligomeric matrix protein (COMP). The mechanisms underlying the mutant-COMP pathology have been defined using the MT-COMP mouse model of PSACH that has the common D469del mutation. Mutant-COMP protein does not fold properly, and it is retained in the rough endoplasmic reticulum (rER) of chondrocytes rather than being exported to the extracellular matrix (ECM), driving ER stress that stimulates oxidative stress and inflammation, driving a self-perpetuating cycle. CHOP (ER stress signaling protein) and TNFα inflammation drive high levels of mTORC1 …
Molecular Regulation Of Neutrophil Swarming In Health And Disease: Lessons From The Phagocyte Oxidase, Zhimin Song, Sourav Bhattacharya, Regina A Clemens, Mary C Dinauer
Molecular Regulation Of Neutrophil Swarming In Health And Disease: Lessons From The Phagocyte Oxidase, Zhimin Song, Sourav Bhattacharya, Regina A Clemens, Mary C Dinauer
2020-Current year OA Pubs
Neutrophil swarming is a complex coordinated process in which neutrophils sensing pathogen or damage signals are rapidly recruited to sites of infections or injuries. This process involves cooperation between neutrophils where autocrine and paracrine positive-feedback loops, mediated by receptor/ligand pairs including lipid chemoattractants and chemokines, amplify localized recruitment of neutrophils. This review will provide an overview of key pathways involved in neutrophil swarming and then discuss the cell intrinsic and systemic mechanisms by which NADPH oxidase 2 (NOX2) regulates swarming, including modulation of calcium signaling, inflammatory mediators, and the mobilization and production of neutrophils. We will also discuss mechanisms by …
Endothelial Cells Are A Key Target Of Ifn-G During Response To Combined Pd-1/Ctla-4 Icb Treatment In A Mouse Model Of Bladder Cancer, Sharon L Freshour, Timothy H-P Chen, Bryan Fisk, Haolin Shen, Matthew Mosior, Zachary L Skidmore, Catrina Fronick, Jennifer K Bolzenius, Obi L Griffith, Vivek K Arora, Malachi Griffith
Endothelial Cells Are A Key Target Of Ifn-G During Response To Combined Pd-1/Ctla-4 Icb Treatment In A Mouse Model Of Bladder Cancer, Sharon L Freshour, Timothy H-P Chen, Bryan Fisk, Haolin Shen, Matthew Mosior, Zachary L Skidmore, Catrina Fronick, Jennifer K Bolzenius, Obi L Griffith, Vivek K Arora, Malachi Griffith
2020-Current year OA Pubs
To explore mechanisms of response to combined PD-1/CTLA-4 immune checkpoint blockade (ICB) treatment in individual cell types, we generated scRNA-seq using a mouse model of invasive urothelial carcinoma with three conditions: untreated tumor, treated tumor, and tumor treated after CD4
High-Dimensional Deconstruction Of Pancreatic Cancer Identifies Tumor Microenvironmental And Developmental Stemness Features That Predict Survival, Erik P Storrs, Prathamesh Chati, Abul Usmani, Ian Sloan, Bradley A Krasnick, Peter K Harris, Chloe M Sachs, Faridi Qaium, Chris Wetzel, S Peter Goedegebuure, Thomas Hollander, Hephzibah Anthony, Jennifer Ponce, Shahed Badiyan, Hyun Kim, David G Denardo, Gabriel D Lang, Natalie D Cosgrove, Vladimir M Kushnir, Dayna S Early, Kian-Huat Lim, William G Hawkins, Li Ding, Ryan C Fields, Koushik K Das, Aadel A Chaudhuri, Et Al.
High-Dimensional Deconstruction Of Pancreatic Cancer Identifies Tumor Microenvironmental And Developmental Stemness Features That Predict Survival, Erik P Storrs, Prathamesh Chati, Abul Usmani, Ian Sloan, Bradley A Krasnick, Peter K Harris, Chloe M Sachs, Faridi Qaium, Chris Wetzel, S Peter Goedegebuure, Thomas Hollander, Hephzibah Anthony, Jennifer Ponce, Shahed Badiyan, Hyun Kim, David G Denardo, Gabriel D Lang, Natalie D Cosgrove, Vladimir M Kushnir, Dayna S Early, Kian-Huat Lim, William G Hawkins, Li Ding, Ryan C Fields, Koushik K Das, Aadel A Chaudhuri, Et Al.
