Medicine and Health Sciences Commons^™

Assessing Covid-19 Testing Strategies In K-12 Schools In Underserved Populations: Study Protocol For A Cluster-Randomized Trial, Samantha Hayes, Sara Malone, Brittany Bonty, Nancy Mueller, Summer M Reyes, Sydney A Reyes, Christina Evans, Myisha Wilcher-Roberts, Tremayne Watterson, Sewuese Akuse, Jamee Shelley, Grace Yuan, Ian Lackey, Jasmine Prater, Brock Montgomery, Cynthia Williams, Sheretta T Butler-Barnes, Kelly Harris, Charlene Caburnay, Nikole Lobb Dougherty, Jingxia Liu, Albert Lai, Julie Neidich, Stephanie Fritz, Jason G Newland

2020-Current year OA Pubs

BACKGROUND: Since March 2020, COVID-19 has disproportionately impacted communities of color within the United States. As schools have shifted from virtual to in-person learning, continual guidance is necessary to understand appropriate interventions to prevent SARS-CoV-2 transmission. Weekly testing of students and staff for SARS-CoV-2 within K-12 school setting could provide an additional barrier to school-based transmission, especially within schools unable to implement additional mitigation strategies and/or are in areas of high transmission. This study seeks to understand the role that weekly SARS-CoV-2 testing could play in K-12 schools. In addition, through qualitative interviews and listening sessions, this research hopes to …

A Reference Tissue Atlas For The Human Kidney, Jens Hansen, Sanjay Jain, Et Al

2020-Current year OA Pubs

Kidney Precision Medicine Project (KPMP) is building a spatially specified human kidney tissue atlas in health and disease with single-cell resolution. Here, we describe the construction of an integrated reference map of cells, pathways, and genes using unaffected regions of nephrectomy tissues and undiseased human biopsies from 56 adult subjects. We use single-cell/nucleus transcriptomics, subsegmental laser microdissection transcriptomics and proteomics, near-single-cell proteomics, 3D and CODEX imaging, and spatial metabolomics to hierarchically identify genes, pathways, and cells. Integrated data from these different technologies coherently identify cell types/subtypes within different nephron segments and the interstitium. These profiles describe cell-level functional organization of …

Prostate Cancer Therapy Personalization Via Multi-Modal Deep Learning On Randomized Phase Iii Clinical Trials, Andre Esteva, Jeff M Michalski, Et Al

2020-Current year OA Pubs

Prostate cancer is the most frequent cancer in men and a leading cause of cancer death. Determining a patient's optimal therapy is a challenge, where oncologists must select a therapy with the highest likelihood of success and the lowest likelihood of toxicity. International standards for prognostication rely on non-specific and semi-quantitative tools, commonly leading to over- and under-treatment. Tissue-based molecular biomarkers have attempted to address this, but most have limited validation in prospective randomized trials and expensive processing costs, posing substantial barriers to widespread adoption. There remains a significant need for accurate and scalable tools to support therapy personalization. Here …

Social Determinants Of Health And Cancer Screening Implementation And Outcomes In The Usa: A Systematic Review Protocol, Ariella R Korn, Callie Walsh-Bailey, Meagan Pilar, Brittney Sandler, Prema Bhattacharjee, W Todd Moore, Ross C Brownson, Karen M Emmons, April Y Oh

2020-Current year OA Pubs

BACKGROUND: Improving the delivery, uptake, and implementation of cancer screening to meet evidence-based recommendations is needed to reduce persistent cancer health disparities in the USA. Current national public health targets emphasize the role of social determinants of health (SDOH) on cancer screening. However, there remains a need to explicate these linkages, toward the goal of identifying and implementing effective interventions that target and address SDOH to reduce inequities in cancer screening.

