Medicine and Health Sciences Commons^™

Characteristics Of Antifungal Utilization For Hospitalized Children In The United States, Lourdes Eguiguren, Brian R Lee, Jason G Newland, Matthew P Kronman, Adam L Hersh, Jeffrey S Gerber, Grace M Lee, Hayden T Schwenk

2020-Current year OA Pubs

OBJECTIVE: To characterize antifungal prescribing patterns, including the indication for antifungal use, in hospitalized children across the United States.

DESIGN: We analyzed antifungal prescribing data from 32 hospitals that participated in the SHARPS Antibiotic Resistance, Prescribing, and Efficacy among Children (SHARPEC) study, a cross-sectional point-prevalence survey conducted between June 2016 and December 2017.

METHODS: Inpatients aged <18 years with an active systemic antifungal order were included in the analysis. We classified antifungal prescribing by indication (ie, prophylaxis, empiric, targeted), and we compared the proportion of patients in each category based on patient and antifungal characteristics.

RESULTS: Among 34,927 surveyed patients, 2,095 (6%) received at least 1 systemic antifungal and there were 2,207 antifungal prescriptions. Most patients had an underlying oncology or bone marrow transplant diagnosis (57%) or were premature (13%). The most prescribed antifungal was fluconazole (48%) and the …

Nivolumab Plus Docetaxel In Patients With Chemotherapy-Naïve Metastatic Castration-Resistant Prostate Cancer: Results From The Phase Ii Checkmate 9kd Trial, Karim Fizazi, Russell K Pachynski, Et Al.

2020-Current year OA Pubs

BACKGROUND: Docetaxel has immunostimulatory effects that may promote an immunoresponsive prostate tumour microenvironment, providing a rationale for combination with nivolumab (programmed death-1 inhibitor) for metastatic castration-resistant prostate cancer (mCRPC).

METHODS: In the non-randomised, multicohort, global phase II CheckMate 9KD trial, 84 patients with chemotherapy-naive mCRPC, ongoing androgen deprivation therapy and ≤2 prior novel hormonal therapies (NHTs) received nivolumab 360 mg and docetaxel 75 mg/m

RESULTS: The confirmed ORR (95% confidence interval [CI]) was 40.0% (25.7-55.7), and the confirmed PSA

CONCLUSIONS: Nivolumab plus docetaxel has clinical activity in patients with chemotherapy-naïve mCRPC. Safety was consistent with the individual components. These results …

Cognitive And Brain Reserve Predict Decline In Adverse Driving Behaviors Among Cognitively Normal Older Adults, Samantha A Murphy, Ling Chen, Jason M Doherty, Prerana Acharyya, Noah Riley, Ann M Johnson, Alexis Walker, Hailee Domash, Maren Jorgensen, Sayeh Bayat, David B Carr, Beau M Ances, Ganesh M Babulal

2020-Current year OA Pubs

Daily driving is a multi-faceted, real-world, behavioral measure of cognitive functioning requiring multiple cognitive domains working synergistically to complete this instrumental activity of daily living. As the global population of older adult continues to grow, motor vehicle crashes become more frequent among this demographic. Cognitive reserve (CR) is the brain's adaptability or functional robustness despite damage, while brain reserve (BR) refers the structural, neuroanatomical resources. This study examined whether CR and BR predicted changes in adverse driving behaviors in cognitively normal older adults. Cognitively normal older adults (Clinical Dementia Rating 0) were enrolled from longitudinal studies at the Knight Alzheimer's …

Reduced Expression In Preterm Birth Of Sflt-1 And Plgf With A High Sflt-1/Plgf Ratio In Extracellular Vesicles Suggests A Potential Biomarker, Sama Hussein, Weina Ju, Stephanie Pizzella, Michael Flory, Chu Chu, Yong Wang, Nanbert Zhong

2020-Current year OA Pubs

Preterm birth may have a pathological impact on intrauterine development of the fetal brain, resulting in developmental disabilities. In this study, we examine the expression of soluble Fms-like tyrosine kinase 1 (sFLT-1) and placental growth factor (PlGF), which is one of the vascular endothelial growth factors (VEGFs), as these play a key role in angiogenesis; in particular, we examine their effect on the sFLT-1/PlGF ratio in cases of preterm birth as compared to typical pregnancies. Enzyme-linked immunosorbent assay was performed on samples of maternal-derived plasma and extracellular vesicles-exosomes (EVs-EXs) isolated at the third trimester, consisting of 17 samples from cases …

Prescribing Unproven Cancer Drugs: Physician Perspectives On Expanded Access And Right To Try, Haley Manley, Bryan A Sisk, Zubin Master, Christopher Thomas Scott

2020-Current year OA Pubs

BACKGROUND: For gravely ill patients who have no treatment options and who are ineligible for clinical trials, the US Food and Drug Administration (FDA) established the Expanded Access Program (EAP). Motivated by efforts to weaken FDA regulation and sold as providing greater access to experimental drugs, the federal Right to Try Act (RTT) was passed in 2017. It reduces FDA oversight by not requiring physicians to report safety data and foregoes approval of protocols by local institutional review boards.

