Digital Commons Network^™

Hyperpolarization-Activated Cyclic Nucleotide-Gated Cation Channel 3 Promotes Hcc Development In A Female-Biased Manner, Yueqi Zhang, Xinhui Liu, Kairui Sun, Yue Luo, Jack Yang, Aimin Li, Matti Kiupel, Stefanie Fenske, Martin Biel, Qing-Sheng Mi, Hongbing Wang, Hua Xiao

Dermatology Articles

Sex differences in hepatocellular carcinoma (HCC) development are regulated by sex and non-sex chromosomes, sex hormones, and environmental factors. We previously reported that Ncoa5(+/-) mice develop HCC in a male-biased manner. Here we show that NCOA5 expression is reduced in male patient HCCs while the expression of an NCOA5-interacting tumor suppressor, TIP30, is lower in female HCCs. Tip30 heterozygous deletion does not change HCC incidence in Ncoa5(+/-) male mice but dramatically increases HCC incidence in Ncoa5(+/-) female mice, accompanied by hepatic hyperpolarization-activated cyclic nucleotide-gated cation channel 3 (HCN3) overexpression. HCN3 overexpression cooperates with MYC to promote mouse HCC development, whereas …

Neural Modulation Enhancement Using Connectivity-Based Eeg Neurofeedback With Simultaneous Fmri For Emotion Regulation, Amin Dehghani, Hamid Soltanian-Zadeh, Gholam-Ali Hossein-Zadeh

Research Administration Articles

Emotion regulation plays a key role in human behavior and overall well-being. Neurofeedback is a non-invasive self-brain training technique used for emotion regulation to enhance brain function and treatment of mental disorders through behavioral changes. Previous neurofeedback research often focused on using activity from a single brain region as measured by fMRI or power from one or two EEG electrodes. In a new study, we employed connectivity-based EEG neurofeedback through recalling positive autobiographical memories and simultaneous fMRI to upregulate positive emotion. In our novel approach, the feedback was determined by the coherence of EEG electrodes rather than the power of …

A Bibliometric Analysis Of The Rise Of Chatgpt In Medical Research, Nikki M. Barrington, Nithin Gupta, Basel Musmar, David Doyle, Nicholas Panico, Nikhil Godbole, Taylor K. Reardon, Randy S. D'Amico

Neurology Articles

The rapid emergence of publicly accessible artificial intelligence platforms such as large language models (LLMs) has led to an equally rapid increase in articles exploring their potential benefits and risks. We performed a bibliometric analysis of ChatGPT literature in medicine and science to better understand publication trends and knowledge gaps. Following title, abstract, and keyword searches of PubMed, Embase, Scopus, and Web of Science databases for ChatGPT articles published in the medical field, articles were screened for inclusion and exclusion criteria. Data were extracted from included articles, with citation counts obtained from PubMed and journal metrics obtained from Clarivate Journal …

A Phase I Clinical Trial Of Oncolytic Adenovirus Mediated Suicide And Interleukin-12 Gene Therapy In Patients With Recurrent Localized Prostate Adenocarcinoma, Shyam Nyati, Hans Stricker, Kenneth N. Barton, Pin Li, Mohamed A. Elshaikh, Haythem Y. Ali, Stephen L. Brown, Clara Hwang, James O. Peabody, Svend O. Freytag, Benjamin Movsas, Farzan Siddiqui

Radiation Oncology Articles

In a phase I dose escalation and safety study (NCT02555397), a replication-competent oncolytic adenovirus expressing yCD, TK and hIL-12 (Ad5-yCD/mutTKSR39rep-hIL-12) was administered in 15 subjects with localized recurrent prostate cancer (T1c-T2) at increasing doses (1 × 1010, to 1 × 1012 viral particles) followed by 7-day treatment of 5-fluorocytosine (5-FC) and valganciclovir (vGCV). The primary endpoint was toxicity through day 30 while the secondary and exploratory endpoints were quantitation of IL-12, IFNγ, CXCL10 and peripheral blood mononuclear cells (PBMC). The study maximum tolerated dose (MTD) was not reached indicating 1012 viral particles was safe. Total 115 adverse events were observed, …

