tbuckley/cabot-search huggingface dataset:
68Ga-PSMA Uptake Patterns of Clear Cell Renal Carcinoma Across Different Histopathological Subtypes
Authors: Melis Oflas, Yasemin Ozluk, Oner Sanli, Zeynep Gozde Ozkan, Serkan Kuyumcu
Journal: Clinical Nuclear Medicine (2021)

Abstract 68 Ga–prostate-specific membrane antigen (PSMA) PET/CT is a well-established imaging modality in patients with prostate cancer; however, PSMA expression is also reported in the tumor-associated neovasculature, including but not limited to hepatocellular carcinoma, breast cancer, and renal cell carcinoma. Herein, we present 2 patients diagnosed with different histopathological subtypes of renal cell carcinoma who underwent 68 Ga-PSMA PET/CT before surgery. Both cases have different PSMA expression characteristics and are presented along with pathological findings.
Pandemic preparedness and COVID-19: an exploratory analysis of infection and fatality rates, and contextual factors associated with preparedness in 177 countries, from Jan 1, 2020, to Sept 30, 2021
Authors: Thomas J Bollyky, Erin N Hulland, Ryan M Barber, James K Collins, Samantha Kiernan, Mark Moses, David M Pigott, Robert C Reiner Jr, Reed J D Sorensen, Cristiana Abbafati, Christopher Adolph, Adrien Allorant, Joanne O Amlag, Aleksandr Y Aravkin, Bree Bang-Jensen, Austin Carter, Rachel Castellano, Emma Castro, Suman Chakrabarti, Emily Combs, Xiaochen Dai, William James Dangel, Carolyn Dapper, Amanda Deen, Bruce B Duncan, Lucas Earl, Megan Erickson, Samuel B Ewald, Tatiana Fedosseeva, Alize J Ferrari, Abraham D Flaxman, Nancy Fullman, Emmanuela Gakidou, Bayan Galal, John Gallagher, John R Giles, Gaorui Guo, Jiawei He, Monika Helak, Bethany M Huntley, Bulat Idrisov, Casey Johanns, Kate E LeGrand, Ian D Letourneau, Akiaja Lindstrom, Emily Linebarger, Paulo A Lotufo, Rafael Lozano, Beatrice Magistro, Deborah Carvalho Malta, Johan Månsson, Ana M Mantilla Herrera, Fatima Marinho, Alemnesh H Mirkuzie, Ali H Mokdad, Lorenzo Monasta, Paulami Naik, Shuhei Nomura, James Kevin O'Halloran, Christopher M Odell, Latera Tesfaye Olana, Samuel M Ostroff, Maja Pasovic, Valeria Maria de Azeredo Passos, Louise Penberthy, Grace Reinke, Damian Francesco Santomauro, Maria Inês Schmidt, Aleksei Sholokhov, Emma Spurlock, Christopher E Troeger, Elena Varavikova, Anh T Vo, Theo Vos, Rebecca Walcott, Ally Walker, Simon D Wigley, Charles Shey Wiysonge, Nahom Alemseged Worku, Yifan Wu, Sarah Wulf Hanson, Peng Zheng, Simon I Hay, Christopher J L Murray, Joseph L Dieleman
Journal: The Lancet (2022)

National rates of COVID-19 infection and fatality have varied dramatically since the onset of the pandemic. Understanding the conditions associated with this cross-country variation is essential to guiding investment in more effective preparedness and response for future pandemics.
FDG PET/CT in Tenosynovial Giant Cell Tumor of the Lumbar Facet Joint
Authors: Jian Zhang, Yuhan Li, Yanfang Zhu, Ying Duan, Yuzhao Zhu
Journal: Clinical Nuclear Medicine (2021)

Tenosynovial giant cell tumor rarely affects the facet joints of the spine. We describe FDG PET/CT findings in a case of tenosynovial giant cell tumor arising from the left L2 to L3 facet joint. The tumor caused osteolytic bone destruction of the facet joint and showed intense FDG uptake with SUVmax of 10.4. This case indicates tenosynovial giant cell tumor should be included in the differential diagnosis of abnormal facet joint FDG accumulation.
Perspectives on Drug Development in Multiple Myeloma—Looking Forward to 2025
Authors: Peter M. Voorhees, Andrzej J. Jakubowiak, Shaji K. Kumar, Bindu Kanapuru, Andrea C. Baines, Vishal Bhatnagar, Rachel Ershler, Marc R. Theoret, Nicole J. Gormley, Richard Pazdur
Journal: Clinical Cancer Research (2021)

