Digital Commons Network^™

Nkp46+ Ilc3s Promote Early Neutrophil Defense Against Clostridioides Difficile Infection Through Gm-Csf Secretion, José L Fachi, Sarah De Oliveira, Susan Gilfillan, Alina Ulezko Antonova, Jinchao Hou, Marco A R Vinolo, Marco Colonna

2020-Current year OA Pubs

No abstract provided.

The Upfront Project: Tailored Implementation And Evaluation Of A Patient Decision Aid To Support Shared Decision-Making About Management Of Symptomatic Uterine Fibroids, Rachel C Forcino, Mary Politi, Et Al.

2020-Current year OA Pubs

OBJECTIVE: To evaluate implementation of a patient decision aid for symptomatic uterine fibroid management to improve shared decision-making at five clinical settings across the United States.

METHODS: We used a type 3 hybrid effectiveness-implementation stepped-wedge design and the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) planning and evaluation framework. We conducted clinician training, monthly reach tracking with feedback to site clinical leads, patient and clinician surveys, and visit audio-recordings. Implementation strategies included assessment of organizational readiness for shared decision-making, synchronous clinician training, audit and feedback of decision aid reach, and access to multiple decision aid formats. Outcomes and analyses included patient-level …

Actionable Structural Variant Detection Via Rns-Ngs And Dna-Ngs In Patients With Advanced Non-Small Cell Lung Cancer, Dwight Owen, Daniel Morgensztern, Et Al.

2020-Current year OA Pubs

IMPORTANCE: The National Comprehensive Cancer Network (NCCN) guidelines for non-small cell lung cancer suggest that RNA next-generation sequencing (NGS) may improve the detection of fusions and splicing variants compared with DNA-NGS alone. However, there is limited adoption of RNA-NGS in routine oncology clinical care today.

OBJECTIVE: To analyze clinical evidence from a diverse cohort of patients with advanced lung adenocarcinoma and compare the detection of NCCN-recommended actionable structural variants (aSVs; fusions and splicing variants) via concurrent DNA and RNA-NGS vs DNA-NGS alone.

DESIGN, SETTING, AND PARTICIPANTS: This multisite, retrospective cohort study examined patients sequenced between February 2021 and October 2023 …

Quality Of Publicly Available Information About Urinary Tract Infections, Viktoria Schmitz, Zoe Troubh, Michael Durkin, Kevin Hsueh, Katheryn Ney, Brian D Carpenter, Shinbee Waldron, Mary C Politi, Cdc Prevention Epicenters Program

2020-Current year OA Pubs

No abstract provided.

Race, Gender, And Faculty Retention In Academic Medicine, Taneisha S Scheuermann, Lauren Clark, Nasrin Sultana, Nathalia Machado, Elena Shergina, Deepika Polineni, Grace H Shih, Robert D Simari, Jo A Wick, Kimber P Richter

2020-Current year OA Pubs

IMPORTANCE: Poor retention may be associated with lack of faculty diversity in academic medicine.

OBJECTIVE: To examine differences in faculty retention by gender, degree type, and race and ethnicity using data from US medical schools.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study analyzed data from 155 medical schools for 1978 to 2021, which were obtained from the Association of American Medical Colleges. Retention rates were calculated by gender, race and ethnicity, and degree type. Time to attrition was estimated using Kaplan-Meier curves and adjusted Cox proportional hazards models were used to examine the differences in retention by gender and race. …

Deletion Of Fgfr2 In Ductal Basal Epithelium With Tamoxifen Induces Obstructive Meibomian Gland Dysfunction, Xiaowei Yang, Xingwu Zhong, Haotian Lin, Andrew J W Huang, Lixing W Reneker

2020-Current year OA Pubs

PURPOSE: Fibroblast growth factor receptor 2 (Fgfr2) is crucial for the homeostasis of meibomian gland (MG). However, the role of Fgfr2 in MG ductal epithelial progenitors remains to be delineated. Herein, we created a new transgenic mouse model with conditional deletion of Fgfr2 from MG ductal progenitors and investigated the cell-specific role in the pathogenesis of obstructive meibomian gland dysfunction.