Detection Of Diagnostic And Prognostic Methylation-Based Signatures In Liquid Biopsy Specimens From Patients With Meningiomas, Grayson A. Herrgott, James M. Snyder, Ruicong She, Tathiane M. Malta, Thais S. Sabedot, Ian Y. Lee, Jacob Pawloski, Guilherme G. Podolsky-Gondim, Karam P. Asmaro, Jiaqi Zhang, Cara E. Cannella, Kevin K. Nelson, Bartow Thomas, Ana C. De Carvalho, Laura A. Hasselbach, Kelly M. Tundo, Rehnuma Newaz, Andrea D. Transou, Natalia S. Morosini, Victor Francisco, Laila M. Poisson, Dhananjay A. Chitale, Abir Mukherjee, Maritza S. Mosella, Adam M. Robin, Tobias Walbert, Mark Rosenblum, Tom Mikkelsen, Steven N. Kalkanis, Daniela P. C Tirapelli, Daniel J. Weisenberger, Carlos G. Carlotti, Jack Rock, Ana V. Castro, Houtan Noushmehr

Neurosurgery Articles

Recurrence of meningiomas is unpredictable by current invasive methods based on surgically removed specimens. Identification of patients likely to recur using noninvasive approaches could inform treatment strategy, whether intervention or monitoring. In this study, we analyze the DNA methylation levels in blood (serum and plasma) and tissue samples from 155 meningioma patients, compared to other central nervous system tumor and non-tumor entities. We discover DNA methylation markers unique to meningiomas and use artificial intelligence to create accurate and universal models for identifying and predicting meningioma recurrence, using either blood or tissue samples. Here we show that liquid biopsy is a …

Neighborhood Disadvantage And Neural Correlates Of Threat And Reward Processing In Survivors Of Recent Trauma, E. Kate Webb, Timothy D. Ely, Grace E. Rowland, Lauren A. M Lebois, Sanne J. H Van Rooij, Steven E. Bruce, Tanja Jovanovic, Stacey L. House, Francesca L. Beaudoin, Xinming An, Thomas C. Neylan, Gari D. Clifford, Sarah D. Linnstaedt, Laura T. Germine, Kenneth A. Bollen, Scott L. Rauch, John P. Haran, Alan B. Storrow, Christopher A. Lewandowski, Paul I. Musey, Phyllis L. Hendry, Sophia Sheikh, Christopher W. Jones, Brittany E. Punches, Robert A. Swor, Jose L. Pascual, Mark J. Seamon, Elizabeth M. Datner, Claire Pearson, David A. Peak, Roland C. Merchant, Robert M. Domeier, Niels K. Rathlev, Paulina Sergot, Leon D. Sanchez, Ronald C. Kessler, Karestan C. Koenen, Samuel A. Mclean, Jennifer S. Stevens, Kerry J. Ressler, Nathaniel G. Harnett

Emergency Medicine Articles

IMPORTANCE: Differences in neighborhood socioeconomic characteristics are important considerations in understanding differences in risk vs resilience in mental health. Neighborhood disadvantage is associated with alterations in the function and structure of threat neurocircuitry.

OBJECTIVE: To investigate associations of neighborhood disadvantage with white and gray matter and neural reactivity to positive and negative stimuli in the context of trauma exposure.

DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study, survivors of trauma who completed sociodemographic and posttraumatic symptom assessments and neuroimaging were recruited as part of the Advancing Understanding of Recovery After Trauma (AURORA) study between September 2017 and June 2021. Data …

Racial, Ethnic, And Sex Diversity In Academic Medical Leadership, Austin M. Meadows, Madelyn M. Skinner, Alaa A. Hazime, Russell G. Day, Jessi A. Fore, Charles S. Day

Orthopedics Articles

IMPORTANCE: For the past 50 years, significant gaps have existed in gender and racial diversity across various medical specialties, despite the many benefits of a diverse physician workforce. One proposed approach to increasing diversity is top-down diversification, in which diverse leadership results in increased minority and female workforce representation.

OBJECTIVE: To investigate the changes in academic medical leadership diversity from 2007 to 2019 and to assess the recent leadership diversity of various specialties compared with the averages across all specialties.

