tbuckley/cabot-search huggingface dataset:
Genomic and Transcriptomic Analysis of Relapsed and Refractory Childhood Solid Tumors Reveals a Diverse Molecular Landscape and Mechanisms of Immune Evasion
Authors: Sara A. Byron, William P.D. Hendricks, Abhinav B. Nagulapally, Jacqueline M. Kraveka, William S. Ferguson, Valerie I. Brown, Don E. Eslin, Deanna Mitchell, Albert Cornelius, William Roberts, Michael S. Isakoff, Javier E. Oesterheld, Randal K. Wada, Jawhar Rawwas, Kathleen Neville, Peter E. Zage, Virginia L. Harrod, Genevieve Bergendahl, Elizabeth VanSickle, Karl Dykema, Jeffrey Bond, Hsien-Chao Chou, Jun S. Wei, Xinyu Wen, Hue V. Reardon, Alison Roos, Sara Nasser, Tyler Izatt, Daniel Enriquez, Apurva M. Hegde, Faith Cisneros, Austin Christofferson, Bryce Turner, Szabolcs Szelinger, Jonathan J. Keats, Rebecca F. Halperin, Javed Khan, Giselle L. Saulnier Sholler, Jeffrey M. Trent
Journal: Cancer Research (2021)

Abstract Children with treatment-refractory or relapsed (R/R) tumors face poor prognoses. As the genomic underpinnings driving R/R disease are not well defined, we describe here the genomic and transcriptomic landscapes of R/R solid tumors from 202 patients enrolled in Beat Childhood Cancer Consortium clinical trials. Tumor mutational burden (TMB) was elevated relative to untreated tumors at diagnosis, with one-third of tumors classified as having a pediatric high TMB. Prior chemotherapy exposure influenced the mutational landscape of these R/R tumors, with more than 40% of tumors demonstrating mutational signatures associated with platinum or temozolomide chemotherapy and two tumors showing treatment-associated hypermutation. Immunogenomic profiling found a heterogenous pattern of neoantigen and MHC class I expression and a general absence of immune infiltration. Transcriptional analysis and functional gene set enrichment analysis identified cross-pathology clusters associated with development, immune signaling, and cellular signaling pathways. While the landscapes of these R/R tumors reflected those of their corresponding untreated tumors at diagnosis, important exceptions were observed, suggestive of tumor evolution, treatment resistance mechanisms, and mutagenic etiologies of treatment. Significance: Tumor heterogeneity, chemotherapy exposure, and tumor evolution contribute to the molecular profiles and increased mutational burden that occur in treatment-refractory and relapsed childhood solid tumors.
Gut bacterial dysbiosis and instability is associated with the onset of complications and mortality in COVID-19
Authors: David Schult, Sandra Reitmeier, Plamena Koyumdzhieva, Tobias Lahmer, Moritz Middelhoff, Johanna Erber, Jochen Schneider, Juliane Kager, Marina Frolova, Julia Horstmann, Lisa Fricke, Katja Steiger, Moritz Jesinghaus, Klaus-Peter Janssen, Ulrike Protzer, Klaus Neuhaus, Roland M. Schmid, Dirk Haller, Michael Quante
Journal: Gut Microbes (2022)

There is a growing debate about the involvement of the gut microbiome in COVID-19, although it is not conclusively understood whether the microbiome has an impact on COVID-19, or vice versa, especially as analysis of amplicon data in hospitalized patients requires sophisticated cohort recruitment and integration of clinical parameters. Here, we analyzed fecal and saliva samples from SARS-CoV-2 infected and post COVID-19 patients and controls considering multiple influencing factors during hospitalization. 16S rRNA gene sequencing was performed on fecal and saliva samples from 108 COVID-19 and 22 post COVID-19 patients, 20 pneumonia controls and 26 asymptomatic controls. Patients were recruited over the first and second corona wave in Germany and detailed clinical parameters were considered. Serial samples per individual allowed intra-individual analysis. We found the gut and oral microbiota to be altered depending on number and type of COVID-19-associated complications and disease severity. The occurrence of individual complications was correlated with low-risk (e.g., Faecalibacterium prausznitzii) and high-risk bacteria (e.g., Parabacteroides ssp.). We demonstrated that a stable gut bacterial composition was associated with a favorable disease progression. Based on gut microbial profiles, we identified a model to estimate mortality in COVID-19. Gut microbiota are associated with the occurrence of complications in COVID-19 and may thereby influencing disease severity. A stable gut microbial composition may contribute to a favorable disease progression and using bacterial signatures to estimate mortality could contribute to diagnostic approaches. Importantly, we highlight challenges in the analysis of microbial data in the context of hospitalization.
Exposing and overcoming the fixed-effect fallacy through crowd science
Authors: Wilson Cyrus-Lai, Warren Tierney, Martin Schweinsberg, Eric Luis Uhlmann
Journal: Behavioral and Brain Sciences (2022)

