Digital Commons Network^™

Variation In North American Infectious Disease Specialists' Practice Regarding Oral And Suppressive Antibiotics For Adult Osteoarticular Infections: Results Of An Emerging Infections Network (Ein) Survey, Nicolás Cortés-Penfield, Susan E Beekmann, Philip M Polgreen, Keenan Ryan, Jonas Marschall, Poorani Sekar

2020-Current year OA Pubs

BACKGROUND: Osteoarticular infections (OAIs) are commonly treated with prolonged intravenous (IV) antimicrobials. The Oral versus Intravenous Antibiotics for Bone and Joint Infection (OVIVA) trial demonstrated that oral (PO) antibiotics are noninferior to IV antibiotics in the treatment of OAIs. We surveyed infectious disease (ID) physicians about their use of PO antibiotics in the treatment of OAIs.

METHODS: An Emerging Infection Network survey with 9 questions regarding antibiotic prescribing for the treatment of OAIs was sent to 1475 North American ID physicians. The questions were mostly multiple choice and focused on the use of definitive oral antibiotic therapy (defined as oral …

Migraine Headache In Patients With Spontaneous Coronary Artery Dissection: A Report Of The Iscad Registry, Bryan J Wells, Kathryn Lindley, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Spontaneous coronary artery dissection (SCAD) is a nonatherosclerotic cause of myocardial infarction. Migraine headache has been reported to be common among patients with SCAD, but the degree of migraine-related disability has not been quantified.

METHODS: Clinical data and headache variables were obtained from the baseline assessment of the prospective, multicenter iSCAD Registry. Migraine-related disability was quantified using the self-reported Migraine Disability Assessment (MIDAS). Demographic, clinical, psychosocial, and medical characteristics from data entry forms were compared between patients with and without migraine.

RESULTS: Of the 773 patients with available data, 46% reported previous or current migraines. Those with migraines were …

Mendelian Segregation And High Recombination Rates Facilitate Genetic Analyses In Cryptosporidium Parvum, Abigail Kimball, Lisa Funkhouser-Jones, Wanyi Huang, Rui Xu, William H. Witola, L. David Sibley

2020-Current year OA Pubs

Very little is known about the process of meiosis in the apicomplexan parasite Cryptosporidium despite the essentiality of sex in its life cycle. Most cell lines only support asexual growth of Cryptosporidium parvum (C. parvum), but stem cell derived intestinal epithelial cells grown under air-liquid interface (ALI) conditions support the sexual cycle. To examine chromosomal dynamics during meiosis in C. parvum, we generated two transgenic lines of parasites that were fluorescently tagged with mCherry or GFP on chromosomes 1 or 5, respectively. Infection of ALI cultures or Ifngr1-/- mice with mCherry and GFP parasites resulted in cross-fertilization and the formation …

Infectious Diseases Physician Management Of Cryptococcal Meningitis In North America-Is Single High-Dose Liposomal Amphotericin B Being Used?, Nathan C Bahr, Susan E Beekmann, Philip M Polgreen, Jeremey B Walker, Andrej Spec, David R Boulware, John W Baddley

2020-Current year OA Pubs

BACKGROUND: Several recent randomized trials have been conducted in resource-limited settings for cryptococcal meningitis that have rapidly innovated international guidelines. The 2010 Infectious Diseases Society of America (IDSA) cryptococcal meningitis guideline has not been updated with recent trials. The 2022 AMBITION-cm trial found that a single 10-mg/kg dose of liposomal amphotericin B plus daily flucytosine and fluconazole for 2 weeks was noninferior to 1 week of amphotericin B deoxycholate with flucytosine. It is unknown whether physicians in high-resource settings are using this regimen or more traditional regimens.