DESIGN, SETTING, AND PARTICIPANTS: This was a cross-sectional analysis of physicians in varying academic roles in 2007, 2019, and 2020. …

Biomarker-Directed Therapy In Black And White Men With Metastatic Castration-Resistant Prostate Cancer, Clara Hwang, Nicholas C. Henderson, Shih-Chun Chu, Brandon Holland, Frank C. Cackowski, Amanda B. Pilling, Albert Jang, Shoshana Rothstein, Matthew Labriola, Joseph J. Park, Alyssa Ghose, Mehmet A. Bilen, Seema Mustafa, Deepak Kilari, Michael J. Pierro, Bicky Thapa, Abhishek Tripathi, Rohan Garje, Aditya Ravindra, Vadim S. Koshkin, Erik Hernandez, Michael T. Schweizer, Andrew J. Armstrong, Rana R. Mckay, Tanya B. Dorff, Ajjai S. Alva, Pedro C. Barata

Hematology/Oncology Articles

IMPORTANCE: Black men have higher incidence and mortality from prostate cancer. Whether precision oncology disparities affect Black men with metastatic castration-resistant prostate cancer (mCRPC) is unknown.

OBJECTIVE: To compare precision medicine data and outcomes between Black and White men with mCRPC.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used data collected by the Prostate Cancer Precision Medicine Multi-Institutional Collaborative Effort (PROMISE) consortium, a multi-institutional registry with linked clinicogenomic data, from April 2020 to December 2021. Participants included Black and White patients with mCRPC with molecular data. Data were analyzed from December 2021 to May 2023.

EXPOSURES: Database-reported race and …

A Patient Perspective On Applying Intermittent Fasting In Gynecologic Cancer, Ashley Redding, Sara Santarossa, Dana Murphy, Mary P. Udumula, Adnan R. Munkarah, Miriana Hijaz, Ramandeep Rattan

Women's Health Articles

OBJECTIVE: Researchers sought patient feedback on a proposed randomized controlled trial (RCT) in which gynecological cancer patients would modify their diets with intermittent fasting to gain insight into patients' perspectives, receptivity, and potential obstacles. A convenience sample of 47 patients who met the inclusion criteria of the proposed RCT provided their feedback on the feasibility and protocols of the RCT using a multi-method approach consisting of focus groups (n = 8 patients) and surveys (n = 36 patients).

RESULTS: Patients were generally receptive to the concept of intermittent fasting, and many expressed an interest in attempting it themselves. Patients agreed …

Measuring Deliberate Reflection In Residents: Validation And Psychometric Properties Of A Measurement Tool, Richard H. Blum, Christine L. Mai, John D. Mitchell, Daniel Saddawi-Konefka, Jeffrey B. Cooper, George Shorten, Audrey Dunngalvin

Anesthesiology Articles

PURPOSE: Reflective capacity is "the ability to understand critical analysis of knowledge and experience to achieve deeper meaning." In medicine, there is little provision for post-graduate medical education to teach deliberate reflection. The feasibility, scoring characteristics, reliability, validation, and adaptability of a modified previously validated instrument was examined for its usefulness assessing reflective capacity in residents as a step toward developing interventions for improvement.

METHODS: Third-year residents and fellows from four anesthesia training programs were administered a slightly modified version of the Reflection Evaluation for Learners' Enhanced Competencies Tool (REFLECT) in a prospective, observational study at the end of the …

Editorial: Influence Of Sleep And Recurrent Circadian Disruption On Cardiometabolic Health, Wellbeing, And Safety: From Shiftwork To Monday Mornings, Philip Cheng, Dorothee Fischer, Dayna A. Johnson, Andrew W. Mchill

Sleep Medicine Articles

No abstract provided.

Training Certified Detectives To Track Down The Intrinsic Shortcuts In Covid-19 Chest X-Ray Data Sets, Ran Zhang, Dalton Griner, John W. Garrett, Zhihua Qi, Guang-Hong Chen

Diagnostic Radiology Articles

Deep learning faces a significant challenge wherein the trained models often underperform when used with external test data sets. This issue has been attributed to spurious correlations between irrelevant features in the input data and corresponding labels. This study uses the classification of COVID-19 from chest x-ray radiographs as an example to demonstrate that the image contrast and sharpness, which are characteristics of a chest radiograph dependent on data acquisition systems and imaging parameters, can be intrinsic shortcuts that impair the model's generalizability. The study proposes training certified shortcut detective models that meet a set of qualification criteria which can …

Examining Sociodemographic Correlates Of Opioid Use, Misuse, And Use Disorders In The All Of Us Research Program, Hsueh-Han Yeh, Cathyrn Petlz-Rauchman, Christine C. Johnson, Pamala A. Pawloski, David Chesla, Stephen C. Waring, Alan B. Stevens, Mara Epstein, Christine Lm Joseph, Lisa R. Miller-Matero, Hongsheng Gui, Amy Tang, Eric Boerwinkle, Mine Cicek, Cheryl R. Clark, Elizabeth Cohn, Kelly Gebo, Roxana Loperena, Kelsey Mayo, Stephen Mockrin, Lucila Ohno-Machado, Sheri Schully, Andrea H. Ramirez, Jun Qian, Brian K. Ahmedani

Center for Health Policy and Health Services Research Articles

BACKGROUND: The All of Us Research Program enrolls diverse US participants which provide a unique opportunity to better understand the problem of opioid use. This study aims to estimate the prevalence of opioid use and its association with sociodemographic characteristics from survey data and electronic health record (EHR).

