Medical Specialties Commons^™

Novel Oppositional Defiant Disorder Or Conduct Disorder 24 Months After Traumatic Brain Injury In Children And Adolescents, Daniel S Lowet, Florin Vaida, John R Hesselink, Linda Ewing-Cobbs, Russell J Schachar, Sandra B Chapman, Erin D Bigler, Elisabeth A Wilde, Ann E Saunders, Tony T Yang, Olga Tymofiyeva, Mingxiong Huang, Jeffrey E Max

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Objective: The authors sought to identify predictive factors of new-onset or novel oppositional defiant disorder or conduct disorder assessed 24 months after traumatic brain injury (TBI).

Methods: Children ages 5 to 14 years who had experienced TBI were recruited from consecutive hospital admissions. Soon after injury, participants were assessed for preinjury characteristics, including psychiatric disorders, socioeconomic status (SES), psychosocial adversity, and family function, and the presence and location of lesions were documented by MRI. Psychiatric outcomes, including novel oppositional defiant disorder or conduct disorder, were assessed 24 months after injury.

Results: Of the children without preinjury oppositional defiant disorder, conduct …

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

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INTRODUCTION/OBJECTIVE: Chronic pain disorders affect about 20% of adults in the United States, and it disproportionately affects individuals living in the neighborhoods of extreme socioeconomic disadvantage. In many instances, chronic pain has been noted to arise from an aggregation of multiple risk factors and events. Therefore, it is of importance to recognize the modifiable risk factors. The aim of this study was to investigate the comorbid medical conditions and risk factors associated with chronic pain disorders in patients aged 65 years and older.

METHODS: Our team retrospectively reviewed medical records of elderly patients (65 years and older) who were evaluated …

Real-World Analysis Of Safety And Efficacy Of Car T-Cell Therapy In Lymphoma Patients With Decreased Kidney Function, Omar Mamlouk, Paolo Strati, Lei Feng, Ryan Sun, Amy Ayers, Raphael E Steiner, Ranjit Nair, Christopher Flowers, Jeremy L Ramdial, Neeraj Saini, Samer A Srour, Richard E Champlin, Partow Kebriaei, Loretta J Nastoupil, Maria A Rodriguez, Elizabeth J Shpall, Yago Nieto, Jason Westin, Sattva S Neelapu, Sreedhar Mandayam, Sairah Ahmed

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No abstract provided.

Measurement Of 8-Hydroxy-2′-Deoxyguanosine In Serum And Cerebrospinal Fluid Of Horses With Neuroaxonal Degeneration And Other Causes Of Proprioceptive Ataxia, Megan Palmisano, Jeaneen Kulp, Susan Bender, Darko Stefanovski, Mary Robinson, Amy Johnson

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BACKGROUND: Eight-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of oxidative damage evaluated in human neurodegenerative disease, has potential to correlate with postmortem diagnosis of neuroaxonal dystrophy/degenerative myeloencephalopathy (NAD/DM) in horses.

HYPOTHESIS: We hypothesized that 8-OHdG will be higher in CSF and serum from NAD/DM horses compared with horses with other neurologic diseases (CVSM, EPM) and a control group of neurologically normal horses. We also hypothesized that 8-OHdG will be higher in CSF compared with serum from NAD/DM horses.

ANIMALS: Fifty client-owned horses with postmortem diagnoses: 20 NAD/DM, 10 CVSM, 10 EPM, and 10 control horses. Serum and CSF samples were obtained between November …

Human Minor Salivary Glands: A Readily Available Source Of Salivary Stem/Progenitor Cells For Regenerative Applications, Caitlynn M L Barrows, Danielle Wu, Simon Young, Mary C Farach-Carson