METHODS: Peritoneal injection of tamoxifen (TAM) at 50 µg/gm for three consecutive days was performed to induce conditional deletion of Fgfr2 in two-month-old Krt5Fgfr2CKO or Krt5Fgfr2CKO-mTmG mice. Phenotypes of MG after Fgfr2 deletion were monitored by meibography, lipid staining, and …

Performance Of Risk Models For Antimicrobial Resistance In Adult Patients With Sepsis, M Cristina Vazquez Guillamet, Hanyang Liu, Andrew Atkinson, Victoria J Fraser, Chenyang Lu, Marin H Kollef

2020-Current year OA Pubs

IMPORTANCE: The results of prediction models that stratify patients with sepsis and risk of resistant gram-negative bacilli (GNB) infections inform treatment guidelines. However, these models do not extrapolate well across hospitals.

OBJECTIVE: To assess whether patient case mix and local prevalence rates of resistance contributed to the variable performance of a general risk stratification GNB sepsis model for community-onset and hospital-onset sepsis across hospitals.

DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective cohort study conducted from January 2016 and October 2021. Adult patients with sepsis at 10 acute-care hospitals in rural and urban areas across Missouri and Illinois were included. …

Improving Risk Stratification For 2022 European Leukemianet Favorable-Risk Patients With Acute Myeloid Leukemia, Kellie J Archer, Geoffrey L Uy, Et Al.

2020-Current year OA Pubs

Assignment of patients diagnosed with acute myeloid leukemia (AML) to the 2022 European LeukemiaNet (ELN) favorable genetic risk group has important clinical implications, as allogeneic stem cell transplantation in first complete remission (CR) is not advised due to a relatively good outcome of patients receiving chemotherapy alone and transplant-associated mortality. However, not all favorable genetic risk patients experience long-term relapse-free survival (RFS), making recognition of patients who would most likely be cured of high importance. We analyzed 297 patients aged < 60 years with

Race And Ethnicity, Gender, And Promotion Of Physicians In Academic Medicine, Lauren Clark, Elena Shergina, Nathalia Machado, Taneisha S Scheuermann, Nasrin Sultana, Deepika Polineni, Grace H Shih, Robert D Simari, Jo A Wick, Kimber P Richter

2020-Current year OA Pubs

IMPORTANCE: The ranks of academic physicians do not reflect the diversity of the US population. To create a diverse and effective medical workforce, it is important to know the extent to which gender, race and ethnicity, and the intersection of these factors are associated with career advancement.

OBJECTIVE: To assess whether race and ethnicity and gender are associated with appointment to or promotion within academic medicine.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used Association of American Medical Colleges data on graduates of all US MD-granting medical schools from 1979 to 2019 merged with faculty appointment data since 2000. Data …

Multicenter Validation Of An Rna-Based Assay To Predict Anti-Pd-1 Disease Control In Patients With Recurrent Or Metastatic Head And Neck Squamous Cell Carcinoma: The Predapt Study, Kevin C Flanagan, Jessica Ley, Douglas Adkins, Eric J Duncavage, Et Al.

2020-Current year OA Pubs

BACKGROUND: Despite advances in cancer care and detection, >65% of patients with squamous cell cancer of the head and neck (HNSCC) will develop recurrent and/or metastatic disease. The prognosis for these patients is poor with a 5-year overall survival of 39%. Recent treatment advances in immunotherapy, including immune checkpoint inhibitors like pembrolizumab and nivolumab, have resulted in clinical benefit in a subset of patients. There is a critical clinical need to identify patients who benefit from these antiprogrammed cell death protein 1 (anti-PD-1) immune checkpoint inhibitors.

METHODS: Here, we report findings from a multicenter observational study, PREDicting immunotherapy efficacy from …

Distinct Escherichia Coli Transcriptional Profiles In The Guts Of Recurrent Uti Sufferers Revealed By Pangenome Hybrid Selection, Mark G Young, Jesús Bazan Villicana, Philippe Azimzadeh, Andrew Kau, Karen W Dodson, Henry L Schreiber 4th, Scott J Hultgren, Et Al.