METHODS: A total of 214,206 participants were included in this study who competed survey modules and shared EHR data. Adjusted logistic regressions were used to explore the associations between sociodemographic characteristics and opioid use.

RESULTS: The lifetime prevalence of street opioids was 4%, and the nonmedical use of prescription opioids was 9%. …

Human Microbiome Variation Associated With Race And Ethnicity Emerges As Early As 3 Months Of Age, Elizabeth K. Mallott, Alexandra R. Sitarik, Leslie D. Leve, Camille Cioffi, Carlos A. Camargo, Kohei Hasegawa, Seth R. Bordenstein

Public Health Sciences Articles

Human microbiome variation is linked to the incidence, prevalence, and mortality of many diseases and associates with race and ethnicity in the United States. However, the age at which microbiome variability emerges between these groups remains a central gap in knowledge. Here, we identify that gut microbiome variation associated with race and ethnicity arises after 3 months of age and persists through childhood. One-third of the bacterial taxa that vary across caregiver-identified racial categories in children are taxa reported to also vary between adults. Machine learning modeling of childhood microbiomes from 8 cohort studies (2,756 samples from 729 children) distinguishes …

Outcomes Associated With Sars-Cov-2 Reinfection In Individuals With Natural And Hybrid Immunity, Geehan Suleyman, Raef Fadel, Kunj Patel, Al Muthanna Shadid, Haim Bernardo Cotlear Stuart, Michael Kattula, Andrea Janis, Mohamed Maki, Shing Chao, George Alangaden, Indira Brar

Infectious Diseases Articles

BACKGROUND: Studies comparing SARS-CoV-2 reinfection outcomes among individuals with previous infection (natural immunity) and previous infection plus vaccination (hybrid immunity) are limited.

METHODS: Retrospective cohort study comparing SARS-CoV-2 reinfection among patients with hybrid immunity (cases) and natural immunity (controls) from March 2020 to February 2022. Reinfection was defined as positive PCR> 90 days after initial laboratory-confirmed SARS-CoV-2 infection. Outcomes included time to reinfection, symptom severity, COVID-19-related hospitalization, critical COVID-19 illness (need for intensive care unit, invasive mechanical ventilation, or death), length of stay (LOS).

RESULTS: A total of 773 (42%) vaccinated and 1073 (58%) unvaccinated patients with reinfection were included. …

Graft-Versus-Host Disease: Teaching Old Drugs New Tricks At Less Cost, Shatha Farhan, Shernan G. Holtan

Hematology/Oncology Articles

Graft-versus-host disease (GVHD) remains a major cause of morbidity and mortality after allogeneic stem cell transplantation (SCT). Currently, more patients can receive SCT. This is attributed to the use of reduced intensity regimens and the use of different GVHD prophylaxis that breaks the barrier of human leukocyte antigen, allowing an increase in the donor pool. Once an area with relatively few clinical trial options, there has been an increase in interest in GVHD prophylaxis and treatment, which has led to many US Food and Drug Administration (FDA) approvals. Although there is considerable excitement over novel therapies, many patients may not …

A First-In-Human, Dose-Escalation Study Of The Methionine Aminopeptidase 2 Inhibitor M8891 In Patients With Advanced Solid Tumors, Michael A. Carducci, Ding Wang, Christina Habermehl, Matthias Bödding, Felix Rohdich, Floriane Lignet, Klaus Duecker, Oleksandr Karpenko, Linda Pudelko, Claude Gimmi, Patricia Lorusso

Hematology/Oncology Articles

Methionine aminopeptidase 2 (MetAP2) is essential to endothelial cell growth and proliferation during tumor angiogenesis. M8891 is a novel orally bioavailable, potent, selective, reversible MetAP2 inhibitor with antiangiogenic and antitumor activity in preclinical studies. The safety, tolerability, pharmacokinetics, and pharmacodynamics of M8891 monotherapy were assessed in a phase I, first-in-human, multicenter, open-label, single-arm, dose-escalation study (NCT03138538). Patients with advanced solid tumors received 7-80 mg M8891 once daily in 21-day cycles. The primary endpoint was dose-limiting toxicity (DLT) during cycle 1, with the aim to determine the maximum tolerated dose (MTD). Twenty-seven patients were enrolled across six dose levels. Two DLTs …

