tbuckley/cabot-search huggingface dataset:
Remodeling of the tumor/tumor microenvironment ecosystem during KRAS G12C inhibitor clinical resistance in lung cancer
Authors: Tadashi Manabe, Trever G. Bivona
Journal: Journal of Clinical Investigation (2022)

KRAS G12C inhibitors such as sotorasib and adagrasib are often effective in KRAS G12C-driven non-small cell lung cancer (NSCLC) patients. However, acquired resistance limits long-term patient survival. In this issue of the JCI, Tsai et al. present a comprehensive genetic analysis of multiple tumors with acquired sotorasib resistance obtained through an autopsy of a patient with KRAS G12C-mutant NSCLC. This analysis of pre- and posttreatment tumors uncovered cancer cell-intrinsic and -extrinsic features of resistance, including reactivation of KRAS-mediated signaling, reprogramming of metabolism, epithelial-mesenchymal transition, and tumor microenvironment changes. This elegant study demonstrates the multifaceted nature of KRAS G12C inhibitor clinical resistance and potential avenues to overcome resistance.
Community-Acquired Pneumonia
Authors: Michael B. Rothberg
Journal: Annals of Internal Medicine (2022)

Community-acquired pneumonia is an important cause of morbidity and mortality. It can be caused by bacteria, viruses, or fungi and can be prevented through vaccination with pneumococcal, influenza, and COVID-19 vaccines. Diagnosis requires suggestive history and physical findings in conjunction with radiographic evidence of infiltrates. Laboratory testing can help guide therapy. Important issues in treatment include choosing the proper venue, timely initiation of the appropriate antibiotic or antiviral, appropriate respiratory support, deescalation after negative culture results, switching to oral therapy, and short treatment duration.
Does Timing of Ventricular Tachycardia Ablation Affect Prognosis in Patients With an Implantable Cardioverter Defibrillator? Results From the Multicenter Randomized PARTITA Trial
Authors: Paolo Della Bella, Francesca Baratto, Pasquale Vergara, Patrizia Bertocchi, Matteo Santamaria, Pasquale Notarstefano, Leonardo Calò, Daniela Orsida, Luca Tomasi, Marcello Piacenti, Stefano Sangiorgio, Francesco Pentimalli, Etienne Pruvot, João De Sousa, Frederic Sacher, Massimo Tritto, Luca Rebellato, Thomas Deneke, Salvo Andrea Romano, Martina Nesti, Alessio Gargaro, Daniele Giacopelli, Giovanni Peretto, Andrea Radinovic
Journal: Circulation (2022)

Background: Optimal timing for catheter ablation of ventricular tachycardia is an important unresolved issue. There are no randomized trials evaluating the benefit of ablation after the first implantable cardioverter defibrillator (ICD) shock. Methods: We conducted a 2-phase, prospective, multicenter, randomized clinical trial. Patients with ischemic or nonischemic dilated cardiomyopathy and primary or secondary prevention indication for ICD were enrolled in an initial observational phase until first appropriate shock (phase A). After reconsenting, patients were randomly assigned 1:1 in phase B to immediate ablation (within 2 months from shock delivery) or continuation of standard therapy. The primary end point was a composite of death from any cause or hospitalization for worsening heart failure. Amiodarone intake was not allowed except for documented atrial tachyarrhythmias. On July 23, 2021, phase B of the trial was interrupted as a result of the first interim analysis on the basis of the Bayesian adaptive design. Results: Of the 517 patients enrolled in phase A, 154 (30%) had ventricular tachycardia, 56 (11%) received an appropriate shock over a median follow-up of 2.4 years (interquartile range, 1.4–4.4), and 47 of 56 (84%) agreed to participate in phase B. After 24.2 (8.5–24.4) months, the primary end point occurred in 1 of 23 (4%) patients in the ablation group and 10 of 24 (42%) patients in the control group (hazard ratio, 0.11 [95% CI, 0.01–0.85]; P =0.034). The results met the prespecified termination criterion of &gt;99% Bayesian posterior probability of superiority of treatment over standard therapy. No deaths were observed in the ablation group versus 8 deaths (33%) in the control group ( P =0.004); there was 1 worsening heart failure hospitalization in the ablation group (4%) versus 4 in the control group (17%; P =0.159). ICD shocks were less frequent in the ablation group (9%) than in the control group (42%; P =0.039). Conclusions: Ventricular tachycardia ablation after first appropriate shock was associated with a reduced risk of the combined death or worsening heart failure hospitalization end point, lower mortality, and fewer ICD shocks. These findings provide support for considering ventricular tachycardia ablation after the first ICD shock. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01547208.
Assessment of Epidemiology Capacity in State Health Departments — United States, 2021
Authors: Jessica Arrazola, Sarah Auer
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