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Resident stem/progenitor cells within the secretory salivary glands offer a potential therapeutic resource for use in the regeneration of salivary glands needed to restore saliva production in patients with chronic xerostomia, or dry mouth. Methods were developed previously to isolate human stem/progenitor cells (hS/PCs) from major salivary glands (parotid/submandibular). Abundant minor salivary glands located in readily accessible locations in the oral cavity and lip could provide an additional valuable therapeutic resource. An advantage of this cell resource is that these minor glands about the size of grape seeds can be harvested from healthy donors using minimally invasive surgical procedures. The …

Promising Response Of Olaparib In Patient With Germline Atm-Mutated Metastatic Gastric Cancer, Kok Hoe Chan, Darius Rutazanaa, Curtis Wray, Nirav Thosani, Victor Yang, Putao Cen

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Gastric cancer ranks as the fifth leading cause of global cancer incidences, exhibiting varied prevalence influenced by geographical, ethnic, and lifestyle factors, as well as Helicobacter pylori infection. The ATM gene on chromosome 11q22 is vital for genomic stability as an initiator of the DNA damage response, and mutations in this gene have been associated with various cancers. Poly ADP-ribose polymerase (PARP) inhibitors, such as olaparib, have shown efficacy in cancers with homologous recombination repair deficiencies, notably in those with ATM mutations. Here, we present a case of a 66-year-old patient with germline ATM-mutated metastatic gastric cancer with very high …

Microstructural Organization Of Distributed White Matter Associated With Fine Motor Control In Us Service Members With Mild Traumatic Brain Injury, Benjamin S C Wade, David F Tate, Eamonn Kennedy, Erin D Bigler, Gerald E York, Brian A Taylor, Maya Troyanskaya, Elizabeth S Hovenden, Naomi Goodrich-Hunsaker, Mary R Newsome, Emily L Dennis, Tracy Abildskov, Mary Jo Pugh, William C Walker, Kimbra Kenney, Aaron Betts, Robert Shih, Robert C Welsh, Elisabeth A Wilde

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Mild traumatic brain injury (mTBI) is the most common form of brain injury. While most individuals recover from mTBI, roughly 20% experience persistent symptoms, potentially including reduced fine motor control. We investigate relationships between regional white matter organization and subcortical volumes associated with performance on the Grooved Pegboard (GPB) test in a large cohort of military Service Members and Veterans (SM&Vs) with and without a history of mTBI(s). Participants were enrolled in the Long-term Impact of Military-relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium. SM&Vs with a history of mTBI(s) (n = 847) and without mTBI (n = …

Practical Quality Improvement Changes For A Low-Resourced Pediatric Unit, Phoebe H Yager, Kevin Mary Callans, Aubrey Samost-Williams, Jose A Bonilla, Luis J G Flores, Susana C A Hasbun, Angel E A Rodríguez, Alejandra B A Cárdenas, Alexia M L Núñez, Asitha D L Jayawardena, Evelyn J Zablah, Christopher J Hartnick

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Background: This work describes a sustainable and replicable initiative to optimize multi-disciplinary care and uptake of clinical best practices for patients in a pediatric intensive care unit in Low/Middle Income Countries and to understand the various factors that may play a role in the reduction in child mortality seen after implementation of the Quality Improvement Initiative.

Methods: This was a longitudinal assessment of a quality improvement program with the primary outcome of intubated pediatric patient mortality. The program was assessed 36 months following implementation of the quality improvement intervention using a t-test with linear regression to control for co-variates. …

Persistent Microbial Infections And Idiopathic Pulmonary Fibrosis – An Insight Into Non-Typeable Haemophilus Influenza Pathogenesis, Anthony Shadid, Haydn E Rich, Hunter Devaughn, Aleksey Domozhirov, Marie-Françoise Doursout, Tingting Weng-Mills, Kristin L Eckel-Mahan, Harry Karmouty-Quintana, Marcos I Restrepo, Pooja Shivshankar