Propofol Inhibits Glioma Stem Cell Growth And Migration And Their Interaction With Microglia Via Bdnf-As And Extracellular Vesicles, Rephael Nizar, Simona Cazacu, Cunli Xiang, Matan Krasner, Efrat Barbiro-Michaely, Doron Gerber, Jonathan Schwartz, Iris Fried, Shira Yuval, Aharon Brodie, Gila Kazimirsky, Naama Amos, Ron Unger, Stephen L. Brown, Lisa Rogers, Donald H. Penning, Chaya Brodie

Neurosurgery Articles

Glioblastoma (GBM) is the most common and aggressive primary brain tumor. GBM contains a small subpopulation of glioma stem cells (GSCs) that are implicated in treatment resistance, tumor infiltration, and recurrence, and are thereby considered important therapeutic targets. Recent clinical studies have suggested that the choice of general anesthetic (GA), particularly propofol, during tumor resection, affects subsequent tumor response to treatments and patient prognosis. In this study, we investigated the molecular mechanisms underlying propofol's anti-tumor effects on GSCs and their interaction with microglia cells. Propofol exerted a dose-dependent inhibitory effect on the self-renewal, expression of mesenchymal markers, and migration of …

Developing An In-Depth Understanding Of Patient And Caregiver Engagement Across Care Transitions From Hospital: Protocol For A Qualitative Study Exploring Experiences In Canada, Jacobi Elliott, Paula Van Wyk, Roy Butler, Justine L. Giosa, Joanie Sims Gould, Catherine E. Tong, Mary Margaret Taabazuing, Helen Johnson, Paige Coyne, Fallon Mitchell, Alexandra Whate, Anne Callon, Judith Carson, Paul Stolee

Public Health Sciences Articles

INTRODUCTION: Patient and caregiver engagement is critical, and often compromised, at points of transition between care settings, which are more common, and more challenging, for patients with complex medical problems. The consequences of poor care transitions are well-documented, both for patients and caregivers, and for the healthcare system. With an ageing population, there is greater need to focus on care transition experiences of older adults, who are often more medically complex, and more likely to require care from multiple providers across settings. The overall goal of this study is to understand what factors facilitate or hinder patient and caregiver engagement …

Developing A National-Scale Exposure Index For Combined Environmental Hazards And Social Stressors And Applications To The Environmental Influences On Child Health Outcomes (Echo) Cohort, Sheena E. Martenies, Mingyu Zhang, Anne E. Corrigan, Anton Kvit, Timothy Shields, William Wheaton, Deana Around Him, Judy Aschner, Maria M. Talavera-Barber, Emily S. Barrett, Theresa M. Bastain, Casper Bendixsen, Carrie V. Breton, Nicole R. Bush, Ferdinand Cacho, Carlos A. Camargo, Kecia N. Carroll, Brian S. Carter, Andrea E. Cassidy-Bushrow, Whitney Cowell, Lisa A. Croen, Dana Dabelea, Cristiane S. Duarte, Anne L. Dunlop, Todd M. Everson, Rima Habre, Tina V. Hartert, Jennifer B. Helderman, Alison E. Hipwell, Margaret R. Karagas, Barry M. Lester, Kaja Z. Lewinn, Sheryl Magzamen, Rachel Morello-Frosch, Thomas G. O'Connor, Amy M. Padula, Michael Petriello, Sheela Sathyanarayana, Joseph B. Stanford, Tracey J. Woodruff, Rosalind J. Wright, Amii M. Kress

Public Health Sciences Articles

Tools for assessing multiple exposures across several domains (e.g., physical, chemical, and social) are of growing importance in social and environmental epidemiology because of their value in uncovering disparities and their impact on health outcomes. Here we describe work done within the Environmental influences on Child Health Outcomes (ECHO)-wide Cohort Study to build a combined exposure index. Our index considered both environmental hazards and social stressors simultaneously with national coverage for a 10-year period. Our goal was to build this index and demonstrate its utility for assessing differences in exposure for pregnancies enrolled in the ECHO-wide Cohort Study. Our unitless …