METHODS: We developed an electronic survey in June 2023 to better understand whether …

Shared Vision For Improving Outcomes For Serious Fungal Diseases: Report Of A Patient, Caregiver, And Clinician Summit, Rob Purdie, Lisa A Tushla, Jonathan Ferretti, Gonzalo Kiko Castro, Ricky Watson, Thomas Davis, Brianna Raborg, Patrick B Mazi, Angela Stroman, Carolynn Thomas Jones, Thomas J Walsh, Tom M Chiller, Peter G Pappas, John Meyer, Andrej Spec

2020-Current year OA Pubs

BACKGROUND: Recently, increasing focus on patient input into research and healthcare improvements has fostered expanded patient-centered advocacy efforts. This first pan-fungal disease summit, part of the MYCology Advocacy, Research, & Education effort, brought together patients, caregivers, and mycology experts to better document patient experiences with invasive fungal disease (IFD) and establish priorities for mycology education, advocacy, and research.

METHODS: Patients who had suffered from IFD, their caregivers, clinicians, industry representatives, government officials, and patient advocacy professionals were invited. Patients and caregivers shared their stories and struggles with IFD. Breakout sessions separated mycology experts from patients and caregivers for further discussions …

The First Reported Case Of Treating The Ultra-Central Thorax With Cone Beam Computed Tomography-Guided Stereotactic Adaptive Radiotherapy (Ct-Star), Stephanie Zhao, Robbie Beckert, Xiaodong Zhao, Eric Laugeman, Clifford G. Robinson, Gregory Vlacich, Pamela P. Samson, Joshua P. Schiff

2020-Current year OA Pubs

Stereotactic body radiotherapy (SBRT) to the central and ultra-central thorax is associated with infrequent but potentially serious adverse events. Adaptive SBRT, which provides more precise treatment planning and inter-fraction motion management, may allow the delivery of ablative doses to ultra-central tumors with effective local control and improved toxicity profiles. Herein, we describe the first reported case of cone beam computed tomography (CBCT)-guided stereotactic adaptive radiotherapy (CT-STAR) in the treatment of ultra-central non-small cell lung cancer (NSCLC) in a prospective clinical trial (NCT05785845). An 80-year-old man with radiographically diagnosed early-stage NSCLC presented for definitive management of an enlarging ultra-central lung nodule. …

Anomalous Left Superior Vena Cava Predisposing To Recurrent Brain Abscesses: A Case Report And Review Of The Literature, Adnan Shaik, Karan Joseph, Rahim Abo Kasem, Angela Downes, Muhammed B. Janjua

2020-Current year OA Pubs

Brain abscess is a devastating illness, with a high risk of morbidity and mortality. Recurrent brain abscess poses a challenge to diagnosis while treatment options may differ. Right to left shunt is a lesser-explored etiology for recurrent brain abscesses. PubMed literature review was performed to study all published studies with reference to right to left cardiac shunt as a possible etiology for the recurrent brain abscesses. The authors also report a case of a young male who developed recurrent brain abscess after previous resection and treatment. Right to left cardiac shunting of deoxygenated blood is an etiology for recurrent brain …

Faculty Onboarding For Workforce Readiness And Belonging, Melissa M. Masaracchia, Scott D. Markowitz, Norah R. Janosy, Kim M. Strupp

2020-Current year OA Pubs

INTRODUCTION: An academic anesthesiology department benefits from recruiting faculty from various centers, from new graduates to experienced clinicians. Two critical objectives for a department are getting the faculty members up-to-speed thoroughly and efficiently and retaining the faculty members to benefit from their contributions over time. Onboarding plays a pivotal role in meeting both objectives. A successful onboarding process is critical to the enculturation of new employees into an existing work environment. Organizations focusing on improving onboarding practices increase overall success, decrease attrition, and enhance member performance and satisfaction. In this study, we examine our onboarding practices and then create structured …

Leveraging Digital Media To Promote Youth Mental Health: Flipping The Script On Social Media-Related Risk, Jessica L Hamilton, John Torous, Hannah S Szlyk, Candice Biernesser, Kaylee P Kruzan, Michaeline Jensen, Jazmin Reyes-Portillo, Brian A Primack, Jamie Zelazny, Paul Weigle

2020-Current year OA Pubs

PURPOSE OF REVIEW: Despite growing public concern about the negative impact of digital media for mental health problems, there are key ways in which digital media can be leveraged to prevent such outcomes. This article reviews research exploring the ways that digital media, particularly social media, can be used to prevent negative mental health outcomes and promote youth mental health and well-being.