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Interstitial lung disease (ILD) is characterized by chronic inflammation and scarring of the lungs, of which idiopathic pulmonary fibrosis (IPF) is the most devastating pathologic form. Idiopathic pulmonary fibrosis pathogenesis leads to loss of lung function and eventual death in 50% of patients, making it the leading cause of ILD-associated mortality worldwide. Persistent and subclinical microbial infections are implicated in the acute exacerbation of chronic lung diseases. However, while epidemiological studies have highlighted pollutants, gastric aspirate, and microbial infections as major causes for the progression and exacerbation of IPF, the role of persistent microbial infections in the pathogenesis of IPF …

Combining Neuroimaging And Brain Stimulation To Test Alternative Causal Pathways For Nicotine Addiction In Schizophrenia, Xiaoming Du, Fow-Sen Choa, Joshua Chiappelli, Heather Bruce, Mark Kvarta, Ann Summerfelt, Yizhou Ma, William T Regenold, Kevin Walton, George F Wittenberg, Stephanie Hare, Si Gao, Andrew Van Der Vaart, Zhiwei Zhao, Shuo Chen, Peter Kochunov, L Elliot Hong

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The smoking rate is high in patients with schizophrenia. Brain stimulation targeting conventional brain circuits associated with nicotine addiction has also yielded mixed results. We aimed to identify alternative circuitries associated with nicotine addiction in both the general population and schizophrenia, and then test whether modulation of such circuitries may alter nicotine addiction behaviors in schizophrenia. In Study I of 40 schizophrenia smokers and 51 non-psychiatric smokers, cross-sectional neuroimaging analysis identified resting state functional connectivity (rsFC) between the dorsomedial prefrontal cortex (dmPFC) and multiple extended amygdala regions to be most robustly associated with nicotine addiction severity in healthy controls and …

Refinement Of An Emergency Department-Based, Advance Care Planning Intervention For Patients With Cognitive Impairment And Their Caregivers, Kei Ouchi, Christopher Joshi, Jenson Kaithamattam, Seth A Gale, Gad A Marshall, Alison Pietras, Wei Wang, Edward W Boyer, James A Tulsky, Susan D Block, Dorene Rentz, Mara A Schonberg

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Background and objectives: Advance care planning (ACP) conversations are important to provide goal-concordant care (i.e., the care that matches the patient's previously stated goals) near end of life. While 31% of older adults presenting to the emergency department (ED) have dementia, only 39% have previously had ACP conversations. We refined and piloted an ED-based, motivational interview designed to stimulate ACP conversations (ED GOAL) for patients living with cognitive impairment and their caregivers.

Research design and methods: We systematically refined ED GOAL and then conducted an acceptability study in an urban, academic medical center. We prospectively enrolled adults aged 50+ with …

Editorial: Immunological Aspects Of Emerging And Re-Emerging Zoonoses, Wei Wang, Jingxin Li, Yuejin Liang, Wenping Gong

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No abstract provided.

Unicentric Castleman Disease: Illustration Of Its Morphologic Spectrum And Review Of The Differential Diagnosis, Siba El Hussein, Andrew G Evans, Hong Fang, Wei Wang, L Jeffrey Medeiros

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Context: Unicentric Castleman disease (UCD) is a dynamic entity with a wide spectrum of morphologic findings. UCD can be further subdivided into hyaline-vascular and mixed/plasmacytic variants. Hyaline-vascular UCD has both follicular and interfollicular (stromal) changes, and occasionally these lesions show a skewed representation of either the follicular or stromal compartments. Plasmacytosis is usually minimal in the hyaline-vascular variant. The mixed/plasmacytic variant of UCD is composed of sheets of plasma cells often associated with a variable number of follicles with regressive changes.

