Medicine and Health Sciences Commons^™

Epigenetic Underpinnings Of Tumor-Immune Dynamics In Prostate Cancer Immune Suppression, Duminduni Hewa Angappulige, Nupam P Mahajan, Kiran Mahajan

2020-Current year OA Pubs

Prostate cancer (PC) is immunosuppressive and refractory to immunotherapy. Infiltration of myeloid-derived suppressor cells (MDSCs) and senescent-like neutrophils and T cell exhaustion are observed in the tumor microenvironment (TME) following androgen receptor (AR) antagonism with antiandrogens or androgen ablation. De novo post-translational acetylation of the AR, HOXB13, and H2A at K609, K13, and K130, respectively, and phosphorylation of H4 at Y88 have emerged as key epigenetic modifications associated with castration-resistant PC (CRPC). The resulting chromatin changes are integrated into cellular processes via phosphorylation of the AR, ACK1, ATPF1A, and SREBP1 at Y267, Y284, Y243/Y246, and Y673/Y951, respectively. In this review, …

Who's Essential Medicines And Aware: Recommendations On First- And Second-Choice Antibiotics For Empiric Treatment Of Clinical Infections, Lorenzo Moja, Sumanth Gandra, Et Al.

2020-Current year OA Pubs

The WHO Model List of Essential Medicines (EML) prioritizes medicines that have significant global public health value. The EML can also deliver important messages on appropriate medicine use. Since 2017, in response to the growing challenge of antimicrobial resistance, antibiotics on the EML have been reviewed and categorized into three groups: Access, Watch, and Reserve, leading to a new categorization called AWaRe. These categories were developed taking into account the impact of different antibiotics and classes on antimicrobial resistance and the implications for their appropriate use. The 2023 AWaRe classification provides empirical guidance on 41 essential antibiotics for over 30 …

Eaat4-Dependent Effects On Glutamatergic Signaling In The Cerebellar Molecular Layer, Christopher Chen

Dissertations (1934 -)

Glutamatergic signaling is fundamental to human behavior and its dysfunction is implicated in a wide range of neurological and neurodegenerative disorders. Excitatory amino-acid transporters (EAATs) – of which four primary subtypes (EAAT1, EAAT2, EAAT3, and EAAT4) exist in the human brain – are primary regulators of glutamate signaling. Endogenously-expressed at either low (EAAT4-low) or high (EAAT4-high) concentration in cerebellar Purkinje cells, EAAT4 has been shown to regulate Purkinje cell activity in the cerebellar molecular layer. However, differences in glutamatergic signaling at the circuit and single-synaptic levels in EAAT4-low and EAAT4-high regions are poorly understood. To characterize EAAT4-specific effects on excitatory …

A Targeted Proteomics Method For Quantifying Plasma Apolipoprotein Kinetics In Individual Mice Using Stable Isotope Labeling, Baohai Shao, Masami Shimizu-Albergine, Farah Kramer, Jenny E Kanter, Jay W Heinecke, Tomas Vaisar, Bettina Mittendorfer, Bruce W Patterson, Karin E Bornfeldt

2020-Current year OA Pubs

Altered apolipoprotein kinetics play a critical role in promoting dyslipidemia and atherogenesis. Human apolipoprotein kinetics have been extensively evaluated, but similar studies in mice are hampered by the lack of robust methods suitable for the small amounts of blood that can be collected at sequential time points from individual mice. We describe a targeted liquid chromatography tandem mass spectrometry method for simultaneously quantifying the stable isotope enrichment of several apolipoproteins represented by multiple peptides in serial blood samples (15 μl each) obtained after retro-orbital injection of

Mechanisms Of Neuromuscular Fatigability In Individuals With Multiple Sclerosis, Mitra Rouhani

Dissertations (1934 -)

