tbuckley/cabot-search huggingface dataset:
Abstract 16: County-Level Racial Residential Segregation and Sedentary Behavior in US Adults
Authors: Moniruzzaman Mohammad, Yangyang Deng, Sheikh Mohammed Shariful Islam, Kelly Jones, David Berrigan, Charles Matthews, Kosuke Tamura
Journal: Circulation (2024)

Introduction: Sedentary behavior (SB) is highly prevalent and shows an increasing trend in United States (US) adults, resulting in adverse health outcomes, such as cardiovascular disease, cancer, and diabetes. Yet, potential environmental determinants of SB, including racial residential segregation, remain understudied. Hypothesis: County-level segregation will be associated with sedentary time in a nationwide sample of US adults, and this relationship will be moderated by sex. Methods: We analyzed data from 2637 US adults aged 20-75 years (mean age [45.1 years], female [50.6%] from the population-based AmeriSpeak panel in 2019. Participants completed the Activities Completed over Time in 24-hours (ACT24) previous-day recall, a validated population-level measure of total daily SB (hours/day). County segregation was expressed as the isolation index at the county level for non-Hispanic (NH) White, NH Black, and Hispanic adults (vs all other races/ethnicities). The isolation index ranges from 0 to 1, with a higher value indicating higher segregation and therefore, a higher average probability of contact among residents of the minority group and, thus, a lower probability of contact among residents of the minority group and all other races/ethnicities. We used survey-weighted linear regression models to assess the relationships of race-specific isolation index with time spent in SB, adjusting for age, sex, marital status, education, occupation, household income, body mass index, census region, and county-level poverty. Additionally, we stratified these relationships by sex. Results: Overall, US adults reported a mean of 9.5 hours/day of sedentary time. Counties with higher NH White isolation showed a significant inverse relationship with sedentary time (β = -1.52, 95% confidence interval [-2.75, -0.29], p = 0.017). Counties with higher NH Black isolation showed a non-significant inverse relationship with sedentary time (β = -0.30 [-2.53, 1.94], p = 0.790), and counties with higher Hispanic isolation showed a non-significant positive relationship (β = 0.32, [-1.64, 2.28], p = 0.743). In sex-stratified analysis, only NH White isolation among White females showed a significant inverse relationship with sedentary time (β = -2.14 [-4.19, -0.09], p = 0.041). Conclusions: NH White adults, particularly females, residing in more segregated counties reported less sedentary time in this population-based nationwide sample of US adults. SB was not strongly associated with isolation for NH Black and Hispanic adults. Future studies could aim to replicate (or not) our findings with larger samples of underrepresented minority populations and further explore potential mechanisms for sex related variation in the association between residential segregation and sedentary behavior.
Abstract 12: Blood Pressure Phenotypes, Subclinical Cerebrovascular Diseases and Coronary Artery Calcification in Japanese Men
Authors: Nomin Bayaraa, Yuichiro Yano, Nazar Mohd Azahar, Phap Tran Ngoc Hoang, Takashi Hisamatsu, Keiko Kondo, Sayuki Torii, Aya Kadota, Akira Fujiyoshi, Takayoshi Ohkubo, Akihiko Shiino, Kazuhiko Nozaki, Hirotsugu Ueshima, Katsuyuki Miura
Journal: Circulation (2024)

Introduction: Hypertension, with its various phenotypes including white-coat hypertension (WCHT), masked hypertension (MHT), and sustained hypertension (SHT), is a known risk factor for cardiovascular diseases (CVDs). Yet, it remains unclear whether the association between subclinical CVD and hypertension varies based on its phenotype, and if this relationship differs depending on the location of atherosclerosis. Hypothesis: We hypothesized that MHT, WCHT, and SHT are associated with greater subclinical cerebrovascular diseases and coronary artery calcification (CAC) compared to normotension. Methods: In this community-based observational study of Shiga Epidemiological Study of Subclinical Atherosclerosis (SESSA), a total of 740 male participants underwent brain magnetic resonance imaging (MRI) to assess the presence of lacunar infarction, white-matter hyperintensities (WMHs), microbleed, and intracranial artery stenosis (ICAS) between 2012 and 2015. They also underwent office blood pressure (BP) measurements, home BP monitoring for at least 5 consecutive days, and CAC assessments between 2010-2014. The final analysis included 686 participants without a history of CVDs. Results: Of the 686 participants, the mean age was 68.0 years (SD±8.3) and 39.3% were receiving antihypertensive medicine. Using a multivariable logistic regression analysis, WCHT, MHT, and SHT each were significantly associated with higher risk for microbleeds compared to the normotensive group (see Table). However, the association of WCHT with microbleeds was evident in participants on antihypertensive medication (Odds ratios 7.98, 95% confidence interval 2.10-30.24), but was absent in those not taking such medication (Odds ratios 1.23, 95% confidence interval 0.31-4.83). SHT was associated with lacunar infarction, ICAS and CAC compared to the normotensive group (see Table). Conclusions: In Japanese men, WCHT, MHT, and SHT were associated with subclinical cerebrovascular diseases, whereas only SHT was associated to CAC.
Abstract P137: Patient Level Determinants of Glycemic Control Among Patients With Type 2 Diabetes Mellitus in Primary Health Facilities in Ghana
Authors: Thomas Hinneh, Oluwabunmi V Ogungbe, Faith Metlock, Bernard Abeiku Mensah, Diana Baptiste, Yvonne Commodore-Mensah
Journal: Circulation (2024)

