Medicine and Health Sciences Commons^™

Liquid Biopsy In Triple-Negative Breast Cancer: Unlocking The Potential Of Precision Oncology, R Mazzeo, J Sears, L Palmero, S Bolzonello, A A Davis, L Gerratana, F Puglisi

2020-Current year OA Pubs

In the era of precision oncology, the management of triple-negative breast cancer (TNBC) is rapidly changing and becoming more complicated with a variety of chemotherapy, immunotherapy, and targeted treatment options. Currently, TNBC treatment is based on prognostic and predictive factors including immunohistochemical biomarkers [e.g. programmed death-ligand 1 (PD-L1)] and germline BRCA mutations. Given the current limitation of existing biomarkers, liquid biopsies may serve as clinically useful tools to determine treatment efficacy and response in both the (neo)adjuvant and metastatic settings, for detecting early relapse, and for monitoring clonal evolution during treatment. In this review, we comprehensively summarize current and future …

Three Classes Of Propofol Binding Sites On Gabaa Receptors, Zi-Wei Chen, Satyanarayana M Chintala, John Bracamontes, Yusuke Sugasawa, Spencer R Pierce, Balazs R Varga, Edward H Smith, Christopher J Edge, Nicholas P Franks, Wayland W L Cheng, Gustav Akk, Alex S Evers

2020-Current year OA Pubs

Propofol is a widely used anesthetic and sedative that acts as a positive allosteric modulator of gamma-aminobutyric acid type A (GABA

New Insights Into Innate Immunity In Alzheimer's Disease: From Apoe Protective Variants To Therapies, Yun Chen, David M Holtzman

2020-Current year OA Pubs

Recent discoveries of rare variants of human APOE may shed light on novel therapeutic strategies for Alzheimer's disease (AD). Here, we highlight the newly identified protective variant [APOE3 Christchurch (APOE3ch, R136S)] as an example. We summarize human AD and mouse amyloidosis and tauopathy studies from the past 5 years that have been associated with this R136S variant. We also propose a potential mechanism for how this point mutation might lead to protection against AD pathology, from the molecular level, to cells, to mouse models, and potentially, to humans. Lastly, we extend our discussion of the recent insights gained regarding different …

Multi-Site Eeg Studies In Early Infancy: Methods To Enhance Data Quality, Abigail Dickinson, John Zempel, Natasha Marrus, John R Pruett Jr, Et Al.

2020-Current year OA Pubs

Brain differences linked to autism spectrum disorder (ASD) can manifest before observable symptoms. Studying these early neural precursors in larger and more diverse cohorts is crucial for advancing our understanding of developmental pathways and potentially facilitating earlier identification. EEG is an ideal tool for investigating early neural differences in ASD, given its scalability and high tolerability in infant populations. In this context, we integrated EEG into an existing multi-site MRI study of infants with a higher familial likelihood of developing ASD. This paper describes the comprehensive protocol established to collect longitudinal, high-density EEG data from infants across five sites as …

Caregiver Wellness After Traumatic Brain Injury (Cg-Well): Protocol For A Randomized Clinical Trial, Natalie Kreitzer, Stephanie Fink, Opeolu Adeoye, Brad Kurowski G, Shari Wade, Heidi Sucharew, Tamilyn Bakas

2020-Current year OA Pubs

INTRODUCTION: After injury, survivors of moderate to severe traumatic brain injury (msTBI) depend on informal family caregivers. Upwards of 77 % of family caregivers experience poor outcomes, such as adverse life changes, poor health-related quality of life, and increased depressive symptoms. Caregivers frequently report minimal support or training to prepare them for their new role. The majority of previously developed caregiver and caregiver/survivor dyad interventions after msTBI focus on providing information to either survivors only, or to long-term caregivers, rather than to the new caregiver. This manuscript describes the protocol of an ongoing randomized control trial, Caregiver Wellness after TBI …

Development And Optimization Of A Diluted Whole Blood Elispot Assay To Test Immune Function, Ricardo F Ungaro, Richard S Hotchkiss, Isaiah R Turnbull, Et Al.