METHODS: We will conduct a systematic review of English language peer-reviewed original research articles published between 2010 and 2021 that describe observational (qualitative and quantitative) and intervention studies conducted …

Neutrophil-To-Lymphocyte Ratios In Patients Undergoing Aortic Valve Replacement: The Partner Trials And Registries, Bahira Shahim, Alan Zajarias, Et Al

2020-Current year OA Pubs

Background The neutrophil-to-lymphocyte ratio (NLR) as a marker of systemic inflammation has been associated with worse prognosis in several chronic disease states, including heart failure. However, few data exist on the prognostic impact of elevated baseline NLR or change in NLR levels during follow-up in patients undergoing transcatheter or surgical aortic valve replacement (TAVR or SAVR) for aortic stenosis. Methods and Results NLR was available in 5881 patients with severe aortic stenosis receiving TAVR or SAVR in PARTNER (Placement of Aortic Transcatheter Valves) I, II, and S3 trials/registries (median [Q1, Q3] NLR, 3.30 [2.40, 4.90]); mean NLR, 4.10; range, 0.5-24.9) …

Potential Impact Of 2017 American College Of Cardiology/American Heart Association Hypertension Guideline On Contemporary Practice: A Cross-Sectional Analysis From Ncdr Pinnacle Registry, Aliza Hussain, Salim S Virani, Luke Zheng, Ty J Gluckman, William B Borden, Frederick A Masoudi, Thomas M Maddox

2020-Current year OA Pubs

Background Clinical implications of change in the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guideline on the diagnosis and management of hypertension, compared with recommendations by 2014 expert panel and Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7), are not known. Methods and Results Using data from the NCDR (National Cardiovascular Data Registry) PINNACLE (Practice Innovation and Clinical Excellence) Registry (January 2013-Decemver 2016), we compared the proportion and clinical characteristics of patients seen in cardiology practices diagnosed with hypertension, recommended antihypertensive treatment, and achieving blood pressure (BP) goals …

Serotonin Type 3 Receptor Subunit Gene Polymorphisms Associated With Psychosomatic Symptoms In Irritable Bowel Syndrome: A Multicenter Retrospective Study, Sabrina Berens, Gregory Sayuk, Et Al

2020-Current year OA Pubs

BACKGROUND: Single-nucleotide polymorphisms (SNPs) of the serotonin type 3 receptor subunit (

AIM: To assess the association of

METHODS: In this retrospective study, 623 participants with IBS were recruited from five specialty centers in Germany, Sweden, the United States, the United Kingdom, and Ireland. Depressive, anxiety, and somatization symptoms and sociodemographic characteristics were collected. Four functional SNPs -

RESULTS: Depressive and anxiety symptoms significantly worsened with increasing numbers of minor

CONCLUSION: We have provided the first evidence that

Precise Topology Of Adjacent Domain-General And Sensory-Biased Regions In The Human Brain, Moataz Assem, Sneha Shashidhara, Matthew F Glasser, John Duncan

2020-Current year OA Pubs

Recent functional MRI studies identified sensory-biased regions across much of the association cortices and cerebellum. However, their anatomical relationship to multiple-demand (MD) regions, characterized as domain-general due to their coactivation during multiple cognitive demands, remains unclear. For a better anatomical delineation, we used multimodal MRI techniques of the Human Connectome Project to scan subjects performing visual and auditory versions of a working memory (WM) task. The contrast between hard and easy WM showed strong domain generality, with essentially identical patterns of cortical, subcortical, and cerebellar MD activity for visual and auditory materials. In contrast, modality preferences were shown by contrasting …

The Aryl Hydrocarbon Receptor Instructs The Immunomodulatory Profile Of A Subset Of Clec4a4 Eosinophils Unique To The Small Intestine, Wei-Le Wang, Jun Kasamatsu, Satoru Joshita, Susan Gilfillan, Blanda Di Luccia, Santosh K Panda, Do-Hyun Kim, Pritesh Desai, Jennifer K Bando, Stanley Ching-Cheng Huang, Kentaro Yomogida, Steven J Van Dyken, Marina Cella, Marco Colonna, Et Al