In 2021, during the COVID-19 response, the Council of State and Territorial Epidemiologists (CSTE) conducted its seventh periodic Epidemiology Capacity Assessment (ECA), a national assessment that evaluates trends in applied epidemiology workforce size, funding, and epidemiology capacity at state health departments.* A standardized web-based questionnaire was sent to state epidemiologists in 50 states and the District of Columbia (DC). The questionnaire assessed the number of current and optimal epidemiologist positions; sources of epidemiology activity and personnel funding; and each health department's self-perceived capacity to lead activities, provide subject matter expertise, and obtain and manage resources for the three essential public health services (EPHS) most closely linked to epidemiology.† CSTE enumerated 4,136 epidemiology positions across the United States, with an additional 2,196 positions needed to provide basic public health services. From 2017 to 2021, the number of epidemiologists in state health departments increased 23%, an increase primarily accounted for by the number of those supporting the COVID-19 response§. The number of staff members decreased in program areas of infectious diseases, chronic diseases, and maternal and child health (MCH). Federal funding supports most epidemiology activities (85%) and epidemiology personnel (83%). Overall capacity to deliver the EPHS has declined, and epidemiology workforce and capacity needs remain unmet. More epidemiologists and sustainable funding are needed to consistently and effectively deliver EPHS. Additional resources (e.g., funding for competitive compensation and pathways for career advancement) are essential for recruitment and retention of epidemiologists to support public health activities across all program areas.
Report of the Lancet Commission on the Value of Death: bringing death back into life
Authors: Libby Sallnow, Richard Smith, Sam H Ahmedzai, Afsan Bhadelia, Charlotte Chamberlain, Yali Cong, Brett Doble, Luckson Dullie, Robin Durie, Eric A Finkelstein, Sam Guglani, Melanie Hodson, Bettina S Husebø, Allan Kellehear, Celia Kitzinger, Felicia Marie Knaul, Scott A Murray, Julia Neuberger, Seamus O'Mahony, M R Rajagopal, Sarah Russell, Eriko Sase, Katherine E Sleeman, Sheldon Solomon, Ros Taylor, Mpho Tutu van Furth, Katrina Wyatt
Journal: The Lancet (2022)
Abstract P114: Effects Of Losartan And The Dash Diet On Serum Urate
Authors: Noelle Castilla-Ojo, Ruth-Alma N Turkson-Ocran, Paul R Conlin, Lawrence J Appel, Edgar R Miller, Stephen P Juraschek
Journal: Circulation (2022)

Background: The DASH diet and losartan each lower blood pressure (BP) and concurrently affect many cardiometabolic biomarkers. Whether these BP-lowering treatments reduce serum urate, a pro-oxidant associated with cardiovascular health and gout, is uncertain. Objective: To determine the independent effects of the DASH diet and losartan on serum urate. Methods: We randomized 55 participants with elevated BP in parallel fashion to the DASH or control diet, the standard American diet. While on their assigned diet, participants were randomized in a two-period cross-over design to losartan or placebo, each for 4-weeks. Serum urate was measured at baseline and at the end of each period. Diets were designed to maintain a constant weight constant. We examined the independent effects of DASH (vs control) or losartan (vs placebo) on serum urate, overall and among those with baseline serum urate ≥6 mg/dL, using generalized estimating equations. Results: Of 55 randomized participants, mean age of participants was 52 years, 58% were women, and 64% were Black. Mean (±SD) baseline SBP/DBP was 146±12/91±9 and mean (±SD) serum urate was 5.2±1.2 mg/dL. Losartan significantly decreased serum urate (overall mean difference -0.23 mg/dL; 95% CI: -0.40, -0.05). The DASH diet did not significantly reduce urate levels overall (mean difference -0.05 mg/dL; 95% CI: -0.39, 0.28), but did decrease levels in participants with elevated baseline urate levels (≥6 mg/dL), with a mean difference of -0.33 mg/dL (95% CI: -0.87, 0.21; P -interaction =0.007 across hyperuricemia groups). Conclusions: In adults with elevated BP, losartan significantly reduced serum urate, while the DASH diet only significantly decreased serum urate among participants with higher urate at baseline. Additional research should explore potential mechanisms, as well as the effects of these treatments on clinical outcomes (e.g. gout).
Abstract MP37: Contributions Of Social Determinants Of Health And Cardiometabolic Risk Factors To Racial/ethnic Disparities In Premature Mortality In The United States
Authors: Kathryn Foti, Dan Wang, Yvonne Commodore-Mensah, Josef Coresh, Elizabeth Selvin
Journal: Circulation (2022)