2020-Current year OA Pubs
Numerous cell states are known to comprise the pancreatic ductal adenocarcinoma (PDAC) tumor microenvironment (TME). However, the developmental stemness and co-occurrence of these cell states remain poorly defined. Here, we performed single-cell RNA sequencing (scRNA-seq) on a cohort of treatment-naive PDAC time-of-diagnosis endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) samples (n = 25). We then combined these samples with surgical resection (n = 6) and publicly available samples to increase statistical power (n = 80). Following annotation into 25 distinct cell states, cells were scored for developmental stemness, and a customized version of the Ecotyper tool was used to identify communities …
Burosumab Vs Phosphate/Active Vitamin D In Pediatric X-Linked Hypophosphatemia: A Subgroup Analysis By Dose Level, Erik A Imel, Michael P Whyte, Andrew Biggin, Et Al.
Burosumab Vs Phosphate/Active Vitamin D In Pediatric X-Linked Hypophosphatemia: A Subgroup Analysis By Dose Level, Erik A Imel, Michael P Whyte, Andrew Biggin, Et Al.
2020-Current year OA Pubs
CONTEXT: In an open-label, randomized, controlled, phase 3 trial in 61 children aged 1 to 12 years with X-linked hypophosphatemia (XLH), burosumab improved rickets vs continuing conventional therapy with active vitamin D and phosphate.
OBJECTIVE: We conducted an analysis to determine whether skeletal responses differed when switching to burosumab vs continuing higher or lower doses of conventional therapy.
METHODS: Conventional therapy dose groups were defined as higher-dose phosphate [greater than 40 mg/kg] (HPi), lower-dose phosphate [40 mg/kg or less] (LPi), higher-dose alfacalcidol [greater than 60 ng/kg] or calcitriol [greater than 30 ng/kg] (HD), and lower-dose alfacalcidol [60 ng/kg or less] …
Extrinsic And Intrinsic Preanalytical Variables Affecting Liquid Biopsy In Cancer, Syeda Maheen Batool, Siddarth Rawal, Richard J Cote, Mark Watson, Et Al.
Extrinsic And Intrinsic Preanalytical Variables Affecting Liquid Biopsy In Cancer, Syeda Maheen Batool, Siddarth Rawal, Richard J Cote, Mark Watson, Et Al.
2020-Current year OA Pubs
Liquid biopsy, through isolation and analysis of disease-specific analytes, has evolved as a promising tool for safe and minimally invasive diagnosis and monitoring of tumors. It also has tremendous utility as a companion diagnostic allowing detection of biomarkers in a range of cancers (lung, breast, colon, ovarian, brain). However, clinical implementation and validation remains a challenge. Among other stages of development, preanalytical variables are critical in influencing the downstream cellular and molecular analysis of different analytes. Although considerable progress has been made to address these challenges, a comprehensive assessment of the impact on diagnostic parameters and consensus on standardized and …
Macrocephaly And Developmental Delay Caused By Missense Variants In Rab5c, Klaas Koop, Weimin Yuan, Bo Zhang, Zachary D Dawson, Anika Lindsey, Huiyan Huang, Dustin Baldridge, Gary A Silverman, Stephen C Pak, Tim Schedl, Et Al.
Macrocephaly And Developmental Delay Caused By Missense Variants In Rab5c, Klaas Koop, Weimin Yuan, Bo Zhang, Zachary D Dawson, Anika Lindsey, Huiyan Huang, Dustin Baldridge, Gary A Silverman, Stephen C Pak, Tim Schedl, Et Al.