2020-Current year OA Pubs

Sepsis remains a leading cause of death worldwide with no proven immunomodulatory therapies. Stratifying Patient Immune Endotypes in Sepsis ('SPIES') is a prospective, multicenter observational study testing the utility of ELISpot as a functional bioassay specifically measuring cytokine-producing cells after stimulation to identify the immunosuppressed endotype, predict clinical outcomes in septic patients, and test potential immune stimulants for clinical development. Most ELISpot protocols call for the isolation of PBMC prior to their inclusion in the assay. In contrast, we developed a diluted whole blood (DWB) ELISpot protocol that has been validated across multiple laboratories. Heparinized whole blood was collected from …

Prophylactic Antibiotics For Excision Of Premalignant Vulvar Lesions: A Pilot Randomized Controlled Trial, Mary M Mullen, Whitney R Grither, Hannah Millimet, David G Mutch, Andrea R Hagemann, Carolyn K Mccourt, Matthew A Powell, Premal H Thaker, Dineo Khabele, Lindsay M Kuroki

2020-Current year OA Pubs

No prospective data have been described to inform guidelines on antibiotic prophylaxis for partial vulvectomies. Thus, we conducted a single-center, pilot, double-blind randomized controlled trial to assess the effectiveness of prophylactic antibiotics to prevent wound complications after partial vulvectomies. Patients were randomly assigned 1:1 to preoperative antibiotics or no preoperative antibiotics. The primary outcome of 30-day postoperative wound complications occurred in 31 (62 %) of all patients, with no differences between groups. The most common wound complications were superficial separation (54.2 % antibiotic prophylaxis vs. 65.3 % no prophylaxis, p = 0.37) and surgical site infection (0 % antibiotic prophylaxis …

The Dallas Donation After Circulatory Death Transplantation Summit: Expanding Donation After Circulatory Death Procedures Through Process Improvement, Broader Utilization, And Innovation, Michele Finotti, William C. Chapman, Et Al.

2020-Current year OA Pubs

Despite a significant increase in utilization over the past decade, the number of donation after circulatory death (DCD) organs that are procured and transplanted in the United States (US) remains well below its potential. There is still room for expansion, as utilizing DCD organs to the fullest extent is currently the most viable solution to the persistent mismatch between supply and demand in transplantation. We convened a multidisciplinary transplantation summit to examine various aspects of DCD, with faculty members from around the world with clinical and academic interest in DCD donation and transplantation, including abdominal and cardiothoracic surgeons, organ procurement …

Cardiovascular Outcomes, Health-Promoting Behaviors, And Social Determinants: Structural Racism And The Behavioral Risk Factor Surveillance System, Jaclyn K. Schwartz, Emily A. Kringle, Suzanne Perea Burns, Catherine R. Hoyt, Kelly M. Harris, Sami Tayeb

2020-Current year OA Pubs

No abstract provided.

Effect Of Universal Masking On Non-Severe Acute Respiratory Syndrome Coronavirus 2 Healthcare-Associated Respiratory Viral Infections, Satish Munigala, Patrick R Ching, Helen Wood, R J Waken, Josephine Fox, Heather Gasama, Robert Russell, Melanie L Yarbrough, David K Warren

2020-Current year OA Pubs

BACKGROUND: Respiratory viral infections are common and are a major cause of morbidity and mortality. We evaluated the impact of universal masking implemented during the coronavirus disease 2019 (COVID-19) pandemic on other healthcare-associated respiratory viral infections (HA-RIs) in an academic medical center.

