tbuckley/cabot-search huggingface dataset:
Fusion Oncogenes Are Associated With Increased Metastatic Capacity and Persistent Disease in Pediatric Thyroid Cancers
Authors: Aime T. Franco, Julio C. Ricarte-Filho, Amber Isaza, Zachary Jones, Neil Jain, Sogol Mostoufi-Moab, Lea Surrey, Theodore W. Laetsch, Marilyn M. Li, Jessica Clague DeHart, Erin Reichenberger, Deanne Taylor, Ken Kazahaya, N. Scott Adzick, Andrew J. Bauer
Journal: Journal of Clinical Oncology (2022)

In 2014, data from a comprehensive multiplatform analysis of 496 adult papillary thyroid cancer samples reported by The Cancer Genome Atlas project suggested that reclassification of thyroid cancer into molecular subtypes,
Gasdermin D inhibition confers antineutrophil-mediated cardioprotection in acute myocardial infarction
Authors: Kai Jiang, Zizhuo Tu, Kun Chen, Yue Xu, Feng Chen, Sheng Xu, Tingting Shi, Jie Qian, Lan Shen, John Hwa, Dandan Wang, Yaozu Xiang
Journal: Journal of Clinical Investigation (2021)

Acute myocardial infarction (AMI) induces blood leukocytosis, which correlates inversely with patient survival. The molecular mechanisms leading to leukocytosis in the infarcted heart remain poorly understood. Using an AMI mouse model, we identified gasdermin D (GSDMD) in activated leukocytes early in AMI. We demonstrated that GSDMD is required for enhanced early mobilization of neutrophils to the infarcted heart. Loss of GSDMD resulted in attenuated IL-1β release from neutrophils and subsequent decreased neutrophils and monocytes in the infarcted heart. Knockout of GSDMD in mice significantly reduced infarct size, improved cardiac function, and increased post-AMI survival. Through a series of bone marrow transplantation studies and leukocyte depletion experiments, we further clarified that excessive bone marrow–derived and GSDMD-dependent early neutrophil production and mobilization (24 hours after AMI) contributed to the detrimental immunopathology after AMI. Pharmacological inhibition of GSDMD also conferred cardioprotection after AMI through a reduction in scar size and enhancement of heart function. Our study provides mechanistic insights into molecular regulation of neutrophil generation and mobilization after AMI, and supports GSDMD as a new target for improved ventricular remodeling and reduced heart failure after AMI.
Abstract EP39: Examining Capabilities, Opportunity, And Motivation For Healthy Eating Behaviors In Latin American Restaurants: A Quantitative Application Of The COM-B Model To Inform Future Interventions
Authors: Melissa Fuster, Maria Santos, Terry T Huang, Margaret A Handley
Journal: Circulation (2022)