Subjective fatigue and pain are commonly reported in people with MS (pwMS), as is neuromuscular fatigability. The dynamometry protocols used to measure neuromuscular fatigability in pwMS varied substantially in terms of components, leading to inconsistent findings regarding the extent of neuromuscular fatigability and its central and peripheral mechanisms in pwMS compared to non-MS controls. This dissertation aimed to compare neuromuscular fatigability and its underlying mechanisms following a sustained maximal to intermittent submaximal ankle dorsiflexion in pwMS, grouped by disease severity, and non-MS controls. Additionally, we aimed to determine the impact of physical activity, muscle oxidative capacity, and exercise-induced pain on …

Situation Awareness Preparation And Prebriefing: Fostering The Cognitive Processes Of Thinking Like A Nurse In Simulation, Amanda Lynn Potter

Dissertations (1934 -)

Situation awareness (SA) is linked with actionable decision-making and clinical judgment in nursing practice. The cognitive processes used in developing SA, outlined in Endsley’s (1995) model, is the framework underpinning this study and are interwoven into the National Council of State Boards of Nursing Clinical Judgment Measurement Model (NCJMM). Cultivating these cognitive processes through prebriefing and simulation designed to intentionally develop SA, is a recommended practice currently seen in aviation and military training. There is a lack of vigorous research testing whether a specific intervention during clinical simulation can develop SA in nursing students. In addition, fostering SA in the …

Using The Consolidated Framework For Implementation Research (Cfir) To Guide Implementation Of Cardio-Oncology Services, Jessica Miller Clouser, Colleen A Mcmullen, Akosua K Adu, Gretchen Wells, Amit Arbune, Jing Li

2020-Current year OA Pubs

INTRODUCTION: Cardio-oncology focuses on diagnosing and preventing adverse cardiovascular outcomes in cancer patients. Interdisciplinary cardio-oncology services address the spectrum of prevention, detection, monitoring, and treatment of cancer patients at risk of cardio-toxicity and aim to improve the continuum of cardiac care for oncology patients. The goal of this study was to engage clinician and administrative stakeholders to assess multilevel needs, barriers, and expectations regarding cardio oncology services.

METHODS: We interviewed clinicians and administrators at an academic medical center using the Consolidated Framework for Implementation Research (CFIR) to understand multilevel determinants influencing cardio-oncology service implementation. We also conducted a web-based survey …

Feasibility Of Surface-Guidance Combined With Cbct For Intra-Fractional Breath-Hold Motion Management During Ethos Rt, Taeho Kim, Eric Laugeman, Kendall Kiser, Joshua Schiff, Shanti Marasini, Alex Price, H Michael Gach, Nels Knutson, Pamela Samson, Clifford Robinson, Casey Hatscher, Lauren Henke

2020-Current year OA Pubs

PURPOSE: High-quality CBCT and AI-enhanced adaptive planning techniques allow CBCT-guided stereotactic adaptive radiotherapy (CT-STAR) to account for inter-fractional anatomic changes. Studies of intra-fractional respiratory motion management with a surface imaging solution for CT-STAR have not been fully conducted. We investigated intra-fractional motion management in breath-hold Ethos-based CT-STAR and CT-SBRT (stereotactic body non-adaptive radiotherapy) using optical surface imaging combined with onboard CBCTs.

METHODS: Ten cancer patients with mobile lower lung or upper abdominal malignancies participated in an IRB-approved clinical trial (Phase I) of optical surface image-guided Ethos CT-STAR/SBRT. In the clinical trial, a pre-configured gating window (± 2 mm in AP …

Safety And Effectiveness Of Diazepam Nasal Spray In Male And Female Patients: Post Hoc Analysis Of Data From A Phase 3 Safety Study, James W Wheless, Robert Edward Hogan, Charles S Davis, Enrique Carrazana, Adrian L Rabinowicz