RECENT FINDINGS: Research indicates that media can be protective against mental health problems and promote mental health by enabling social support and destigmatizing mental illness, especially for youth with limited resources. Media also can be leveraged to identify …

Retrospective Multicenter Cohort Study On Safety And Electroencephalographic Response To Lacosamide For Neonatal Seizures, Moninder Kaur, Rejean M Guerriero, Renée A Shellhaas, Et Al.

2020-Current year OA Pubs

BACKGROUND: There is growing evidence supporting the safety and effectiveness of lacosamide in older children. However, minimal data are available for neonates. We aimed to determine the incidence of adverse events associated with lacosamide use and explore the electroencephalographic seizure response to lacosamide in neonates.

METHODS: A retrospective cohort study was conducted using data from seven pediatric hospitals from January 2009 to February 2020. For safety outcomes, neonates were followed for ≤30 days from index date. Electroencephalographic response of lacosamide was evaluated based on electroencephalographic reports for ≤3 days.

RESULTS: Among 47 neonates, 98% received the first lacosamide dose in …

Genome-Wide Association Studies And Mendelian Randomization Analyses Provide Insights Into The Causes Of Early-Onset Colorectal Cancer, R S Laskar, Y Cao, Et Al.

2020-Current year OA Pubs

BACKGROUND: The incidence of early-onset colorectal cancer (EOCRC; diagnosed < 50 years of age) is rising globally; however, the causes underlying this trend are largely unknown. CRC has strong genetic and environmental determinants, yet common genetic variants and causal modifiable risk factors underlying EOCRC are unknown. We conducted the first EOCRC-specific genome-wide association study (GWAS) and Mendelian randomization (MR) analyses to explore germline genetic and causal modifiable risk factors associated with EOCRC.

PATIENTS AND METHODS: We conducted a GWAS meta-analysis of 6176 EOCRC cases and 65 829 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), the Colorectal Transdisciplinary Study (CORECT), the Colon Cancer Family Registry (CCFR), and the UK Biobank. We then used the EOCRC GWAS to investigate 28 modifiable risk factors using two-sample MR.

RESULTS: We found two novel risk loci for EOCRC at 1p34.1 and 4p15.33, which were not previously associated with CRC risk. We identified a deleterious coding variant (rs36053993, G396D) at polyposis-associated DNA repair gene MUTYH …

Late-Season Influenza Vaccine Effectiveness Against Medically Attended Outpatient Illness, United States, December 2022-April 2023, Jessie R Chung, Stacey L House, Tara Curley, Et Al.

2020-Current year OA Pubs

BACKGROUND: The 2022-23 US influenza season peaked early in fall 2022.

METHODS: Late-season influenza vaccine effectiveness (VE) against outpatient, laboratory-confirmed influenza was calculated among participants of the US Influenza VE Network using a test-negative design.

RESULTS: Of 2561 participants enrolled from December 12, 2022 to April 30, 2023, 91 laboratory-confirmed influenza cases primarily had A(H1N1)pdm09 (6B.1A.5a.2a.1) or A(H3N2) (3C.2a1b.2a.2b). Overall, VE was 30% (95% confidence interval -9%, 54%); low late-season activity precluded estimation for most subgroups.

CONCLUSIONS: 2022-23 late-season outpatient influenza VE was not statistically significant. Genomic characterization may improve the identification of influenza viruses that circulate postinfluenza peak.

Ascc1 Structures And Bioinformatics Reveal A Novel Helix-Clasp-Helix Rna-Binding Motif Linked To A Two-Histidine Phosphodiesterase, Naga Babu Chinnam, Jennifer M Soll, Nima Mosammaparast, Et Al.