Radiomics Characterization Of Tissues In An Animal Brain Tumor Model Imaged Using Dynamic Contrast Enhanced (Dce) Mri, Hassan Bagher-Ebadian, Stephen L. Brown, Mohammad M. Ghassemi, Tavarekere N. Nagaraja, Benjamin Movsas, James R. Ewing, Indrin J. Chetty

Radiation Oncology Articles

Here, we investigate radiomics-based characterization of tumor vascular and microenvironmental properties in an orthotopic rat brain tumor model measured using dynamic-contrast-enhanced (DCE) MRI. Thirty-two immune compromised-RNU rats implanted with human U-251N cancer cells were imaged using DCE-MRI (7Tesla, Dual-Gradient-Echo). The aim was to perform pharmacokinetic analysis using a nested model (NM) selection technique to classify brain regions according to vasculature properties considered as the source of truth. A two-dimensional convolutional-based radiomics analysis was performed on the raw-DCE-MRI of the rat brains to generate dynamic radiomics maps. The raw-DCE-MRI and respective radiomics maps were used to build 28 unsupervised Kohonen self-organizing-maps …

Dynamic Contrast Enhanced (Dce) Mri Estimation Of Vascular Parameters Using Knowledge-Based Adaptive Models, Hassan Bagher-Ebadian, Stephen L. Brown, Mohammad M. Ghassemi, Tavarekere N. Nagaraja, Olivia G. Valadie, Prabhu C. Acharya, Glauber Cabral, George Divine, Robert A. Knight, Ian Y. Lee, Jun Xu, Benjamin Movsas, Indrin J. Chetty, James R. Ewing

Radiation Oncology Articles

We introduce and validate four adaptive models (AMs) to perform a physiologically based Nested-Model-Selection (NMS) estimation of such microvascular parameters as forward volumetric transfer constant, K(trans), plasma volume fraction, v(p), and extravascular, extracellular space, v(e), directly from Dynamic Contrast-Enhanced (DCE) MRI raw information without the need for an Arterial-Input Function (AIF). In sixty-six immune-compromised-RNU rats implanted with human U-251 cancer cells, DCE-MRI studies estimated pharmacokinetic (PK) parameters using a group-averaged radiological AIF and an extended Patlak-based NMS paradigm. One-hundred-ninety features extracted from raw DCE-MRI information were used to construct and validate (nested-cross-validation, NCV) four AMs for estimation of model-based regions …

The Management Of Hepatocellular Carcinoma. Current Expert Opinion And Recommendations Derived From The 24th Esmo/World Congress On Gastrointestinal Cancer, Barcelona, 2022, Michel Ducreux, Ghassan K. Abou-Alfa, Tanios S. Bekaii-Saab, Jordan D. Berlin, Andrés Cervantes, Thierry De Baere, Cathy Eng, Peter Galle, Sharlene Gill, Thomas Gruenberger, Karin Haustermans, Angela Lamarca, Pierre Laurent-Puig, Josep M. Llovet, Florian Lordick, Teresa Macarulla, Deborah Mukherji, Kei Muro, Radka Obermannova, Juan Manuel O'Connor, Eileen O'Reilly, Pia Österlund, Philip A. Philip, Gerald Prager, Erika Ruiz-Garcia, Bruno Sangro, Thomas Seufferlein, Josep Tabernero, Chris Verslype, Harpreet Wasan, Eric Van Cutsem

Hematology/Oncology Articles

This article summarises expert discussion on the management of patients with hepatocellular carcinoma (HCC), which took place during the 24th World Gastrointestinal Cancer Congress (WGICC) in Barcelona, July 2022. A multidisciplinary approach is mandatory to ensure an optimal diagnosis and staging of HCC, planning of curative and therapeutic options, including surgical, embolisation, ablative strategies, or systemic therapy. Furthermore, in many patients with HCC, underlying liver cirrhosis represents a challenge and influences the therapeutic options.

Association Of Mutation And Expression Of The Brother Of The Regulator Of Imprinted Sites (Boris) Gene With Breast Cancer Progression, Mohammad Salman Akhtar, Naseem Akhter, Arshi Talat, Raed A. Alharbi, Abdulmajeed A. A Sindi, Faisal Klufah, Hanan E. Alyahyawi, Abdulmohsen Alruwetei, Abrar Ahmad, Mazin A. Zamzami, Svs Deo, Syed Akhtar Husain, Osama A. Badi, Mohammad Jahir Khan

Neurology Articles

INTRODUCTION: The BORIS, 11 zinc-finger transcription factors, is a member of the cancer-testis antigen (CTA) family. It is mapped to chromosome number 20q13.2 and this region is genetically linked to the early onset of breast cancer. The current study analyzed the correlation between BORIS mutations and the expression of the protein in breast cancer cases.