Introduction: Latin American restaurants (LARs) are an increasingly important food source with the potential to positively influence diets to promote cardiovascular health. Yet, modifiable factors influencing food choices in LARs remain unclear. Determinants frameworks, such as the Capabilities, Opportunities, and Motivation for Behavior (COM-B Model) can help identify key drivers of dietary behaviors for informing intervention design. Objectives: (1) Apply the COM-B model to understand healthy eating behavior at LARs; (2) Examine differences in COM-B factors by ethnicity (Latin/Hispanic background), age, income, gender, and education. Methods: We developed a Likert scale to quantitatively assess the capabilities (physical and psychological), opportunities (social and physical), and motivation (reflective and automatic) factors associated with healthy eating in LARs. The scale was applied as part of an online survey with adults in the United States that reported eating food from LARs at least once a month (n=509). Bivariate analyses were used to examine the association between COM-B scores and demographic characteristics. Results: Within a possible range of 0-12, the mean COM-B total score was 7.35±1.97. Higher overall scores were significantly associated with being from a Latin background (p=0.04) and having a higher income (p=0.02). Within a possible range of 0-2 for COM-B area scores, the lowest score was found for Psychological Capability (0.95±0.97), where higher mean scores were found among men (p=0.03), older age (p=0.04), and those with higher education (p&lt;0.001). The Social Opportunity score (1.04±0.48) was significantly associated with being younger (p=0.001) and of Latin background (p&lt;0.001), while the Physical Opportunity score (1.27±0.55) was highest among those with lower education (p=0.04) and age (p=0.008). Reflective motivation presented the highest mean score (1.46±0.37) and was positively associated with high income (p=0.019) and education (p&lt;0.001). No significant association with demographic characteristics was found for the Automatic Motivation and Physical Capability scores (1.21±0.53 and 1.43±0.73, respectively). Conclusions: This work addresses a research gap to inform future interventions to improve community food environments through work with LARs. The application of the COM-B revealed areas for intervention, particularly the need to improve knowledge (Psychological Capability) and social opportunity, the areas with the lowest scores, to promote healthier eating behaviors at LARs. Future research can be used to promote innovative ways to change perceptions of Latin foods in LARs and awareness of existing healthy offerings, which at the same time may help motivate LARs owners in increasing healthy offerings.
A New Way to Contain Unaffordable Medication Costs — Exercising the Government’s Existing Rights
Authors: Alfred B. Engelberg, Jerry Avorn, Aaron S. Kesselheim
Journal: New England Journal of Medicine (2022)

Existing laws could be used to help make many drugs more affordable. One gives the government a royalty-free license to use patented inventions that were discovered using federal funding; the other gives the government immunity from being sued for patent infringement.
18F-FDG Versus 68Ga-FAPI PET/CT in Visualizing Primary Hepatic Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue
Authors: Yizhen Pang, Long Zhao, Qihang Shang, Tinghua Meng, Haojun Chen
Journal: Clinical Nuclear Medicine (2021)

The prevalence of primary hepatic mucosa-associated lymphoid tissue lymphomas is extremely low. In this case, we present 18F-FDG and 68Ga-FAPI PET/CT findings in a 76-year-old man with pathologically confirmed primary hepatic extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue. 68Ga-FAPI PET/CT showed a better tumor-to-background ratio than 18F-FDG PET/CT in the hepatic lesion because there is little 68Ga-FAPI uptake in the liver parenchyma. This case indicates that 68Ga-FAPI PET/CT may be an alternate method for evaluating hepatic involvement of lymphoma, especially for the non-FDG-avid lymphomas.
Long-Term Exposure to Transportation Noise and Risk for Type 2 Diabetes in a Nationwide Cohort Study from Denmark
Authors: Jesse D. Thacher, Aslak H. Poulsen, Ulla A. Hvidtfeldt, Ole Raaschou-Nielsen, Jørgen Brandt, Camilla Geels, Jibran Khan, Thomas Münzel, Mette Sørensen
Journal: Environmental Health Perspectives (2021)