METHODS: A retrospective cohort study was performed among all inpatients aged ≥18 years admitted between 1 May 2019 and 30 June 2022. Universal masking was implemented in May 2020 at our hospital and state-level mask mandates had been lifted by May 2021. We evaluated and compared the HA-RI rates, adjusted for monthly community-onset viral infections, during the premasking …

Generation Of An Induced Pluripotent Stem Cell Line (Biortci001-A) From A Healthy Adult Indigenous Nigerian Participant, Zaid Muhammad, Phoebe W Brown, Larema Babazau, Abdulrahman I Alkhamis, Baba W Goni, Haruna A Nggada, Kefas M Mbaya, Selina Wray, Isa H Marte, Celeste M Karch, Louise C Serpell, Mahmoud B Maina

2020-Current year OA Pubs

Genetic backgrounds influence cellular phenotypes, drug responses, and health outcomes, yet most human iPSC lines are derived from individuals of European descent, with lines from indigenous Africans particularly scarce. Addressing this gap, we generated iPSCs from dermal fibroblasts of a healthy 60-year-old indigenous Nigerian male of the Babur ethnic group using Sendai virus. The iPSC line displayed a normal karyotype, was characterized for pluripotency markers and differentiated into neural progenitor cells and astrocytes. To enhance African representation in research, this iPSC line will be available to the scientific community, with ongoing efforts focused on creating an open-access African iPSC biobank. …

Discovery Of Genomic And Transcriptomic Pleiotropy Between Kidney Function And Soluble Receptor For Advanced Glycation End Products Using Correlated Meta-Analyses: The Long Life Family Study, Mary F Feitosa, Shiow J Lin, Sandeep Acharya, Bharat Thyagarajan, Mary K Wojczynski, Allison L Kuipers, Alexander Kulminski, Kaare Christensen, Joseph M Zmuda, Michael R Brent, Michael A Province

2020-Current year OA Pubs

Patients with chronic kidney disease (CKD) have increased oxidative stress and chronic inflammation, which may escalate the production of advanced glycation end-products (AGEs). High soluble receptor for AGE (sRAGE) and low estimated glomerular filtration rate (eGFR) levels are associated with CKD and aging. We evaluated whether eGFR calculated from creatinine and cystatin C share pleiotropic genetic factors with sRAGE. We employed whole-genome sequencing and correlated meta-analyses on combined genome-wide association study (GWAS) p-values in 4182 individuals (age range: 24-110) from the Long Life Family Study (LLFS). We also conducted transcriptome-wide association studies (TWAS) on whole blood in a subset of …

Pkmyt1 Is A Marker Of Treatment Response And A Therapeutic Target For Cdk4/6 Inhibitor-Resistance In Er+ Breast Cancer, Anran Chen, Cynthia X Ma, Et Al.

2020-Current year OA Pubs

Endocrine therapies (ET) with cyclin-dependent kinase 4/6 (CDK4/6) inhibition are the standard treatment for estrogen receptor-α-positive (ER+) breast cancer, however drug resistance is common. In this study, proteogenomic analyses of patient-derived xenografts (PDXs) from patients with 22 ER+ breast cancer demonstrated that protein kinase, membrane-associated tyrosine/threonine one (PKMYT1), a WEE1 homolog, is estradiol (E2) regulated in E2-dependent PDXs and constitutively expressed when growth is E2-independent. In clinical samples, high PKMYT1 mRNA levels associated with resistance to both ET and CDK4/6 inhibition. The PKMYT1 inhibitor lunresertib (RP-6306) with gemcitabine selectively and synergistically reduced the viability of ET and palbociclib-resistant ER+ breast …

Early Detection Of Malignant And Premalignant Peripheral Nerve Tumors Using Cell-Free Dna Fragmentomics, R Taylor Sundby, Paul A Jones, Divya Srihari, Amy E Armstrong, Stacey Chamberlain, Sanita Burgic, Kara Weekley, John S A Chrisinger, Angela C Hirbe, Et Al.

2020-Current year OA Pubs

PURPOSE: Early detection of neurofibromatosis type 1 (NF1)-associated peripheral nerve sheath tumors (PNST) informs clinical decision-making, enabling early definitive treatment and potentially averting deadly outcomes. In this study, we describe a cell-free DNA (cfDNA) fragmentomic approach that distinguishes nonmalignant, premalignant, and malignant forms of PNST in the cancer predisposition syndrome, NF1.