Objective: To illustrate the differential diagnosis of UCD, as it is quite broad and includes lymphomas, plasma cell neoplasms, …

Absolute Concentration Estimation Of Covid-19 Convalescent And Post-Vaccination Igg Antibodies, Melvin E Klegerman, Tao Peng, Ira Seferovich, Mohammad H Rahbar, Manouchehr Hessabi, Amirali Tahanan, Audrey Wanger, Carolyn Z Grimes, Luis Z Ostrosky-Zeichner, Kent Koster, Jeffrey D Cirillo, Dinuka Abeydeera, Steve De Lira, David D Mcpherson

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Soon after commencement of the SARS-CoV-2 disease outbreak of 2019 (COVID-19), it became evident that the receptor-binding domain of the viral spike protein is the target of neutralizing antibodies that comprise a critical element of protective immunity to the virus. This study addresses the relative lack of information regarding actual antibody concentrations and binding affinities in convalescent plasma (CP) samples from COVID-19 patients and extends these analyses to post-vaccination (PV) samples to estimate protective IgG antibody (Ab) levels. A direct enzyme-linked immunosorbent assay (ELISA) was used to measure IgG anti-spike protein (SP) antibodies (Abs) relative to human chimeric spike S1 …

Highly Variable Timing Renders Immunotherapy Efficacy And Toxicity Impractical Biomarkers Of One Another In Clinical Practice, Mitchell S Von Itzstein, Yuqiu Yang, Yiqing Wang, David Hsiehchen, Thomas Y Sheffield, Farjana Fattah, Vinita Popat, Murtaza Ahmed, Jade Homsi, Jonathan E Dowell, Sawsan Rashdan, Jay Lohrey, Hans J Hammers, Randall S Hughes, Tao Wang, Yang Xie, David E Gerber

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Background: A useful clinical biomarker requires not only association but also a consistent temporal relationship. For instance, chemotherapy-induced neutropenia and epidermal growth-factor inhibitor-related acneiform rash both occur within weeks of treatment initiation, thereby providing information prior to efficacy assessment. Although immune checkpoint inhibitor (ICI)-associated immune-related adverse events (irAE) have been associated with therapeutic benefit, irAE may have delayed and highly variable onset. To determine whether ICI efficacy and irAE could serve as clinically useful biomarkers for predicting each other, we determined the temporal relationship between initial efficacy assessment and irAE onset in a diverse population treated with ICI.

Methods: Using …

Optimizing Delirium Care In The Era Of Age-Friendly Health System, Min Ji Kwak, Sharon K Inouye, Donna M Fick, Alice Bonner, Terry Fulmer, Emily Carter, Victor Tabbush, Kerri Maya, Nicholas Reed, Christine Waszynski, Esther S Oh

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Delirium is a significant geriatric condition associated with adverse clinical and economic outcomes. The cause of delirium is usually multifactorial, and person-centered multicomponent approaches for proper delirium management are required. In 2017, the John A. Hartford Foundation and the Institute for Healthcare Improvement (IHI) launched a national initiative, Age-Friendly Health System (AFHS), promoting the use of a framework called 4Ms (what matters, medication, mentation, and mobility). The 4Ms framework's primary goal is to provide comprehensive and practical person-centered care for older adults and it aligns with the core concepts of optimal delirium management. In this special article, we demonstrate how …

An Image-Driven Micromechanical Approach To Characterize Multiscale Remodeling In Infarcted Myocardium, Emilio A Mendiola, Sunder Neelakantan, Qian Xiang, Shuda Xia, Jianyi Zhang, Vahid Serpooshan, Peter Vanderslice, Reza Avazmohammadi

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Myocardial infarction (MI) is accompanied by the formation of a fibrotic scar in the left ventricle (LV) and initiates significant alterations in the architecture and constituents of the LV free wall (LVFW). Previous studies have shown that LV adaptation is highly individual, indicating that the identification of remodeling mechanisms post-MI demands a fully subject-specific approach that can integrate a host of structural alterations at the fiber-level to changes in bulk biomechanical adaptation at the tissue-level. We present an image-driven micromechanical approach to characterize remodeling, assimilating new biaxial mechanical data, histological studies, and digital image correlation data within an in-silico framework …