METHODS: This study explored the views of 17 neuro-oncologists from 15 different academic medical centers with varying experience with EAP and …

Adverse Events Related To Ultrasound-Guided Regional Anesthesia Performed By Emergency Physicians: Systematic Review Protocol, Sean P. Stickles, Deborah Shipley Kane, Chadd K. Kraus, Robert J. Strony, Enyo A. Ablordeppey, Michelle M. Doering, Daniel Theodoro, Jacques Simon Lee, Christopher R. Carpenter

2020-Current year OA Pubs

The use of ultrasound-guided regional anesthesia for pain management has become increasingly prevalent in Emergency Medicine, with studies noting excellent pain control while sparing opioid use. However, the use of ultrasound-guided regional anesthesia may be hampered by concern about risks for patient harm. This systematic review protocol describes our approach to evaluate the incidence of adverse events from the use of ultrasound-guided regional anesthesia by Emergency Physicians as described in the literature. This project will also seek to document the scope of ultrasound-guided regional anesthesia applications being performed in Emergency Medicine literature, and potentially serve as a framework for future …

The Association Of Prescription Opioid Use With Suicide Attempts: An Analysis Of Statewide Medical Claims Data, Chongliang Luo, Kun Chen, Riddhi Doshi, Nathaniel Rickles, Yong Chen, Harold Schwartz, Robert H. Aseltine

2020-Current year OA Pubs

BACKGROUND: Suicides and opioid overdose deaths are among the most pressing public health concerns in the US. However direct evidence for the association between opioid use and suicidal behavior is limited. The objective of this article is to examine the association between frequency and dose of prescription opioid use and subsequent suicide attempts.

METHODS AND FINDINGS: This retrospective cohort study analyzed 4 years of statewide medical claims data from the Connecticut All-Payer Claims Database. Commercially insured adult patients in Connecticut (n = 842,773) who had any medical claims beginning in January 2012 were followed through December 2015. The primary outcome …

Glutathione S-Transferase Alpha 4 Promotes Proliferation And Chemoresistance In Colorectal Cancer Cells, Zhanhu Zhang, Lili Xu, Lin Huang, Tianqi Li, Jane Y Wang, Chunhua Ma, Xiaoyun Bian, Xiaoyan Ren, Haibo Li, Xingmin Wang

2020-Current year OA Pubs

Glutathione

Checkpoint Blockade-Induced Cd8+ T Cell Differentiation In Head And Neck Cancer Responders, Liye Zhou, Paul Zolkind, Obi Griffith, Et Al

2020-Current year OA Pubs

BACKGROUND: Immune checkpoint blockade (ICB) response in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) is limited to 15%-20% of patients and underpinnings of resistance remain undefined.

METHODS: Starting with an anti-PD1 sensitive murine HNSCC cell line, we generated an isogenic anti-PD1 resistant model. Mass cytometry was used to delineate tumor microenvironments of both sensitive parental murine oral carcinoma (MOC1) and resistant MOC1esc1 tumors. To examine heterogeneity and clonal dynamics of tumor infiltrating lymphocytes (TILs), we applied paired single-cell RNA and TCR sequencing in three HNSCC models.

RESULTS: Anti-PD1 resistant MOC1esc1 line displayed a conserved cell intrinsic immune evasion signature. …

Metabolic Mechanisms Connecting Alzheimer's And Parkinson's Diseases: Potential Avenues For Novel Therapeutic Approaches, Jerry R Colca, Brian N Finck

2020-Current year OA Pubs

Alzheimer's (AD) and Parkinson's Diseases (PD) are common neurodegenerative disorders growing in incidence and prevalence and for which there are no disease-modifying treatments. While there are considerable complexities in the presentations of these diseases, the histological pictures of these pathologies, as well as several rare genetic predispositions for each, point to the involvement of maladaptive protein processing and inflammation. Importantly, the common presentations of AD and PD are connected to aging and to dysmetabolism, including common co-diagnosis of metabolic syndrome or diabetes. Examination of anti-diabetic therapies in preclinical models and in some observational clinical studies have suggested effectiveness of the …