The multiple myeloma treatment landscape has evolved considerably over the last 20 years with the development of multiple therapies with novel mechanisms of action and new combination regimens. However, the recent failure of several large phase III trials, coupled with an increased understanding of the mutational landscape of multiple myeloma has provided opportunities to explore optimal strategies for future multiple myeloma drug development. The Office of Oncologic Diseases at the FDA held an educational symposium, "Drug Development in MM-Project 2025," in November 2019. The symposium brought together select U.S.-based academic thought leaders in the field of multiple myeloma to explore issues relevant to regulatory science in the field, including considerations for trial design, combination strategies, control arms, and precision medicine. This article summarizes the highlights of this educational symposium held at the FDA, including discussions on the future development of novel drugs and drug combinations and biomarker-directed therapies for patients with multiple myeloma.
The effect of maternal SARS-CoV-2 infection timing on birth outcomes: a retrospective multicentre cohort study
Authors: Samantha N Piekos, Ryan T Roper, Yeon Mi Hwang, Tanya Sorensen, Nathan D Price, Leroy Hood, Jennifer J Hadlock
Journal: The Lancet Digital Health (2022)

The impact of maternal SARS-CoV-2 infection remains unclear. In this study, we evaluated the risk of maternal SARS-CoV-2 infection on birth outcomes and how this is modulated by the pregnancy trimester in which the infection occurs. We also developed models to predict gestational age at delivery for people following a SARS-CoV-2 infection during pregnancy.
Abstract P123: IL1RN Gene Polymorphism And The Development Of Acute Myocardial Infarction In Young Patients
Authors: Svetlana Glova
Journal: Circulation (2022)

IL-1RA is a member of the interleukin-1 cytokine family. IL1Ra is secreted by various types of cells, including immune cells, epithelial cells, and adipocytes, and is a natural inhibitor of the pro-inflammatory effect of IL1. This protein inhibits the activity of interleukin 1, alpha (IL1A) and interleukin 1, beta (IL1B) and modulates various interleukin 1-related immune and inflammatory responses. Hypothesis: The aim of this study was to investigate the relationship between IL1RN gene polymorphism and the development of acute myocardial infarction (AMI) in young patients. Material/methods: In a case-control study, we investigated polymorphisms in the IL1RN gene (rs4251961) using quantitative real-time polymerase chain reaction analysis. The study was conducted with AMI (age range: 36 to 55 years; mean: 42.74 ± 12.47 years) with 11 healthy people in the control group. We also studied the interaction between genetic polymorphism and inflammatory agents such as CRP, IL 1, IL 6. All indicators were calculated using the statistical program Statistica 12.0, a P-value &lt;0.05 was considered statistically significant. Results: Statistically significant differences in the distribution of rs4251961 genotypes were observed between the two groups. Carriers of the T allele had a significantly higher risk of developing AMI than carriers of the C allele (P &lt;0.05). Subjects carrying the TT and TC haplotypes have a significantly increased incidence of coronary artery disease. We also found that the CYP1B1 rs1056836 polymorphism had a synergistic effect with CRP levels on the risk of coronary heart disease. Conclusions: The rs4251961 gene polymorphism is closely associated with the development of AMI in patients with coronary artery disease. There is a mutual synergistic effect between the inflammatory response and IL1RN gene polymorphism in relation to the development of CAD complications. Functional polymorphisms of the IL1RN gene can affect the susceptibility and progression of CAD, increase the pro-inflammatory response, and destabilize the atherosclerotic plaque.
Trends in Depressive Symptoms and Associated Factors During Residency, 2007 to 2019
Authors: Yu Fang, Amy S.B. Bohnert, Karina Pereira-Lima, Jennifer Cleary, Elena Frank, Zhuo Zhao, Walter Dempsey, Srijan Sen
Journal: Annals of Internal Medicine (2021)