Perceptions Of The Addictiveness Of Low-Nicotine Cigarettes Versus Typical Cigarettes And Exposure To Tobacco Industry-Sponsored Corrective Campaign, Onyema Greg Chido-Amajuoyi, Dale S Mantey, Efehi Igbinomwanhia, Onyinye Omega-Njemnobi, Henry Onyeaka, Robert K Yu, Israel Agaku, Sanjay Shete

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Background: In 2017, the U.S. Food and Drug Administration (FDA) announced a regulatory plan to reduce the nicotine content of cigarettes. This study examines the association of exposure to industry-sponsored corrective statements on perceptions of the addictiveness of low-nicotine cigarettes relative to typical cigarettes within the general US population.

Methods: The study comprised 4975 US adult respondents of the 2019 Health Information National Trends Survey (HINTS 5, Cycle 3). Multinomial logistic regression models were used to examine associations between exposure to tobacco industry corrective messages and perceptions of the addictiveness of low-nicotine cigarettes relative to typical cigarettes.

Results: In the …

Explainable Suicide Phenotyping From Initial Psychiatric Evaluation Notes Using Reasoning Large Language Models, Zehan Li, Wanjing Wang, Lokesh Shahani, Rodrigo M Vieira, Salih Selek, Jair Soares, Hongfang Liu, Ming Huang

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Clinical phenotyping is the process of extracting patient's observable symptoms and traits to better understand their disease condition. Suicide phenotyping focuses more on behavioral and cognitive characteristics, such as suicide ideation, attempt, and self-injury, to identify suicide risks and improve interventions. In this study, we leveraged the latest reasoning models, namely 4o, o1, and o3-mini, to perform note-level multi-label classification and reasoning generation tasks using previously annotated psychiatric evaluation notes from a safety-net psychiatric inpatient hospital in Harris County, Texas. Compared with the previously finetuned GPT-3.5 model, the out-of-box reasoning models prompted with in-context learning achieved comparable and better performance, …

Monet: A Database For Prediction Of Neoantigens Derived From Microsatellite Loci, Nan Deng, Krishna M Sinha, Eduardo Vilar

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BACKGROUND: Microsatellite instability (MSI) secondary to mismatch repair (MMR) deficiency is characterized by insertions and deletions (indels) in short DNA sequences across the genome. These indels can generate neoantigens, which are ideal targets for precision immune interception. However, current neoantigen databases lack information on neoantigens arising from coding microsatellites. To address this gap, we introduce The MicrOsatellite Neoantigen Discovery Tool (MONET).

METHOD: MONET identifies potential mutated tumor-specific neoantigens (neoAgs) by predicting frameshift mutations in coding microsatellite sequences of the human genome. Then MONET annotates these neoAgs with key features such as binding affinity, stability, expression, frequency, and potential pathogenicity using …

Are Published Cancer Care Trial Protocols With Traditional Chinese Medicine Interventions Concordant With Spirit-Tcm Extension 2018? A Scoping Review On Published Trial Protocols Between 2019 And 2022, Hezheng Lai, Peiying Yang, Xin Shelley Wang, David Lim, Anderson Lam, Yucong Shi, Yishi Huang, Xiaoshu Zhu

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BACKGROUND: The SPIRIT-TCM Extension 2018 was created to guide the design and reporting of Traditional Chinese Medicine (TCM) clinical trial protocols. This study aims to investigate the extent of concordance with this guideline in the relevant field of cancer care research.

METHODS: A scoping review of TCM cancer trial protocols published in English and Chinese since January 2019 was conducted. Five major academic databases (MEDLINE, EMBASE, CINAHL, CENTRAL, and China National Knowledge Infrastructure) were searched. Concordance with the SPIRIT-TCM Extension 2018 was assessed by descriptive analysis.

RESULTS: Fifty-three TCM cancer care trial protocols were identified, comprising 23 acupuncture, 26 Chinese …

Postmortem-Derived Ipsc Models In Substance Use Disorders Research, Emily Frances Mendez, Consuelo Walss-Bass

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No abstract provided.