Introduction: Racial/ethnic disparities in premature mortality in the US arise from complex social, structural, and historical factors. We examined the extent to which differences in social determinants of health (SDoH), cardiometabolic risk factors, and health conditions explained the excess risk of premature mortality. Methods: We used nationally representative data for adults aged ≥20 years from the 1999-2010 National Health and Nutrition Examination Surveys with mortality linkage through 2015. We calculated the age-sex-adjusted hazard ratios (HRs) for premature mortality (death &lt;75 years of age) comparing non-Hispanic (NH) Black and Hispanic adults to NH white adults. We used Cox models to determine the excess risk mediated by SDoH, cardiometabolic risk factors, and health conditions by calculating the percent reduction in the HR compared to the age-sex-adjusted model. Results: We included 11,854 NH White, 4,201 NH Black, and 5,997 Hispanic adults. The risk of premature mortality was higher among NH Black (HR: 1.7 (95% confidence interval [CI] 1.5-1.9) and Hispanic (HR: 1.5, 95% CI 1.2-1.9) adults than NH White adults. Adjusting for SDoH ( Figure ) attenuated the HRs and explained 62% and 60% of the excess risk among NH Black and Hispanic adults, respectively. Adding cardiometabolic risk factors and health conditions to the age-sex-adjusted model explained 54% of the excess risk among NH Black adults, but only 13% among Hispanic adults. Adjusting for SDoH, cardiometabolic risk factors, and health conditions together explained 73% of the excess risk among NH Black and 54% of excess risk among Hispanic adults. Discussion: Differences in SDoH explained 60% of the excess risk of premature mortality among NH Black and Hispanic adults. Differences in health status further explained some of the excess risk among NH Black, but not Hispanic, adults. Interventions to address SDoH and their downstream health consequences may reduce racial disparities in premature mortality and advance health equity.
Dengue virus infections among European travellers, 2015 to 2019
Authors: Céline M Gossner, Nelly Fournet, Christina Frank, Beatriz Fernández-Martínez, Martina Del Manso, Joana Gomes Dias, Henriette de Valk
Journal: Eurosurveillance (2022)

BackgroundDengue is a disease with major impacts on public health in tropical and subtropical countries. In Europe, in the past decade, few autochthonous outbreaks were described.AimWe aimed to identify factors associated with frequency of dengue virus infection among European travellers and at assessing how surveillance data could support preparedness against autochthonous outbreaks within Europe.MethodsWe performed a descriptive analysis of travel-related dengue cases reported by European countries from 2015 through 2019. Using flight passenger data, we calculated travellers' infection rates (TIR). We investigated the following associations: (i) between TIR and incidence rate in selected countries of infection and (ii) between number of travel-related cases and occurrence of autochthonous outbreaks within Europe.ResultsThere were 11,478 travel-related dengue cases and the TIR was 2.8 cases per 100,000 travellers. Most cases were infected in Asia (71%), predominantly in south-eastern Asia. The TIR was highest among travellers returning from Asia (6.1/100,000). There was an association between the incidence rate in the country of infection and the TIR but no association between the number of travel-related cases and occurrence of autochthonous outbreaks in Europe.ConclusionsThe likelihood of infection in travellers is a function of the ongoing epidemiological situation in the country of exposure. The number of travel-related cases alone is not sufficient to estimate the likelihood of autochthonous outbreaks where vectors are present in Europe. Additional contributing factors such as adequate vectorial capacity and suitable environmental conditions are required.
Molecular imprinting of glycoproteins: From preparation to cancer theranostics
Authors: Muhammad Mujahid Ali, Shoujun Zhu, Farrukh Raza Amin, Dilshad Hussain, Zhenxia Du, Lianghai Hu
Journal: Theranostics (2022)