Efforts to address the high depression rates among training physicians have been implemented at various levels of the U.S. medical education system. The cumulative effect of these efforts is unknown.To assess how the increase in depressive symptoms with residency has shifted over time and to identify parallel trends in factors that have previously been associated with resident physician depression.Repeated annual cohort study.U.S. health care organizations.First-year resident physicians (interns) who started training between 2007 and 2019.Depressive symptoms (9-item Patient Health Questionnaire [PHQ-9]) assessed at baseline and quarterly throughout internship.Among 16 965 interns, baseline depressive symptoms increased from 2007 to 2019 (PHQ-9 score, 2.3 to 2.9; difference, 0.6 [95% CI, 0.3 to 0.8]). The prevalence of baseline predictors of greater increase in depressive symptoms with internship also increased across cohorts. Despite the higher prevalence of baseline risk factors, the average change in depressive symptoms with internship decreased 24.4% from 2007 to 2019 (change in PHQ-9 score, 4.1 to 3.0; difference, -1.0 [CI, -1.5 to -0.6]). This change across cohorts was greater among women (4.7 to 3.3; difference, -1.4 [CI, -1.9 to -0.9]) than men (3.5 to 2.9; difference, -0.6 [CI, -1.2 to -0.05]) and greater among nonsurgical interns (4.1 to 3.0; difference, -1.1 [CI, -1.6 to -0.6]) than surgical interns (4.0 to 3.2; difference, -0.8 [CI, -1.2 to -0.4]). In parallel to the decrease in depressive symptom change, there were increases in sleep hours, quality of faculty feedback, and use of mental health services and a decrease in work hours across cohorts. The decrease in work hours was greater for nonsurgical than surgical interns. Further, the increase in mental health treatment across cohorts was greater for women than men.Data are observational and subject to biases due to nonrandom sampling, missing data, and unmeasured confounders, limiting causal conclusions.Although depression during physician training remains high, the average increase in depressive symptoms associated with internship decreased between 2007 and 2019.National Institute of Mental Health.
THE CERAMIDE- AND PHOSPHATIDYLCHOLINE- BASED CORONARY EVENT RISK TEST2 (CERT2) AND CARDIOVASCULAR MORTALITY IN MEN AND WOMEN WITH TYPE 2 DIABETES
Authors: Andreas Leiherer, Axel Muendlein, Christoph H. Saely, Barbara Larcher, Arthur Mader, Maximilian Maechler, Lukas Sprenger, Valentin Grabher, Reijo Laaksonen, Mitja Laaperi, Antti Jylha, Peter Fraunberger, Heinz Drexel
Journal: Journal of the American College of Cardiology (2022)
Unusual Presentation of Helicobacter pylori Infection as PSMA-Avid Gastric Mass
Authors: Ritesh Ramesh Suthar, Archi Agrawal, Kedar Deodhar, Nilendu Purandare, Sneha Shah, Ameya Puranik, Sayak Choudhury, Venkatesh Rangarajan
Journal: Clinical Nuclear Medicine (2022)

Abstract 68 Ga-PSMA PET/CT is one of the most common imaging uses for prostate cancer imaging. Although initially thought to be specific for prostate cancer, there are many evidences that are coming of its concentration in many other neoplastic and nonneoplastic pathologies. Helicobacter pylori is the most common bacteria causing gastric inflammation and usually presents with gastroduodenal ulcer. Here we present one unusual case of benign gastric mass formation caused by H. pylori infection with PSMA concentration.
Tumor Cell IDO Enhances Immune Suppression and Decreases Survival Independent of Tryptophan Metabolism in Glioblastoma
Authors: Lijie Zhai, April Bell, Erik Ladomersky, Kristen L. Lauing, Lakshmi Bollu, Brenda Nguyen, Matthew Genet, Miri Kim, Peiwen Chen, Xinlei Mi, Jennifer D. Wu, Matthew J. Schipma, Brian Wray, John Griffiths, Richard D. Unwin, Simon J. Clark, Rajesh Acharya, Riyue Bao, Craig Horbinski, Rimas V. Lukas, Gary E. Schiltz, Derek A. Wainwright
Journal: Clinical Cancer Research (2021)

