tbuckley/cabot-search huggingface dataset:
Comparable Cardiorenal Benefits of SGLT2 Inhibitors and GLP-1RAs in Asian and White Populations: An Updated Meta-analysis of Results From Randomized Outcome Trials
Authors: Huilin Tang, Stephen E. Kimmel, Steven M. Smith, Kenneth Cusi, Weilong Shi, Matthew Gurka, Almut G. Winterstein, Jingchuan Guo
Journal: Diabetes Care (2022)

BACKGROUND Whether the cardiorenal benefits of sodium–glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1RAs) are comparable between White and Asian populations remains unclear. PURPOSE To compare the cardiorenal benefits of SGLT2 inhibitors and GLP-1RAs between White and Asian populations and to compare the cardiorenal benefits between the two agents in Asian patients. DATA SOURCES Electronic databases were searched up to 28 March 2021. STUDY SELECTION We included the cardiovascular (CV) and renal outcome trials of SGLT2 inhibitors and GLP-1RAs where investigators reported major adverse CV events (MACE), CV death/hospitalization for heart failure (HHF), or composite renal outcomes with stratification by race. DATA EXTRACTION We extracted the hazard ratio of each outcome stratified by race (Asian vs. White populations). DATA SYNTHESIS In 10 SGLT2 inhibitor trials, there was no significant difference between Asian and White populations for MACE (P = 0.55), CV death/HHF (P = 0.87), or composite renal outcomes (P = 0.97). In seven GLP-1RA trials, we observed a similar MACE benefit between Asian and White populations (P = 0.10). In our networkmeta-analysis we found a comparable benefit for MACE between SGLT2 inhibitors and GLP-1RAs in Asian patients. LIMITATIONS The data were from stratified analyses. CONCLUSIONS There appear to be comparable cardiorenal benefits of SGLT2 inhibitors and GLP-1RAs between Asian and White participants enrolled in CV and renal outcome trials; the two therapies seem to have similar CV benefits for Asian participants.
A Survey on Shape-Constraint Deep Learning for Medical Image Segmentation
Authors: Simon Bohlender, Ilkay Oksuz, Anirban Mukhopadhyay
Journal: IEEE Reviews in Biomedical Engineering (2021)

Since the advent of U-Net, fully convolutional deep neural networks and its many variants have completely changed the modern landscape of deep-learning based medical image segmentation. However, the over-dependence of these methods on pixel-level classification and regression has been identified early on as a problem. Especially when trained on medical databases with sparse available annotation, these methods are prone to generate segmentation artifacts such as fragmented structures, topological inconsistencies and islands of pixel. These artifacts are especially problematic in medical imaging since segmentation is almost always a pre-processing step for some downstream evaluations like surgical planning, visualization, prognosis, or treatment planning. However, one common thread across all these downstream tasks is the demand of anatomical consistency. To ensure the segmentation result is anatomically consistent, approaches based on Markov/ Conditional Random Fields, Statistical Shape Models, Active Contours are becoming increasingly popular over the past 5 years. In this review paper, a broad overview of recent literature on bringing explicit anatomical constraints for medical image segmentation is given, the shortcomings and opportunities are discussed and the potential shift towards implicit shape modelling is elaborated. We review the most relevant papers published until the submission date and provide a tabulated view with method details for quick access.
Advances in Gender-Transformative Approaches to Health Promotion
Authors: Jane Fisher, Shelly Makleff
Journal: Annual Review of Public Health (2022)