EXPERIMENTAL DESIGN: cfDNA was isolated from plasma samples of a novel cohort of 101 patients with NF1 and 21 healthy controls and underwent whole-genome sequencing. We investigated diagnosis-specific signatures of copy-number alterations with in silico size selection as well as fragment profiles. Fragmentomics were analyzed using complementary feature types: …

A Modular Chemigenetic Calcium Indicator For Multiplexed In Vivo Functional Imaging, Helen Farrants, Christian Monroy Hernandez, Yao Chen, Et Al.

2020-Current year OA Pubs

Genetically encoded fluorescent calcium indicators allow cellular-resolution recording of physiology. However, bright, genetically targetable indicators that can be multiplexed with existing tools in vivo are needed for simultaneous imaging of multiple signals. Here we describe WHaloCaMP, a modular chemigenetic calcium indicator built from bright dye-ligands and protein sensor domains. Fluorescence change in WHaloCaMP results from reversible quenching of the bound dye via a strategically placed tryptophan. WHaloCaMP is compatible with rhodamine dye-ligands that fluoresce from green to near-infrared, including several that efficiently label the brain in animals. When bound to a near-infrared dye-ligand, WHaloCaMP shows a 7× increase in fluorescence …

Cross-Ancestry Genetic Investigation Of Schizophrenia, Cannabis Use Disorder, And Tobacco Smoking, Emma C Johnson, Isabelle Austin-Zimmerman, Hayley H A Thorpe, Daniel F Levey, David A A Baranger, Sarah M C Colbert, Ditte Demontis, Jibran Y Khokhar, Lea K Davis, Howard J Edenberg, Marta Di Forti, Sandra Sanchez-Roige, Joel Gelernter, Arpana Agrawal

2020-Current year OA Pubs

Individuals with schizophrenia frequently experience co-occurring substance use, including tobacco smoking and heavy cannabis use, and substance use disorders. There is interest in understanding the extent to which these relationships are causal, and to what extent shared genetic factors play a role. We explored the relationships between schizophrenia (Scz; European ancestry N = 161,405; African ancestry N = 15,846), cannabis use disorder (CanUD; European ancestry N = 886,025; African ancestry N = 120,208), and ever-regular tobacco smoking (Smk; European ancestry N = 805,431; African ancestry N = 24,278) using the largest available genome-wide studies of these phenotypes in individuals of …

A Retrospective Assessment Of Guideline Adherence And Treatment Outcomes From Clostridioides Difficile Infection Following The Idsa 2021 Clinical Guideline Update: Clostridioides Difficile Infection, Erik R Dubberke, Qinghua Li, Engels N Obi, Vladimir Turzhitsky, Fakhar Siddiqui, Brian H Nathanson

2020-Current year OA Pubs

BACKGROUND: The 2021 update to the Infectious Diseases Society of America

METHODS: This retrospective, observational study used the PINC AI Healthcare Database on adult patients who received CDI treatment between 1/2020 and 6/2021 (pre period) and between 10/2021 and 9/2022 (post period). We examined treatment patterns of fidaxomicin, vancomycin, and metronidazole, as well as clinical and health care resource use outcomes of patients treated exclusively with fidaxomicin vs vancomycin, using nearest-neighbor propensity matching and hierarchical regression methods. As a sensitivity analysis, we repeated the fidaxomicin vs vancomycin comparisons among patients with recurrent and nonrecurrent index infections.

RESULTS: A total of …

Sequential Early-Life Viral Infections Modulate The Microbiota And Adaptive Immune Responses To Systemic And Mucosal Vaccination, Yuhao Li, Jerome M. Molleston, Crystal Lovato, Jasmine Wright, Isabel Erickson, Duyen Bui, Andrew H. Kim, Harshad Ingle, Somya Aggarwal, Lila S Nolan, Ahmed O. Hassan, Lynne Foster, Michael S. Diamond, Megan T. Baldridge