2020-Current year OA Pubs

Low-abundance members of microbial communities are difficult to study in their native habitats, including Escherichia coli, a minor but common inhabitant of the gastrointestinal tract, and key opportunistic pathogen of the urinary tract. While multi-omic analyses have detailed interactions between uropathogenic Escherichia coli (UPEC) and the bladder mediating urinary tract infection (UTI), little is known about UPEC in its pre-infection reservoir, the gastrointestinal tract, partly due to its low relative abundance (<1%). To sensitively explore the genomes and transcriptomes of diverse gut E. coli, we develop E. coli PanSelect, which uses probes designed to specifically capture E. coli's broad pangenome. We demonstrate its ability to enrich diverse E. coli by orders of magnitude, in a mock community and in human stool from a study investigating recurrent UTI (rUTI). Comparisons of transcriptomes between gut E. coli of women with and without history of rUTI suggest rUTI gut E. coli are responding to increased oxygen and nitrate, suggestive of mucosal inflammation, which may have implications for recurrent disease. E. coli PanSelect is well suited for investigations of in vivo E. coli biology in other low-abundance environments, and the framework described here has broad applicability to other diverse, low-abundance organisms.

Effect Of Surgical Fixation Timing On In-Hospital Mortality And Morbidity Of Distal Femur Fractures, Joseph T Gutbrod, Dustin Stwalley, Anna N Miller

2020-Current year OA Pubs

INTRODUCTION: The literature lacks a large-scale study investigating the effect of surgical fixation timing on early mortality and morbidity outcomes in distal femur fractures. The aims of this study were to determine the effect of fixation timing on in-hospital mortality and morbidity outcomes for operatively treated distal femur fractures retrospectively using large database data.

METHODS: This study is a retrospective analysis using data from the National Trauma Data Bank. Patients were stratified into a fragility cohort (age ≥ 60, ISS < 16) and polytrauma cohort (age < 60, ISS ≥16), with both cohorts analyzed separately. Within each cohort, patients were split into three fixation timing groups: within 24 h, between 24 and 48 h, and greater than 48 h from presentation to the hospital. Fixation-timing groups were compared based on the primary outcome of in-hospital mortality rate. Secondary outcomes included hospital length of stay (LOS), ICU length of stay (ICU LOS), days on a ventilator, and complications.

RESULTS: The fragility and polytrauma cohorts included 22,045 and 5,905 patients, respectively. The in-hospital mortality rate was 1.23 % in …

Assessing Radiology And Radiation Therapy Needs For Cancer Care In Low-And-Middle-Income Countries: Insight From A Global Survey Of Departmental And Institutional Leaders, Stephanie A Parker, Yao Hao, Et Al.

2020-Current year OA Pubs

PURPOSE: The global cancer burden and mortality rates are increasing, with significant disparities in access to care in low- and middle-income countries (LMICs). This study aimed to identify radiology and radiation therapy needs in LMICs from the perspective of departmental and institutional leaders.

METHODS AND MATERIALS: A survey was developed and conducted by the American Association of Physicists in Medicine Global Needs Assessment Committee and the American Association of Physicists in Medicine International Council. The survey, organized into 5 sections (Introduction, Infrastructure Needs, Education Needs, Research Needs, and General Information), was open to respondents from March 1, to August 16, …

Relationship Between Mri Brain-Age Heterogeneity, Cognition, Genetics And Alzheimer's Disease Neuropathology, Mathilde Antoniades, Pamela Lamontagne, Tammie Benzinger, Daniel S Marcus, John C Morris, Et Al.