Exploring The Role Of Low-Density Neutrophils During Mycobacterium Tuberculosis Infection, Ananda N Rankin, Skyler V Hendrix, Sumanta K Naik, Christina L Stallings

2020-Current year OA Pubs

Tuberculosis (TB) is caused by infection with the bacterium

A Callosal Biomarker Of Behavioral Intervention Outcomes For Autism Spectrum Disorder? A Case-Control Feasibility Study With Diffusion Tensor Imaging, Javier Virues-Ortega, Nicole S. Mckay, Jessica C. Mccormack, Nerea Lopez, Rosalie Liu, Ian Kirk

2020-Current year OA Pubs

Tentative results from feasibility analyses are critical for planning future randomized control trials (RCTs) in the emerging field of neural biomarkers of behavioral interventions. The current feasibility study used MRI-derived diffusion imaging data to investigate whether it would be possible to identify neural biomarkers of a behavioral intervention among people diagnosed with autism spectrum disorder (ASD). The corpus callosum has been linked to cognitive processing and callosal abnormalities have been previously found in people diagnosed with ASD. We used a case-control design to evaluate the association between the type of intervention people diagnosed with ASD had previously received and their …

Maternal Perceptions About Sensory Interventions In The Neonatal Intensive Care Unit: An Exploratory Qualitative Study, Julia Lisle, Kylie Buma, Joan Smith, Marinthea Richter, Prutha Satpute, Roberta Pineda

2020-Current year OA Pubs

Background: Mothers play an important role in providing positive sensory experiences to their infants during NICU hospitalization. However, little is known regarding maternal perceptions about sensory-based interventions in the NICU. Further, understanding maternal perceptions was an important part of the process during development of the Supporting and Enhancing NICU Sensory Experiences (SENSE) program.

Methods: Twenty mothers of very preterm infants were interviewed after NICU discharge and asked open-ended questions about sensory-based interventions they performed in the NICU and probed about their perceptions related to the development of a sensory-based guideline and the use of volunteers to provide sensory-based interventions when …

The Role Of Neutrophil Extracellular Traps In Acute Lung Injury, Davide Scozzi, Fuyi Liao, Alexander S Krupnick, Daniel Kreisel, Andrew E Gelman

2020-Current year OA Pubs

Acute lung injury (ALI) is a heterogeneous inflammatory condition associated with high morbidity and mortality. Neutrophils play a key role in the development of different forms of ALI, and the release of neutrophil extracellular traps (NETs) is emerging as a common pathogenic mechanism. NETs are essential in controlling pathogens, and their defective release or increased degradation leads to a higher risk of infection. However, NETs also contain several pro-inflammatory and cytotoxic molecules than can exacerbate thromboinflammation and lung tissue injury. To reduce NET-mediated lung damage and inflammation, DNase is frequently used in preclinical models of ALI due to its capability …

Is Characteristic Frequency Limiting Real-Time Electrocochleography During Cochlear Implantation?, Amit Walia, Matthew A Shew, Shannon M Lefler, Dorina Kallogjeri, Cameron C Wick, Timothy A Holden, Nedim Durakovic, Amanda J Ortmann, Jacques A Herzog, Craig A Buchman

2020-Current year OA Pubs

Objectives: Electrocochleography (ECochG) recordings during cochlear implantation have shown promise in estimating the impact on residual hearing. The purpose of the study was (1) to determine whether a 250-Hz stimulus is superior to 500-Hz in detecting residual hearing decrement and if so; (2) to evaluate whether crossing the 500-Hz tonotopic, characteristic frequency (CF) place partly explains the problems experienced using 500-Hz.

Design: Multifrequency ECochG comprising an alternating, interleaved acoustic complex of 250- and 500-Hz stimuli was used to elicit cochlear microphonics (CMs) during insertion. The largest ECochG drops (≥30% reduction in CM) were identified. After insertion, ECochG responses were measured …

A Conformational Variant Of P53 (U-P53az) As Blood-Based Biomarker For The Prediction Of The Onset Of Symptomatic Alzheimer's Disease, S Piccirella, L Van Neste, C Fowler, C L Masters, J Fripp, J D Doecke, C Xiong, D Uberti, P Kinnon

2020-Current year OA Pubs

BACKGROUND: Ongoing research seeks to identify blood-based biomarkers able to predict onset and progression of Alzheimer's disease (AD).