Background: Glycemic control among patients with type 2 diabetes mellitus (T2DM) has implications for the risk of complications. Despite the increasing burden of T2DM in sub-Saharan Africa, research on glycemic control remains scanty. Objective: To assess individual-level determinants of glycemic control among patients with T2DM who were on treatment. Methods: A retrospective review of medical records of patients with T2DM in four primary health clinics in the Bono Region of Ghana was conducted. Glycemic control was classified as controlled (fasting blood glucose [FBG] &lt;7.0 mmol/l) and uncontrolled (FBG ≥7 mmol/l) using WHO guidelines for glycemic control. Patient-level characteristics were selected as predictors based on their potential association with glycemic outcomes. A multivariable logistic regression model was fitted to examine the association between patient-level characteristics and glycemic control. Results: Medical records of 637 patients were included, mean age of 61 (±12.2) years, 77% females and 59% farmers. Prevalent complications were Peripheral Neuropathy (17%) and Retinopathy (4%). The mean FBG was 9.7mmol/l (±3.9). Twenty-seven percent (27%) of the patients had glycemic control, with a higher proportion among middle-aged patients (36-65). Patients older than 65 years had higher odds of glycemic control compared to those between 20-35 (adjusted odds ratio OR = 1.83, [95% CI: (1.13 3.54)] p=0.049). Patients without any complications had higher odds of glycemic control compared with those with complications (adjusted OR (AOR) 1.80 [95% CI: 1.07 3.02] p=0.029) (Table) Conclusions: Age and diabetes-related complications were significantly associated with glycemic control. Intensive treatment strategies should be implemented to improve glycemic control among younger adults to reduce the risk of complications. Health system interventions for people with diabetes must recognize the age dimension of glycemic control in Ghana.
Csk restrains BCR-mediated ROS production and contributes to germinal center selection and affinity maturation
Authors: Takeshi Inoue, Yuma Matsumoto, Chie Kawai, Mao Ito, Shigeyuki Nada, Masato Okada, Tomohiro Kurosaki
Journal: The Journal of Experimental Medicine (2024)

Compared with naïve B cells, the B cell receptor (BCR) signal in germinal center (GC) B cells is attenuated; however, the significance of this signaling attenuation has not been well defined. Here, to investigate the role of attenuation of BCR signaling, we employed a Csk mutant mouse model in which Csk deficiency in GC B cells resulted in augmentation of net BCR signaling with no apparent effect on antigen presentation. We found that Csk is required for GC maintenance and efficient antibody affinity maturation. Mechanistically, ROS-induced apoptosis was exacerbated concomitantly with mitochondrial dysfunction in Csk-deficient GC B cells. Hence, our data suggest that attenuation of the BCR signal restrains hyper-ROS production, thereby protecting GC B cells from apoptosis and contributing to efficient affinity maturation.
Patient-centricity in digital measure development: co-evolution of best practice and regulatory guidance
Authors: Suvekshya Aryal, Jennifer M. Blankenship, Shelby L. Bachman, Soohyun Hwang, Yaya Zhai, Jennifer C. Richards, Ieuan Clay, Kate Lyden
Journal: npj Digital Medicine (2024)