Glycoprotein imprinted polymers have rapidly grown as excellent receptors for cancer targeting, diagnostics, inhibition, and nanomedicines as they specifically target glycans and glycosites overexpressed in various tumors.Compared to natural antibodies, they are easy to synthesize, stable, and cost-efficient.Currently, no study specifically discusses glycoproteins imprinting strategies for cancer theranostics.In this review, firstly we explored various factors involved in designing and synthesis of glycoprotein imprinted materials, including, the characteristics and choice of monomers for imprinting, types of templates and their interactions involved, and the imprinting methods.Secondly, the integration of these MIPs with different probes that have been applied for in vitro and in vivo targeting for cancer diagnostics including biosensing and bioimaging, and image-guided therapeutic applications as nanomedicines.These Glycoprotein imprinted polymers have been found to specifically target the glycoprotein biomarkers and glycosylated cell receptors overexpressed in different cancers and have been reported as excellent diagnostic tools.As nanomedicines, they have been potentially employed in various modes of cancer therapy such as targeted drug delivery, photodynamic therapy, photothermal therapy, and nanoMIPs themselves as therapeutics for locally killing tumor cells.Although the research is still in its early stages and no real-world clinical trials on humans have been conducted, nanoMIPs have a promising future in this field.We believe these findings will pave the way for MIPs in advanced diagnostics, antibody treatment, and immunotherapy as future nanomedicine for real-world cancer theranostics.
Abstract 052: Social Determinants Of Health And Uncontrolled Blood Pressure In A National Cohort Of Black And White US Adults
Authors: Oluwasegun P Akinyelure, Byron C Jaeger, Suzanne Oparil, April P Carson, Monika Safford, George Howard, Paul Muntner, Shakia T Hardy
Journal: Circulation (2022)

Background: Hypertension and uncontrolled blood pressure (BP) are the largest contributors to racial disparities in life expectancy. Determining the contribution of social determinants of health (SDOH) to racial differences in uncontrolled BP could help identify ways to achieve the American Heart Association’s 2030 impact goal of equitably improving healthy life expectancy. Methods: We analyzed data from 7,497 Black and 7,306 White US adults taking antihypertensive medication from the REasons for Geographic and Racial Differences in Stroke study to determine the association between SDOH and uncontrolled BP. SDOH were defined using the Healthy People 2030 domains of education, economic stability, social context, neighborhood environment and healthcare access. Uncontrolled BP was defined as systolic BP ≥130 mm Hg or diastolic BP ≥80 mm Hg. Results: Among participants taking antihypertensive medication (mean age 66.3 years, 50.7% Black, 57.1% female), 68.0% of Black and 59.0% of White participants had uncontrolled BP. After multivariable adjustment, uncontrolled BP (prevalence ratio; 95% CI) was more common among those with less than a high school education (1.06; 1.02 – 1.09), annual household income &lt;$20,000 (1.12; 1.06 – 1.18) and $20,000 to &lt;$35,000 (1.09; 1.04 – 1.15) versus ≥$75,000; without health insurance (1.08; 1.03 – 1.14) and residing in a disadvantaged neighborhood (1.04; 1.01 – 1.07), a zip code with high poverty (1.03; 1.00 – 1.07) or a health professional shortage area (1.07; 1.05 – 1.10). For each SDOH, the proportion of participants with uncontrolled BP was higher among Black compared with White adults. After multivariable adjustment, having a higher number of adverse SDOH was associated with a higher prevalence of uncontrolled BP among both Black and White adults (Table). Conclusion: SDOH were associated with uncontrolled BP among both Black and White adults taking antihypertensive medication.
Pelvic Plexiform Schwannoma on 18F-FDG PET/MRI
Authors: Yuping Zeng, Jiandong Luo, Jieyu Nie, Xiaoming Leng
Journal: Clinical Nuclear Medicine (2021)

Abstract Plexiform schwannoma (PS), a subtype of schwannoma, is a rare benign nerve sheath tumor characterized by a multinodular plexiform growth pattern. It is usually confined to the head and neck or skin. Pelvic PS is an extremely rare occurrence and signifies a challenge for the imaging diagnosis. In this work, we present a 42-year-old woman with pelvic PS, who was initially suspected of malignant tumor on 18 F-FDG PET/MRI but confirmed as PS by postoperative pathology. We consider that this case would contribute to the literature and provide a further insight into diagnosing this kind of rare tumor.
Incidence of Pancreatic Cancer by Age and Sex in the US From 2000 to 2018
Authors: Baobao Cai, Kai Zhang, Yi Miao
Journal: JAMA (2022)