Gender is an important determinant of health, but explicit attention to gender is often missing in health promotion. We build on Pederson and colleagues’ gender-transformative framework for health promotion to propose four guiding principles for gender-transformative health promotion. First, health promotion must address gender norms directly if it is to improve health outcomes. Second, it should move beyond individual change to engage explicitly with structural and social determinants of health. Third, it should address underlying gender-related determinants in order to influence health outcomes. And fourth, it requires complexity-informed design, implementation, and evaluation. We provide background on key concepts that are essential for designing, implementing, and evaluating gender-transformative health promotion: gender norms, socioecological approaches, and the gender system. We give examples of the four principles in practice, using the case of postnatal mental health promotion in Australia and sexuality education in Mexico. These four principles can be applied to health promotion efforts across contexts and outcomes to address the harmful gender norms that contribute to poor health as a part of broader efforts to improve health and well-being.
FOLLOW-UP OF HOSPITALIZED COVID-19 SURVIVORS: ASSESSMENT OF SHORT AND LONG-TERM CARDIOVASCULAR SEQUELAE AFTER SARS-COV-2 INFECTION
Authors: Lucia Ilaria Birtolo, Prosperi Silvia, Sara Monosilio, Sara Cimino, Domenico Filomena, Letizia D'Antoni, Santi Francavilla, Marco Francone, Nicola Galea, Paolo Severino, Patrizia Pasculli, Maria Chiara Colaiacomo, Angelo Petroianni, Cristina Chimenti, Carlo Lavalle, Roberto Badagliacca, Paolo Palange, Claudio Maria Mastroianni, Carlo Catalano, Francesco Pugliese, Maria Ciardi, Viviana Maestrini, Massimo Mancone, Francesco Fedele
Journal: Journal of the American College of Cardiology (2022)
Abstract P079: Comparing General Versus Disease-specific Patient-reported Outcomes Instruments Among Patients With Peripheral Artery Disease
Authors: Chloe Powell, Gloria Kim, Mary Byrnes, Katherine Gallagher, Matthew A Corriere
Journal: Circulation (2022)

Objectives: Patient-reported outcomes (PRO) are championed for assessment of peripheral artery disease (PAD) outcomes. Both general and PAD-specific instruments are available, but associations with clinical and demographic variables are unknown. We initiated a cohort study of PRO among patients with PAD and evaluated baseline correlations between PRO, clinical, and demographic variables. Methods: Patients were recruited from a diagnostic unit based on ankle brachial index (ABI). QOL was assessed using one PAD-specific (VascuQol6) and two general instruments (PROMIS Physical Function Short Form 6b &amp; PROMIS Pain Interference Short Form 6a). Associations between PRO were evaluated with correlation coefficients. Associations with clinical and demographic variables were evaluated with simple and multivariable models. Results: 93 patients participated. All PRO were significantly correlated; greatest correlation was between VascuQol6 and PROMIS Pain Interference (-0.84; P&lt;0.001). Lowest correlation was between PROMIS Physical Function and VascuQol6 (-0.611; P&lt;0.001) (Figure). VascuQol-6 was associated with age (P=0.002), ABI (P=0,002), and symptom level (P=0.001). Physical Function scores were associated with smoking (P=0.058), neuropathy (P=0.003), symptom category (P=0.078), and symptom level (P=0.043). Pain Interference scores were associated with age (P=0.007), symptom category (P=0.010), and symptom level (P=0.01). Conclusions: QOL scores correlate with factors related and unrelated to PAD. Different measures may be helpful for capturing specific QOL domains and clinical factors. *Normalized T-scores
Differential prognostic impact of IDH1 and IDH2 mutations in chronic myelomonocytic leukemia
Authors: Connor Walsh, Anthony Hunter, Terra Lasho, Christy Finke, Rhett Ketterling, Rami Komrokji, Ayalew Tefferi, Abhishek Mangaonkar, Matthew Howard, Naseema Gangat, Aref Al-Kali, Najla Al Ali, Eric Padron, Mrinal M. Patnaik
Journal: Leukemia (2022)
Comparison of Lung Function in Healthy Nigerian Children Living in Nigeria and in the United Kingdom
Authors: Michele Arigliani, Sooky Lum, Chiara Zuiani, Emma Raywood, Livingstone Gayus Dogara, Ramatu Zubair, Luigi Castriotta, Ashel Dache Sunday, Baba Inusa, Paola Cogo
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

"Comparison of Lung Function in Healthy Nigerian Children Living in Nigeria and in the United Kingdom." American Journal of Respiratory and Critical Care Medicine, 206(2), pp. 221–224
Multicenter Analysis of Genomically Targeted Single Patient Use Requests for Pediatric Neoplasms
Authors: Himalee S. Sabnis, David S. Shulman, Benjamin Mizukawa, Nancy Bouvier, Ahmet Zehir, Jason Fangusaro, Vanessa A. Fabrizio, Chanta Whitlow, Marilyn Winchester, Laura Agresta, Brian Turpin, Daniel S. Wechsler, Steven G. DuBois, Julia Glade-Bender, Sharon M. Castellino, Neerav Shukla
Journal: Journal of Clinical Oncology (2021)