By organizing crowds of scientists to independently tackle the same research questions, we can collectively overcome the generalizability crisis. Strategies to draw inferences from a heterogeneous set of research approaches include aggregation, for instance, meta-analyzing the effect sizes obtained by different investigators, and parsing, attempting to identify theoretically meaningful moderators that explain the variability in results.
Abstract MP01: Disentangling The Relationship Between Genetic Predisposition And Social Environment In The Development Of Myocardial Infarction
Authors: Chenkai Wu, Chen Sheng
Journal: Circulation (2022)

Background: The interrelatedness between social determinants of health impedes researchers to identify important social factors for cardiovascular health. A new approach is needed to quantify the aggregate effect of social factors and develop person-centered interventions. In addition, it remains largely unknown whether social environment could offset the increased risk of cardiovascular disease among genetically predisposed persons. Objective: This study aimed to create a polysocial score to comprehensively quantify the effect of a variety of social factors of myocardial infarction (MI) and examine the synergistic effect of genetic and social factors for predicting MI. Methods: Data are from the 2006 or 2008 wave of the Health and Retirement Study. Social determinants of health encompassed five social domains: economic stability, neighborhood and physical environment, education, community and social context, and healthcare system. We used the forward stepwise logistic regression to derive a polysocial score model for 10-year incidence of MI. We calculated the incidence rate by each polygenic score tertile and polysocial score tertile. We used the interaction approach to examine the synergistic effect of polygenic score (continuously) and polysocial score (continuously) on MI. Results: 4,372 participants (55% female) initially free of MI were included. A polysocial score for MI was created using five social determinants of health. Participants with intermediate (OR=0.72; 95% CI, 0.54, 0.95) and high (OR=0.46; 95% CI, 0.33, 0.64) polysocial scores had lower odds of MI than those with low polysocial scores. In each tertile of polygenic score, higher polysocial score was associated with a lower incidence of MI. Compared with persons with a low polygenic and a high polysocial score, those with a high polygenic and low polysocial score had a 5-fold higher odds of MI (95% CI: 2.51, 11.50). A desirable social environment, indicated by a high polysocial score, could offset the increased risk of MI among persons with a high genetic risk. The incidence rate of MI was 7 per 1,000 person-years (PYs) for persons with a low genetic predisposition but an undesirable polysocial score and was 7 per 1,000 person-years (PYs) for those with a high genetic predisposition but a desirable polysocial score. Results persisted after adjustment of sex, age, and race/ethnicity (white and black). Conclusion: The polysocial approach may offer possible solutions to monitor social environments and suggestions for older people to improve their social status for cardiovascular health regardless of level of genetic predisposition. Establishment of a desirable social environment could offset the increased risk of cardiovascular disease associated with genetics.
Editor's Note: ITPR1 Protects Renal Cancer Cells against Natural Killer Cells by Inducing Autophagy
Authors: Yosra Messai, Muhammad Zaeem Noman, Meriem Hasmim, Bassam Janji, Andrés Tittarelli, Marie Boutet, Véronique Baud, Elodie Viry, Katy Billot, Arash Nanbakhsh, Thouraya Ben Safta, Catherine Richon, Sophie Ferlicot, Emmanuel Donnadieu, Sophie Couve, Betty Gardie, Florence Orlanducci, Laurence Albiges, Jerome Thiery, Daniel Olive, Bernard Escudier, Salem Chouaib
Journal: Cancer Research (2022)