2020-Current year OA Pubs
Rab GTPases are important regulators of intracellular vesicular trafficking. RAB5C is a member of the Rab GTPase family that plays an important role in the endocytic pathway, membrane protein recycling and signaling. Here we report on 12 individuals with nine different heterozygous de novo variants in RAB5C. All but one patient with missense variants (n = 9) exhibited macrocephaly, combined with mild-to-moderate developmental delay. Patients with loss of function variants (n = 2) had an apparently more severe clinical phenotype with refractory epilepsy and intellectual disability but a normal head circumference. Four missense variants were investigated experimentally. In vitro biochemical …
Prostate Cancer Immunotherapy: Improving Clinical Outcomes With A Multi-Pronged Approach, Dhivya Sridaran, Elliot Bradshaw, Carl Deselm, Russell Pachynski, Kiran Mahajan, Nupam P Mahajan
Prostate Cancer Immunotherapy: Improving Clinical Outcomes With A Multi-Pronged Approach, Dhivya Sridaran, Elliot Bradshaw, Carl Deselm, Russell Pachynski, Kiran Mahajan, Nupam P Mahajan
2020-Current year OA Pubs
Cancer immunotherapy has gained traction in recent years owing to remarkable tumor clearance in some patients. Despite the notable success of immune checkpoint blockade (ICB) in multiple malignancies, engagement of the immune system for targeted prostate cancer (PCa) therapy is still in its infancy. Multiple factors contribute to limited response, including the heterogeneity of PCa, the cold tumor microenvironment, and a low number of neoantigens. Significant effort is being invested in improving immune-based PCa therapies. This review is a summary of the status of immunotherapy in treating PCa, with a discussion of multiple immune modalities, including vaccines, adoptively transferred T …
The Liquid Biopsy Consortium: Challenges And Opportunities For Early Cancer Detection And Monitoring, Syeda Maheen Batool, Mark Watson, Rebecca Aft, Siddarth Rawal, Richard J Cote, Et Al.
The Liquid Biopsy Consortium: Challenges And Opportunities For Early Cancer Detection And Monitoring, Syeda Maheen Batool, Mark Watson, Rebecca Aft, Siddarth Rawal, Richard J Cote, Et Al.
2020-Current year OA Pubs
The emerging field of liquid biopsy stands at the forefront of novel diagnostic strategies for cancer and other diseases. Liquid biopsy allows minimally invasive molecular characterization of cancers for diagnosis, patient stratification to therapy, and longitudinal monitoring. Liquid biopsy strategies include detection and monitoring of circulating tumor cells, cell-free DNA, and extracellular vesicles. In this review, we address the current understanding and the role of existing liquid-biopsy-based modalities in cancer diagnostics and monitoring. We specifically focus on the technical and clinical challenges associated with liquid biopsy and biomarker development being addressed by the Liquid Biopsy Consortium, established through the National …
Focused Ultrasound-Mediated Delivery Of Anti-Programmed Cell Death-Ligand 1 Antibody To The Brain Of A Porcine Model, Siaka Fadera, Chinwendu Chukwu, Andrew H Stark, Yimei Yue, Lu Xu, Chih-Yen Chien, Jinyun Yuan, Hong Chen
Focused Ultrasound-Mediated Delivery Of Anti-Programmed Cell Death-Ligand 1 Antibody To The Brain Of A Porcine Model, Siaka Fadera, Chinwendu Chukwu, Andrew H Stark, Yimei Yue, Lu Xu, Chih-Yen Chien, Jinyun Yuan, Hong Chen
2020-Current year OA Pubs
Immune checkpoint inhibitor (ICI) therapy has revolutionized cancer treatment by leveraging the body's immune system to combat cancer cells. However, its effectiveness in brain cancer is hindered by the blood-brain barrier (BBB), impeding the delivery of ICIs to brain tumor cells. This study aimed to assess the safety and feasibility of using focused ultrasound combined with microbubble-mediated BBB opening (FUS-BBBO) to facilitate trans-BBB delivery of an ICI, anti-programmed cell death-ligand 1 antibody (aPD-L1) to the brain of a large animal model. In a porcine model, FUS sonication of targeted brain regions was performed after intravenous microbubble injection, which was followed …