2020-Current year OA Pubs

Activating signal co-integrator complex 1 (ASCC1) acts with ASCC-ALKBH3 complex in alkylation damage responses. ASCC1 uniquely combines two evolutionarily ancient domains: nucleotide-binding K-Homology (KH) (associated with regulating splicing, transcriptional, and translation) and two-histidine phosphodiesterase (PDE; associated with hydrolysis of cyclic nucleotide phosphate bonds). Germline mutations link loss of ASCC1 function to spinal muscular atrophy with congenital bone fractures 2 (SMABF2). Herein analysis of The Cancer Genome Atlas (TCGA) suggests ASCC1 RNA overexpression in certain tumors correlates with poor survival, Signatures 29 and 3 mutations, and genetic instability markers. We determined crystal structures of Alvinella pompejana (Ap) ASCC1 and Human (Hs) …

Changes In Online Marketing And Sales Practices Among Non-Medical Cannabis Retailers In 5 Us Cities, 2022 To 2023, Yuxian Cui, Zongshuan Duan, Cassidy R Loparco, Katie Vinson, Katelyn F Romm, Yan Wang, Patricia A Cavazos-Rehg, Erin Kasson, Y Tony Yang, Carla J Berg

2020-Current year OA Pubs

OBJECTIVES: Given the evolving cannabis marketplace (e.g., products, marketing strategies), this study examined online cannabis marketing practices over time.

METHODS: In 2022 and 2023, researchers assessed website content (e.g., age verification, sales, delivery, warnings, ad content, promotional strategies) among 175 randomly-selected cannabis retailers' websites across 5 US cities (Denver, Colorado; Seattle, Washington; Portland, Oregon; Las Vegas, Nevada; Los Angeles [LA], California, n=∼35/city). Analyses compared data from 2022 vs. 2023 and considered regulatory factors across cities.

RESULTS: Similar to 2022, in 2023, 76.6 % required age verification for site entry, 85.1 % used social media promotion, and 90.9 % offered online …

Bcar4 Expression As A Predictive Biomarker For Endocrine Therapy Resistance In Breast Cancer, Muheng Liao, Jace Webster, Emily M Coonrod, Katherine N Weilbaecher, Christopher A Maher, Nicole M White

2020-Current year OA Pubs

BACKGROUND: Breast cancer, particularly the estrogen receptor positive (ER+) subtype, remains a leading cause of cancer-related death among women. Endocrine therapy is the most effective treatment for ER+ breast cancer; however, the development of resistance presents a significant challenge. This study explored the role of the breast cancer antiestrogen resistance 4 (BCAR4) gene as a potential driver of resistance and a pivotal biomarker in breast cancer.

PATIENTS AND METHODS: The researchers undertook a comprehensive analysis of 1743 patients spanning 6 independent cohorts. They examined the association of BCAR4 expression with patient outcomes across all breast cancer types and the PAM50 …

Aeeg In The First 3 Days After Extremely Preterm Delivery Relates To Neurodevelopmental Outcomes, Roberta Pineda, Zachary Vesoulis, Nathalie El Ters, Amit Mathur

2020-Current year OA Pubs

OBJECTIVES: Investigate relationships between aEEG in the first 72 h in extremely preterm infants with 1) infant, medical, and environmental factors, and 2) infant feeding and neurobehavioral outcomes at term and school-age.

METHODS: Sixty-four preterm infants (≤28 weeks gestation) were enrolled within the first 24-hours of life and had two-channel aEEG until 72 h of life. Standardized neurobehavioral and feeding assessments were conducted at term, and parent-reported outcomes were documented at 5-7 years.

RESULTS: Lower aEEG Burdjalov scores (adjusted for gestational age) were related to vaginal delivery (p = 0.04), cerebral injury (p = 0.01), Black race (p < 0.01) and having unmarried parents (p = 0.02). Lower Burdjalov scores related to less NICU Network Neurobehavioral Scale arousal (p = 0.002) at term and poorer BRIEF global executive function (p = 0.004), inhibition (p = 0.007), working memory (p = 0.02), material organization (p = 0.0008), metacognition (p = 0.01), and behavioral regulation (p = 0.02) at 5-7 years. We did not observe relationships of early aEEG to feeding outcomes or sensory processing measures.