2020-Current year OA Pubs

C-type lectin domain family 4, member a4 (Clec4a4) is a C-type lectin inhibitory receptor specific for glycans thought to be exclusively expressed on murine CD8α− conventional dendritic cells. Using newly generated Clec4a4-mCherry knock-in mice, we identify a subset of Clec4a4-expressing eosinophils uniquely localized in the small intestine lamina propria. Clec4a4+ eosinophils evinced an immunomodulatory signature, whereas Clec4a4− eosinophils manifested a proinflammatory profile. Clec4a4+ eosinophils expressed high levels of aryl hydrocarbon receptor (Ahr), which drove the expression of Clec4a4 as well as other immunomodulatory features, such as PD-L1. The abundance of Clec4a4+ eosinophils was dependent on dietary AHR ligands, increased with …

Prefrontal Cortex Supports Speech Perception In Listeners With Cochlear Implants, Arefeh Sherafati, Noel Dwyer, Aahana Bajracharya, Mahlega Samira Hassanpour, Adam T Eggebrecht, Jill B Firszt, Joseph P Culver, Jonathan E Peelle

2020-Current year OA Pubs

Cochlear implants are neuroprosthetic devices that can restore hearing in people with severe to profound hearing loss by electrically stimulating the auditory nerve. Because of physical limitations on the precision of this stimulation, the acoustic information delivered by a cochlear implant does not convey the same level of acoustic detail as that conveyed by normal hearing. As a result, speech understanding in listeners with cochlear implants is typically poorer and more effortful than in listeners with normal hearing. The brain networks supporting speech understanding in listeners with cochlear implants are not well understood, partly due to difficulties obtaining functional neuroimaging …

Biophysical Physiology Of Phosphoinositide Rapid Dynamics And Regulation In Living Cells, Jill B Jensen, Bjoern H Falkenburger, Eamonn J Dickson, Lizbeth De La Cruz, Gucan Dai, Jongyun Myeong, Seung-Ryoung Jung, Martin Kruse, Oscar Vivas, Byung-Chang Suh, Bertil Hille

2020-Current year OA Pubs

Phosphoinositide membrane lipids are ubiquitous low-abundance signaling molecules. They direct many physiological processes that involve ion channels, membrane identification, fusion of membrane vesicles, and vesicular endocytosis. Pools of these lipids are continually broken down and refilled in living cells, and the rates of some of these reactions are strongly accelerated by physiological stimuli. Recent biophysical experiments described here measure and model the kinetics and regulation of these lipid signals in intact cells. Rapid on-line monitoring of phosphoinositide metabolism is made possible by optical tools and electrophysiology. The experiments reviewed here reveal that as for other cellular second messengers, the dynamic …

Identifying Colorectal Cancer Caused By Biallelic Mutyh Pathogenic Variants Using Tumor Mutational Signatures, Peter Georgeson, Yin Cao, Et Al

2020-Current year OA Pubs

Carriers of germline biallelic pathogenic variants in the MUTYH gene have a high risk of colorectal cancer. We test 5649 colorectal cancers to evaluate the discriminatory potential of a tumor mutational signature specific to MUTYH for identifying biallelic carriers and classifying variants of uncertain clinical significance (VUS). Using a tumor and matched germline targeted multi-gene panel approach, our classifier identifies all biallelic MUTYH carriers and all known non-carriers in an independent test set of 3019 colorectal cancers (accuracy = 100% (95% confidence interval 99.87-100%)). All monoallelic MUTYH carriers are classified with the non-MUTYH carriers. The classifier provides evidence for a …

Quantifying Concordant Genetic Effects Of De Novo Mutations On Multiple Disorders, Hanmin Guo, Lin Hou, Yu Shi, Sheng Chih Jin, Xue Zeng, Boyang Li, Richard P Lifton, Martina Brueckner, Hongyu Zhao, Qiongshi Lu

2020-Current year OA Pubs

Exome sequencing on tens of thousands of parent-proband trios has identified numerous deleterious de novo mutations (DNMs) and implicated risk genes for many disorders. Recent studies have suggested shared genes and pathways are enriched for DNMs across multiple disorders. However, existing analytic strategies only focus on genes that reach statistical significance for multiple disorders and require large trio samples in each study. As a result, these methods are not able to characterize the full landscape of genetic sharing due to polygenicity and incomplete penetrance. In this work, we introduce EncoreDNM, a novel statistical framework to quantify shared genetic effects between …