The editors are publishing this note to alert readers to a concern about this article. We detected that the actin bands in the Western blot analysis in Fig. 2A (representing siRNA-CT, siRNA-HIF2α-1, and siRNA-HIF2α-2) were duplicated and used in Fig. 4B (representing siRNA-HIF2α-1, -2, and -3) and in Fig. 4C (representing VHL C162F, VHL Y98H, and VHL WT). Because of the length of time since the publication of this article, the original data were not available.
Abstract P051: Healthy For Life: A Shift To Virtual Nutrition Education To Improve Confidence And Dietary Behaviors
Authors: Heather Gavras, Olivia Jones, Remy Poudel
Journal: Circulation (2022)

Introduction: Less than 10% of U.S. adults meet the guidelines for whole grains, fruits, and vegetables each day. The Healthy for Life community-based program aims to change confidence and health behaviors, by equipping individuals with new skills for healthy living. As a result of the COVID-19 pandemic in 2020 and 2021, the program pivoted from in-person to a virtual implementation model. This required more advanced planning due to additional logistics to ensure a skills-based learning environment. Objectives: To examine the effectiveness of the Healthy for Life program over time, specifically: o Changes in participant confidence in the preparation of healthy foods at home o Changes in participant consumption of fruits, vegetables, and whole grains o Changes in participant frequency of healthy shopping habits Methods: A community engagement program was implemented and evaluated in 17 community centers in 2020-2021 to measure changes in participant confidence to prepare healthy meals at home, consumption of fruits, vegetables and whole grains, and frequency of healthy shopping habits. Community center facilitators administered the same pre/post survey to participants at the first educational experience, and then again at the final experience. Facilitators entered the participant data into an online survey portal. Analysis was conducted with 235 participants who completed both pre and post surveys. Two-way repeated ordinal regression was used to assess changes in key metrics over time. Results: Participants were predominately female (90.6%), about two-thirds (65.2%) were between 25-55 years old, and most identified as non-Hispanic White/Caucasian (42.6%) or Black/African American (35.7%). Close to half (45.9%) of participants had a college degree or higher, over a quarter (28.1%) received benefits from SNAP and/or WIC, and more than two-thirds (63.8%) indicated they are the only person in their household preparing meals. Almost half (49.3%) of respondents attended the suggested minimum of 4 educational experiences. On average, respondents statistically significantly increased their daily fruit &amp; vegetable consumption by 1.21 serving(s). In addition, over one-third (34%) of respondents increased their level of confidence to prepare healthy meals at home and (37%) respondents increased their level of confidence to substitute healthier cooking and food preparation methods. Close to half (47.2%) respondents reported increased frequency of reading food labels and checking the nutritional values when purchasing food. Conclusions: Despite the shift to virtual implementation, the Healthy for Life community education program, was still effective in improving participant confidence and dietary behaviors over time. However, additional research studies are required to further assess whether virtual implementation of this type of intervention will continue to be effective.
Frequent premature atrial contractions as a signalling marker of atrial cardiomyopathy, incident atrial fibrillation, and stroke
Authors: José Maria Farinha, Dhiraj Gupta, Gregory Y H Lip
Journal: Cardiovascular Research (2022)

Premature atrial contractions are a common cardiac phenomenon. Although previously considered a benign electrocardiographic finding, they have now been associated with a higher risk of incident atrial fibrillation (AF) and other adverse outcomes such as stroke and all-cause mortality. Since premature atrial contractions can be associated with these adverse clinical outcomes independently of AF occurrence, different explanations have being proposed. The concept of atrial cardiomyopathy, where AF would be an epiphenomenon outside the causal pathway between premature atrial contractions and stroke has received traction recently. This concept suggests that structural, functional, and biochemical changes in the atria lead to arrhythmia occurrence and thromboembolic events. Some consensus about diagnosis and treatment of this condition have been published, but this is based on scarce evidence, highlighting the need for a clear definition of excessive premature atrial contractions and for prospective studies regarding antiarrhythmic therapies, anticoagulation or molecular targets in this group of patients.
Evaluating live microbiota biobanking using an <i>ex vivo</i> microbiome assay and metaproteomics
Authors: Xu Zhang, Krystal Walker, Janice Mayne, Leyuan Li, Zhibin Ning, Alain Stintzi, Daniel Figeys
Journal: Gut Microbes (2022)