2020-Current year OA Pubs

Increasing evidence points to the microbial exposome as a critical factor in maturing and shaping the host immune system, thereby influencing responses to immune challenges such as infections or vaccines. To investigate the effect of early-life viral exposures on immune development and vaccine responses, we inoculated mice with six distinct viral pathogens in sequence beginning in the neonatal period, and then evaluated their immune signatures before and after intramuscular or intranasal vaccination against SARS-CoV-2. Sequential viral infection drove profound changes in all aspects of the immune system, including increasing circulating leukocytes, altering innate and adaptive immune cell lineages in tissues, …

Ms Treatment De-Escalation: Review And Commentary, Krzysztof Selmaj, Hans-Peter Hartung, Marcin P Mycko, Igor Selmaj, Anne H Cross

2020-Current year OA Pubs

Almost all currently licensed disease-modifying therapies (DMTs) for MS treatment require prolonged if not lifelong administration. Yet, as people age, the immune system has increasingly reduced responsiveness, known as immunosenescence. Many MS DMTs reduce the responsiveness of the immune system, increasing the risks for infections and possibly cancers. As people with MS (pwMS) age, it is recognized that inflammatory MS activity declines. Several studies have addressed de-escalation of DMTs for relapsing MS under special circumstances. Here, we review evidence for de-escalating DMTs as a strategy that is particularly relevant to pwMS of older age. Treatment de-escalation can involve various strategies, …

Metabolically Active Neutrophils Represent A Permissive Niche For Mycobacterium Tuberculosis, J Tucker Andrews, G V R Krishna Prasad, Jennifer A Philips, Et Al.

2020-Current year OA Pubs

Mycobacterium tuberculosis (Mtb)-infected neutrophils are often found in the airways of patients with active tuberculosis (TB), and excessive recruitment of neutrophils to the lung is linked to increased bacterial burden and aggravated pathology in TB. The basis for the permissiveness of neutrophils for Mtb and the ability to be pathogenic in TB has been elusive. Here, we identified metabolic and functional features of neutrophils that contribute to their permissiveness in Mtb infection. Using single-cell metabolic and transcriptional analyses, we found that neutrophils in the Mtb-infected lung displayed elevated mitochondrial metabolism, which was largely attributed to the induction of activated neutrophils …

Type I Ifn Signaling In The Absence Of Irgm1 Promotes M. Tuberculosis Replication In Immune Cells By Suppressing T Cell Responses, Sumanta K Naik, Michael E Mcnehlan, Yassin Mreyoud, Rachel L Kinsella, Asya Smirnov, Chanchal Sur Chowdhury, Samuel R Mckee, Neha Dubey, Reilly Woodson, Darren Kreamalmeyer, Christina L Stallings

2020-Current year OA Pubs

Polymorphisms in the IRGM gene are associated with susceptibility to tuberculosis in humans. A murine ortholog of Irgm, Irgm1, is also essential for controlling Mycobacterium tuberculosis (Mtb) infection in mice. Multiple processes have been associated with IRGM1 activity that could impact the host response to Mtb infection, including roles in autophagy-mediated pathogen clearance and expansion of activated T cells. However, what IRGM1-mediated pathway is necessary to control Mtb infection in vivo and the mechanistic basis for this control remains unknown. We dissected the contribution of IRGM1 to immune control of Mtb pathogenesis in vivo and found that Irgm1 deletion leads …

Assessing The Response Results Of An Mhealth-Based Patient Experience Survey Among People Receiving Hiv Care In Lusaka, Zambia: Cohort Study, Jacob Mutale, Kombatende Sikombe, Boroma Mwale, Mwansa Lumpa, Sandra Simbeza, Chama Bukankala, Njekwa Mukamba, Aaloke Mody, Laura K Beres, Charles B Holmes, Carolyn Bolton Moore, Elvin H Geng, Izukanji Sikazwe, Jake M Pry

2020-Current year OA Pubs

BACKGROUND: This pilot study evaluates the effectiveness of mobile talk-time incentives in maintaining participation in a longitudinal mobile health (mHealth) data collection program among people living with HIV in Lusaka, Zambia. While mHealth tools, such as mobile phone surveys, provide vital health feedback, optimal incentive strategies to ensure long-term engagement remain limited. This study explores how different incentive levels affect response rates in multiple survey rounds, providing insights into effective methods for encouraging ongoing participation, especially in the context of Zambia's prepaid mobile system and multi-SIM usage, a common practice in sub-Saharan Africa.