2020-Current year OA Pubs

BACKGROUND: Brain ageing is highly heterogeneous, as it is driven by a variety of normal and neuropathological processes. These processes may differentially affect structural and functional brain ageing across individuals, with more pronounced ageing (older brain age) during midlife being indicative of later development of dementia. Here, we examined whether brain-ageing heterogeneity in unimpaired older adults related to neurodegeneration, different cognitive trajectories, genetic and amyloid-beta (Aβ) profiles, and to predicted progression to Alzheimer's disease (AD).

METHODS: Functional and structural brain age measures were obtained for resting-state functional MRI and structural MRI, respectively, in 3460 cognitively normal individuals across an age …

Cohort Expansion And Genotype-Phenotype Analysis Of Rab11a-Associated Neurodevelopmental Disorder, Maria Carla Borroto, Jorge L Granadillo, Et Al.

2020-Current year OA Pubs

BACKGROUND: GTPases of the Rab family are important orchestrators of membrane trafficking, and their dysregulation has been linked to a variety of neuropathologies. In 2017, we established a causal link between RAB11A variants and developmental and epileptic encephalopathy. In this study, we expand the phenotype of RAB11A-associated neurodevelopmental disorder and explore genotype-phenotype correlations.

METHODS: We assessed 16 patients with pathogenic or likely pathogenic RAB11A variants, generally de novo, heterozygous missense variants. One individual had a homozygous nonsense variant, although concomitant with a pathogenic LAMA2 variant, which made their respective contributions to the phenotype difficult to discriminate.

RESULTS: We reinforce the …

Transmembrane Protein 53 Craniotubular Dysplasia (Omim # 619727): The Skeletal Disease And Consequent Blindness Of This New Disorder, Michael P Whyte, Robert S Weinstein, Paul H Phillips, William H Mcalister, Raghuhr H Ramakrishnaiah, G Bradley Schaefer, Rongsheng Cai, Michele R Hutchison, Shenghui Duan, Gary S Gottesman, Steven Mumm

2020-Current year OA Pubs

Craniotubular dysplasia, Ikegawa type (OMIM #619727) denotes the autosomal recessive skeletal disease identified in 2021 featuring blindness acquired in childhood. Five young members of four Indian families harbored a homozygous indel within TMEM53 (OMIM *619722), the gene that encodes transmembrane protein 53 (TMEM53). When intact, TMEM53 spans the nuclear envelope of osteoprogenitor cells, dampens BMP-SMAD signaling, and thereby slows bone formation. Consequently, defective TMEM53 accelerates osteogenesis. Herein, an American boy is compound heterozygous for a novel deletion and a novel missense mutation within TMEM53. His vision and sensorineural hearing became impaired. Radiographic survey revealed diploic thickening of his skull, broad …

Concurrent Optogenetic Motor Mapping Of Multiple Limbs In Awake Mice Reveals Cortical Organization Of Coordinated Movements, Nischal Khanal, Jonah A Padawer-Curry, Trevor Voss, Kevin A Schulte, Annie R Bice, Adam Q Bauer

2020-Current year OA Pubs

BACKGROUND: Motor mapping allows for determining the macroscopic organization of motor circuits and corresponding motor movement representations on the cortex. Techniques such as intracortical microstimulation (ICMS) are robust, but can be time consuming and invasive, making them non-ideal for cortex-wide mapping or longitudinal studies. In contrast, optogenetic motor mapping offers a rapid and minimally invasive technique, enabling mapping with high spatiotemporal resolution. However, motor mapping has seen limited use in tracking 3-dimensonal, multi-limb movements in awake animals. This gap has left open questions regarding the underlying organizational principles of motor control of coordinated, ethologically-relevant movements involving multiple limbs.

OBJECTIVE: Our …

Precision Functional Mapping To Advance Developmental Psychiatry Research, Alyssa K Labonte, M Catalina Camacho, Julia Moser, Sanju Koirala, Timothy O Laumann, Scott Marek, Damien Fair, Chad M Sylvester

2020-Current year OA Pubs

Many psychiatric conditions have their roots in early development. Individual differences in prenatal brain function (which is influenced by a combination of genetic risk and the prenatal environment) likely interact with individual differences in postnatal experience, resulting in substantial variation in brain functional organization and development in infancy. Neuroimaging has been a powerful tool for understanding typical and atypical brain function and holds promise for uncovering the neurodevelopmental basis of psychiatric illness; however, its clinical utility has been relatively limited thus far. A substantial challenge in this endeavor is the traditional approach of averaging brain data across groups despite individuals …

Adjuvant Trastuzumab Emtansine Versus Paclitaxel Plus Trastuzumab For Stage I Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: 5-Year Results And Correlative Analyses From Atempt, Paolo Tarantino, Ron Bose, Et Al.