Abstract Digital health technologies (DHTs) have the potential to modernize drug development and clinical trial operations by remotely, passively, and continuously collecting ecologically valid evidence that is meaningful to patients’ lived experiences. Such evidence holds potential for all drug development stakeholders, including regulatory agencies, as it will help create a stronger evidentiary link between approval of new therapeutics and the ultimate aim of improving patient lives. However, only a very small number of novel digital measures have matured from exploratory usage into regulatory qualification or efficacy endpoints. This shows that despite the clear potential, actually gaining regulatory agreement that a new measure is both fit-for-purpose and delivers value remains a serious challenge. One of the key stumbling blocks for developers has been the requirement to demonstrate that a digital measure is meaningful to patients. This viewpoint aims to examine the co-evolution of regulatory guidance in the United States (U.S.) and best practice for integration of DHTs into the development of clinical outcome assessments. Contextualizing guidance on meaningfulness within the larger shift towards a patient-centric drug development approach, this paper reviews the U.S. Food and Drug Administration (FDA) guidance and existing literature surrounding the development of meaningful digital measures and patient engagement, including the recent examples of rejections by the FDA that further emphasize patient-centricity in digital measures. Finally, this paper highlights remaining hurdles and provides insights into the established frameworks for development and adoption of digital measures in clinical research.
Emerging Chemodynamic Nanotherapeutics for Cancer Treatment
Authors: Dongqi Sun, Xinxin Sun, Xuan Zhang, Jiaping Wu, Xianbao Shi, Jin Sun, Cong Luo, Zhonggui He, Shenwu Zhang
Journal: Advanced Healthcare Materials (2024)

Abstract Chemodynamic therapy (CDT) has emerged as a transformative paradigm in the realm of reactive oxygen species ‐mediated cancer therapies, exhibiting its potential as a sophisticated strategy for precise and effective tumor treatment. CDT primarily relies on metal ions and hydrogen peroxide to initiate Fenton or Fenton‐like reactions, generating cytotoxic hydroxyl radicals. Its notable advantages in cancer treatment are demonstrated, including tumor specificity, autonomy from external triggers, and a favorable side‐effect profile. Recent advancements in nanomedicine are devoted to enhancing CDT, promising a comprehensive optimization of CDT efficacy. This review systematically elucidates cutting‐edge achievements in chemodynamic nanotherapeutics, exploring strategies for enhanced Fenton or Fenton‐like reactions, improved tumor microenvironment modulation, and precise regulation in energy metabolism. Moreover, a detailed analysis of diverse CDT‐mediated combination therapies is provided. Finally, the review concludes with a comprehensive discussion of the prospects and intrinsic challenges to the application of chemodynamic nanotherapeutics in the domain of cancer treatment.
Anastrozole Dose Escalation for Optimal Estrogen Suppression in Postmenopausal Early-Stage Breast Cancer: A Prospective Trial
Authors: Tufia C. Haddad, Vera J. Suman, Karthik V. Giridhar, Kostandinos Sideras, Donald W. Northfelt, Brenda J. Ernst, Ciara C. O’Sullivan, Ravinder J. Singh, Zeruesenay Desta, Prema P. Peethambaram, Timothy J. Hobday, Saranya Chumsri, Roberto A. Leon-Ferre, Kathryn J. Ruddy, Siddhartha Yadav, Jodi L. Taraba, Barbara Goodnature, Matthew P. Goetz, Liewei Wang, James N. Ingle
Journal: Clinical Cancer Research (2024)

We previously reported that postmenopausal women with estrogen receptor-α-positive breast cancer receiving adjuvant anastrozole 1 mg/day (ANA1) with estrone (E1) ≥1.3 pg/mL and estradiol (E2) ≥0.5 pg/mL [inadequate estrogen suppression (IES)] had a threefold increased risk of a breast cancer event. The objective of this study was to determine if increasing anastrozole to 10 mg/day (ANA10) could result in adequate estrogen suppression (AES: E1 <1.3 pg/mL and/or E2 <0.5 pg/mL) among those with IES on ANA1.
Non–Small Cell Lung Cancer, Version 4.2024
Authors: Gregory J. Riely, Douglas E. Wood, David S. Ettinger, Dara L. Aisner, Wallace Akerley, Jessica R. Bauman, Ankit Bharat, Debora S. Bruno, Joe Y. Chang, Lucian R. Chirieac, Malcolm DeCamp, Aakash P. Desai, Thomas J. Dilling, Jonathan Dowell, Gregory A. Durm, Scott Gettinger, Travis E. Grotz, Matthew A. Gubens, Aditya Juloori, Rudy P. Lackner, Michael Lanuti, Jules Lin, Billy W. Loo, Christine M. Lovly, Fabien Maldonado, Erminia Massarelli, Daniel Morgensztern, Trey C. Mullikin, Thomas Ng, Dawn Owen, Dwight H. Owen, Sandip P. Patel, Tejas Patil, Patricio M. Polanco, Jonathan Riess, Theresa A. Shapiro, Aditi P. Singh, James Stevenson, Alda Tam, Tawee Tanvetyanon, Jane Yanagawa, Stephen C. Yang, Edwin Yau, Kristina M. Gregory, Lisa Hang
Journal: Journal of the National Comprehensive Cancer Network (2024)