Her4 And Egfr Activate Cell Signaling In Nrg1 Fusion-Driven Cancers: Implications For Her2-Her3-Specific Versus Pan-Her Targeting Strategies, Hibiki Udagawa, Monique B Nilsson, Jacqulyne P Robichaux, Junqin He, Alissa Poteete, Hong Jiang, Simon Heeke, Yasir Y Elamin, Yuji Shibata, Shingo Matsumoto, Kiyotaka Yoh, Shogo Okazaki, Takashi Masuko, Igor Odintsov, Romel Somwar, Marc Ladanyi, Koichi Goto, John V Heymach

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Introduction: NRG1 gene fusions are clinically actionable alterations identified in NSCLC and other tumors. Previous studies have reported that NRG1 fusions signal through HER2 and HER3 but, thus far, strategies targeting HER3 specifically or HER2-HER3 signaling have exhibited modest activity in patients with NSCLC bearing NRG1 fusions. Although NRG1 fusion proteins can bind HER4 in addition to HER3, the contribution of HER4 and other HER family members in NRG1 fusion-positive cancers is not fully understood.

Methods: We investigated the role of HER4 and EGFR-HER3 signaling in NRG1 fusion-positive cancers using Ba/F3 models engineered to express various HER family members in …

Investigation Of Autosegmentation Techniques On T2-Weighted Mri For Off-Line Dose Reconstruction In Mr-Linac Workflow For Head And Neck Cancers, Brigid A Mcdonald, Carlos E Cardenas, Nicolette O'Connell, Sara Ahmed, Mohamed A Naser, Kareem A Wahid, Jiaofeng Xu, Dan Thill, Raed J Zuhour, Shane Mesko, Alexander Augustyn, Samantha M Buszek, Stephen Grant, Bhavana V Chapman, Alexander F Bagley, Renjie He, Abdallah S R Mohamed, John Christodouleas, Kristy K Brock, Clifton D Fuller

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Background: In order to accurately accumulate delivered dose for head and neck cancer patients treated with the Adapt to Position workflow on the 1.5T magnetic resonance imaging (MRI)-linear accelerator (MR-linac), the low-resolution T2-weighted MRIs used for daily setup must be segmented to enable reconstruction of the delivered dose at each fraction.

Purpose: In this pilot study, we evaluate various autosegmentation methods for head and neck organs at risk (OARs) on on-board setup MRIs from the MR-linac for off-line reconstruction of delivered dose.

Methods: Seven OARs (parotid glands, submandibular glands, mandible, spinal cord, and brainstem) were contoured on 43 images by …

The Mir-17-92 Cluster In Cardiac Health And Disease, Yuhan Cao, Mingjie Zheng, Maham A Sewani, Jun Wang

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MicroRNAs (miRs) are small noncoding RNAs that play important roles in both physiological and pathological processes through post-transcriptional regulation. The miR-17-92 cluster includes six individual members: miR-17, miR-18a, miR-19a, miR-19b-1, miR-20a, and miR-92a-1. The miR-17-92 cluster has been extensively studied and reported to broadly function in cancer biology, immunology, neurology, pulmonology, and cardiology. This review focuses on its roles in heart development and cardiac diseases. We briefly introduce the nature of the miR-17-92 cluster and its crucial roles in both normal development and the pathogenesis of various diseases. We summarize the recent progress in understanding the versatile roles of miR-17-92 …

Pathologic Processing Of Lung Cancer Resection Specimens After Neoadjuvant Therapy, Annikka Weissferdt, Cheuk H Leung, Heather Lin, Boris Sepesi, William N William, Stephen G Swisher, Tina Cascone, J Jack Lee, Abujiang Pataer