Direct Cost Variance Analysis Of Peroral Endoscopic Myotomy Vs Heller Myotomy For Management Of Achalasia: A Tertiary Referral Center Experience, Syedreza Ali Haider, Gregory S Bills, C Prakash Gyawali, Passisd Laoveeravat, Jordan Miller, Samir Softic, Mihir S Wagh, Moamen Gabr
Direct Cost Variance Analysis Of Peroral Endoscopic Myotomy Vs Heller Myotomy For Management Of Achalasia: A Tertiary Referral Center Experience, Syedreza Ali Haider, Gregory S Bills, C Prakash Gyawali, Passisd Laoveeravat, Jordan Miller, Samir Softic, Mihir S Wagh, Moamen Gabr
2020-Current year OA Pubs
BACKGROUND: Laparoscopic Heller myotomy (LHM) has been the traditional surgical treatment for achalasia. Recently, peroral endoscopic myotomy (POEM) has demonstrated similar clinical outcomes with shorter procedure times. Studies comparing the direct cost-effectiveness of POEM
AIM: To compare costs of POEM
METHODS: This retrospective chart review aimed to compare the outcomes and cost of clinical care between patients who underwent POEM and LHM procedures for achalasia. The study was conducted at a tertiary academic center from January 2019 to December 2020. Clinical outcomes, including post-operative Eckardt scores and adverse events, were assessed and compared between the two groups. Direct cost variance …
Dual Task Measures In Older Adults With And Without Cognitive Impairment: Response To Simultaneous Cognitive-Exercise Training And Minimal Clinically Important Difference Estimates, I-Chen Chen, I-Ching Chuang, Ku-Chou Chang, Chih-Hung Chang, Ching-Yi Wu
Dual Task Measures In Older Adults With And Without Cognitive Impairment: Response To Simultaneous Cognitive-Exercise Training And Minimal Clinically Important Difference Estimates, I-Chen Chen, I-Ching Chuang, Ku-Chou Chang, Chih-Hung Chang, Ching-Yi Wu
2020-Current year OA Pubs
BACKGROUND: Responsiveness and minimal clinically important difference (MCID) are critical indices to understand whether observed improvement represents a meaningful improvement after intervention. Although simultaneous cognitive-exercise training (SCET; e.g., performing memory tasks while cycling) has been suggested to enhance the cognitive function of older adults, responsiveness and MCID have not been established. Hence, we aimed to estimate responsiveness and MCIDs of two dual task performance involving cognition and hand function in older adults with and without cognitive impairment and to compare the differences in responsiveness and MCIDs of the two dual task performance between older adults with and without cognitive impairment. …
Time- And Region-Dependent Blood-Brain Barrier Impairment In A Rat Model Of Organophosphate-Induced Status Epilepticus, Pedro N Bernardino, Brad A Hobson, Sydney L Huddleston, Peter M Andrew, Jeremy A Macmahon, Naomi H Saito, Valerie A Porter, Donald A Bruun, Danielle J Harvey, Joel R Garbow, Angie Gelli, Abhijit J Chaudhari, Pamela J Lein
Time- And Region-Dependent Blood-Brain Barrier Impairment In A Rat Model Of Organophosphate-Induced Status Epilepticus, Pedro N Bernardino, Brad A Hobson, Sydney L Huddleston, Peter M Andrew, Jeremy A Macmahon, Naomi H Saito, Valerie A Porter, Donald A Bruun, Danielle J Harvey, Joel R Garbow, Angie Gelli, Abhijit J Chaudhari, Pamela J Lein
2020-Current year OA Pubs
Acute organophosphate (OP) intoxication can trigger seizures that progress to status epilepticus (SE), and survivors often develop chronic morbidities, including spontaneous recurrent seizures (SRS). The pathogenic mechanisms underlying OP-induced SRS are unknown, but increased BBB permeability is hypothesized to be involved. Previous studies reported BBB leakage following OP-induced SE, but key information regarding time and regional distribution of BBB impairment during the epileptogenic period is missing. To address this data gap, we characterized the spatiotemporal progression of BBB impairment during the first week post-exposure in a rat model of diisopropylfluorophosphate-induced SE, using MRI and albumin immunohistochemistry. Increased BBB permeability, which …