OBJECTIVE: This study aimed to assess the …

Continuous Adaptation Of Conversation Aids For Uterine Fibroids Treatment Options In A Four-Year Multi-Center Implementation Project, Danielle Schubbe, Tessa Madden, Et Al.

2020-Current year OA Pubs

BACKGROUND: Fibroids are non-cancerous uterine growths that can cause symptoms impacting quality of life. The breadth of treatment options allows for patient-centered preference. While conversation aids are known to facilitate shared decision making, the implementation of these aids for uterine fibroids treatments is limited. We aimed to develop two end-user-acceptable uterine fibroids conversation aids for an implementation project. Our second aim was to outline the adaptations that were made to the conversation aids as implementation occurred.

METHODS: We used a multi-phase user-centered participatory approach to develop a text-based and picture-enhanced conversation aid for uterine fibroids. We conducted a focus group …

Negative Effect Of Treatment With Mglur5 Negative Allosteric Modulator Afq056 On Blood Biomarkers In Young Individuals With Fragile X Syndrome, Dragana Protic, Stephanie Morris, Et Al.

2020-Current year OA Pubs

BACKGROUND: Fragile X syndrome, with an approximate incidence rate of 1 in 4000 males to 1 in 8000 females, is the most prevalent genetic cause of heritable intellectual disability and the most common monogenic cause of autism spectrum disorder. The full mutation of the Fragile X Messenger Ribonucleoprotein-1 gene, characterized by an expansion of CGG trinucleotide repeats (>200 CGG repeats), leads to fragile X syndrome. Currently, there are no targeted treatments available for fragile X syndrome. In a recent large multi-site trial, FXLEARN, the effects of the mGluR5 negative allosteric modulator, AFQ056 (mavoglurant), were investigated, but did not show …

Inorganic Polyphosphate Promotes Colorectal Cancer Growth Via Trpm8 Receptor Signaling Pathway, Valentina Arrè, Chen Shen, Et Al.

2020-Current year OA Pubs

BACKGROUND: Colorectal cancer (CRC) is characterized by a pro-inflammatory microenvironment and features high-energy-supply molecules that assure tumor growth. A still less studied macromolecule is inorganic polyphosphate (iPolyP), a high-energy linear polymer that is ubiquitous in all forms of life. Made up of hundreds of repeated orthophosphate units, iPolyP is essential for a wide variety of functions in mammalian cells, including the regulation of proliferative signaling pathways. Some evidence has suggested its involvement in carcinogenesis, although more studies need to be pursued. Moreover, iPolyP regulates several homeostatic processes in animals, spanning from energy metabolism to blood coagulation and tissue regeneration.

RESULTS: …

A Multicenter, Randomized, Non-Comparative, Phase Ii Study Of Nivolumab ± Ipilimumab For Patients With Metastatic Sarcoma (Alliance A091401): Expansion Cohorts And Correlative Analyses, Nathan D Seligson, James L Chen, Austin C Goodrich, Brian A Van Tine, Jordan D Campbell, Allison L Richards, Cristina R Antonescu, David A Liebner, Mohammed M Milhem, Howard Streicher, William D Tap, Gary K Schwartz, Suzanne George, Sandra P D'Angelo

2020-Current year OA Pubs

BACKGROUND: In this open-label, randomized, non-comparative, multicenter phase II study (Alliance A091401) we report on three expansion cohorts treated with nivolumab (N) with and without ipilimumab (N+I) and provide a multi-omic correlative analysis of actionable biomarkers.

METHODS: Patients were randomized (non-comparative) to receive either N or N+I. The primary endpoint was a 6-month confirmed response rate (CRR) defined by Response Evaluation Criteria in Solid Tumors version 1.1. Secondary endpoints included treatment-related adverse events (TRAEs), progression-free survival, and overall survival. Multi-omic correlative analyses were conducted using samples from both the primary and expansion cohorts.