2020-Current year OA Pubs

PURPOSE: Long-term outcomes of patients with stage I human epidermal growth factor receptor 2 (HER2)-positive breast cancer receiving adjuvant trastuzumab emtansine (T-DM1) remain undefined, and prognostic predictors represent an unmet need.

METHODS: In the ATEMPT phase II trial, patients with stage I centrally confirmed HER2-positive breast cancer were randomly assigned 3:1 to adjuvant T-DM1 for 1 year or paclitaxel plus trastuzumab (TH). Coprimary objectives were to compare the incidence of clinically relevant toxicities between arms and to evaluate invasive disease-free survival (iDFS) with T-DM1. Correlative analyses included the HER2DX genomic tool, multiomic evaluations of HER2 heterogeneity, and predictors of thrombocytopenia. …

A Phase 1 First-In-Human Study Of The Mcl-1 Inhibitor Azd5991 In Patients With Relapsed/Refractory Hematologic Malignancies, Pinkal Desai, Amanda Cashen, Et Al.

2020-Current year OA Pubs

PURPOSE: AZD5991, a human MCL-1 inhibitor, was assessed for safety, tolerability, pharmacokinetics, and antitumor activity as monotherapy and in combination with venetoclax in patients with relapsed or refractory hematologic malignancies.

PATIENTS AND METHODS: In the monotherapy cohort (n = 61), patients with hematologic malignancies received AZD5991 intravenously in escalating doses either once or twice weekly, following intrapatient dose escalation, during a 3-week cycle. In the combination cohort (n = 17), patients with acute myeloid leukemia and myelodysplastic syndrome received escalating doses of AZD5991 and venetoclax during either a 3- or 4-week cycle. Primary objectives were safety and maximum tolerated dose; …

Il-10r Inhibition Reprograms Tumor-Associated Macrophages And Reverses Drug Resistance In Multiple Myeloma, Jennifer Sun, Monica Shokeen, Barbara Muz, Kinan Alhallak, Chaelee Park, Berit Lubben, Yixuan Chen, Ola Adebayo, Hannah Bash, Sarah Kelley, Mark Fiala, Diane E Bender, Ravi Vij, Abdel Kareem Azab, Et Al.

2020-Current year OA Pubs

Multiple myeloma (MM) is the cancer of plasma cells within the bone marrow and remains incurable. Tumor-associated macrophages (TAMs) within the tumor microenvironment often display a pro-tumor phenotype and correlate with tumor proliferation, survival, and therapy resistance. IL-10 is a key immunosuppressive cytokine that leads to recruitment and development of TAMs. In this study, we investigated the role of IL-10 in MM TAM development as well as the therapeutic application of IL-10/IL-10R/STAT3 signaling inhibition. We demonstrated that IL-10 is overexpressed in MM BM and mediates M2-like polarization of TAMs in patient BM, 3D co-cultures in vitro, and mouse models. In …

Psychiatric Neuroimaging Designs For Individualised, Cohort, And Population Studies, Martin Gell, Stephanie Noble, Timothy O Laumann, Steven M Nelson, Brenden Tervo-Clemmens

2020-Current year OA Pubs

Psychiatric neuroimaging faces challenges to rigour and reproducibility that prompt reconsideration of the relative strengths and limitations of study designs. Owing to high resource demands and varying inferential goals, current designs differentially emphasise sample size, measurement breadth, and longitudinal assessments. In this overview and perspective, we provide a guide to the current landscape of psychiatric neuroimaging study designs with respect to this balance of scientific goals and resource constraints. Through a heuristic data cube contrasting key design features, we discuss a resulting trade-off among small sample, precision longitudinal studies (e.g., individualised studies and cohorts) and large sample, minimally longitudinal, population …