Biobanking of live microbiota is becoming indispensable for mechanistic and clinical investigations of drug-microbiome interactions and fecal microbiota transplantation. However, there is a lack of methods to rapidly and systematically evaluate whether the biobanked microbiota maintains their cultivability and functional activity. In this study, we use a rapid ex vivo microbiome assay and metaproteomics to evaluate the cultivability and the functional responses of biobanked microbiota to treatment with a prebiotic (fructo-oligosaccharide, FOS). Our results indicate that the microbiota cultivability and their functional responses to FOS treatment were well maintained by freezing in a deoxygenated glycerol buffer at -80°C for 12 months. We also demonstrate that the fecal microbiota is functionally stable for 48 hours on ice in a deoxygenated glycerol buffer, allowing off-site fecal sample collection and shipping to laboratory for live microbiota biobanking. This study provides a method for rapid evaluation of the cultivability of biobanked live microbiota. Our results show minimal detrimental influences of long-term freezing in deoxygenated glycerol buffer on the cultivability of fecal microbiota.
If these myocytes could talk, they would speak the language of metabolites
Authors: Logan R.J. Bailey, Jennifer Davis
Journal: Journal of Clinical Investigation (2022)

Cardiac wound healing following ischemic injury requires a well-described spatiotemporal progression of events involving multiple cell types and cell-cell interactions. While cellular crosstalk among immune cell, endothelial cell, and fibroblast populations is known to regulate these progressive phases, the role of cardiac myocytes in controlling the wound-healing program is unclear. In this issue of the JCI, Li et al. describe a mechanism of cellular crosstalk between cardiac myocytes and fibroblasts that disrupts nonmyocyte cell function and worsens wound healing outcomes following myocardial infarction (MI). This tour de force study used an arsenal of multidisciplinary approaches to identify a central role for the ectonucleotidase ENPP1 in this process. These findings have clear therapeutic implications, as the authors identified a small molecular inhibitor of ENPP1 that improved post-MI outcomes in mice. These exciting data provide impactful mechanistic information that advance the field’s understanding of cardiac repair and remodeling.
18F-FDG PET/CT Demonstrating Crossed Cerebellar Diaschisis Due to Germ Cell Tumor of the Basal Ganglia
Authors: Francesco Dondi, Mattia Bertoli, Giulia Volpi, Francesco Bertagna, Raffaele Giubbini
Journal: Clinical Nuclear Medicine (2022)

Abstract Germ cell tumors of the basal ganglia are rare neoplasms that usually present with hemiparesis or other neurological symptoms. MR and PET/CT with different tracers have demonstrated their usefulness for the correct assessment of disease. Crossed cerebellar diaschisis refers to a depression in metabolism of a cerebellar hemisphere as a result of contralateral supratentorial lesions. We present a case in which MR and PET/CT were crucial for the assessment of left basal ganglia germ cell tumors with the presence of crossed cerebellar diaschisis.
High-fidelity imaging of amyloid-beta deposits with an ultrasensitive fluorescent probe facilitates the early diagnosis and treatment of Alzheimer's Disease
Authors: Rongrong Tao, Ning Wang, Tianruo Shen, Yuhang Tan, Yong Ren, Wenjing Wei, Meihua Liao, Davin Tan, Chunzhi Tang, Nenggui Xu, Huan Wang, Xiaogang Liu, Xin Li
Journal: Theranostics (2022)