Glioblastoma (GBM) is an incurable primary brain tumor that has not benefited from immunotherapy to date. More than 90% of GBM expresses the tryptophan (Trp) metabolic enzyme, indoleamine 2,3-dioxygenase 1 (IDO). This observation supported the historical hypothesis that IDO suppresses the antitumor immune response solely through a mechanism that requires intratumoral Trp depletion. However, recent findings led us to investigate the alternative hypothesis that IDO suppresses the anti-GBM immune response independent of its association with Trp metabolism.IDO-deficient GBM cell lines reconstituted with IDO wild-type or IDO enzyme-null cDNA were created and validated in vitro and in vivo. Microarray analysis was conducted to search for genes that IDO regulates, followed by the analysis of human GBM cell lines, patient GBM and plasma, and The Cancer Genome Atlas (TCGA) database. Ex vivo cell coculture assays, syngeneic and humanized mouse GBM models, were used to test the alternative hypothesis.Nonenzymic tumor cell IDO activity decreased the survival of experimental animals and increased the expression of complement factor H (CFH) and its isoform, factor H like protein 1 (FHL-1) in human GBM. Tumor cell IDO increased CFH and FHL-1 expression independent of Trp metabolism. Increased intratumoral CFH and FHL-1 levels were associated with poorer survival among patients with glioma. Similar to IDO effects, GBM cell FHL-1 expression increased intratumoral regulatory T cells (Treg) and myeloid-derived suppressor cells while it decreased overall survival in mice with GBM.Our study reveals a nonmetabolic IDO-mediated enhancement of CFH expression and provides a new therapeutic target for patients with GBM.
Global, regional, and national causes of under-5 mortality in 2000–19: an updated systematic analysis with implications for the Sustainable Development Goals
Authors: Jamie Perin, Amy Mulick, Diana Yeung, Francisco Villavicencio, Gerard Lopez, Kathleen L Strong, David Prieto-Merino, Simon Cousens, Robert E Black, Li Liu
Journal: The Lancet Child & Adolescent Health (2021)

Causes of mortality are a crucial input for health systems for identifying appropriate interventions for child survival. We present an updated series of cause-specific mortality for neonates and children younger than 5 years from 2000 to 2019.
Disparities in breast cancer survival between women with and without HIV across sub-Saharan Africa (ABC-DO): a prospective, cohort study
Authors: Steady Chasimpha, Valerie McCormack, Herbert Cubasch, Maureen Joffe, Annelle Zietsman, Moses Galukande, Groesbeck Parham, Leeya F Pinder, Angelica Anele, Charles A Adisa, Awa Ukonye Offiah, Benjamin O Anderson, Pauline Boucheron, Milena Foerster, Joachim Schüz, Isabel dos-Santos-Silva
Journal: The Lancet HIV (2022)
False-Positive Uptake in Splenic Hemangioma on 68Ga-PSMA PET/CT Scan for Late Biochemical Recurrence of Prostate Cancer
Authors: Éder Silveira Brazão, André Marcondes Braga Ribeiro, Eduardo Nobrega Pereira Lima, Walter Henriques da Costa, Stênio de Cássio Zequi
Journal: Clinical Nuclear Medicine (2021)

Abstract A 71-year-old man underwent 68 Ga-PSMA PET/CT for evaluation of a late biochemical recurrence after radical prostatectomy. An intense PSMA uptake was identified in spleen. Additional evaluation with a contrast-enhanced MRI showed a splenic lesion consistent with splenic hemangioma.
Comparison of confound adjustment methods in the construction of gene co-expression networks
Authors: Alanna C. Cote, Hannah E. Young, Laura M. Huckins
Journal: Genome biology (2022)