Posttreatment Surveillance Intensity And Overall Survival In Prostate Cancer Survivors (Aft-30), Ronald C Chen, Ramsankar Basak, Stacie Dusetzina, Deborah S Usinger, Zahed Mohammed, Aaron D Falchook, Jessica R Schumacher, Amanda B Francescatti, Amanda Cuddy, George J Chang, Benjamin D Kozower, Caprice C Greenberg, Anne K Barber, Aaron J Katz

2020-Current year OA Pubs

BACKGROUND: Posttreatment surveillance affects millions of cancer survivors, but empiric data to guide clinical practice are lacking. This study assessed whether the intensity of surveillance testing after radical prostatectomy or radiation therapy for localized prostate cancer is associated with overall survival.

METHODS: Men diagnosed with localized prostate cancer between 2005 and 2010 who underwent radical prostatectomy or radiation therapy at a Commission on Cancer-accredited facility were randomly sampled. Primary data collected from 10 147 patients sampled across 1007 facilities were linked with existing data from the National Cancer Database. Analysis examined whether intensity of surveillance measured as the number of …

Determining The N-Glycan And Collagen/Extracellular Matrix Protein Compositions In A Novel Outcome Cohort Of Prostate Cancer Tissue Microarrays Using Maldi-Msi, Jordan P Hartig, Joseph E Ippolito, Et Al.

2020-Current year OA Pubs

Using matrix-assisted laser desorption/ionization mass spectrometry imaging techniques on a unique cohort of prostate cancer tissues, we highlighted several molecular characteristics of matrix that have potential to act as early predictors of prostate cancer metastasis.

The Post-Transplant Lymphoproliferative Disorders-Metagenomic Shotgun Microbial Sequencing (Ptld-Msms) Study Methods And Protocol, Vikas R. Dharnidharka, Kristine M. Wylie, Todd N. Wylie, Marianna B. Ruzinova, Charles W. Goss, Gregory A. Storch, Neha Mehta-Shah, Derek Byers, Leslie Walther, Lujain Jaza, Hongjie Gu, Mansi Agarwal, Et Al.

2020-Current year OA Pubs

Post-transplant lymphoproliferative disorders (PTLDs) remain a feared complication of transplantation, with significant morbidity and mortality. The oncogenic Epstein-Barr virus (EBV) is a key pathogenic driver in 50%-80% of cases. Numerous prognostic indices, comprising multiple clinical, epidemiological and tumor characteristics, including EBV tumor positivity, do not consistently associate with worse patient survival, suggesting a potential role for EBV genome variants in determining outcome. However, the precision medicine tools for determining if a viral genome variant is pathogenic are very limited compared with human genome variants. Further, targeted studies have not implicated a specific viral etiological agent in EBV-negative PTLD. Using novel …

Tocilizumab Prophylaxis Following Axicabtagene Ciloleucel In Relapsed Or Refractory Large B-Cell Lymphoma, Frederick L Locke, Nancy L Bartlett, Et Al.

2020-Current year OA Pubs

Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved in patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Most patients treated with axi-cel experience cytokine release syndrome (CRS) and/or adverse neurologic events (NEs). To explore potential approaches for reducing CAR T-cell-related toxicities with axi-cel, several safety expansion cohorts were added to the pivotal ZUMA-1 trial. ZUMA-1 Cohort 3 was an exploratory safety cohort that investigated the use of the IL-6 receptor-blocking antibody tocilizumab and anticonvulsant levetiracetam as prophylaxis against CRS and NEs in patients treated with axi-cel. Patients with R/R LBCL were enrolled in Cohort …