BACKGROUND: Epidemiologic studies have linked transportation noise to increased morbidity and mortality, particularly for cardiovascular outcomes.However, studies investigating metabolic outcomes such as diabetes are limited and have focused only on noise exposures estimated for the loudest residential façade.OBJECTIVES: We aimed to examine the influence of long-term residential exposure to transportation noise at the loudest and quietest residential façades and the risk for type 2 diabetes.METHODS: Road traffic and railway noise exposures (Lden) at the most and least exposed façades were estimated for all dwellings in Denmark during 1990-2017.Aircraft noise was estimated in 5-dB categories.Ten-year time-weighted mean noise exposures were estimated for 3:56 million individuals ≥35 years of age.From 2000 to 2017, 233,912 incident cases of type 2 diabetes were identified using hospital and prescription registries, with a mean follow-up of 12.9 y.We used Cox proportional hazards models adjusting for individual-and area-level covariates and long-term residential air pollution.The population-attributable fraction (PAF) was also computed.RESULTS: Hazard ratios (HRs) and 95% confidence intervals (CIs) for type 2 diabetes in association with 10-dB increases in 10-y mean road traffic noise at the most and least exposed façades, respectively, were 1.05 (95% CI: 1.04, 1.05) and 1.09 (95% CI: 1.08, 1.10).Following subsequent adjustment for fine particulate matter [particulate matter ≤2:5 lm in aerodynamic diameter] (10-y mean), the HRs (CIs) were 1.03 (95% CI: 1.03, 1.04) and 1.08 (95% CI: 1.07, 1.09), respectively.For railway noise, the HRs per 10-dB increase in 10-y mean exposure were 1.03 (95% CI: 1.02, 1.04) and 1.02 (95% CI: 1.01, 1.04) for the most and least exposed façades, respectively.Categorical models supported a linear exposure-outcome relationship for road traffic noise and, to a lesser extent, for railway noise.Aircraft noise >45 dB was associated with a 1-4% higher likelihood of type 2 diabetes compared with those who were unexposed.We found road traffic and railway noise associated with a PAF of 8.5% and 1.4%, respectively, of the diabetes cases.DISCUSSION: Long-term exposure to road, railway, and possibly aircraft traffic noise was associated with an increased risk of type 2 diabetes in a nationwide cohort of Danish adults.Our findings suggest that diabetes should be included when estimating the burden of disease due to transportation noise.
In vivo imaging of the human eye using a 2-photon-excited fluorescence scanning laser ophthalmoscope
Authors: Jakub Boguslawski, Grazyna Palczewska, Slawomir Tomczewski, Jadwiga Milkiewicz, Piotr Kasprzycki, Dorota Stachowiak, Katarzyna Komar, Marcin J. Marzejon, Bartosz L. Sikorski, Arkadiusz Hudzikowski, Aleksander Głuszek, Zbigniew Łaszczych, Karol Karnowski, Grzegorz Soboń, Krzysztof Palczewski, Maciej Wojtkowski
Journal: Journal of Clinical Investigation (2021)

BackgroundNoninvasive assessment of metabolic processes that sustain regeneration of human retinal visual pigments (visual cycle) is essential to improve ophthalmic diagnostics and to accelerate development of new treatments to counter retinal diseases. Fluorescent vitamin A derivatives, which are the chemical intermediates of these processes, are highly sensitive to UV light; thus, safe analyses of these processes in humans are currently beyond the reach of even the most modern ocular imaging modalities.MethodsWe present a compact, 2-photon-excited fluorescence scanning laser ophthalmoscope and spectrally resolved images of the human retina based on 2-photon excitation (TPE) with near-infrared light. A custom Er:fiber laser with integrated pulse selection, along with intelligent postprocessing of data, enables excitation with low laser power and precise measurement of weak signals.ResultsWe demonstrate spectrally resolved TPE fundus images of human subjects. Comparison of TPE data between human and mouse models of retinal diseases revealed similarity with mouse models that rapidly accumulate bisretinoid condensation products. Thus, visual cycle intermediates and toxic byproducts of this metabolic pathway can be measured and quantified by TPE imaging.ConclusionOur work establishes a TPE instrument and measurement method for noninvasive metabolic assessment of the human retina. This approach opens the possibility for monitoring eye diseases in the earliest stages before structural damage to the retina occurs.FundingNIH, Research to Prevent Blindness, Foundation for Polish Science, European Regional Development Fund, Polish National Agency for Academic Exchange, and Polish Ministry of Science and Higher Education.
Praluzatamab Ravtansine, a CD166-Targeting Antibody–Drug Conjugate, in Patients with Advanced Solid Tumors: An Open-Label Phase I/II Trial
Authors: Valentina Boni, Mary J. Fidler, Hendrik-Tobias Arkenau, Alexander Spira, Funda Meric-Bernstam, Nataliya Uboha, Rachel E. Sanborn, Randy F. Sweis, Patricia LoRusso, Misako Nagasaka, Javier Garcia-Corbacho, Shadia Jalal, James J. Harding, Stella K. Kim, Iris H.C. Miedema, Danielle J. Vugts, Marc C. Huisman, Gerben J.C. Zwezerijnen, Guus A.M.S. van Dongen, C. Willemien Menke van der Houven van Oordt, Song Wang, Tam Dang, Ivan A. Zein, Olga Vasiljeva, Susan K. Lyman, Virginia Paton, Alison Hannah, Joyce F. Liu
Journal: Clinical Cancer Research (2022)