MATERIALS AND METHODS: A population-based study including a total of 155 breast cancer tissue samples and an equal number of normal adjacent tissues from Indian female breast cancer patients was carried out. Mutations of the BORIS gene were detected by polymerase chain reaction-single standard confirmation …

Importance Of Missingness In Baseline Variables: A Case Study Of The All Of Us Research Program, Robert M. Cronin, Xiaoke Feng, Lina Sulieman, Brandy Mapes, Shawn Garbett, Ashley Able, Ryan Hale, Mick P. Couper, Heather Sansbury, Brian K. Ahmedani, Qingxia Chen

Center for Health Policy and Health Services Research Articles

OBJECTIVE: The All of Us Research Program collects data from multiple information sources, including health surveys, to build a national longitudinal research repository that researchers can use to advance precision medicine. Missing survey responses pose challenges to study conclusions. We describe missingness in All of Us baseline surveys.

STUDY DESIGN AND SETTING: We extracted survey responses between May 31, 2017, to September 30, 2020. Missing percentages for groups historically underrepresented in biomedical research were compared to represented groups. Associations of missing percentages with age, health literacy score, and survey completion date were evaluated. We used negative binomial regression to evaluate …

Sex-Biased Immunological Processes Drive Hidradenitis Suppurativa, Kelly Z. Young, Peter Dimitrion, Li Zhou, Indra Adrianto, Qing-Sheng Mi

Dermatology Articles

Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition that can manifest with abscesses, sinus tracts, and scarring in the intertriginous areas of the body. HS is characterized by immune dysregulation, featuring elevated levels of myeloid cells, T helper (Th) cells, and pro-inflammatory cytokines, particularly those involved in Th1- and Th17-mediated immunity. In most epidemiological studies, HS shows a strong female sex bias, with reported female-to-male ratios estimated at roughly 3:1, suggesting that sex-related factors contribute to HS pathophysiology. In this article, we review the role of intrinsic and extrinsic factors that contribute to immunological differences between the sexes and …

Maternal Sars-Cov-2 Infection And Prematurity: The Southern Michigan Covid-19 Collaborative, Ray Bahado-Singh, Adi L. Tarca, Yasmin G. Hasbini, Robert J. Sokol, Madhurima Keerthy, Gregory Goyert, Theodore Jones, Lisa Thiel, Pooja Green, Youssef Youssef, Courtney Townsel, Shyla Vengalil, Paige Paladino, Amy Wright, Mariam Ayyash, Gayathri Vadlamudi, Marta Szymanska, Sonia Sajja, Onur Turkoglu, Grace Sterenberg, Alexandra R. Mangus, Micheal Baracy, Maria Gibbons, Karlee Grace, Kaitlyn Houston, Jessica Norman, Dereje W. Gudicha, Sonia S. Hassan

Women's Health Articles

OBJECTIVE: COVID-19 has been reported to increase the risk of prematurity, however, due to the frequent absence of unaffected controls as well as inadequate accounting for confounders in many studies, the question requires further investigation. We sought to determine the impact of COVID-19 disease on preterm birth (PTB) overall, as well as related subcategories such as early prematurity, spontaneous, medically indicated preterm birth, and preterm labor (PTL). We assessed the impact of confounders such as COVID-19 risk factors, a-priori risk factors for PTB, symptomatology, and disease severity on rates of prematurity.