Adjustment for confounding sources of expression variation is an important preprocessing step in large gene expression studies, but the effect of confound adjustment on co-expression network analysis has not been well-characterized. Here, we demonstrate that the choice of confound adjustment method can have a considerable effect on the architecture of the resulting co-expression network. We compare standard and alternative confound adjustment methods and provide recommendations for their use in the construction of gene co-expression networks from bulk tissue RNA-seq datasets.
FSTL1 Secreted by Activated Fibroblasts Promotes Hepatocellular Carcinoma Metastasis and Stemness
Authors: Jia-Jian Loh, Tsz-Wai Li, Lei Zhou, Tin-Lok Wong, Xue Liu, Victor W.S. Ma, Chung-Mau Lo, Kwan Man, Terence K. Lee, Wen Ning, Man Tong, Stephanie Ma
Journal: Cancer Research (2021)

The tumor microenvironment plays a critical role in maintaining the immature phenotype of tumor-initiating cells (TIC) to promote cancer. Hepatocellular carcinoma (HCC) is a unique disease in that it develops in the setting of fibrosis and cirrhosis. This pathologic state commonly shows an enrichment of stromal myofibroblasts, which constitute the bulk of the tumor microenvironment and contribute to disease progression. Follistatin-like 1 (FSTL1) has been widely reported as a proinflammatory mediator in different fibrosis-related and inflammatory diseases. Here we show FSTL1 expression to be closely correlated with activated fibroblasts and to be elevated in regenerative, fibrotic, and disease liver states in various mouse models. Consistently, FSTL1 lineage cells gave rise to myofibroblasts in a CCL4-induced hepatic fibrosis mouse model. Clinically, high FSTL1 in fibroblast activation protein-positive (FAP+) fibroblasts were significantly correlated with more advanced tumors in patients with HCC. Although FSTL1 was expressed in primary fibroblasts derived from patients with HCC, it was barely detectable in HCC cell lines. Functional investigations revealed that treatment of HCC cells and patient-derived 3D organoids with recombinant FSTL1 or with conditioned medium collected from hepatic stellate cells or from cells overexpressing FSTL1 could promote HCC growth and metastasis. FSTL1 bound to TLR4 receptor, resulting in activation of AKT/mTOR/4EBP1 signaling. In a preclinical mouse model, blockade of FSTL1 mitigated HCC malignancy and metastasis, sensitized HCC tumors to sorafenib, prolonged survival, and eradicated the TIC subset. Collectively, these data suggest that FSTL1 may serve as an important novel diagnostic/prognostic biomarker and therapeutic target in HCC. SIGNIFICANCE: This study shows that FSTL1 secreted by activated fibroblasts in the liver microenvironment augments hepatocellular carcinoma malignancy, providing a potential new strategy to improve treatment of this aggressive disease.
Convection Enhanced Delivery of the Oncolytic Adenovirus Delta24-RGD in Patients with Recurrent GBM: A Phase I Clinical Trial Including Correlative Studies
Authors: Erik H.P. van Putten, Anne Kleijn, Victor W. van Beusechem, David Noske, Cor H.J. Lamers, Anna L. de Goede, Sander Idema, Daphna Hoefnagel, Jenneke J. Kloezeman, Juan Fueyo, Frederick F. Lang, Charlotte E. Teunissen, René M. Vernhout, Cathy Bakker, Winald Gerritsen, David T. Curiel, Arnold Vulto, Martine L.M. Lamfers, Clemens M.F. Dirven
Journal: Clinical Cancer Research (2022)

Abstract Purpose: Testing safety of Delta24-RGD (DNX-2401), an oncolytic adenovirus, locally delivered by convection enhanced delivery (CED) in tumor and surrounding brain of patients with recurrent glioblastoma. Patients and Methods: Dose-escalation phase I study with 3+3 cohorts, dosing 107 to 1 × 1011 viral particles (vp) in 20 patients. Besides clinical parameters, adverse events, and radiologic findings, blood, cerebrospinal fluid (CSF), brain interstitial fluid, and excreta were sampled over time and analyzed for presence of immune response, viral replication, distribution, and shedding. Results: Of 20 enrolled patients, 19 received the oncolytic adenovirus Delta24-RGD, which was found to be safe and feasible. Four patients demonstrated tumor response on MRI, one with complete regression and still alive after 8 years. Most serious adverse events were attributed to increased intracranial pressure caused by either an inflammatory reaction responding to steroid treatment or viral meningitis being transient and self-limiting. Often viral DNA concentrations in CSF increased over time, peaking after 2 to 4 weeks and remaining up to 3 months. Concomitantly Th1- and Th2-associated cytokine levels and numbers of CD3+ T and natural killer cells increased. Posttreatment tumor specimens revealed increased numbers of macrophages and CD4+ and CD8+ T cells. No evidence of viral shedding in excreta was observed. Conclusions: CED of Delta24-RGD not only in the tumor but also in surrounding brain is safe, induces a local inflammatory reaction, and shows promising clinical responses.
A Rare Pitfall in Bone Mineral Densitometry
Authors: Mine Araz, Gizem Sutcu, llknur Surucu Kara, Tuba Eminoglu, Elgin Ozkan
Journal: Clinical Nuclear Medicine (2022)