Praluzatamab ravtansine (CX-2009) is a conditionally activated Probody drug conjugate (PDC) comprising an anti-CD166 mAb conjugated to DM4, with a protease-cleavable linker and a peptide mask that limits target engagement in normal tissue and circulation. The tumor microenvironment is enriched for proteases capable of cleaving the linker, thereby releasing the mask, allowing for localized binding of CX-2009 to CD166. CX-2009 was evaluated in a phase I/II clinical trial for patients with advanced solid tumors.Eligible patients had metastatic cancer receiving ≥2 prior treatments. CX-2009 was administered at escalating doses every 3 weeks (0.25-10 mg/kg) or every 2 weeks (4-6 mg/kg). Primary objective was to determine the safety profile and recommended phase II dose (RP2D).Of 99 patients enrolled, the most prevalent subtype was breast cancer (n = 45). Median number of prior therapies was 5 (range, 1-19). Dose-limiting toxicities were observed at 8 mg/kg every 3 weeks and 6 mg/kg every 2 weeks. On the basis of tolerability, the RP2D was 7 mg/kg every 3 weeks. Tumor regressions were observed at doses ≥4 mg/kg. In the hormone receptor-positive/HER2-nonamplified breast cancer subset (n = 22), 2 patients (9%) had confirmed partial responses, and 10 patients (45%) had stable disease. Imaging with zirconium-labeled CX-2009 confirmed uptake in tumor lesions and shielding of major organs. Activated, unmasked CX-2009 was measurable in 18 of 22 posttreatment biopsies.CD166 is a novel, ubiquitously expressed target. CX-2009 is the first conditionally activated antibody-drug conjugate to CD166 to demonstrate both translational and clinical activity in a variety of tumor types.
68Ga-DOTA-FAPI-04 PET/CT Imaging in a Case of SAPHO Syndrome
Authors: Tingting Xu, Yilin Huang, Yan Zhao, Peng Wang, Yue Chen
Journal: Clinical Nuclear Medicine (2021)

A 66-year-old woman presented with anterior chest wall and knee joints pain and multiple skin lesions. 99mTc-MDP bone scintigraphy showed increased bone density in the sternal angle with abnormal bone metabolism. The patient was enrolled in a 68Ga-DOTA-FAPI-04 PET/CT tumor clinical trial, and it showed increased tracer uptake in the sternum and right knee joint. Subsequently, ultrasound of the right knee joint confirmed the existence of synovitis, and no malignant components were found in sternal biopsy. The patient's final diagnosis was synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome. The case confirmed that 68Ga-DOTA-FAPI-04 imaging is helpful for evaluating the involved sites of SAPHO syndrome.
Early Convalescent Plasma for High-Risk Outpatients with Covid-19
Authors: Frederick K Korley, Valerie Durkalski-Mauldin, Sharon D Yeatts, Kevin Schulman, Robertson D Davenport, Larry J Dumont, Nahed El Kassar, Lydia D Foster, Jennifer M Hah, Siddartha Jaiswal, Alesia Kaplan, Ezekiel Lowell, John F McDyer, James Quinn, Darrell J Triulzi, Carol Van Huysen, Valerie L W Stevenson, Kabir Yadav, Christopher W Jones, Bory Kea, Aaron Burnett, Joshua C Reynolds, Colin F Greineder, Nathan L Haas, David G Beiser, Robert Silbergleit, William Barsan, Clifton W Callaway
Journal: New England Journal of Medicine (2021)