OBJECTIVE: The unfolded conformational variant of p53 (U-p53AZ), previously observed in AD individuals, was evaluated in plasma samples from individuals participating in the Australian Imaging, Biomarkers and Lifestyle (AIBL) cohort for diagnostic and prognostic assessment, validated on a neuropsychological-based diagnosis, over the course of six years.

DESIGN: Retrospective Longitudinal Prognostic biomarker study.

SETTING: Single-center study based on the AIBL cohort.

PARTICIPANTS: 482 participants of the AIBL cohort, aged 60-85 years, without uncontrolled diabetes, vascular disease, severe depression or psychiatric illnesses.

MEASUREMENTS: The …

The Burden Of Critical Illness In Hospitalized Children In Low- And Middle-Income Countries: Protocol For A Systematic Review And Meta-Analysis, Teresa B Kortz, Kenneth E Remy, Et Al.

2020-Current year OA Pubs

BACKGROUND: The majority of childhood deaths occur in low- and middle-income countries (LMICs). Many of these deaths are avoidable with basic critical care interventions. Quantifying the burden of pediatric critical illness in LMICs is essential for targeting interventions to reduce childhood mortality.

OBJECTIVE: To determine the burden of hospitalization and mortality associated with acute pediatric critical illness in LMICs through a systematic review and meta-analysis of the literature.

DATA SOURCES AND SEARCH STRATEGY: We will identify eligible studies by searching MEDLINE, EMBASE, CINAHL, and LILACS using MeSH terms and keywords. Results will be limited to infants or children (ages >28 …

Post-Transplant Thrombotic Microangiopathy Due To A Pathogenic Mutation In Complement Factor I In A Patient With Membranous Nephropathy: Case Report And Review Of Literature, Maryam Saleem, Sana Shaikh, Zheng Hu, Nicola Pozzi, Anuja Java

2020-Current year OA Pubs

Thrombotic microangiopathy (TMA) is characterized by microangiopathic hemolytic anemia, thrombocytopenia and organ injury occurring due to endothelial cell damage and microthrombi formation in small vessels. TMA is primary when a genetic or acquired defect is identified, as in atypical hemolytic uremic syndrome (aHUS) or secondary when occurring in the context of another disease process such as infection, autoimmune disease, malignancy or drugs. Differentiating between a primary complement-mediated process and one triggered by secondary factors is critical to initiate timely treatment but can be challenging for clinicians, especially after a kidney transplant due to presence of multiple confounding factors. Similarly, primary …

Leishmania Guyanensis Suppressed Inducible Nitric Oxide Synthase Provoked By Its Viral Endosymbiont, Dmitry Kopelyanskiy, Chantal Desponds, Florence Prevel, Matteo Rossi, Romain Migliorini, Tiia Snäkä, Remzi Onur Eren, Stéphanie Claudinot, Lon-Fye Lye, Manolis Pasparakis, Stephen M Beverley, Nicolas Fasel

2020-Current year OA Pubs

Inducible nitric oxide synthase (iNOS) is essential to the production of nitric oxide (NO), an efficient effector molecule against intracellular human pathogens such as

Automated Measurement Of Net Water Uptake From Baseline And Follow-Up Cts In Patients With Large Vessel Occlusion Stroke, Atul Kumar, Yasheng Chen, Aaron Corbin, Ali Hamzehloo, Amin Abedini, Zeynep Vardar, Grace Carey, Kunal Bhatia, Laura Heitsch, Jamal J Derakhshan, Jin-Moo Lee, Rajat Dhar

2020-Current year OA Pubs

Quantifying the extent and evolution of cerebral edema developing after stroke is an important but challenging goal. Lesional net water uptake (NWU) is a promising CT-based biomarker of edema, but its measurement requires manually delineating infarcted tissue and mirrored regions in the contralateral hemisphere. We implement an imaging pipeline capable of automatically segmenting the infarct region and calculating NWU from both baseline and follow-up CTs of large-vessel occlusion (LVO) patients. Infarct core is extracted from CT perfusion images using a deconvolution algorithm while infarcts on follow-up CTs were segmented from non-contrast CT (NCCT) using a deep-learning algorithm. These infarct masks …

The Past, Present, And Future Of A Human T-Cell Leukemia Virus Type 1 Vaccine, Joshua J Tu, Victoria Maksimova, Lee Ratner, Amanda R Panfil