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) provide recommendations for the treatment of patients with NSCLC, including diagnosis, primary disease management, surveillance for relapse, and subsequent treatment. The panel has updated the list of recommended targeted therapies based on recent FDA approvals and clinical data. This selection from the NCCN Guidelines for NSCLC focuses on treatment recommendations for advanced or metastatic NSCLC with actionable molecular biomarkers.
Abstracts From the NCCN 2024 Annual Conference
Authors: Chad Tang, Kieko Hara, Alexander Sherry, Alejandra Serrano, Larisa Kostousov, Sharia Hernandez, Wei Lu, Li Shen, Amishi Shah, Eric Jonasch, Jose Karam, Surena Matin, Nizar Tannir, Jing Wang, Pavlos Msaouel, Kanishka Sircar, Luisa Solis, Zachary Frosch, Clark Meshack, Caitlin Meeker, Asya Varshavsky-Yanovsky, Rashmi Khanal, Michael Bromberg, Ashwin Chandar, Emmanuel Quien, Jordan Carter, Shazia Nakhoda, Marcus Messmer, Charissa Montgomery, Jason Incorvati, Nadia Ali, Michael Styler, Carolyn Fang
Journal: Journal of the National Comprehensive Cancer Network (2024)
Bladder Cancer, Version 3.2024
Authors: Thomas W. Flaig, Philippe E. Spiess, Michael Abern, Neeraj Agarwal, Rick Bangs, Mark K. Buyyounouski, Kevin Chan, Sam S. Chang, Paul Chang, Terence Friedlander, Richard E. Greenberg, Khurshid A. Guru, Harry W. Herr, Jean Hoffman-Censits, Hristos Kaimakliotis, Amar U. Kishan, Shilajit Kundu, Subodh M. Lele, Ronac Mamtani, Omar Y. Mian, Jeff Michalski, Jeffrey S. Montgomery, Mamta Parikh, Anthony Patterson, Charles Peyton, Elizabeth R. Plimack, Mark A. Preston, Kyle Richards, Wade J. Sexton, Arlene O. Siefker-Radtke, Tyler Stewart, Debasish Sundi, Matthew Tollefson, Jonathan Tward, Jonathan L. Wright, Carly J. Cassara, Lisa A. Gurski
Journal: Journal of the National Comprehensive Cancer Network (2024)

Bladder cancer, the sixth most common cancer in the United States, is most commonly of the urothelial carcinoma histologic subtype. The clinical spectrum of bladder cancer is divided into 3 categories that differ in prognosis, management, and therapeutic aims: (1) non-muscle-invasive bladder cancer (NMIBC); (2) muscle invasive, nonmetastatic disease; and (3) metastatic bladder cancer. These NCCN Guidelines Insights detail recent updates to the NCCN Guidelines for Bladder Cancer, including changes in the fifth edition of the WHO Classification of Tumours: Urinary and Male Genital Tumours and how the NCCN Guidelines aligned with these updates; new and emerging treatment options for bacillus Calmette-Guérin (BCG)-unresponsive NMIBC; and updates to systemic therapy recommendations for advanced or metastatic disease.
Optimizing BTK Inhibition in Waldenström Macroglobulinemia
Authors: Shayna Sarosiek, Jorge J. Castillo
Journal: Journal of the National Comprehensive Cancer Network (2024)

Bruton tyrosine kinase (BTK) inhibitors have become a standard of care in the treatment of patients with Waldenström macroglobulinemia (WM) and are the only medications approved by the FDA to treat these patients. As more patients with WM are treated with BTK inhibitors in the United States and worldwide, it is essential to optimize this therapy by selecting the patients who are more likely to benefit from it, and by managing the unique adverse effects associated with these agents. Herein, we propose a genomic-driven approach to selecting patients with WM who are more likely to experience fast, deep, and durable responses to BTK inhibitors, and provide practical strategies for managing adverse effects, including BTK inhibitor dose reductions, switching to other BTK inhibitors, and abandoning BTK inhibitor therapy. Ongoing clinical trials are evaluating covalent and noncovalent BTK inhibitors alone and in combination, as well as BTK degraders, with exciting results, making the horizon for BTK-targeting therapies in WM bright and hopeful.
NCCN News
Authors: Matt Kalaycio, Christopher Lieu, John Sweetenham
Journal: Journal of the National Comprehensive Cancer Network (2024)