The US Food and Drug Administration-expanded access program (EAP) uses a single patient use (SPU) mechanism to provide patient access to investigational agents in situations where no satisfactory or comparable therapy is available. Genomic profiling of de novo and relapsed or refractory childhood cancer has led to increased identification of new drug targets in the last decade. The aim of this study is to examine the SPU experience for genomically targeted therapies in patients with pediatric cancer.All genomically targeted therapeutic SPUs obtained over a 5-year period were evaluated at four large pediatric cancer programs. Data were collected on the type of neoplasm, agents requested, corresponding molecularly informed targets, and clinical outcomes.A total of 45 SPUs in 44 patients were identified. Requests were predominantly made for CNS and solid tumors (84.4%) compared with hematologic malignancies (15.6%). Lack of an available clinical trial was the main reason for SPU initiation (64.4%). The median time from US Food and Drug Administration submission to approval was 3 days (range, 0-12 days) and from Institutional Review Board submission to approval was 5 days (range, 0-50 days). Objective tumor response was seen in 39.5% (15 of 38) of all evaluable SPUs. Disease progression was the primary reason for discontinuation of drug (66.7%) followed by toxicity (13.3%).SPU requests remain an important mechanism for pediatric access to genomically targeted agents given the limited availability of targeted clinical trials for children with high-risk neoplasms. Furthermore, this subset of SPUs resulted in a substantial number of objective tumor responses. The development of a multi-institutional data registry of SPUs may enable systematic review of toxicity and clinical outcomes and provide evidence-based access to new drugs in rare pediatric cancers.
A machine-learning based objective measure for ALS disease severity
Authors: Fernando G. Vieira, Subhashini Venugopalan, Alan S. Premasiri, Maeve McNally, Aren Jansen, Kevin McCloskey, Michael P. Brenner, Steven Perrin
Journal: npj Digital Medicine (2022)

Amyotrophic Lateral Sclerosis (ALS) disease severity is usually measured using the subjective, questionnaire-based revised ALS Functional Rating Scale (ALSFRS-R). Objective measures of disease severity would be powerful tools for evaluating real-world drug effectiveness, efficacy in clinical trials, and for identifying participants for cohort studies. We developed a machine learning (ML) based objective measure for ALS disease severity based on voice samples and accelerometer measurements from a four-year longitudinal dataset. 584 people living with ALS consented and carried out prescribed speaking and limb-based tasks. 542 participants contributed 5814 voice recordings, and 350 contributed 13,009 accelerometer samples, while simultaneously measuring ALSFRS-R scores. Using these data, we trained ML models to predict bulbar-related and limb-related ALSFRS-R scores. On the test set (n = 109 participants) the voice models achieved a multiclass AUC of 0.86 (95% CI, 0.85-0.88) on speech ALSFRS-R prediction, whereas the accelerometer models achieved a median multiclass AUC of 0.73 on 6 limb-related functions. The correlations across functions observed in self-reported ALSFRS-R scores were preserved in ML-derived scores. We used these models and self-reported ALSFRS-R scores to evaluate the real-world effects of edaravone, a drug approved for use in ALS. In the cohort of 54 test participants who received edaravone as part of their usual care, the ML-derived scores were consistent with the self-reported ALSFRS-R scores. At the individual level, the continuous ML-derived score can capture gradual changes that are absent in the integer ALSFRS-R scores. This demonstrates the value of these tools for assessing disease severity and, potentially, drug effects.
Intersectional Analysis of U.S. Medical Faculty Diversity over Four Decades
Authors: Sophia C. Kamran, Karen M. Winkfield, Joan Y. Reede, Neha Vapiwala
Journal: New England Journal of Medicine (2022)

The 2020 U.S. Census data show a rapidly diversifying U.S. population. We sought to evaluate whether clinical faculty and leadership representation at academic medical schools reflects the diversifying population over time. Using data from the Association of American Medical Colleges for the period of 1977 through 2019, we found notable progress in female representation among clinical faculty, with smaller gains among department chairs and medical school deans. Racial and ethnic groups that are underrepresented in medicine are designated as such because their presence within the medical profession is disproportionate to the U.S. Census data. Even with accounting for this underrepresentation, clinical faculty and leadership positions show even starker disparities. Thoughtful policy implementation could help address this persistent underrepresentation among medical school faculty and leadership positions.
The Few yet Fabp4ulous Pancreatic Stellate Cells Give Rise to Protumoral CAFs
Authors: Edna Cukierman
Journal: Cancer Discovery (2022)