Abstract We report a rare case of type 3 Gaucher disease presenting with calcified mesenteric lymph nodes that interfere with bone mineral densitometric measurements.
Retraction Note: MiR-362-5p promotes the malignancy of chronic myelocytic leukaemia via downregulation of GADD45α
Authors: Peng Yang, Fang Ni, Rui-qing Deng, Guo Qiang, Hua Zhao, Ming-zhen Yang, Xin-yi Wang, You-zhi Xu, Li Chen, Dan-lei Chen, Zhi-jun Chen, Li-xin Kan, Si-Ying Wang
Journal: Molecular Cancer (2022)

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s12943-015-0465-3.
Personalized Prediction Model to Risk Stratify Patients With Myelodysplastic Syndromes
Authors: Aziz Nazha, Rami Komrokji, Manja Meggendorfer, Xuefei Jia, Nathan Radakovich, Jacob Shreve, C. Beau Hilton, Yasunubo Nagata, Betty K. Hamilton, Sudipto Mukherjee, Najla Al Ali, Wencke Walter, Stephan Hutter, Eric Padron, David Sallman, Teodora Kuzmanovic, Cassandra Kerr, Vera Adema, David P. Steensma, Amy Dezern, Gail Roboz, Guillermo Garcia-Manero, Harry Erba, Claudia Haferlach, Jaroslaw P. Maciejewski, Torsten Haferlach, Mikkael A. Sekeres
Journal: Journal of Clinical Oncology (2021)

Patients with myelodysplastic syndromes (MDS) have a survival that can range from months to decades. Prognostic systems that incorporate advanced analytics of clinical, pathologic, and molecular data have the potential to more accurately and dynamically predict survival in patients receiving various therapies.A total of 1,471 MDS patients with comprehensively annotated clinical and molecular data were included in a training cohort and analyzed using machine learning techniques. A random survival algorithm was used to build a prognostic model, which was then validated in external cohorts. The accuracy of the proposed model, compared with other established models, was assessed using a concordance (c)index.The median age for the training cohort was 71 years. Commonly mutated genes included SF3B1, TET2, and ASXL1. The algorithm identified chromosomal karyotype, platelet, hemoglobin levels, bone marrow blast percentage, age, other clinical variables, seven discrete gene mutations, and mutation number as having prognostic impact on overall and leukemia-free survivals. The model was validated in an independent external cohort of 465 patients, a cohort of patients with MDS treated in a prospective clinical trial, a cohort of patients with paired samples at different time points during the disease course, and a cohort of patients who underwent hematopoietic stem-cell transplantation.A personalized prediction model on the basis of clinical and genomic data outperformed established prognostic models in MDS. The new model was dynamic, predicting survival and leukemia transformation probabilities at different time points that are unique for a given patient, and can upstage and downstage patients into more appropriate risk categories.
In older patients at high risk for stroke, intensive AF screening with an implantable loop recorder did not reduce stroke
Authors: Mohammed Yousufuddin, Arshad Jahangir
Journal: Annals of Internal Medicine (2022)

Svendsen JH, Diederichsen SZ, Højberg S, et al. Implantable loop recorder detection of atrial fibrillation to prevent stroke (The LOOP Study): a randomised controlled trial. Lancet. 2021;398:1507-16. 34469766.