2020-Current year OA Pubs

Human T-cell leukemia virus type 1 (HTLV-1) is an oncogenic human retrovirus which causes a lifelong infection. An estimated 5-10 million persons are infected with HTLV-1 worldwide - a number which is likely higher due to lack of reliable epidemiological data. Most infected individuals remain asymptomatic; however, a portion of HTLV-1-positive individuals will develop an aggressive CD4+ T-cell malignancy called adult T-cell leukemia/lymphoma (ATL), or a progressive neurodegenerative disease known as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Few treatment options exist for HAM/TSP outside of palliative care and ATL carries an especially poor prognosis given the heterogeneity of the disease and …

Crispr-Cas9 Knock-In Of T513m And G41s Mutations In The Murine Β-Galactosyl-Ceramidase Gene Re-Capitulates Early-Onset And Adult-Onset Forms Of Krabbe Disease, Rima Rebiai, Emily Rue, Steve Zaldua, Duc Nguyen, Giuseppe Scesa, Martin Jastrzebski, Robert Foster, Bin Wang, Xuntian Jiang, Leon Tai, Scott T Brady, Richard Van Breemen, Maria I Givogri, Mark S Sands, Ernesto R Bongarzone

2020-Current year OA Pubs

Krabbe Disease (KD) is a lysosomal storage disorder characterized by the genetic deficiency of the lysosomal enzyme β-galactosyl-ceramidase (GALC). Deficit or a reduction in the activity of the GALC enzyme has been correlated with the progressive accumulation of the sphingolipid metabolite psychosine, which leads to local disruption in lipid raft architecture, diffuse demyelination, astrogliosis, and globoid cell formation. The

Glial Dysfunction And Its Contribution To The Pathogenesis Of The Neuronal Ceroid Lipofuscinoses, Keigo Takahashi, Hemanth R Nelvagal, Jenny Lange, Jonathan D Cooper

2020-Current year OA Pubs

While significant efforts have been made in developing pre-clinical treatments for the neuronal ceroid lipofuscinoses (NCLs), many challenges still remain to bring children with NCLs a cure. Devising effective therapeutic strategies for the NCLs will require a better understanding of pathophysiology, but little is known about the mechanisms by which loss of lysosomal proteins causes such devastating neurodegeneration. Research into glial cells including astrocytes, microglia, and oligodendrocytes have revealed many of their critical functions in brain homeostasis and potential contributions to neurodegenerative diseases. Genetically modified mouse models have served as a useful platform to define the disease progression in the …

Stigma Towards Mental Illness And Help-Seeking Behaviors Among Adult And Child Psychiatrists In Hungary: A Cross-Sectional Study, Dorottya Őri, Péter Szocsics, Tamás Molnár, Fanni Virág Ralovich, Zsolt Huszár, Ágnes Bene, Sándor Rózsa, Zsuzsa Győrffy, György Purebl

2020-Current year OA Pubs

OBJECTIVE: Stigma towards people with mental health problems is a growing issue across the world, to which healthcare providers might contribute. The aim of the present study was to explore psychiatrists' attitudes towards their patients and link them to psychosocial and professional factors.

METHODS: An online questionnaire was used to approach the in- and outpatient psychiatric services across Hungary. A total of 211 trainees and specialists in adult and child psychiatry participated in our study. Their overall stigmatizing attitudes were measured, with focus on attitude, disclosure and help-seeking, and social distance dimensions by using the self-report Opening Minds Stigma Scale …

Semaphorin-Plexin Signaling: From Axonal Guidance To A New X-Linked Intellectual Disability Syndrome, Jacqueline L Steele, Marwan S Shinawi, Et Al.

2020-Current year OA Pubs

BACKGROUND: Semaphorins and plexins are ligands and cell surface receptors that regulate multiple neurodevelopmental processes such as axonal growth and guidance. PLXNA3 is a plexin gene located on the X chromosome that encodes the most widely expressed plexin receptor in fetal brain, plexin-A3. Plexin-A3 knockout mice demonstrate its role in semaphorin signaling in vivo. The clinical manifestations of semaphorin/plexin neurodevelopmental disorders have been less widely explored. This study describes the neurological and neurodevelopmental phenotypes of boys with maternally inherited hemizygous PLXNA3 variants.