What Is The State Of Children's Participation In Qualitative Research On Health Interventions?: A Scoping Study, Jean M Hunleth, Julie S Spray, Corey Meehan, Colleen Walsh Lang, Janet Njelesani

2020-Current year OA Pubs

BACKGROUND: Children are the focus of numerous health interventions throughout the world, yet the extent of children's meaningful participation in research that informs the adaptation, implementation, and evaluation of health interventions is not known. We examine the type, extent, and meaningfulness of children's participation in research in qualitative health intervention research.

METHOD: A scoping study was conducted of qualitative published research with children (ages 6-11 years) carried out as part of health intervention research. Following Arksey and O'Malley's scoping study methodology and aligned with the PRISMA-ScR guidelines on the reporting of scoping reviews, the authors searched, charted, collated, and summarized …

Patched 1 Regulates Smoothened By Controlling Sterol Binding To Its Extracellular Cysteine-Rich Domain, Laurel Mydock-Mcgrane, Kathiresan Krishnan, Douglas F Covey, Et Al

2020-Current year OA Pubs

Smoothened (SMO) transduces the Hedgehog (Hh) signal across the plasma membrane in response to accessible cholesterol. Cholesterol binds SMO at two sites: one in the extracellular cysteine-rich domain (CRD) and a second in the transmembrane domain (TMD). How these two sterol-binding sites mediate SMO activation in response to the ligand Sonic Hedgehog (SHH) remains unknown. We find that mutations in the CRD (but not the TMD) reduce the fold increase in SMO activity triggered by SHH. SHH also promotes the photocrosslinking of a sterol analog to the CRD in intact cells. In contrast, sterol binding to the TMD site boosts …

Molecular Imaging Phenotyping For Selecting And Monitoring Radioligand Therapy Of Neuroendocrine Neoplasms, Amir Iravani, Ashwin Singh Parihar, Timothy Akhurst, Rodney J Hicks

2020-Current year OA Pubs

Neuroendocrine neoplasia (NEN) is an umbrella term that includes a widely heterogeneous disease group including well-differentiated neuroendocrine tumours (NETs), and aggressive neuroendocrine carcinomas (NECs). The site of origin of the NENs is linked to the intrinsic tumour biology and is predictive of the disease course. It is understood that NENs demonstrate significant biologic heterogeneity which ultimately translates to widely varying clinical presentations, disease course and prognosis. Thus, significant emphasis is laid on the pre-therapy evaluation of markers that can help predict tumour behavior and dynamically monitors the response during and after treatment. Most well-differentiated NENs express somatostatin receptors (SSTRs) which …

Macrophages Disseminate Pathogen Associated Molecular Patterns Through The Direct Extracellular Release Of The Soluble Content Of Their Phagolysosomes, Catherine J Greene, Jenny A Nguyen, Samuel M Cheung, Corey R Arnold, Dale R Balce, Ya Ting Wang, Adrian Soderholm, Neil Mckenna, Devin Aggarwal, Rhiannon I Campden, Benjamin W Ewanchuk, Herbert W Virgin, Robin M Yates

2020-Current year OA Pubs

Recognition of pathogen-or-damage-associated molecular patterns is critical to inflammation. However, most pathogen-or-damage-associated molecular patterns exist within intact microbes/cells and are typically part of non-diffusible, stable macromolecules that are not optimally immunostimulatory or available for immune detection. Partial digestion of microbes/cells following phagocytosis potentially generates new diffusible pathogen-or-damage-associated molecular patterns, however, our current understanding of phagosomal biology would have these molecules sequestered and destroyed within phagolysosomes. Here, we show the controlled release of partially-digested, soluble material from phagolysosomes of macrophages through transient, iterative fusion-fission events between mature phagolysosomes and the plasma membrane, a process we term eructophagy. Eructophagy is most active …