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Neoadjuvant treatment of non-small cell lung cancer challenges the traditional processing of pathology specimens. Induction therapy before resection allows evaluation of the efficacy of neoadjuvant agents at the time of surgery. Many clinical trials use pathologic tumor response, measured as major pathologic response (MPR, ≤10% residual viable tumor [RVT]) or complete pathologic response (CPR, 0% RVT) as a surrogate of clinical efficacy. Consequently, accurate pathologic evaluation of RVT is crucial. However, pathologic assessment has not been uniform, which is particularly true for sampling of the primary tumor, which instead of the traditional processing, requires different tissue submission because the focus …

Computer-Aided Craniofacial Superimposition Validation Study: The Identification Of The Leaders And Participants Of The Polish-Lithuanian January Uprising (1863–1864), Rubén Martos, Rosario Guerra, Fernando Navarro, Michela Peruch, Kevin Neuwirth, Andrea Valsecchi, Rimantas Jankauskas, Oscar Ibáñez

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In 2017, a series of human remains corresponding to the executed leaders of the "January Uprising" of 1863-1864 were uncovered at the Upper Castle of Vilnius (Lithuania). During the archeological excavations, 14 inhumation pits with the human remains of 21 individuals were found at the site. The subsequent identification process was carried out, including the analysis and cross-comparison of post-mortem data obtained in situ and in the lab with ante-mortem data obtained from historical archives. In parallel, three anthropologists with diverse backgrounds in craniofacial identification and two students without previous experience attempted to identify 11 of these 21 individuals using …

Responsive Neurostimulation For People With Drug-Resistant Epilepsy And Autism Spectrum Disorder, Madeline C Fields, Christina Marsh, Onome Eka, Emily A Johnson, Lara V Marcuse, Churl-Su Kwon, James J Young, Maite Lavega-Talbott, Mohankumar Kurukumbi, Gretchen Von Allmen, John Zempel, Daniel Friedman, Nathalie Jette, Anuradha Singh, Ji Yeoun Yoo, Leah Blank, Fedor Panov, Saadi Ghatan

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PURPOSE: Individuals with autism spectrum disorder (ASD) have comorbid epilepsy at much higher rates than the general population, and about 30% will be refractory to medication. Patients with drug-resistant epilepsy (DRE) should be referred for surgical evaluation, yet many with ASD and DRE are not resective surgical candidates. The aim of this study was to examine the response of this population to the responsive neurostimulator (RNS) System.

METHODS: This multicenter study evaluated patients with ASD and DRE who underwent RNS System placement. Patients were included if they had the RNS System placed for 1 year or more. Seizure reduction and …

Single-Molecule Fret Analyses Of Nmda Receptors, Ryan J Durham, Vasanthi Jayaraman

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Single-molecule fluorescence resonance energy transfer (smFRET) enables the real-time observation of conformational changes in a single protein molecule of interest. These observations are achieved by attaching fluorophores to proteins of interest in a site-specific manner and investigating the FRET between the fluorophores. Here we describe the method wherein the FRET is studied by adhering the protein molecules to a slide using affinity-based interactions and measuring the fluorophores' fluorescence intensity from a single molecule over time. The resulting information can be used to derive distance values for a point-to-point measurement within a protein or to calculate kinetic transition rates between various …

Tissue Transglutaminase: A Multifunctional And Multisite Regulator In Health And Disease, Zhouzhou Yao, Yuhua Fan, Lizhen Lin, Rodney E Kellems, Yang Xia

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Tissue transglutaminase (TG2) is a widely distributed multifunctional protein involved in a broad range of cellular and metabolic functions carried out in a variety of cellular compartments. In addition to transamidation, TG2 also functions as a Gα signaling protein, a protein disulfide isomerase (PDI), a protein kinase, and a scaffolding protein. In the nucleus, TG2 modifies histones and transcription factors. The PDI function catalyzes the trimerization and activation of heat shock factor-1 in the nucleus and regulates the oxidation state of several mitochondrial complexes. Cytosolic TG2 modifies proteins by the addition of serotonin or other primary amines and in this …