CONCLUSION: Early …

Single-Cell Lineage Capture Across Genomic Modalities With Celltag-Multi Reveals Fate-Specific Gene Regulatory Changes, Kunal Jindal, Mohd Tayyab Adil, Naoto Yamaguchi, Xue Yang, Helen C Wang, Kenji Kamimoto, Guillermo C Rivera-Gonzalez, Samantha A Morris

2020-Current year OA Pubs

Complex gene regulatory mechanisms underlie differentiation and reprogramming. Contemporary single-cell lineage-tracing (scLT) methods use expressed, heritable DNA barcodes to combine cell lineage readout with single-cell transcriptomics. However, reliance on transcriptional profiling limits adaptation to other single-cell assays. With CellTag-multi, we present an approach that enables direct capture of heritable random barcodes expressed as polyadenylated transcripts, in both single-cell RNA sequencing and single-cell Assay for Transposase Accessible Chromatin using sequencing assays, allowing for independent clonal tracking of transcriptional and epigenomic cell states. We validate CellTag-multi to characterize progenitor cell lineage priming during mouse hematopoiesis. Additionally, in direct reprogramming of fibroblasts to …

A Microbiota-Directed Complementary Food Intervention In 12-18-Month-Old Bangladeshi Children Improves Linear Growth, Ishita Mostafa, Matthew C Hibberd, Steven J Hartman, Md Hasan Hafizur Rahman, Mustafa Mahfuz, S M Tafsir Hasan, Per Ashorn, Michael J Barratt, Tahmeed Ahmed, Jeffrey I Gordon

2020-Current year OA Pubs

BACKGROUND: Globally, stunting affects ∼150 million children under five, while wasting affects nearly 50 million. Current interventions have had limited effectiveness in ameliorating long-term sequelae of undernutrition including stunting, cognitive deficits and immune dysfunction. Disrupted development of the gut microbiota has been linked to the pathogenesis of undernutrition, providing potentially new treatment approaches.

METHODS: 124 Bangladeshi children with moderate acute malnutrition (MAM) enrolled (at 12-18 months) in a previously reported 3-month RCT of a microbiota-directed complementary food (MDCF-2) were followed for two years. Weight and length were monitored by anthropometry, the abundances of bacterial strains were assessed by quantifying metagenome-assembled …

Mri And Pathology Comparisons In Rasmussen's Encephalitis: A Multi-Institutional Examination Of Hemispherotomy Outcomes Relative To Imaging And Histological Severity, Alexander Doherty, Kathleen Knudson, Christine Fuller, James L Leach, Anthony C Wang, Neena Marupudi, Rowland H Han, Stuart Tomko, Jeff Ojemann, Matthew D Smyth, Francesco Mangano, Jesse Skoch

2020-Current year OA Pubs

PURPOSE: Rasmussen encephalitis (RE) is a very rare chronic neurological disorder of unilateral inflammation of the cerebral cortex. Hemispherotomy provides the best chance at achieving seizure freedom in RE patients, but with significant risks and variable long-term outcomes. The goal of this study is to utilize our multicenter pediatric cohort to characterize if differences in pathology and/or imaging characterization of RE may provide a window into post-operative seizure outcomes, which in turn could guide decision-making for parents and healthcare providers.

METHODS: This multi-institutional retrospective review of medical record, imaging, and pathology samples was approved by each individual institution's review board. …

Takotsubo Syndrome In Patients With Covid-19: A Systematic Review, Xiaojia Lu, Catherine Teng, Peng Cai, Jing Liang, Yanxuan Wang, Hawa Abu, Yuan Jia Wang, John E Madias, Kan Liu, Qi Liu, Pengyang Li

2020-Current year OA Pubs

BACKGROUND: Respiratory conditions are major physical triggers of takotsubo syndrome (TTS) and portend worse outcomes. However, data on TTS in patients with coronavirus disease-2019 infection (COVID-19) are limited.