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Treatment of Patients with Acute Myeloid Leukemia with the Targeted Alpha-Particle Nanogenerator Actinium-225-Lintuzumab
Authors: Todd L. Rosenblat, Michael R. McDevitt, Jorge A. Carrasquillo, Neeta Pandit-Taskar, Mark G. Frattini, Peter G. Maslak, Jae H. Park, Dan Douer, Dragan Cicic, Steven M. Larson, David A. Scheinberg, Joseph G. Jurcic
Journal: Clinical Cancer Research (2022)

Abstract Purpose: The anti-CD33 antibody lintuzumab has modest activity against acute myeloid leukemia (AML). To increase its potency, lintuzumab was conjugated to actinium-225 (225Ac), a radionuclide yielding 4 α-particles. This first-in-human, phase I trial was conducted to determine the safety, pharmacology, and biological activity of 225Ac-lintuzumab. Patients and Methods: Eighteen patients (median age, 64 years; range, 45–80) with relapsed or refractory AML received a single infusion of 225Ac-lintuzumab at activities of 18.5 to 148 kBq/kg. Results: The maximum tolerated dose was 111 kBq/kg. Dose-limiting toxicities included myelosuppression lasting &amp;gt; 35 days in one patient receiving 148 kBq/kg and death from sepsis in two patients treated with 111 and 148 kBq/kg. Myelosuppression was the most common toxicity. Significant extramedullary toxicities were limited to transient grade 3 liver function abnormalities. Pharmacokinetics were determined by gamma counting serial whole blood, plasma, and urine samples at energy windows for the 225Ac daughters, francium-221 and bismuth-213. Two-phase elimination kinetics were seen with mean plasma t1/2 − α and t1/2 − β of 1.9 and 38 hours, respectively. Peripheral blood blasts were eliminated in 10 of 16 evaluable patients (63%) but only at doses of ≥ 37 kBq/kg. Bone marrow blasts were reduced in 10 of 15 evaluable patients (67%), including 3 patients with marrow blasts ≤ 5% and one patient with a morphologic leukemia-free state. Conclusions: Therapy for AML with the targeted α-particle generator 225Ac-lintuzumab was feasible with an acceptable safety profile. Elimination of circulating blasts or reductions in marrow blasts were observed across all dose levels.
The intersection of COVID-19 and autoimmunity
Authors: Jason S. Knight, Roberto Caricchio, Jean-Laurent Casanova, Alexis J. Combes, Betty Diamond, Sharon E. Fox, David A. Hanauer, Judith A. James, Yogendra Kanthi, Virginia Ladd, Puja Mehta, Aaron M. Ring, Ignacio Sanz, Carlo Selmi, Russell P. Tracy, Paul J. Utz, Catriona A. Wagner, Julia Y. Wang, William J. McCune
Journal: Journal of Clinical Investigation (2021)

Acute COVID-19, caused by SARS-CoV-2, is characterized by diverse clinical presentations, ranging from asymptomatic infection to fatal respiratory failure, and often associated with varied longer-term sequelae. Over the past 18 months, it has become apparent that inappropriate immune responses contribute to the pathogenesis of severe COVID-19. Researchers working at the intersection of COVID-19 and autoimmunity recently gathered at an American Autoimmune Related Diseases Association Noel R. Rose Colloquium to address the current state of knowledge regarding two important questions: Does established autoimmunity predispose to severe COVID-19? And, at the same time, can SARS-CoV-2 infection trigger de novo autoimmunity? Indeed, work to date has demonstrated that 10% to 15% of patients with critical COVID-19 pneumonia exhibit autoantibodies against type I interferons, suggesting that preexisting autoimmunity underlies severe disease in some patients. Other studies have identified functional autoantibodies following infection with SARS-CoV-2, such as those that promote thrombosis or antagonize cytokine signaling. These autoantibodies may arise from a predominantly extrafollicular B cell response that is more prone to generating autoantibody-secreting B cells. This Review highlights the current understanding, evolving concepts, and unanswered questions provided by this unique opportunity to determine mechanisms by which a viral infection can be exacerbated by, and even trigger, autoimmunity. The potential role of autoimmunity in post-acute sequelae of COVID-19 is also discussed.