METHODS: Data-sharing through GeneDx and GeneMatcher allowed identification of individuals with autism or intellectual disabilities (autism/ID) and hemizygous …

Multiple Conserved States Characterize The Twist Landscape Of The Bacterial Actin Homolog Mreb, Benjamin D Knapp, Michael D Ward, Gregory R Bowman, Handuo Shi, Kerwyn Casey Huang

2020-Current year OA Pubs

Filament formation by cytoskeletal proteins is critical to their involvement in myriad cellular processes. The bacterial actin homolog MreB, which is essential for cell-shape determination in many rod-shaped bacteria, has served as a model system for studying the mechanics of cytoskeletal filaments. Previous molecular dynamics (MD) simulations revealed that the twist of MreB double protofilaments is dependent on the bound nucleotide, as well as binding to the membrane or the accessory protein RodZ, and MreB mutations that modulate twist also affect MreB spatial organization and cell shape. Here, we show that MreB double protofilaments can adopt multiple twist states during …

Phase I Clinical Trial Evaluating The Safety And Efficacy Of Adp-A2m10 Spear T Cells In Patients With Mage-A10+ Advanced Non-Small Cell Lung Cancer, George R Blumenschein, Siddhartha Devarakonda, Ramaswamy Govindan, Et Al

2020-Current year OA Pubs

BACKGROUND: ADP-A2M10 specific peptide enhanced affinity receptor (SPEAR) T cells (ADP-A2M10) are genetically engineered autologous T cells that express a high-affinity melanoma-associated antigen A10 (MAGE-A10)-specific T-cell receptor (TCR) targeting MAGE-A10

METHODS: Eligible patients were HLA-A*02 positive with advanced NSCLC expressing MAGE-A10. Patients underwent apheresis; T cells were isolated, transduced with a lentiviral vector containing the TCR targeting MAGE-A10, and expanded. Patients underwent lymphodepletion with varying doses/schedules of fludarabine and cyclophosphamide prior to receiving ADP-A2M10. ADP-A2M10 were administered at 0.08-0.12×10

RESULTS: Eleven patients (male, n=6; female, n=5) with NSCLC (adenocarcinoma, n=8; squamous cell carcinoma, n=3) were treated. Five, three, and three …

Neors: A Neonatal Resting State Fmri Data Preprocessing Pipeline, Vicente Enguix, Jeanette Kenley, David Luck, Julien Cohen-Adad, Gregory Anton Lodygensky

2020-Current year OA Pubs

Resting state functional MRI (rsfMRI) has been shown to be a promising tool to study intrinsic brain functional connectivity and assess its integrity in cerebral development. In neonates, where functional MRI is limited to very few paradigms, rsfMRI was shown to be a relevant tool to explore regional interactions of brain networks. However, to identify the resting state networks, data needs to be carefully processed to reduce artifacts compromising the interpretation of results. Because of the non-collaborative nature of the neonates, the differences in brain size and the reversed contrast compared to adults due to myelination, neonates can't be processed …

Predictors Of Lung Adenocarcinoma With Leptomeningeal Metastases: A 2022 Targeted-Therapy-Assisted Molgpa Model, Milan Zhang, Jiayi Tong, Weifeng Ma, Chongliang Luo, Huiqin Liu, Yushu Jiang, Lingzhi Qin, Xiaojuan Wang, Lipin Yuan, Jiewen Zhang, Fuhua Peng, Yong Chen, Wei Li, Ying Jiang

2020-Current year OA Pubs

Objective: To explore prognostic indicators of lung adenocarcinoma with leptomeningeal metastases (LM) and provide an updated graded prognostic assessment model integrated with molecular alterations (molGPA).

Methods: A cohort of 162 patients was enrolled from 202 patients with lung adenocarcinoma and LM. By randomly splitting data into the training (80%) and validation (20%) sets, the Cox regression and random survival forest methods were used on the training set to identify statistically significant variables and construct a prognostic model. The C-index of the model was calculated and compared with that of previous molGPA models.

Results: The Cox regression and random forest models …

Cilia Action In Islets: Lessons From Mouse Models, Jung Hoon Cho, Jing W Hughes

2020-Current year OA Pubs

Primary cilia as a signaling organelle have garnered recent attention as a regulator of pancreatic islet function. These rod-like sensors exist on all major islet endocrine cell types and transduce a variety of external cues, while dysregulation of cilia function contributes to the development of diabetes. The complex role of islet primary cilia has been examined using genetic deletion targeting various components of cilia. In this review, we summarize experimental models for the study of islet cilia and current understanding of mechanisms of cilia regulation of islet hormone secretion. Consensus from these studies shows that pancreatic cilia perturbation can cause …