The exemplary leadership from our board of directors is invaluable as NCCN defines and advances high-quality, high-value, patient-centered cancer care around the world," said NCCN CEO Crystal S. Denlinger, MD, who took on the role in October of 2023."Their steady guidance during a transitional time helps us maintain our highly trusted, continuously updated, evidence-based, expert consensus recommendations for cancer care, which were accessed more than 15 million times in 2023 alone.I look forward to working even more closely with Matt and Chris and relying on the substantial expertise, caring, and leadership they bring to these positions."Dr. Kalaycio is a leading expert in hematology and medical oncology who specializes in the treatment of leukemia, hematopoietic cell transplantation, and CAR T-cell therapy.He is Vice Chair of Cleveland Clinic Taussig Cancer Institute and a professor of medicine at Cleveland Clinic Lerner College of Medicine of Case Western Reserve University."NCCN is committed to ensuring that all cancer patients receive the latest evidence-based treatment options by not only informing healthcare providers of available treatments but also offering education and support to the patients and their caregivers," said Dr. Kalaycio."
Unveiling Discrepant and Rare Dihydropyrimidine Dehydrogenase (DPYD) Results Using an In-House Genotyping Test: A Case Series
Authors: D. Grace Nguyen, Sarah A. Morris, Annabel Chen, Donald C. Moore, Sarah L. Hanson, Chris Larck, Laura W. Musselwhite, John D. Turner, Mohamed E. Salem, Simeon O. Kwange, Alicia Hamilton, Nury Steuerwald, Jai N. Patel
Journal: Journal of the National Comprehensive Cancer Network (2024)

Fluoropyrimidine chemotherapy is a primary component of many solid tumor treatment regimens, particularly those for gastrointestinal malignancies. Approximately one-third of patients receiving fluoropyrimidine-based chemotherapies experience serious adverse effects. This risk is substantially higher in patients carrying DPYD genetic variants, which cause reduced fluoropyrimidine metabolism and inactivation (ie, dihydropyridine dehydrogenase [DPD] deficiency). Despite the known relationship between DPD deficiency and severe toxicity risk, including drug-related fatalities, pretreatment DPYD testing is not standard of care in the United States. We developed an in-house DPYD genotyping test that detects 5 clinically actionable variants associated with DPD deficiency, and genotyped 827 patients receiving fluoropyrimidines, of which 49 (6%) were identified as heterozygous carriers. We highlight 3 unique cases: (1) a patient with a false-negative result from a commercial laboratory that only tested for the c.1905 + 1G>A (*2A) variant, (2) a White patient in whom the c.557A>G variant (typically observed in people of African ancestry) was detected, and (3) a patient with the rare c.1679T>G (*13) variant. Lastly, we evaluated which DPYD variants are detected by commercial laboratories offering DPYD genotyping in the United States and found 6 of 13 (46%) did not test for all 5 variants included on our panel. We estimated that 20.4% to 81.6% of DPYD heterozygous carriers identified on our panel would have had a false-negative result if tested by 1 of these 6 laboratories. The sensitivity and negative predictive value of the diagnostic tests from these laboratories ranged from 18.4% to 79.6% and 95.1% to 98.7%, respectively. These cases underscore the importance of comprehensive DPYD genotyping to accurately identify patients with DPD deficiency who may require lower fluoropyrimidine doses to mitigate severe toxicities and hospitalizations. Clinicians should be aware of test limitations and variability in variant detection by commercial laboratories, and seek assistance by pharmacogenetic experts or available resources for test selection and result interpretation.
Mechanisms and implications of gamma oscillation plasticity
Authors: Michael T. Craig, Monika H. Bielska, Kate Jeffery
Journal: Trends in Neurosciences (2024)

A recent study by Hadler and colleagues uncovered a novel form of plasticity of gamma oscillations in an ex vivo hippocampal slice preparation which they term 'gamma potentiation'. We discuss the potential cellular mechanisms of this form of plasticity and its functional and translational implications.