Abstract Summary: Cancer-associated fibroblast (CAF) pro– and anti–pancreatic cancer functional dichotomy has been at the center of numerous studies. In this issue of Cancer Discovery, Helms and colleagues demonstrate that although pancreatic stellate cell–derived CAFs constitute a desmoplastic cell minority, these cells play a protumorigenic role via microenvironmental mechanomodulation. See related article by Helms et al., p. 484.
Inactivation of AMPK Leads to Attenuation of Antigen Presentation and Immune Evasion in Lung Adenocarcinoma
Authors: Yajing Gao, Pekka Päivinen, Sushil Tripathi, Eva Domènech-Moreno, Iris P.L. Wong, Kari Vaahtomeri, Ashwini S. Nagaraj, Sarang S. Talwelkar, Marc Foretz, Emmy W. Verschuren, Benoit Viollet, Yan Yan, Tomi P. Mäkelä
Journal: Clinical Cancer Research (2021)

Mutations in STK11 (LKB1) occur in 17% of lung adenocarcinoma (LUAD) and drive a suppressive (cold) tumor immune microenvironment (TIME) and resistance to immunotherapy. The mechanisms underpinning the establishment and maintenance of a cold TIME in LKB1-mutant LUAD remain poorly understood. In this study, we investigated the role of the LKB1 substrate AMPK in immune evasion in human non-small cell lung cancer (NSCLC) and mouse models and explored the mechanisms involved.We addressed the role of AMPK in immune evasion in NSCLC by correlating AMPK phosphorylation and immune-suppressive signatures and by deleting AMPKα1 (Prkaa1) and AMPKα2 (Prkaa2) in a KrasG12D -driven LUAD. Furthermore, we dissected the molecular mechanisms involved in immune evasion by comparing gene-expression signatures, AMPK activity, and immune infiltration in mouse and human LUAD and gain or loss-of-function experiments with LKB1- or AMPK-deficient cell lines.Inactivation of both AMPKα1 and AMPKα2 together with Kras activation accelerated tumorigenesis and led to tumors with reduced infiltration of CD8+/CD4+ T cells and gene signatures associated with a suppressive TIME. These signatures recapitulate those in Lkb1-deleted murine LUAD and in LKB1-deficient human NSCLC. Interestingly, a similar signature is noted in human NSCLC with low AMPK activity. In mechanistic studies, we find that compromised LKB1 and AMPK activity leads to attenuated antigen presentation in both LUAD mouse models and human NSCLC.The results provide evidence that the immune evasion noted in LKB1-inactivated lung cancer is due to subsequent inactivation of AMPK and attenuation of antigen presentation.
Terminal Digit Preference in Pulmonary Hypertension Endpoints
Authors: Jasleen Minhas, Grayson Baird, Dina Appleby, Robyn McClelland, Jeff Min, Jeremy Mazurek, Corey E. Ventetuolo, Nadine Al-Naamani, Steven M. Kawut
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

"Terminal Digit Preference in Pulmonary Hypertension Endpoints." American Journal of Respiratory and Critical Care Medicine, 205(12), pp. 1482–1485
Rostral and Caudal Ventral Tegmental Area GABAergic Inputs to Different Dorsal Raphe Neurons Participate in Opioid Dependence
Authors: Yue Li, Chun-Yue Li, Wang Xi, Sen Jin, Zuo-Hang Wu, Ping Jiang, Ping Dong, Xiao-Bin He, Fu-Qiang Xu, Shumin Duan, Yu-Dong Zhou, Xiao-Ming Li
Journal: Neuron (2021)
Searching for escape-resistant anti–SARS-CoV-2 neutralizing antibodies
Authors: Ranjeet Singh Mahla, Lynn B. Dustin
Journal: Journal of Clinical Investigation (2022)