2020-Current year OA Pubs

Sex differences in drug pharmacokinetics include variations in the expression of the cytochrome P450 enzymes, which are involved in the metabolism of benzodiazepines. It is unclear whether sex influences outcomes associated with intranasally administered drugs. A post hoc analysis of sex differences was conducted to evaluate the effectiveness and safety of diazepam nasal spray, which included examining changes in the number of days between seizure clusters over time (SEIzure interVAL [SEIVAL]). Diazepam nasal spray is approved for acute treatment of seizure clusters in patients with epilepsy aged ≥6 years. Data from a phase 3 safety study were used to determine …

Endoscopic Management Of Recurrent Zenker Diverticula After Failed Surgical Repairs, Sanjay Palat, Harsh Singh, Mahmoud Y Madi, Ahmad Najdat Bazarbashi

2020-Current year OA Pubs

No abstract provided.

The Impact Of Individual-Level Income Predicted From The Brfss On The Association Between Insurance Status And Overall Survival Among Adults With Cancer From The Seer Program, Justin M Barnes, Kimberly J Johnson, Nosayaba Osazuwa-Peters, Matthew B Spraker

2020-Current year OA Pubs

INTRODUCTION: Among patients with cancer in the United States, Medicaid insurance is associated with worse outcomes than private insurance and with similar outcomes as being uninsured. However, prior studies have not addressed the impact of individual-level socioeconomic status, which determines Medicaid eligibility, on the associations of Medicaid status and cancer outcomes. Our objective was to determine whether differences in cancer outcomes by insurance status persist after accounting for individual-level income.

METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was queried for 18-64 year-old individuals with cancer from 2014-2016. Individual-level income was imputed using a model trained on Behavioral Risk …

Early Treatment With Fluvoxamine, Bromhexine, Cyproheptadine, And Niclosamide To Prevent Clinical Deterioration In Patients With Symptomatic Covid-19: A Randomized Clinical Trial, Dhammika Leshan Wannigama, Angela M Reiersen, Et Al.

2020-Current year OA Pubs

BACKGROUND: Repurposed drugs with host-directed antiviral and immunomodulatory properties have shown promise in the treatment of COVID-19, but few trials have studied combinations of these agents. The aim of this trial was to assess the effectiveness of affordable, widely available, repurposed drugs used in combination for treatment of COVID-19, which may be particularly relevant to low-resource countries.

METHODS: We conducted an open-label, randomized, outpatient, controlled trial in Thailand from October 1, 2021, to June 21, 2022, to assess whether early treatment within 48-h of symptoms onset with combinations of fluvoxamine, bromhexine, cyproheptadine, and niclosamide, given to adults with confirmed mild …

The Performance Of 11 Fingertip Pulse Oximeters During Hypoxemia In Healthy Human Participants With Varied, Quantified Skin Pigment, Gregory Leeb, Leonid Shmuylovich, Et Al.

2020-Current year OA Pubs

BACKGROUND: Fingertip pulse oximeters are widely available, inexpensive, and commonly used to make clinical decisions in many settings. Device performance is largely unregulated and poorly characterised, especially in people with dark skin pigmentation.

METHODS: Eleven popular fingertip pulse oximeters were evaluated using the US Food and Drug Administration (FDA) Guidance (2013) and International Organization for Standardization Standards (ISO, 2017) in 34 healthy humans with diverse skin pigmentation utilising a controlled desaturation study with arterial oxygen saturation (SaO 2) plateaus between 70% and 100%. Skin pigmentation was assessed subjectively using a perceived Fitzpatrick Scale (pFP) and objectively using the individual typology …

Degenerative Meniscus Tears Treated Nonoperatively With Platelet-Rich Plasma Yield Variable Clinical And Imaging Outcomes: A Systematic Review, Varun Gopinatth, Anjay K Batra, Jorge Chahla, Matthew V Smith, Matthew J Matava, Robert H Brophy, Derrick M Knapik

2020-Current year OA Pubs

PURPOSE: To perform a systematic review on clinical and radiologic outcomes for meniscus tears treated nonoperatively with platelet-rich plasma (PRP).

METHODS: A literature search was performed according to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using keywords and Boolean operators in SCOPUS, PubMed, Medline, and the Cochrane Central Register for Controlled Trials in April 2023. Inclusion criteria were limited to Level I to IV human studies reporting on outcomes of meniscus tears treated nonoperatively with PRP.

RESULTS: A total of 6 studies, consisting of 184 patients, were identified. There was 1 Level I study and 5 …

Trapdoor Endarterectomy For Coral Reef Plaque Of The Paravisceral Aorta In The Modern Era, Jackson S Burton, Nathan M Droz, Vipul Khetarpaul, Luis A Sanchez, J Westley Ohman

2020-Current year OA Pubs

Coral reef atherosclerosis of the paravisceral aorta is a rare disease whose description is confined to before contemporary vascular surgical techniques. This study aims to describe the characteristics and outcomes of patients with coral reef aorta treated with trapdoor endarterectomy at a single high-volume quaternary referral center since 2010. From 2010 to 2022, 14 patients with coral reef aorta were treated with trapdoor endarterectomy. The patient data were obtained via a retrospective medical record review. The patients were predominantly women (79%) with a median age of 65 years (interquartile range [IQR], 60-70 years). The patients universally had a tobacco smoking …

Hspa9/Mortalin Inhibition Disrupts Erythroid Maturation Through A Tp53-Dependent Mechanism In Human Cd34+ Hematopoietic Progenitor Cells, Christopher Butler, Morgan Dunmire, Jaebok Choi, Gabor Szalai, Anissa Johnson, Wei Lei, Xin Chen, Liang Liu, Wei Li, Matthew J Walter, Tuoen Liu

2020-Current year OA Pubs

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic stem cell malignancies characterized by abnormal hematopoietic cell maturation, increased apoptosis of bone marrow cells, and anemia. They are the most common myeloid blood cancers in American adults. The full complement of gene mutations that contribute to the phenotypes or clinical symptoms in MDS is not fully understood. Around 10%-25% of MDS patients harbor an interstitial heterozygous deletion on the long arm of chromosome 5 [del(5q)], creating haploinsufficiency for a large set of genes, including HSPA9. The HSPA9 gene encodes for the protein mortalin, a highly conserved heat shock protein …

Quality Assurance For Focused Ultrasound-Induced Blood-Brain Barrier Opening Procedure Using Passive Acoustic Detection, Chih-Yen Chien, Lu Xu, Jinyun Yuan, Siaka Fadera, Andrew H Stark, Umeshkumar Athiraman, Eric C Leuthardt, Hong Chen

2020-Current year OA Pubs

BACKGROUND: Focused ultrasound (FUS) combined with microbubbles is a promising technique for noninvasive, reversible, and spatially targeted blood-brain barrier opening, with clinical trials currently ongoing. Despite the fast development of this technology, there is a lack of established quality assurance (QA) strategies to ensure procedure consistency and safety. To address this challenge, this study presents the development and clinical evaluation of a passive acoustic detection-based QA protocol for FUS-induced blood-brain barrier opening (FUS-BBBO) procedure.

METHODS: Ten glioma patients were recruited to a clinical trial for evaluating a neuronavigation-guided FUS device. An acoustic sensor was incorporated at the center of the …

Adipose Tissue Peroxisomal Lipid Synthesis Orchestrates Obesity And Insulin Resistance Through Lxr-Dependent Lipogenesis, Brian Kleiboeker, Anyuan He, Min Tan, Dongliang Lu, Donghua Hu, Xuejing Liu, Parniyan Goodarzi, Fong-Fu Hsu, Babak Razani, Clay F Semenkovich, Irfan J Lodhi

2020-Current year OA Pubs

OBJECTIVE: Adipose tissue mass is maintained by a balance between lipolysis and lipid storage. The contribution of adipose tissue lipogenesis to fat mass, especially in the setting of high-fat feeding, is considered minor. Here we investigated the effect of adipose-specific inactivation of the peroxisomal lipid synthetic protein PexRAP on fatty acid synthase (FASN)-mediated lipogenesis and its impact on adiposity and metabolic homeostasis.

METHODS: To explore the role of PexRAP in adipose tissue, we metabolically phenotyped mice with adipose-specific knockout of PexRAP. Bulk RNA sequencing was used to determine transcriptomic responses to PexRAP deletion and

RESULTS: Adipose-specific PexRAP deletion promoted diet-induced …

Practical Considerations For Delandistrogene Moxeparvovec Gene Therapy In Patients With Duchenne Muscular Dystrophy, Jerry R Mendell, Crystal Proud, Craig M Zaidman, Stefanie Mason, Eddie Darton, Shufang Wang, Christoph Wandel, Alexander P Murphy, Eugenio Mercuri, Francesco Muntoni, Craig M Mcdonald

2020-Current year OA Pubs

BACKGROUND: Delandistrogene moxeparvovec is a gene transfer therapy approved in the United States, United Arab Emirates, and Qatar for the treatment of ambulatory patients aged four through five years with a confirmed Duchenne muscular dystrophy (DMD)-causing mutation in the DMD gene. This therapy was developed to address the underlying cause of DMD through targeted skeletal, respiratory, and cardiac muscle expression of delandistrogene moxeparvovec micro-dystrophin, an engineered, functional dystrophin protein.

METHODS: Drawing on clinical trial experience from Study 101 (NCT03375164), Study 102 (NCT03769116), and ENDEAVOR (Study 103; NCT04626674), we outline practical considerations for delandistrogene moxeparvovec treatment.

RESULTS: Before infusion, the following …

T-Cell Acute Lymphoblastic Leukemia/Lymphoma (T-All) With Negative Screening Immaturity Markers And Gamma-Delta Receptor Expression, Maria Faraz, Anita Parmigiani, Nina Monkash, Anne Chen

2020-Current year OA Pubs

T-cell acute lymphoblastic leukemia/lymphoma (T-ALL) is characterized by the combination of T-cell lineage and the presence of immaturity marker(s). Sometimes, the most common immaturity markers for initial flow cytometry screening in T-ALL may be negative, which can be a diagnostic pitfall. When a lack of common first-line immaturity markers is encountered in combination with gamma/delta T-cell receptor expression, a misdiagnosis of mature gamma-delta T-cell leukemia/lymphoma could be rendered. Here, we discuss two T-ALL cases with the absence of common flow cytometry immaturity markers and positive gamma/delta receptor expression.

Changing Perceptions About The Dermatology Residency Application Process Among Applicants And Program Directors: 2020-2022, Fatuma-Ayaan B. Rinderknecht, Kandice C. Bailey, Danielle E. Novack, Adena E. Rosenblatt, Dana Dunleavy, Bobby D. Naemi, Ilana S. Rosman, Ammar Ahmed, Scott Worswick

2020-Current year OA Pubs

Importance Over the last two years, dermatology has undergone significant reforms in the residency application process in efforts to reduce applicant stress, increase equity, and due to the COVID-19 pandemic. Objective We aimed to determine applicant and program director (PD) perspectives in implementing these changes over the last two application cycles. Design, setting, and participants Anonymous online surveys were administered by the Association of American Medical Colleges (AAMC) to PDs and applicants from the 2021-2022 dermatology residency application cycle. These results were compared with similar online surveys distributed after the 2020-2021 cycle. Results Coordinated interview release was introduced in the …

Threat Experiences Moderate The Link Between Hippocampus Volume And Depression Symptoms Prospectively In Adolescence, Max P Herzberg, Meriah L Dejoseph, Joan Luby, Deanna M Barch

2020-Current year OA Pubs

Identifying neuroimaging risk markers for depression has been an elusive goal in psychopathology research. Despite this, smaller hippocampal volume has emerged as a potential risk marker for depression, with recent research suggesting this association is moderated by family income. The current pre-registered study aimed to replicate and extend these findings by examining the moderating role of family income and three dimensions of environmental experience on the link between hippocampus volume and later depression. Data were drawn from the Adolescent Brain Cognitive Development (ABCD) study and were comprised of 6693 youth aged 9-10 years at baseline. Results indicated that psychosocial threat …