RESULTS: A total of 66 patients were …

How To Utilize Current Guidelines To Manage Patients With Cancer At High Risk For Heart Failure, Michelle Bloom, Jose A Alvarez-Cardona, Sarju Ganatra, Ana Barac, Iskra Pusic, Daniel Lenihan, Susan Dent

2020-Current year OA Pubs

Heart failure (HF) in patients with cancer is associated with high morbidity and mortality. The success of cancer therapy has resulted in an exponential rise in the population of cancer survivors, however cardiovascular disease (CVD) is now a major life limiting condition more than 5 years after cancer diagnosis [Sturgeon, Deng, Bluethmann, et al 40(48):3889-3897, 2019]. Prevention and early detection of CVD, including cardiomyopathy (CM) and HF is of paramount importance. The European Society of Cardiology (ESC) published guidelines on Cardio-Oncology (CO) [Lyon, López-Fernández, Couch, et al 43(41):4229-4361, 2022] detailing cardiovascular (CV) risk stratification, prevention, monitoring, diagnosis, and treatment throughout …

Safety Of Dostarlimab In Combination With Chemotherapy In Patients With Primary Advanced Or Recurrent Endometrial Cancer In A Phase Iii, Randomized, Placebo-Controlled Trial (Engot-En6-Nsgo/Gog-3031/Ruby), Annika Auranen, Matthew A Powell, Et Al.

2020-Current year OA Pubs

BACKGROUND: In Part 1 of the phase III RUBY trial (NCT03981796) in patients with primary advanced or recurrent endometrial cancer (EC), dostarlimab plus carboplatin-paclitaxel (CP) significantly improved progression-free survival and overall survival compared with CP alone. Limited safety data have been reported for the combination of immunotherapies plus chemotherapy in this setting.

OBJECTIVES: The objective of this analysis was to identify the occurrence of treatment-related adverse events (TRAEs) and immune-related adverse events (irAEs) and to describe irAE management in Part 1 of the RUBY trial.

DESIGN: RUBY is a phase III, randomized, double-blind, multicenter study of dostarlimab plus CP compared …

Awareness Of, Willingness To Use, And Experiences With Pre-Exposure Prophylaxis Among Youth In Nigeria, Titilola Gbaja-Biamila, Juliet Iwelunmor, Et Al.

2020-Current year OA Pubs

BACKGROUND: Youth (ages 14-24) in Nigeria have disproportionately high rates of new HIV infection. Pre-exposure prophylaxis could substantially reduce new infections among youth but has not been scaled up. This cross-sectional study aimed to assess Pre-exposure prophylaxis awareness, willingness to use, and prior use of Pre-exposure prophylaxis among youth in Nigeria.

METHODS: This is a secondary analysis of cross-sectional data from a quasi-experimental pilot study (clinical trial NCT04070287). The analysis focused on Pre-exposure prophylaxis awareness, willingness to use, and prior use among 324 youth recruited between September 2019 to March 2020. Descriptive statistics were calculated as frequencies and percentages for …

Length-Scale Study In Deep Learning Prediction For Non-Small Cell Lung Cancer Brain Metastasis, Haowen Zhou, Siyu Lin, Mark Watson, Cory T Bernadt, Oumeng Zhang, Ling Liao, Ramaswamy Govindan, Richard J Cote, Changhuei Yang

2020-Current year OA Pubs

Deep learning-assisted digital pathology has demonstrated the potential to profoundly impact clinical practice, even surpassing human pathologists in performance. However, as deep neural network (DNN) architectures grow in size and complexity, their explainability decreases, posing challenges in interpreting pathology features for broader clinical insights into physiological diseases. To better assess the interpretability of digital microscopic images and guide future microscopic system design, we developed a novel method to study the predictive feature length-scale that underpins a DNN's predictive power. We applied this method to analyze a DNN's capability in predicting brain metastasis from early-stage non-small-cell lung cancer biopsy slides. This …