Attention-Based Cnn-Bilstm For Sleep State Classification Of Spatiotemporal Wide-Field Calcium Imaging Data, Xiaohui Zhang, Eric C Landsness, Hanyang Miao, Wei Chen, Michelle J Tang, Lindsey M Brier, Joseph P Culver, Jin-Moo Lee, Mark A Anastasio

2020-Current year OA Pubs

BACKGROUND: Wide-field calcium imaging (WFCI) with genetically encoded calcium indicators allows for spatiotemporal recordings of neuronal activity in mice. When applied to the study of sleep, WFCI data are manually scored into the sleep states of wakefulness, non-REM (NREM) and REM by use of adjunct EEG and EMG recordings. However, this process is time-consuming, invasive and often suffers from low inter- and intra-rater reliability. Therefore, an automated sleep state classification method that operates on spatiotemporal WFCI data is desired.

NEW METHOD: A hybrid network architecture consisting of a convolutional neural network (CNN) to extract spatial features of image frames and …

Pdgf-Bb Overexpression In P53 Null Oligodendrocyte Progenitors Increases H3k27me3 And Induces Transcriptional Changes Which Favor Proliferation, Dennis Huang, Angeliki Mela, Natarajan V Bhanu, Benjamin A Garcia, Peter Canoll, Patrizia Casaccia

2020-Current year OA Pubs

Proneural gliomas are brain tumors characterized by enrichment of oligodendrocyte progenitor cell (OPC) transcripts and genetic alterations. In this study we sought to identify transcriptional and epigenetic differences between OPCs with Trp53 deletion and PDGF-BB overexpression (BB-p53n) and those carrying only p53 deletion (p53n). In culture, the BB-p53n OPCs display growth characteristics more similar to glioma cells than p53n OPCs. When injected in mouse brains, BB-p53n OPC form tumors, while the p53n OPCs do not. Unbiased histone proteomics and transcriptomic analysis on these OPC populations identified higher levels of the histone H3K27me3 mark and lower levels of the histone H4K20me3. …

Diclofenac Sensitizes Multi-Drug Resistant Acinetobacter Baumannii To Colistin, Fabiana Bisaro, Clay D. Jackson-Litteken, Jenna C. Mcguffey, Anna J. Hooppaw, Sophie Bodrog, Leila Jebeli, Manon Janet-Maitre, Juan C. Ortiz-Marquez, Tim Van Opijnen, Nichollas E. Scott, Gisela Di Venanzio, Mario F. Feldman

2020-Current year OA Pubs

Acinetobacter baumannii causes life-threatening infections that are becoming difficult to treat due to increasing rates of multi-drug resistance (MDR) among clinical isolates. This has led the World Health Organization and the CDC to categorize MDR A. baumannii as a top priority for the research and development of new antibiotics. Colistin is the last-resort antibiotic to treat carbapenem-resistant A. baumannii. Not surprisingly, reintroduction of colistin has resulted in the emergence of colistin-resistant strains. Diclofenac is a non-steroidal anti-inflammatory drug used to treat pain and inflammation associated with arthritis. In this work, we show that diclofenac sensitizes colistin-resistant A. baumannii clinical strains …

A Case Report Of An Unprovoked Neonatal Pulmonary Embolism: Management Strategies And Cardiopulmonary Complications, Aashana Dhruva Cowan, Ezinwanne Rosemary Emelue, George Spyropoulos, Mehul Thakkar, Jorge Di Paola, Andrew Glatz, Edon J Rabinowitz

2020-Current year OA Pubs

BACKGROUND: Neonatal pulmonary embolism is a rare occurrence, especially when idiopathic, instead occurring in patients with identifiable risk factors including severe dehydration, presence or history of a central venous line, or identifiable genetic causes. Given the rarity of paediatric and neonatal pulmonary emboli, few guidelines exist to support the clinician in both the initial resuscitation and ongoing management of the critically ill patient with pulmonary emboli.

CASE SUMMARY: We present a 5-day-old female with unprovoked massive pulmonary embolism and associated haemodynamic compromise. She presented with central cyanosis and weak respiratory effort with hypoxaemia, persistent tachycardia, and hypotension despite initial fluid …