Anatomical Registration Of Intracranial Electrodes. Robust Model-Based Localization And Deformable Smooth Brain-Shift Compensation Methods, Alejandro Omar Blenkmann, Sabine Liliana Leske, Anaïs Llorens, Jack J Lin, Edward F Chang, Peter Brunner, Gerwin Schalk, Jugoslav Ivanovic, Pål Gunnar Larsson, Robert Thomas Knight, Tor Endestad, Anne-Kristin Solbakk

2020-Current year OA Pubs

BACKGROUND: Intracranial electrodes are typically localized from post-implantation CT artifacts. Automatic algorithms localizing low signal-to-noise ratio artifacts and high-density electrode arrays are missing. Additionally, implantation of grids/strips introduces brain deformations, resulting in registration errors when fusing post-implantation CT and pre-implantation MR images. Brain-shift compensation methods project electrode coordinates to cortex, but either fail to produce smooth solutions or do not account for brain deformations.

NEW METHODS: We first introduce GridFit, a model-based fitting approach that simultaneously localizes all electrodes' CT artifacts in grids, strips, or depth arrays. Second, we present CEPA, a brain-shift compensation algorithm combining orthogonal-based projections, spring-mesh models, …

Enhancing Impact: A Call To Action For Equitable Implementation Science, Rachel C Shelton, Ross C Brownson

2020-Current year OA Pubs

Despite investments in evidence-based interventions and Implementation Science, most evidence-based interventions are not widely or routinely adopted, delivered, or sustained in many real-world community and healthcare settings. This gap is even greater in settings and populations experiencing numerous social and structural barriers to health, with important implications for persistent patterns in health inequities. In this Viewpoint, as part of a Special Issue on Advancing the Adaptability of Chronic Disease Prevention and Management through Implementation Science, we outline seven calls to action for the field of Implementation Science, with the goal of encouraging researchers, practitioners, and funders to be more intentional …

Exploring The Association Between Weight Loss-Inducing Medications And Multiple Sclerosis: Insights From The Fda Adverse Event Reporting System Database, Afsaneh Shirani, Anne H Cross, Olaf Stuve

2020-Current year OA Pubs

BACKGROUND: Several studies have demonstrated that early childhood and adolescent obesity are risk factors for multiple sclerosis (MS) susceptibility. Obesity is thought to share inflammatory components with MS through overproduction of pro-inflammatory adipokines (e.g., leptin) and reduction of anti-inflammatory adipokines (e.g, adiponectin). Recently, drug repurposing (i.e. identifying new indications for existing drugs) has garnered significant attention. The US Food and Drug Administration Adverse Event Reporting System (FAERS) database serves not only as a resource for mining adverse drug reactions and safety signals but also for identifying inverse associations and potential medication repurposing opportunities.

OBJECTIVE: We aimed to explore the association …

Incidence And Mortality Of Covid-19-Associated Invasive Fungal Infections Among Critically Ill Intubated Patients: A Multicenter Retrospective Cohort Analysis, Julio C Zuniga-Moya, Benjamin Papadopoulos, Armaghan-E-Rehman Mansoor, Patrick B Mazi, Adriana M Rauseo, Andrej Spec

2020-Current year OA Pubs

BACKGROUND: An association between coronavirus disease 2019 (COVID-19)-associated invasive fungal infections (CAIFIs) and high mortality among intubated patients has been suggested in previous research. However, some of the current evidence was derived from small case series and multicenter studies conducted during different waves of the COVID-19 pandemic. We examined the incidence of CAIFIs and their associated mortality using a large, multicenter COVID-19 database built throughout the pandemic.