METHODS: This was a retrospective cohort study of pregnant …

The Genetic Determinants Of Recurrent Somatic Mutations In 43,693 Blood Genomes, Joshua S. Weinstock, Cecelia A. Laurie, Jai G. Broome, Kent D. Taylor, Xiuqing Guo, Alan R. Shuldiner, Jeffrey R. O'Connell, Joshua P. Lewis, Eric Boerwinkle, Kathleen C. Barnes, Nathalie Chami, Eimear E. Kenny, Ruth J. F Loos, Myriam Fornage, Susan Redline, Brian E. Cade, Frank D. Gilliland, Zhanghua Chen, W. James Gauderman, Rajesh Kumar, Leslie Grammer, Robert P. Schleimer, Bruce M. Psaty, Joshua C. Bis, Jennifer A. Brody, Edwin K. Silverman, Jeong H. Yun, Dandi Qiao, Scott T. Weiss, Jessica Lasky-Su, Dawn L. Demeo, Nicholette D. Palmer, Barry I. Freedman, Donald W. Bowden, Michael H. Cho, Ramachandran S. Vasan, Andrew D. Johnson, Lisa R. Yanek, Lewis C. Becker, Sharon Kardia, Jiang He, Robert Kaplan, Susan R. Heckbert, Nicholas L. Smith, Kerri L. Wiggins, Donna K. Arnett, Marguerite R. Irvin, Hemant Tiwari, Adolfo Correa, Laura M. Raffield, Yan Gao, Mariza De Andrade, Jerome I. Rotter, Stephen S. Rich, Ani W. Manichaikul, Barbara A. Konkle, Jill M. Johnsen, Marsha M. Wheeler, Brian S. Custer, Ravindranath Duggirala, Joanne E. Curran, John Blangero, Hongsheng Gui, Shujie Xiao, Keoki L. Williams, Deborah A. Meyers, Xingnan Li, Victor Ortega, Stephen Mcgarvey, C. Charles Gu, Yii-Der Ida Chen, Wen-Jane Lee, M. Benjamin Shoemaker, Dawood Darbar, Dan Roden, Christine Albert, Charles Kooperberg, Pinkal Desai, Thomas W. Blackwell, Goncalo R. Abecasis, Albert V. Smith, Hyun M. Kang, Rasika Mathias, Pradeep Natarajan, Siddhartha Jaiswal, Alexander P. Reiner, Alexander G. Bick

Administration Articles

Nononcogenic somatic mutations are thought to be uncommon and inconsequential. To test this, we analyzed 43,693 National Heart, Lung and Blood Institute Trans-Omics for Precision Medicine blood whole genomes from 37 cohorts and identified 7131 non-missense somatic mutations that are recurrently mutated in at least 50 individuals. These recurrent non-missense somatic mutations (RNMSMs) are not clearly explained by other clonal phenomena such as clonal hematopoiesis. RNMSM prevalence increased with age, with an average 50-year-old having 27 RNMSMs. Inherited germline variation associated with RNMSM acquisition. These variants were found in genes involved in adaptive immune function, proinflammatory cytokine production, and lymphoid …

Practical Guidance For The Management Of Adverse Events In Patients With Krasg12c-Mutated Non-Small Cell Lung Cancer Receiving Adagrasib, Jun Zhang, Melissa Johnson, Minal Barve, Lyudmila Bazhenova, Marybeth Mccarthy, Rowena Schwartz, Elise Horvath-Walsh, Karen Velastegui, Chunlin Qian, Alexander Spira

Hematology/Oncology Articles

Adagrasib (MRTX849) is a KRASG12C inhibitor with favorable properties, including long half-life (23 h), dose-dependent pharmacokinetics, and central nervous system (CNS) penetration. As of September 1, 2022, a total of 853 patients with KRASG12C-mutated solid tumors, including patients with CNS metastases, had received adagrasib (monotherapy or in combination). Adagrasib-related treatment-related adverse events (TRAEs) are generally mild to moderate in severity, start early in treatment, resolve quickly with appropriate intervention, and result in a low rate of treatment discontinuation. Common TRAEs seen in clinical trials included gastrointestinal-related toxicities (diarrhea, nausea, and vomiting); hepatic toxicities (increased alanine aminotransferase/aspartate aminotransferase) and fatigue, which …

Intra-Arterial Delivery Of Radiopharmaceuticals In Oncology: Current Trends And The Future Of Alpha-Particle Therapeutics, Nathan Kauffman, James Morrison, Kevin O'Brien, Jinda Fan, Kurt R. Zinn

Diagnostic Radiology Articles

A paradigm shift is underway in cancer diagnosis and therapy using radioactivity-based agents called radiopharmaceuticals. In the new strategy, diagnostic imaging measures the tumor uptake of radioactive agent "X" in a patient's specific cancer, and if uptake metrics are realized, the patient can be selected for therapy with radioactive agent "Y". The X and Y represent different radioisotopes that are optimized for each application. X-Y pairs are known as radiotheranostics, with the currently approved route of therapy being intravenous administration. The field is now evaluating the potential of intra-arterial dosing of radiotheranostics. In this manner, a higher initial concentration can …