BackgroundEarly administration of convalescent plasma obtained from blood donors who have recovered from coronavirus disease 2019 (Covid-19) may prevent disease progression in acutely ill, high-risk patients with Covid-19.MethodsIn this randomized, multicenter, single-blind trial, we assigned patients who were being treated in an emergency department for Covid-19 symptoms to receive either one unit of convalescent plasma with a high titer of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or placebo. All the patients were either 50 years of age or older or had one or more risk factors for disease progression. In addition, all the patients presented to the emergency department within 7 days after symptom onset and were in stable condition for outpatient management. The primary outcome was disease progression within 15 days after randomization, which was a composite of hospital admission for any reason, seeking emergency or urgent care, or death without hospitalization. Secondary outcomes included the worst severity of illness on an 8-category ordinal scale, hospital-free days within 30 days after randomization, and death from any cause.Download a PDF of the Research Summary.ResultsA total of 511 patients were enrolled in the trial (257 in the convalescent-plasma group and 254 in the placebo group). The median age of the patients was 54 years; the median symptom duration was 4 days. In the donor plasma samples, the median titer of SARS-CoV-2 neutralizing antibodies was 1:641. Disease progression occurred in 77 patients (30.0%) in the convalescent-plasma group and in 81 patients (31.9%) in the placebo group (risk difference, 1.9 percentage points; 95% credible interval, −6.0 to 9.8; posterior probability of superiority of convalescent plasma, 0.68). Five patients in the plasma group and 1 patient in the placebo group died. Outcomes regarding worst illness severity and hospital-free days were similar in the two groups.ConclusionsThe administration of Covid-19 convalescent plasma to high-risk outpatients within 1 week after the onset of symptoms of Covid-19 did not prevent disease progression. (SIREN-C3PO ClinicalTrials.gov number, NCT04355767.) Quick Take Convalescent Plasma for Outpatients with Covid-19 2m 15s
Effect of immunotherapy time-of-day infusion on overall survival among patients with advanced melanoma in the USA (MEMOIR): a propensity score-matched analysis of a single-centre, longitudinal study
Authors: David C Qian, Troy Kleber, Brianna Brammer, Karen M Xu, Jeffrey M Switchenko, James R Janopaul-Naylor, Jim Zhong, Melinda L Yushak, R Donald Harvey, Chrystal M Paulos, David H Lawson, Mohammad K Khan, Ragini R Kudchadkar, Zachary S Buchwald
Journal: The Lancet Oncology (2021)
Esophageal Oligometastases of the Foot
Authors: John M. Ricely, David Posocco, Simin Dadparvar
Journal: Clinical Nuclear Medicine (2022)

Abstract Acrometastasis is a rare clinical entity, estimated to represent less than 0.3% of all bone metastases. Here, we present a case of esophageal cancer that was treated with esophagectomy, chemotherapy, and radiation therapy and developed oligometastases of the foot after 8 years in remission. The patient developed pain and swelling in his left ankle and foot as the presenting symptom. He underwent radiography and MRI of the affected area, which revealed the lesion. A 99m Tc-MDP whole-body bone scan did not reveal any other sites of metastasis.
Prophylactic scopolamine butylbromide reduced death rattle in patients in the dying phase
Authors: Ashesha Mechineni
Journal: Annals of Internal Medicine (2022)

Source Citation van Esch HJ, van Zuylen L, Geijteman ECT, et al. Effect of prophylactic subcutaneous scopolamine butylbromide on death rattle in patients at the end of life: the SILENCE randomized clinical trial. JAMA. 2021;326:1268-76. 34609452
Tuberous Sclerosis in the Practice of Ultrasound Specialist: a Literature Review with our Own Observations
Authors: S. Yu. Cherdantseva, Yu. E. Cherdantseva, O. P. Kanailova, M. E. Svishcheva
Journal: Radiology - Practice (2021)