Optimizing Allocation Of Curricular Content Across The Undergraduate & Graduate Medical Education Continuum, Samara B Ginzburg, Margaret M Hayes, Brittany L Ranchoff, Eva Aagaard, Katharyn M Atkins, Michelle Barnes, Jennifer B Soep, Andrew C Yacht, Erik K Alexander, Richard M Schwartzstein

2020-Current year OA Pubs

BACKGROUND: Medical educators struggle to incorporate socio-cultural topics into crowded curricula. The "continuum of learning" includes undergraduate and graduate medical education. Utilizing an exemplar socio-cultural topic, we studied the feasibility of achieving expert consensus among two groups of faculty (experts in medical education and experts in social determinants of health) on which aspects of the topic could be taught during undergraduate versus graduate medical education.

METHODS: A modified Delphi method was used to generate expert consensus on which learning objectives of social determinants of health are best taught at each stage of medical education. Delphi respondents included experts in medical …

Genetic, Epigenetic, And Environmental Mechanisms Govern Allele-Specific Gene Expression, Celine L St Pierre, Juan F Macias-Velasco, Jessica P Wayhart, Li Yin, Clay F Semenkovich, Heather A Lawson

2020-Current year OA Pubs

Allele-specific expression (ASE) is a phenomenon in which one allele is preferentially expressed over the other. Genetic and epigenetic factors cause ASE by altering the final composition of a gene's product, leading to expression imbalances that can have functional consequences on phenotypes. Environmental signals also impact allele-specific expression, but how they contribute to this cross talk remains understudied. Here, we explored how genotype, parent-of-origin, tissue, sex, and dietary fat simultaneously influence ASE biases. Male and female mice from a F

A Single-Center Experience Comparing First- Versus Second-Generation Insertable Cardiac Monitors In Pediatric Patients, Nathan Miller, Lisa Roelle, Dean Lorimer Jr, Aarti S Dalal, William B Orr, George F Van Hare, Jennifer N Avari Silva

2020-Current year OA Pubs

Insertable cardiac monitors (ICMs) have undergone advancements in size and functionality over the past decade, resulting in the introduction of small, easily insertable devices capable of long-term remote monitoring. We define first-generation ICMs as implantable cardiac monitoring devices that require an incision and surgical creation of a subcutaneous pocket and second-generation ICMs as devices implanted using a custom-made tool for subcutaneous insertion, respectively. The aim of this study was to understand the differences between first- and second-generation pediatric ICM implants, implant indications, and time to diagnosis. We performed a retrospective, single-center chart review of patients who underwent ICM implantation from …

Sustained Effect Of Lactin-V (Lactobacillus Crispatus Ctv-05) On Genital Immunology Following Standard Bacterial Vaginosis Treatment: Results From A Randomised, Placebo-Controlled Trial, Eric Armstrong, Anke Hemmerling, Steve Miller, Kerianne E. Burke, Sara J. Newmann, Sheldon R. Morris, Hilary Reno, Sanja Huibner, Maria Kulikova, Nico Nagelkerke, Bryan Coburn, Craig R. Cohen, Rupert Kaul

2020-Current year OA Pubs

BACKGROUND: Bacterial vaginosis might increase HIV risk by eliciting genital inflammation and epithelial barrier disruption, whereas vaginal Lactobacillus crispatus is associated with immune quiescence and HIV protection. We investigated the effect of a live biotherapeutic containing L crispatus CTV-05 (LACTIN-V) on genital immunology and key vaginal bacteria.

METHODS: This substudy included women aged 18-45 years who participated in the randomised, placebo-controlled, phase 2b trial of LACTIN-V to reduce bacterial vaginosis recurrence, conducted at four universities and hospitals in the USA. Women with negative results for sexually transmitted infection, pregnancy, and urinary tract infection were provided a 5-day course of vaginal …

Determination Of The Electronic Portal Imaging Device Pixel-Sensitivity-Map For Quality Assurance Applications. Part 1: Comparison Of Methods, Michael Paul Barnes, Baozhou Sun, Brad Michael Oborn, Bishnu Lamichhane, Stuart Szwec, Matthew Schmidt, Bin Cai, Frederick Menk, Peter Greer

2020-Current year OA Pubs

PURPOSE: Calibration of a radiotherapy electronic portal imaging device (EPID) using the pixel-sensitivity-map (PSM) in place of the flood field correction improves the utility of the EPID for quality assurance applications. Multiple methods are available for determining the PSM and this study provides an evaluation to inform on which is superior.

METHODS: Three different empirical methods ("Calvary Mater Newcastle" [CMN], "Varian," and "WashU") and a Monte Carlo-based method of PSM determination were investigated on a single Varian TrueBeam STx linear accelerator (linac) with an aS1200 EPID panel. PSM measurements were performed for each empirical method three successive times using the …

Association Of Molecular Senescence Markers In Late-Life Depression With Clinical Characteristics And Treatment Outcome, Breno S Diniz, Benoit H Mulsant, Charles F Reynolds, Daniel M Blumberger, Jordan F Karp, Meryl A Butters, Ana Paula Mendes-Silva, Erica L Vieira, George Tseng, Eric J Lenze

2020-Current year OA Pubs

Importance: Many older adults with depression do not experience remission with antidepressant treatment, and markers of cellular senescence in late-life depression (LLD) are associated with greater severity of depression, greater executive dysfunction, and higher medical illness burden. Since these clinical characteristics are associated with remission in LLD, molecular and cellular senescence abnormalities could be a possible biological mechanism underlying poor treatment response in this population.

Objective: To examine whether the senescence-associated secretory phenotype (SASP) index was associated with the likelihood of remission from a depressive episode in older adults.

Design, Setting, and Participants: A nonrandomized, open-label clinical trial was conducted …

Horizontal Gene Transfer Provides Insights Into The Deep Evolutionary History And Biology Of Trichinella, Dante Zarlenga, Peter Thompson, Makedonka Mitreva, Bruce A Rosa, Eric Hoberg

2020-Current year OA Pubs

Evolution involves temporal changes in the characteristics of a species that are subsequently propagated or rejected through natural selection. In the case of parasites, host switching also plays a prominent role in the evolutionary process. These changes are rooted in genetic variation and gene flow where genes may be deleted, mutated (sequence), duplicated, rearranged and/or translocated and then transmitted through vertical gene transfer. However, the introduction of new genes is not driven only by Mendelian inheritance and mutation but also by the introduction of DNA from outside a lineage in the form of horizontal gene transfer between donor and recipient …

Deceased Donor Procurement Biopsy Practices, Interpretation, And Histology-Based Decision-Making: A Survey Of Us Kidney Transplant Centers, Krista L. Lentine, Jason R. Wellen, Melissa Lichtenberger, Et Al.

2020-Current year OA Pubs

INTRODUCTION: The utility of kidney procurement biopsies is controversial. Understanding the current landscape of how clinicians obtain and use biopsies in organ evaluation may help inform consensus-building efforts.

METHODS: An electronic survey was distributed to clinicians at US kidney transplant programs (April 22, 2021-June 30, 2021) to evaluate donor biopsy indications, frequency, processing and interpretation, and impact of findings on practices.

RESULTS: Responses from staff involved in organ acceptance (73% surgeons, 20% nephrologists, 6% coordinators) at 95 transplant centers were analyzed, representing 40% of US transplant centers and 50% of recent deceased donor kidney transplant volume. More than a third …

Escape-Noncapture Bigeminy, Lisa M. Roelle, George F. Van Hare

2020-Current year OA Pubs

No abstract provided.

Protein Proximity Networks And Functional Evaluation Of The Casein Kinase 1 Gamma Family Reveal Unique Roles For Ck1Γ3 In Wnt Signaling, Megan J. Agajanian, Frances M. Potjewyd, Brittany M. Bowman, Smaranda Solomon, Kyle M. Lapak, Dhaval P. Bhatt, Jeffery L. Smith, Dennis Goldfarb, Alison D. Axtman, Michael B. Major

2020-Current year OA Pubs

Aberrant activation or suppression of WNT/β-catenin signaling contributes to cancer initiation and progression, neurodegeneration, and bone disease. However, despite great need and more than 40 years of research, targeted therapies for the WNT pathway have yet to be fully realized. Kinases are considered exceptionally druggable and occupy key nodes within the WNT signaling network, but several pathway-relevant kinases remain understudied and "dark." Here, we studied the function of the casein kinase 1γ (CSNK1γ) subfamily of human kinases and their roles in WNT signaling. miniTurbo-based proximity biotinylation and mass spectrometry analysis of CSNK1γ1, CSNK1γ2, and CSNK1γ3 revealed numerous components of the …

Accuracy Of Chest Computed Tomography In Distinguishing Cystic Pleuropulmonary Blastoma From Benign Congenital Lung Malformations In Children, Abigail J Engwall-Gill, Jacqueline M Saito, Rebecca L Hulett Bowling, Et Al.

2020-Current year OA Pubs

Importance: The ability of computed tomography (CT) to distinguish between benign congenital lung malformations and malignant cystic pleuropulmonary blastomas (PPBs) is unclear.

Objective: To assess whether chest CT can detect malignant tumors among postnatally detected lung lesions in children.

Design, Setting, and Participants: This retrospective multicenter case-control study used a consortium database of 521 pathologically confirmed primary lung lesions from January 1, 2009, through December 31, 2015, to assess diagnostic accuracy. Preoperative CT scans of children with cystic PPB (cases) were selected and age-matched with CT scans from patients with postnatally detected congenital lung malformations (controls). Statistical analysis was performed …

Phase I Trial Of Atm Inhibitor M3541 In Combination With Palliative Radiotherapy In Patients With Solid Tumors, Saiama N Waqar, Clifford Robinson, Anthony J Olszanski, Alexander Spira, Melissa Hackmaster, Luisa Lucas, Laura Sponton, Hulin Jin, Ursula Hering, Damien Cronier, Marianna Grinberg, Annick Seithel-Keuth, Ivan Diaz-Padilla, Jordan Berlin

2020-Current year OA Pubs

BACKGROUND: Ataxia telangiectasia mutated (ATM) kinase orchestrates DNA double strand break (DSB) repair; ATM inhibitors may therefore enhance the therapeutic effect of DSB-inducing treatments such as radiotherapy (RT). M3541 is an orally administered selective inhibitor of ATM.

METHODS: This phase I dose-escalation study evaluated the maximum-tolerated dose (MTD), recommended phase II dose(s) (RP2D), safety, pharmacokinetics (PK) and antitumor activity of M3541 in combination with fractionated palliative RT in patients with solid tumors. Fifteen patients received palliative RT (30 Gy in 10 fractions) and escalating doses of M3541 (50-300 mg administered on RT fraction days) guided by a Bayesian 2-parameter logistic …

A Guide For Managing Patients With Stage I Nsclc: Deciding Between Lobectomy, Segmentectomy, Wedge, Sbrt And Ablation-Part 3: Systematic Review Of Evidence Regarding Surgery In Compromised Patients Or Specific Tumors, Brett C. Bade, Justin D. Blasberg, Vincent J. Mase, Ulas Kumbasar, Andrew X. Li, Henry S. Park, Roy H. Decker, David C. Madoff, Whitney S. Brandt, Gavitt A. Woodard, Frank C. Detterbeck

2020-Current year OA Pubs

Background: Clinical decision-making for patients with stage I lung cancer is complex. It involves multiple options [lobectomy, segmentectomy, wedge, stereotactic body radiotherapy (SBRT), thermal ablation], weighing multiple outcomes (e.g., short-, intermediate-, long-term) and multiple aspects of each (e.g., magnitude of a difference, the degree of confidence in the evidence, and the applicability to the patient and setting at hand). A structure is needed to summarize the relevant evidence for an individual patient and to identify which outcomes have the greatest impact on the decision-making.

Methods: A PubMed systematic review from 2000-2021 of outcomes after lobectomy, segmentectomy and wedge resection in …