METHODS: We searched PubMed, Embase, and Cochrane Library databases for case reports for the period 2019-2022 describing TTS in patients with COVID-19 pneumonia (TTS-COVID). We summarized the clinical data and outcomes and compared them to those in patients with TTS with an acute respiratory disease other than COVID-19 as a trigger (TTS-acute respiratory disease) and those with TTS with no respiratory disease (TTS-no respiratory disease).

RESULTS: The mortality rate was higher in …

Chloride/Proton Antiporters Clc3 And Clc5 Support Bone Formation In Mice, Irina L Tourkova, Quitterie C Larrouture, Silvia Liu, Jianhua Luo, Katherine E Shipman, Kelechi M Onwuka, Ora A Weisz, Vladimir Riazanski, Deborah J Nelson, Matthew L Macdonald, Paul H Schlesinger, Harry C Blair

2020-Current year OA Pubs

Acid transport is required for bone synthesis by osteoblasts. The osteoblast basolateral surface extrudes acid by Na

Use Of A Blood Biomarker Test Improves Economic Utility In The Evaluation Of Older Patients Presenting With Cognitive Impairment, William J Canestaro, Randall J Bateman, David M Holtzman, Mark Monane, Joel B Braunstein

2020-Current year OA Pubs

More than 16 million Americans living with cognitive impairment warrant a diagnostic evaluation to determine the cause of this disorder. The recent availability of disease-modifying therapies for Alzheimer's disease (AD) is expected to significantly drive demand for such diagnostic testing. Accurate, accessible, and affordable methods are needed. Blood biomarkers (BBMs) offer advantages over usual care amyloid positron emission tomography (PET) and cerebrospinal fluid (CSF) biomarkers in these regards. This study used a budget impact model to assess the economic utility of the PrecivityAD

Inherited C-Terminal Trex1 Variants Disrupt Homology-Directed Repair To Cause Senescence And Dna Damage Phenotypes In Drosophila, Mice, And Humans, Samuel D Chauvin, Fang R Zhao, W Alexander Stinson, Wei Qian, Prabhakar S Andhey, Maxim N Artyomov, Elisha D O Roberson, Jonathan J Miner, Et Al.

2020-Current year OA Pubs

Age-related microangiopathy, also known as small vessel disease (SVD), causes damage to the brain, retina, liver, and kidney. Based on the DNA damage theory of aging, we reasoned that genomic instability may underlie an SVD caused by dominant C-terminal variants in TREX1, the most abundant 3'-5' DNA exonuclease in mammals. C-terminal TREX1 variants cause an adult-onset SVD known as retinal vasculopathy with cerebral leukoencephalopathy (RVCL or RVCL-S). In RVCL, an aberrant, C-terminally truncated TREX1 mislocalizes to the nucleus due to deletion of its ER-anchoring domain. Since RVCL pathology mimics that of radiation injury, we reasoned that nuclear TREX1 would cause …

Three-Year Outcomes Of Post-Acute Sequelae Of Covid-19, Miao Cai, Yan Xie, Eric J Topol, Ziyad Al-Aly

2020-Current year OA Pubs

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes post-acute sequelae of coronavirus disease 2019 (COVID-19) (PASC) in many organ systems. Risks of these sequelae have been characterized up to 2 years after infection, but longer-term follow-up is limited. Here we built a cohort of 135,161 people with SARS-CoV-2 infection and 5,206,835 controls from the US Department of Veterans Affairs who were followed for 3 years to estimate risks of death and PASC. Among non-hospitalized individuals, the increased risk of death was no longer present after the first year of infection, and risk of incident PASC declined over the 3 …

Factitious Disorder Presenting As Sickle Cell Disease: A Case Report, Jeremy W Jacobs, Brenda J Grossman, Et Al.

2020-Current year OA Pubs

No abstract provided.