METHODS: We conducted a retrospective analysis of the National COVID Cohort Collaborative (N3C) database collected from 76 medical centers in the United States between January 2020 and August 2022. Patients were 18 years …

Medicaid Eligibility Loss Among Dual-Eligible Beneficiaries Before And During Covid-19 Public Health Emergency, Yanlei Ma, Eric T Roberts, Kenton J Johnston, E John Orav, Jose F Figueroa

2020-Current year OA Pubs

IMPORTANCE: Medicaid coverage loss can substantially compromise access to and affordability of health care for dual-eligible beneficiaries. The extent to which this population lost Medicaid coverage before and during the COVID-19 public health emergency (PHE) and the characteristics of beneficiaries more at risk for coverage loss are currently not well known.

OBJECTIVE: To assess the loss of Medicaid coverage among dual-eligible beneficiaries before and during the first year of the PHE, and to examine beneficiary-level and plan-level factors associated with heightened likelihood of losing Medicaid.

DESIGN, SETTING, AND PARTICIPANTS: This repeated cross-sectional study used national Medicare data to estimate annual …

A Protective Role For Type I Interferon Signaling Following Infection With Mycobacterium Tuberculosis Carrying The Rifampicin Drug Resistance-Conferring Rpob Mutation H445y, Suhas Bobba, Kuldeep S. Chauhan, Sadia Akter, Shibali Das, Ekansh Mittal, Barun Mathema, Jennifer A. Philips, Shabaana A. Khader

2020-Current year OA Pubs

Interleukin-1 (IL-1) signaling is essential for controlling virulent Mycobacterium tuberculosis (Mtb) infection since antagonism of this pathway leads to exacerbated pathology and increased susceptibility. In contrast, the triggering of type I interferon (IFN) signaling is associated with the progression of tuberculosis (TB) disease and linked with negative regulation of IL-1 signaling. However, mice lacking IL-1 signaling can control Mtb infection if infected with an Mtb strain carrying the rifampin-resistance conferring mutation H445Y in its RNA polymerase β subunit (rpoB-H445Y Mtb). The mechanisms that govern protection in the absence of IL-1 signaling during rpoB-H445Y Mtb infection are unknown. In this study, …

Interstate Highway Connections And Traced Gun Transfers Between The 48 Contiguous United States, Leah Roberts, Mark H Hoofnagle, Brady Bushover, Ariana N Gobaud, Christina A Mehranbod, Carolyn Fish, Christopher N Morrison

2020-Current year OA Pubs

IMPORTANCE: Interstate gun flow has critical implications for gun violence prevention, as gun transfers across state lines can undermine local gun control policies.

OBJECTIVE: To identify possible gun trafficking routes along interstate highways in the US.

DESIGN, SETTING, AND PARTICIPANTS: This repeated-measures, ecological, cross-sectional study used data from the Bureau of Alcohol, Tobacco, Firearms and Explosives from January 1, 2010, to December 31, 2019, to examine associations between interstate connections via 13 highways that each spanned at least 1000 miles and interstate traced gun transfer counts for the 48 contiguous United States. Analyses were completed in November 2023.

EXPOSURES: Characteristics …

Loncastuximab Tesirine In Relapsed/Refractory Diffuse Large B-Cell Lymphoma: Long-Term Efficacy And Safety From The Phase Ii Lotis-2 Study, Paolo F. Caimi, Brad S Kahl, Et Al.

2020-Current year OA Pubs

Therapies that demonstrate durable, long-term responses with manageable safety and tolerability are needed for patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). Loncastuximab tesirine (loncastuximab tesirine-lpyl [Lonca]), an anti-CD19 antibody conjugated to a potent pyrrolobenzodiazepine dimer, demonstrated single-agent antitumor activity in the pivotal phase II LOTIS-2 study in heavily pretreated patients with R/R DLBCL. Here we present updated efficacy and safety analyses from LOTIS-2, performed for all patients and in subsets of patients with a complete response (CR), including patients with CR who were event-free (no progressive disease or death) for ≥1 year and ≥2 years from cycle 1, …