A major goal of SARS-CoV-2 vaccination is the induction of neutralizing antibodies (nAbs) capable of blocking infection by preventing interaction of the SARS-CoV-2 Spike protein with ACE2 on target cells. Cocktails of monoclonal nAbs can reduce the risk of severe disease if administered early in infection. However, multiple variants of concern (VOCs) have arisen during the pandemic that may escape from nAbs. In this issue of the JCI, Jia Zou, Li Li, and colleagues used yeast display libraries to identify mAbs that bind to Spike proteins with a vast array of single amino acid substitutions. The authors identified mutation-resistant monoclonal nAbs for potential use as therapeutics. Multimerization further improved the potency of selected nAbs. These findings suggest a way forward in development of better nAb cocktails. However, the emergence of the highly mutated omicron (B.1.1.529) variant heightens the importance of finding effective anti–SARS-CoV-2 nAb therapeutics despite rapid viral evolution.
Variation of the Vaginal Microbiome During and After Pregnancy in Chinese Women
Authors: Xiaoai Zhang, Qingzhi Zhai, Jinfeng Wang, Xiuling Ma, Bo Xing, Hang Fan, Zhiying Gao, Fangqing Zhao, Wei Liu
Journal: Genomics Proteomics & Bioinformatics (2022)

Abstract A comprehensive profiling of the vaginal microbial communities and their variability enables an accurate description of the microbiome in women. However, there is a lack of studies available on Chinese women. In the present study, the composition of the vaginal microbiota during pregnancy and the 6-week postpartum period of 454 Chinese women was characterized by sequencing the V3–V4 region of the 16S ribosomal RNA (rRNA) gene. The vaginal microbiome showed variations during pregnancy and the postpartum period based on the abortion history, hypertensive disorders, delivery mode, and maternal age. Co-variation of 22 bacterial taxa, including the Lactobacillus genus and two of its species, may account for the common characteristics of the vaginal microbiome under scenarios of different medical histories and pregnancy outcomes. In contrast, discriminant bacterial species were significantly different between women who had preterm birth (PTB) with and without premature rupture of membranes (PROM), and the community state type (CST) IV-A without any predominant Lactobacillus species in the microbiota was more prevalent during pregnancy in the PROM-PTB cases, suggesting that specific bacterial species could be considered to distinguish between different types of PTB. By providing data on Chinese women, this study will enrich the knowledge of the human microbiome and contribute to a better understanding of the association between the vaginal microbiome and reproductive health.
Abstract P081: Rethinking The Association Of Physical Performance With Blood Pressure Changes In Older Women: Findings Form The Women’S Health Initiative
Authors: Deepika Laddu, Michael LaMonte, Bernhard Haring, Hajwa Kim, Peggy Cawthon, Jennifer Bea, Hailey Banack, Jane A Cauley, Matthew A Allison, Lisa W Martin, Meryl LeBoff, Marcia L Stefanick, Shane A Phillips, Jun Ma
Journal: Circulation (2022)

Rethinking the Association of Physical Performance with Blood Pressure Changes in Older Women: Findings form the Women’s Health Initiative Background: This study evaluated the association between changes in physical performance and blood pressure (BP) (e.g., systolic [SBP], diastolic [DBP], pulse pressure) in older women. Methods: 5627 women (mean age 69.8 ± 3.7 y) with grip strength, chair stand, gait speed performance and clinic-measured BP at baseline and at least one follow-up (years 1, 3 or 6) were included. Generalized estimating equation analysis of multivariable models with standardized point estimates described the longitudinal association between physical performance and BP changes in the overall cohort, and in models stratified by baseline cardiovascular disease (CVD), time-varying antihypertensive medication use (none, ≥1) and enrollment age (65-69 y; 70-79 y). Results: Overall, each z-score unit increment in grip strength was associated with 0.54 mmHg (95% CI 0.06, 1.03) higher SBP, and 0.34 mmHg (95% CI 0.07, 0.62) higher DBP ( Table 1 ). In stratified models, a standardized increment in grip strength was associated with higher SBP in women without CVD (0.74; 95% CI 0.16-1.32), among antihypertensive medication users (0.89; 95% CI 0.41, 1.37) and non-users (0.35; 95% CI 0.01, 0.68), and in those aged 65-69 y (0.64; 95% CI 0.04, 1.23). Similarly, a standardized increment in any of the three performance measures was associated with modestly higher DBP in antihypertensive medication users, and those aged 70-79 y. Associations between any performance measure and pulse pressure change were not significant. Conclusion: These results suggest a positive, and statistically significant relationship between physical performance and BP that appears to be influenced by CVD history, antihypertensive medication use, and age. Total characters with table: 2,213 Table 1: