tbuckley/cabot-search huggingface dataset:
18F-FDG PET/CT Image Analysis of Penicilliosis Marneffei in an Immunocompetent Child Patient
Authors: You Cheng, Wen-Min Li, Jian-Jiang Huang, Shu-Xia Wang, Dan Shao
Journal: Clinical Nuclear Medicine (2022)

Abstract Penicilliosis marneffei is an extremely rare fungal infectious disease that often occurs in hosts with immunodeficiency or immune dysfunction. Penicilliosis marneffei has been seldom reported in children with multiple infiltrations throughout the body. We report a case of a boy with normal immune function who had multiple infiltrations of penicilliosis marneffei and was misdiagnosed with lymphoma by PET/CT.
Up in the Air
Authors: Julia V. Loewenthal, Anand Vaidya, Brittany Duran, Charles N. Pozner, Benjamin M. Scirica
Journal: New England Journal of Medicine (2022)

In Boston, a physician boards an airplane for a transatlantic flight. As the airplane reaches cruising altitude, a member of the flight crew places a call over the intercom, asking, “Is there a nurse or doctor on board?” The physician and a nurse respond to the call. . . .
6MO Pembrolizumab plus ipilimumab or placebo in previously untreated metastatic NSCLC with PD-L1 tumor proportion score ≥50%: KEYNOTE-598 3-year follow-up
Authors: D. Rodriguez Abreu, M. Reck, N. Şendur, K. Park, D.H. Lee, I. Cicin, P.F. Yumuk, F.J. Orlandi, T.A. Leal, N. Soparattanapaisarn, A. Langleben, R. Califano, B. Medgyasszay, T-C. Hsia, G.A. Otterson, T. Woods, E. Jensen, A. Samkari, M. Boyer
Journal: Annals of Oncology (2022)
Subversion of Serotonin Receptor Signaling in Osteoblasts by Kynurenine Drives Acute Myeloid Leukemia
Authors: Marta Galán-Díez, Florence Borot, Abdullah Mahmood Ali, Junfei Zhao, Eva Gil-Iturbe, Xiaochuan Shan, Na Luo, Yongfeng Liu, Xi-Ping Huang, Brygida Bisikirska, Rossella Labella, Irwin Kurland, Bryan L. Roth, Matthias Quick, Siddhartha Mukherjee, Raul Rabadán, Martin Carroll, Azra Raza, Stavroula Kousteni
Journal: Cancer Discovery (2022)

Abstract Remodeling of the microenvironment by tumor cells can activate pathways that favor cancer growth. Molecular delineation and targeting of such malignant-cell nonautonomous pathways may help overcome resistance to targeted therapies. Herein we leverage genetic mouse models, patient-derived xenografts, and patient samples to show that acute myeloid leukemia (AML) exploits peripheral serotonin signaling to remodel the endosteal niche to its advantage. AML progression requires the presence of serotonin receptor 1B (HTR1B) in osteoblasts and is driven by AML-secreted kynurenine, which acts as an oncometabolite and HTR1B ligand. AML cells utilize kynurenine to induce a proinflammatory state in osteoblasts that, through the acute-phase protein serum amyloid A (SAA), acts in a positive feedback loop on leukemia cells by increasing expression of IDO1—the rate-limiting enzyme for kynurenine synthesis—thereby enabling AML progression. This leukemia–osteoblast cross-talk, conferred by the kynurenine–HTR1B–SAA–IDO1 axis, could be exploited as a niche-focused therapeutic approach against AML, opening new avenues for cancer treatment. Significance: AML remains recalcitrant to treatments due to the emergence of resistant clones. We show a leukemia-cell nonautonomous progression mechanism that involves activation of a kynurenine–HTR1B–SAA–IDO1 axis between AML cells and osteoblasts. Targeting the niche by interrupting this axis can be pharmacologically harnessed to hamper AML progression and overcome therapy resistance. This article is highlighted in the In This Issue feature, p. 873
Renal Microcirculation and Function in a Pig Model of Hemorrhagic Shock Resuscitation with Norepinephrine
Authors: Nicolas Libert, Elisabeth Laemmel, Anatole Harrois, Philippe Laitselart, Benjamin Bergis, Pierre Isnard, Fabiola Terzi, Benoit Decante, Olaf Mercier, Eric Vicaut, Jacques Duranteau
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Rationale: Norepinephrine (NE) is commonly used in combination with fluid during resuscitation of hemorrhagic shock, but its impact on kidney microcirculation, oxygenation, and function is still unknown in this setting. Objectives: During hemorrhagic shock resuscitation, does a combination of fluid and NE affect kidney oxygenation tension, kidney microcirculatory perfusion, and 48-hour kidney function, as compared with fluid alone? Methods: Hemorrhagic shock was induced in 24 pigs, and 8 pigs were included as a sham group. Resuscitation of hemorrhagic shock was performed, using a closed-loop device, either by fluid alone (0.9% NaCl; fluid group) or associated with the administration of NE at two doses (moderate dose: mean rate of 0.64 μg ⋅ kg-1 ⋅ min-1; high dose: mean rate of 1.57 μg ⋅ kg-1 ⋅ min-1) to obtain a target systolic arterial pressure of 80 to 90 mm Hg. Resuscitation was followed by transfusion of the withdrawn blood. Measurements and Main Results: The amount of fluid required to reach the target systolic arterial pressure was lower in the NE groups than in the fluid group, with subsequently less hemodilution. NE restored kidney microcirculation, oxygenation, and function in a manner comparable to that achieved with fluid resuscitation alone. There were no histologic differences between animals resuscitated with fluid and those resuscitated with NE. Conclusions: In pigs with hemorrhagic shock, resuscitation with a combination of NE and fluid restored kidney microcirculation and oxygenation, as well as renal function, in a manner comparable to fluid resuscitation alone and without differences between the two NE doses. NE administration led to a fluid volume-sparing effect with subsequently less hemodilution.
Serological responses to COVID-19 Comirnaty booster vaccine, London, United Kingdom, September to December 2021
Authors: Georgina Ireland, Heather Whitaker, Shamez N Ladhani, Frances Baawuah, Sathyvani Subbarao, Ezra Linley, Lenesha Warrener, Michelle O’Brien, Corinne Whillock, Oliver Martin, Paul Moss, Mary E Ramsay, Gayatri Amirthalingam, Kevin E Brown
Journal: Eurosurveillance (2022)

Serum samples were collected pre- and post-booster vaccination with Comirnaty in 626 participants (aged ≥ 50 years) who had received two Comirnaty doses &lt; 30 days apart, two Comirnaty doses ≥ 30 days apart or two Vaxzevria doses ≥ 30 days apart. Irrespective of primary vaccine type or schedule, spike antibody GMTs peaked 2–4 weeks after second dose, fell significantly ≤ 38 weeks later and rose above primary immunisation GMTs 2–4 weeks post-booster. Higher post-booster responses were observed with a longer interval between primary immunisation and boosting.
Finerenone Reduces Risk of Incident Heart Failure in Patients With Chronic Kidney Disease and Type 2 Diabetes: Analyses From the FIGARO-DKD Trial
Authors: Gerasimos Filippatos, Stefan D. Anker, Rajiv Agarwal, Luis M. Ruilope, Peter Rossing, George L. Bakris, Christoph Tasto, Amer Joseph, Peter Kolkhof, Andrea Lage, Bertram Pitt
Journal: Circulation (2021)

Chronic kidney disease and type 2 diabetes are independently associated with heart failure (HF), a leading cause of morbidity and mortality. In the FIDELIO-DKD (Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease) and FIGARO-DKD (Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease) trials, finerenone (a selective, nonsteroidal mineralocorticoid receptor antagonist) improved cardiovascular outcomes in patients with albuminuric chronic kidney disease and type 2 diabetes. These prespecified analyses from FIGARO-DKD assessed the effect of finerenone on clinically important HF outcomes.
Future Perspectives of Cardiovascular Biomarker Utilization in Cancer Survivors: A Scientific Statement From the American Heart Association
Authors: Vlad G. Zaha, Salim S. Hayek, Kevin M. Alexander, Theresa M. Beckie, W. Gregory Hundley, Lavanya Kondapalli, Bonnie Ky, Kasey J. Leger, Wouter C. Meijers, Javid J. Moslehi, Svati H. Shah
Journal: Circulation (2021)

Improving cancer survival represents the most significant effect of precision medicine and personalized molecular and immunologic therapeutics. Cardiovascular health becomes henceforth a key determinant for the direction of overall outcomes after cancer. Comprehensive tissue diagnostic studies undoubtedly have been and continue to be at the core of the fight against cancer. Will a systemic approach integrating circulating blood-derived biomarkers, multimodality imaging technologies, strategic panomics, and real-time streams of digitized physiological data overcome the elusive cardiovascular tissue diagnosis in cardio-oncology? How can such a systemic approach be personalized for application in day-to-day clinical work, with diverse patient populations, cancer diagnoses, and therapies? To address such questions, this scientific statement approaches a broad definition of the biomarker concept. It summarizes the current literature on the utilization of a multitude of established cardiovascular biomarkers at the intersection with cancer. It identifies limitations and gaps of knowledge in the application of biomarkers to stratify the cardiovascular risk before cancer treatment, monitor cardiovascular health during cancer therapy, and detect latent cardiovascular damage in cancer survivors. Last, it highlights areas in biomarker discovery, validation, and clinical application for concerted efforts from funding agencies, scientists, and clinicians at the cardio-oncology nexus.
Managing Central Nervous System Spread of Lung Cancer: The State of the Art
Authors: David Chun Cheong Tsui, D. Ross Camidge, Chad G. Rusthoven
Journal: Journal of Clinical Oncology (2022)

Brain metastases (BrM) are common in both non-small-cell lung cancer and small-cell lung cancer. Substantial progress in BrM management has occurred in the past decade related to advances in both radiation and medical oncology. Recent and ongoing radiation trials have focused on increasing the candidacy for focal therapy of BrM with stereotactic radiosurgery; reducing the toxicity and improving patient selection for whole brain radiotherapy; and, in small-cell lung cancer, evaluating brain magnetic resonance imaging surveillance without prophylactic cranial irradiation, hippocampal avoidance in prophylactic cranial irradiation and whole brain radiotherapy, and the role of upfront stereotactic radiosurgery for BrM. In medical oncology, the development of multiple tyrosine kinase inhibitors with encouraging CNS activity and emerging data on the CNS activity of immune checkpoint inhibitors in some patients have opened the door to novel systemic and multidisciplinary treatment strategies for the management of BrM. Future research will focus on more robust characterizations of the CNS activity of targeted therapy and immunotherapies, as well as optimal integration and patient selection for multidisciplinary strategies involving CNS-active drugs, radiation therapy, and CNS surveillance.
Abstract P122: Addressed-based Sampling Of People Living In Rural Southeast Usa
Authors: Edwin R van den Heuvel, Robert P Agans, William D Kalsbeek, Suzanne E Judd, Vasan S Ramachandran
Journal: Circulation (2022)

Introduction: The RURAL cohort study addresses critical knowledge gaps regarding heart and lung disorders in rural Southeastern USA. Using CDC mortality data, RURAL selected ten counties from four states (Alabama, Mississippi, Louisiana, and Kentucky) that are ecologically paired for their five-year low and high CVD mortality rates. RURAL will recruit a representative sample of 4600 participants using addressed-based sampling and an intensive community engagement, yet representative sampling from rural areas is challenging. Hypothesis: Address-based sampling using dedicated mailings and telephone calls will yield representative samples from the ten target counties. Methods: A dynamic sampling strategy was implemented to obtain balanced response rates for sex, age groups and race. An initial wave of random addresses was used to estimate response rates. A second wave with Bernoulli probabilities was used to reduce overrepresented subgroups. Finally, a third wave with requests for referrals (network sampling) will be used to increase underrepresented subgroups. Eligible participants collected from households and referrals are rostered, complete a baseline exam, undergo an mHealth assessment and are scheduled for a medical examination in a mobile examination unit (MEU). Results: Sampling of 693 participants from 19,460 inhabitants in age range 25 to 64 years started in Dallas County, Alabama. Address sizes, rostered participants and sample size imbalances are listed in the Table. Bernoulli probabilities [55-64 men: 80%; 55-65 women: 55%; 45-55 women:76%] corrected the imbalance in response rates for sex and age groups 45-54 and 55-64 (see Table). Referrals in wave 2 will further balance the sample. Conclusion: Our initial sampling experiences in rural Alabama showed lower than expected response rates and imbalances across subgroups. These results emphasize the importance of network sampling with well-adjusted Bernoulli probabilities for representative sampling in rural areas.
Reducing Caretaker Burden, Protecting Young Brains and Bodies
Authors: Lynne L Levitsky
Journal: New England Journal of Medicine (2022)

The year 2021 has been celebrated as the centennial of the discovery of insulin, a feat that prolonged the lives of millions of persons with type 1 diabetes but cured none of them. In the coming century, we can look forward to improved mechanical devices to mimic the actions of the human endocrine pancreas and, potentially, to breakthroughs in immunology and tissue engineering that may lead to true cures for type 1 diabetes mellitus. Management of type 1 diabetes remains complex, technically difficult, and time-consuming. Intensive technical treatment in adults and children today includes the use of subcutaneous insulin pumps . . .
Extranodal NK/T-Cell Lymphoma With Widespread Cutaneous and Subcutaneous Involvement on 18F-FDG PET/CT
Authors: Nuh Filizoglu, Salih Ozguven, Tunc Ones, Halil Turgut Turoglu, Tanju Yusuf Erdil
Journal: Clinical Nuclear Medicine (2022)

Nasal-type extranodal natural killer/T-cell lymphoma is an aggressive rare type of lymphoma that mostly affects the nasal cavity and adjacent areas. However, some patients can present with distant nodal or extranodal involvement including the Waldeyer ring, gastrointestinal tract, genitourinary organs, lung, thyroid, skin, or adrenal glands. Herein, we present a unique case of extranodal natural killer/T-cell lymphoma with widespread cutaneous and subcutaneous involvement on 18 F-FDG PET/CT.
Imaging of Cancer γ-Secretase Activity Using an Inhibitor-Based PET Probe
Authors: Pengju Nie, Teja Kalidindi, Veronica L. Nagle, Xianzhong Wu, Thomas Li, George P. Liao, Georgia Frost, Kelly E. Henry, Blesida Punzalan, Lukas M. Carter, Jason S. Lewis, Naga Vara Kishore Pillarsetty, Yue-Ming Li
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Abnormal Notch signaling promotes cancer cell growth and tumor progression in various cancers. Targeting γ-secretase, a pivotal regulator in the Notch pathway, has yielded numerous γ-secretase inhibitors (GSIs) for clinical investigation in the last 2 decades. However, GSIs have demonstrated minimal success in clinical trials in part due to the lack of specific and precise tools to assess γ-secretase activity and its inhibition in vivo. Experimental Design: We designed an imaging probe based on GSI Semagacestat structure and synthesized the radioiodine-labeled analogues [131I]- or [124I]-PN67 from corresponding trimethyl-tin precursors. Both membrane- and cell-based ligand-binding assays were performed using [131I]-PN67 to determine the binding affinity and specificity for γ-secretase in vitro. Moreover, we evaluated [124I]-PN67 by PET imaging in mammary tumor and glioblastoma mouse models. Results: The probe was synthesized through iodo-destannylation using chloramine-T as an oxidant with a high labeling yield and efficiency. In vitro binding results demonstrate the high specificity of this probe and its ability for target replacement study by clinical GSIs. PET imaging studies demonstrated a significant (P &amp;lt; 0.05) increased in the uptake of [124I]-PN67 in tumors versus blocking or sham control groups across multiple mouse models, including 4T1 allograft, MMTV-PyMT breast cancer, and U87 glioblastoma allograft. Ex vivo biodistribution and autoradiography corroborate these results, indicating γ-secretase specific tumor accumulation of [124I]-PN67. Conclusions: [124I]-PN67 is a novel PET imaging agent that enables assessment of γ-secretase activity and target engagement of clinical GSIs.
ENO1 suppresses cancer cell ferroptosis by degrading the mRNA of iron regulatory protein 1
Authors: Tong Zhang, Linchong Sun, Yijie Hao, Caixia Suo, Shengqi Shen, Haoran Wei, Wenhao Ma, Pinggen Zhang, Ting Wang, Xuemei Gu, Shi-Ting Li, Zhaolin Chen, Ronghui Yan, Yi Zhang, Yongping Cai, Rongbin Zhou, Weidong Jia, Fang Huang, Ping Gao, Huafeng Zhang
Journal: Nature Cancer (2021)
Cabotegravir for the prevention of HIV-1 in women: results from HPTN 084, a phase 3, randomised clinical trial
Authors: Sinead Delany-Moretlwe, James P Hughes, Peter Bock, Samuel Gurrion Ouma, Portia Hunidzarira, Dishiki Kalonji, Noel Kayange, Joseph Makhema, Patricia Mandima, Carrie Mathew, Elizabeth Spooner, Juliet Mpendo, Pamela Mukwekwerere, Nyaradzo Mgodi, Patricia Nahirya Ntege, Gonasagrie Nair, Clemensia Nakabiito, Harriet Nuwagaba-Biribonwoha, Ravindre Panchia, Nishanta Singh, Bekezela Siziba, Jennifer Farrior, Scott Rose, Peter L Anderson, Susan H Eshleman, Mark A Marzinke, Craig W Hendrix, Stephanie Beigel-Orme, Sybil Hosek, Elizabeth Tolley, Nirupama Sista, Adeola Adeyeye, James F Rooney, Alex Rinehart, William R Spreen, Kimberly Smith, Brett Hanscom, Myron S Cohen, Mina C Hosseinipour
Journal: The Lancet (2022)
EGFR Inhibition Enhances the Cellular Uptake and Antitumor-Activity of the HER3 Antibody–Drug Conjugate HER3–DXd
Authors: Heidi M. Haikala, Timothy Lopez, Jens Köhler, Pinar O. Eser, Man Xu, Qing Zeng, Tyler J. Teceno, Kenneth Ngo, Yutong Zhao, Elena V. Ivanova, Arrien A. Bertram, Brittaney A. Leeper, Emily S. Chambers, Anika E. Adeni, Luke J. Taus, Mari Kuraguchi, Paul T. Kirschmeier, Channing Yu, Yoshinobu Shiose, Yasuki Kamai, Yang Qiu, Cloud P. Paweletz, Prafulla C. Gokhale, Pasi A. Jänne
Journal: Cancer Research (2021)

Abstract Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) are the standard-of-care treatment for EGFR-mutant non–small cell lung cancers (NSCLC). However, most patients develop acquired drug resistance to EGFR TKIs. HER3 is a unique pseudokinase member of the ERBB family that functions by dimerizing with other ERBB family members (EGFR and HER2) and is frequently overexpressed in EGFR-mutant NSCLC. Although EGFR TKI resistance mechanisms do not lead to alterations in HER3, we hypothesized that targeting HER3 might improve efficacy of EGFR TKI. HER3–DXd is an antibody–drug conjugate (ADC) comprised of HER3-targeting antibody linked to a topoisomerase I inhibitor currently in clinical development. In this study, we evaluated the efficacy of HER3–DXd across a series of EGFR inhibitor–resistant, patient-derived xenografts and observed it to be broadly effective in HER3-expressing cancers. We further developed a preclinical strategy to enhance the efficacy of HER3–DXd through osimertinib pretreatment, which increased membrane expression of HER3 and led to enhanced internalization and efficacy of HER3–DXd. The combination of osimertinib and HER3–DXd may be an effective treatment approach and should be evaluated in future clinical trials in EGFR-mutant NSCLC patients. Significance: EGFR inhibition leads to increased HER3 membrane expression and promotes HER3–DXd ADC internalization and efficacy, supporting the clinical development of the EGFR inhibitor/HER3–DXd combination in EGFR-mutant lung cancer. See related commentary by Lim et al., p. 18
Abstract MP36: Association Between The Quality Of Plant-based Diets And Risk Of Frailty
Authors: Mercedes Sotos-Prieto, Ellen A Struijk, Teresa T Fung, Fernando Rodriguez-Artalejo, Walter Willett, Frank B Hu, Esther Lopez-Garcia
Journal: Circulation (2022)

Importance: The Mediterranean diet, and other dietary patterns rich in fruits and vegetables, have been linked to lower risk of frailty in older adults. However, not all plant-based diets are necessarily healthful, and no previous study has evaluated the role of the quality of plant-based dietary patterns in frailty risk. Objective: To assess the association between plant-based diet quality and risk of frailty. Design, setting, and participants: Prospective cohort with 82,234 women aged ≥60y from the Nurses’ Health Study, who were followed from 1990 through 2014. The dates of analysis were April 14 to -June 23, 2021. Exposures: Dietary data were collected every 4-y using a validated semi-quantitative food frequency questionnaire. The plant-based diet quality was assessed with 2 indices (range 18 - 90 points).: a) Healthful Plant-Based Diet Index (hPDI), where healthy plant foods (whole grains, fruits, vegetables, nuts, legumes, vegetable oils, tea/coffee) received positive scores, while less healthy plant foods (fruit juices, sweetened beverages, refined grains, potatoes, sweets/desserts) and animal foods received reverse scores; and b) Unhealthful Plant-Based Diet Index (uPDI) where positive scores were given to less healthy plant foods and reverse scores to healthy plant foods and animal foods. Main outcomes: Frailty incidence was assessed every 4 years, being defined as having ≥3 of the following 5 criteria from the FRAIL scale: fatigue, low strength, reduced aerobic capacity, having ≥5 illnesses, and weight loss ≥5%. Methods: Multivariable-adjusted Cox proportional-hazards models were used to estimate hazard ratios (HRs), and their 95% confidence interval (CI). Results: We identified 12,910 incident cases of frailty over 1,176,401 person-year follow-up. In the multivariable analysis, the hPDI was inversely associated with the risk of frailty (HR for the highest vs. lowest quintile: 0.69, 95% CI: 0.65-0.73; p-trend&lt;0.001). In addition, a 10-unit increment in the hPDI was associated with a relative 20% lower risk of frailty. Conversely, a direct association was found between the uPDI and risk of frailty (HR highest vs. lowest quintile: 1.41, 95% CI: 1.32-1.49]; p-trend&lt;0.001). These associations were consistent for each frailty criterion, among participants with no frailty criteria at baseline, after excluding participants with diabetes, cancer, and CVD at baseline, for alternative versions of the PDIs, in subgroup analysis by categories of potential confounders, and in latency analysis. Conclusions and relevance: A healthful plant-based diet was associated with lower risk of frailty whereas an unhealthful plant-based diet was associated with higher risk.
Ceritinib in paediatric patients with anaplastic lymphoma kinase-positive malignancies: an open-label, multicentre, phase 1, dose-escalation and dose-expansion study
Authors: Matthias Fischer, Lucas Moreno, David S Ziegler, Lynley V Marshall, C Michel Zwaan, Meredith S Irwin, Michela Casanova, Constantino Sabado, Beate Wulff, Mario Stegert, Luojun Wang, Felipe K Hurtado, Fabrice Branle, Birgit Geoerger, Johannes H Schulte
Journal: The Lancet Oncology (2021)