Tuberous sclerosis (TBS) is a genetically determined orphan disease when many benign tumors (hamartomas) are formed in various organs and systems. The complexity of diagnosis is associated with a wide variety of clinical forms of the disease. Despite the benign nature of hamartomas, they cause dysfunction of the body, which leads to disability and a reduction in the life expectancy of patients. The lesions of the brain and heart are most characteristic for the early onset of the disease in infants and neonatal children. The article presents morphological changes in the central nervous system and heart, compares these changes with ultrasound and magnetic resonance imaging data. With the help of two clinical cases, the high sensitivity of neurosonography, as the primary method of examination of the brain, and the possibility of early diagnostics of the tuberous-sclerosis complex are shown. The publication also contains a literature review, clinical and diagnostic criteria of tuberous sclerosis, brief information about pathogenetic treatment in young children and a large number of illustrations.
hUC-MSC-mediated recovery of subacute spinal cord injury through enhancing the pivotal subunits β3 and γ2 of the GABA<sub>A</sub> receptor
Authors: Tingting Cao, Huan Chen, Weiping Huang, Sisi Xu, Peilin Liu, Weiwei Zou, Mao Pang, Ying Xu, Xiaochun Bai, Bin Liu, Limin Rong, Zhong-Kai Cui, Mangmang Li
Journal: Theranostics (2022)

Spinal cord injury (SCI) remains an incurable neurological disorder leading to permanent and profound neurologic deficits and disabilities. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) are particularly appealing in SCI treatment to curtail damage, restore homeostasis and possible neural relay. However, the detailed mechanisms underlying hUC-MSC-mediated functional recovery of SCI have not been fully elucidated. The purpose of our current study is to identify novel therapeutic targets and depict the molecular mechanisms underlying the hUC-MSC-mediated recovery of subacute SCI.
Abstract P116: Hypertension Severity As Quantified By Hypertension Daily Dose (HDD) And Blood Pressure And Risk Of Stroke In The REGARDS Study
Authors: Ying K Loo, Katherine Wilkinson, Tyler A Harkness, George Howard, Virginia J Howard, Suzanne E Judd, Neil A Zakai, Paul Muntner, Lillian Min, Suzanne Oparil, Timothy B Plante
Journal: Circulation (2022)

Background: Hypertension is a modifiable stroke risk factor, but hypertension severity isn't completely captured by blood pressure (BP) alone. Prior studies have shown that among adults with similar systolic BP, those taking a greater number of antihypertensive medications have greater stroke risk. However, count of antihypertension medications does not consider relative dose across classes and incompletely characterizes hypertension medical therapy. The recently described Hypertension Daily Dose (HDD) metric quantifies total dose of BP-lowering medications across multiple classes. The association between HDD and BP with stroke risk is unknown. Objective: Determine stroke risk by HDD and BP levels. Methods: We included Black and White adults from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study without prevalent stroke at visit 2 (2013-2017; treated as baseline) with follow-up data and full BP assessment. We classified systolic BP using JNC7 groupings and HDD by no BP medications and tertiles among those on BP medications. Cox proportional hazards models estimated hazard ratios (HR) for incident stroke by HDD group and BP group. Results: Of 13,265 participants included (mean age 72 [SD 8.5], 36% Black race, 56% women), 344 incident stroke events occurred during a median follow-up of 5.5 years. The stroke rate was higher among Black than White participants (5.6 vs. 5.0/1000 person-years). Relative to no BP medications and normotension, those with systolic BP ≥140 mm Hg and HDD in tertiles ≥2 had a 2.3x to 3.7x greater risk of incident stroke ( Table ). Those with systolic BP &lt;140 mm Hg had similar stroke risk across HDD groupings. Conclusion: Among Black and White US adults without prevalent stroke, higher HDD was associated with greater risk of incident stroke in those with systolic BP ≥140 mm Hg, possibly reflecting greater disease severity and treatment resistance. These findings support aggressive BP control with antihypertensive medications to lower stroke risk among adults with hypertension.