Subunit Communication Within Dimeric Sf1 Dna Helicases, Binh Nguyen, John Hsieh, Christopher J Fischer, Timothy M Lohman

2020-Current year OA Pubs

Monomers of the Superfamily (SF) 1 helicases, E. coli Rep and UvrD, can translocate directionally along single stranded (ss) DNA, but must be activated to function as helicases. In the absence of accessory factors, helicase activity requires Rep and UvrD homo-dimerization. The ssDNA binding sites of SF1 helicases contain a conserved aromatic amino acid (Trp250 in Rep and Trp256 in UvrD) that stacks with the DNA bases. Here we show that mutation of this Trp to Ala eliminates helicase activity in both Rep and UvrD. Rep(W250A) and UvrD(W256A) can still dimerize, bind DNA, and monomers still retain ATP-dependent ssDNA translocase …

Haptic Curing With Endolaser After Lens Tilt In The Yamane Technique, James C Liu, Arsham Sheybani

2020-Current year OA Pubs

PURPOSE: To describe a case of intraocular lens (IOL) tilt following transscleral IOL fixation with the Yamane technique and subsequent correction of tilt using 810-nm endoscopic diode laser.

OBSERVATIONS: Our patient required lens exchange and secondary IOL implantation due to a dislocated 1-piece IOL in the bag causing iris chafe. After routine IOL fixation with the Yamane technique and a Zeiss CT Lucia 602 lens, the IOL tilted significantly in the immediate postoperative period. The lens tilt was subsequently corrected in the operating room using endolaser to melt and reshape (cure) the optic-haptic junction.

CONCLUSIONS: IOL tilt is a known …

Factors Associated With Incomplete Resection For Large, Locally Invasive Non-Small Cell Lung Cancer, Whitney S. Brandt, Zhizhou Yang, Brendan T. Heiden, Pamela P. Samson, Daniel Morgensztern, Saiama N. Waqar, Bryan F. Meyers, Ruben G. Nava, G. Alexander Patterson, Benjamin D. Kozower, Varun Puri

2020-Current year OA Pubs

BACKGROUND: Large, node-negative but locally invasive non-small cell lung cancer (NSCLC) is associated with increased perioperative risk but improved survival if a complete resection is obtained. Factors associated with positive margins in this population are not well-studied.

METHODS: We performed a retrospective cohort study using National Cancer Database (NCDB) for adult patients with >5 cm, clinically node-negative NSCLC with evidence of invasion of nearby structures [2006-2015]. Patients were classified as having major structure involvement (azygous vein, pulmonary artery/vein, vena cava, carina/trachea, esophagus, recurrent laryngeal/vagus nerve, heart, aorta, vertebrae) or chest wall invasion (rib pleura, chest wall, diaphragm). Our primary outcome …

The Debranching Enzyme Dbr1 Regulates Lariat Turnover And Intron Splicing, Luke Buerer, Brittany A Townley, Nima Mosammaparast, Et Al.

2020-Current year OA Pubs

The majority of genic transcription is intronic. Introns are removed by splicing as branched lariat RNAs which require rapid recycling. The branch site is recognized during splicing catalysis and later debranched by Dbr1 in the rate-limiting step of lariat turnover. Through generation of a viable DBR1 knockout cell line, we find the predominantly nuclear Dbr1 enzyme to encode the sole debranching activity in human cells. Dbr1 preferentially debranches substrates that contain canonical U2 binding motifs, suggesting that branchsites discovered through sequencing do not necessarily represent those favored by the spliceosome. We find that Dbr1 also exhibits specificity for particular 5' …

Tcaf1 Promotes Trpv2-Mediated Ca2+ Release In Response To Cytosolic Dna To Protect Stressed Replication Forks, Lingzhen Kong, Chen Cheng, Abigael Cheruiyot, Jiayi Yuan, Yichan Yang, Sydney Hwang, Daniel Foust, Ning Tsao, Emily Wilkerson, Nima Mosammaparast, Michael B Major, David W Piston, Shan Li, Zhongsheng You

2020-Current year OA Pubs

The protection of the replication fork structure under stress conditions is essential for genome maintenance and cancer prevention. A key signaling pathway for fork protection involves TRPV2-mediated Ca