Background: Imaging amyloid-beta (Aβ) deposits with high fidelity in naturally aging brains is crucial for the early diagnosis of Alzheimer's disease (AD).However, this is impeded by the lack of highly sensitive probes.Methods: By conducting computational modelling to quantitatively fine-tune the twisted intramolecular charge transfer (TICT) tendency of Thioflavin T (ThT) analogues, we developed an ultrasensitive probe AH-2.AH-2 retained the binding affinity and binding mode of ThT towards Aβ deposits, and exhibited ca 10-fold less background fluorescence and 5-10 folds of improved signal-to-background contrast upon binding Aβ deposits.These desirable features endowed AH-2 the sensitivity to detect Aβ deposition in naturally aging wild-type mice.Results: AH-2 imaging revealed that Aβ puncta signals appeared near the nuclei in young mice and spread through the intracellular and extracellular compartments in older mice.Moreover, Aβ deposits were observed to emerge earlier in mice cerebral cortex than in the hippocampus region.Given this desirable sensitivity and good spatiotemporal resolution, AH-2 was successfully applied in the preclinical evaluation of Aβ-targeted treatment by melatonin.Conclusions: We expect that AH-2 is promising for early diagnosis of AD and will serve as a sensitive tool for studying Aβ-related AD pathology.
Comparative Effectiveness of an Automated Text Messaging Service for Monitoring COVID-19 at Home
Authors: M. Kit Delgado, Anna U. Morgan, David A. Asch, Ruiying Xiong, Austin S. Kilaru, Kathleen C. Lee, David Do, Ari B. Friedman, Zachary F. Meisel, Christopher K. Snider, Doreen Lam, Andrew Parambath, Christian Wood, Chidinma M. Wilson, Michael Perez, Deena L. Chisholm, Sheila Kelly, Christina J. O’Malley, Nancy Mannion, Ann Marie Huffenberger, Susan McGinley, Mohan Balachandran, Neda Khan, Nandita Mitra, Krisda H. Chaiyachati
Journal: Annals of Internal Medicine (2021)

Although most patients with SARS-CoV-2 infection can be safely managed at home, the need for hospitalization can arise suddenly.
Decade-Long Remissions of Leukemia Sustained By the Persistence of Activated CD4+ CAR T-Cells
Authors: J. Joseph Melenhorst, Gregory M Chen, Meng Wang, David L. Porter, Peng Gao, Shovik Bandyopadhyay, Iulian Pruteanu-Malinici, Christopher L Nobles, Sayantan Maji, Noelle V Frey, Saar Gill, Lifeng Tian, Irina Kulikovskaya, Megan M Davis, Joseph A Fraietta, Jennifer L Brogdon, Regina Young, David E Ambrose, Anne Chew, Bruce L Levine, Don L. Siegel, Cécile Alanio, E. John Wherry, Frederic D. Bushman, Simon F Lacey, Kai Tan, Carl H June
Journal: Blood (2021)
Fresh Tissue Multi-omics Profiling Reveals Immune Classification and Suggests Immunotherapy Candidates for Conventional Chondrosarcoma
Authors: Binghao Li, Guoqi Li, Xiaobo Yan, Dan Zhu, Patrick P. Lin, Zenan Wang, Hao Qu, Xuexin He, Yanbiao Fu, Xiuliang Zhu, Peng Lin, Jiangnan Zhang, Xiaoya Li, Hui Dai, Huabiao Chen, Mark C. Poznansky, Nong Lin, Zhaoming Ye
Journal: Clinical Cancer Research (2021)

There is still no standard nonsurgical regimen for conventional chondrosarcoma (CHS). We aimed to identify whether any CHSs have a favored microenvironment for immunotherapy via multidimensional evaluation of the immunologic characteristics of this tumor.We obtained 98 newly-diagnosed CHS fresh tumors from several institutions and performed comprehensive analysis of data from CyTOF, whole-exome sequencing, and flow cytometry in 22 cases. Clinical data from immunotherapy responders and nonresponders were compared to explore possible biomarkers of immunotherapy response. Mechanism studies were conducted to interpret the biomarker phenotype.Based on the integrated data of single-cell CyTOF and flow cytometry, the CHS immune-microenvironment phenotypes were classified into three groups: subtype I, the "granulocytic-myeloid-derived suppressor cell (G-MDSC) dominant" cluster, with high number of HLA-DR- CD14- myeloid cells; subtype II, the "immune exhausted" cluster, with high exhausted T-cell and dendritic-cell infiltration; and subtype III, the "immune desert" cluster, with few immune cells. Immune cell-rich subtypes (subtype I and II) were characterized by IDH mutation, pathologic high grade, and peritumoral edema, while subtype I cases were exclusively featured by myxoid transformation. In clinical practice involving 12 individuals who received PD-1 antibody immunotherapy, all of the 3 cases with controlled diseases were retrospectively classified as subtype II. In mechanism, IDH mutation significantly elevated chemokine levels and immune-cell infiltration in immune-inactivated tumors.This study is the first to provide immune characterization of CHS, representing a major step to precise immunotherapy against this malignancy. Immunotherapy is promising for the "immune exhausted" subtype of patients with CHS.
Pretreatment Lymphocyte Count Predicts Benefit From Concurrent Chemotherapy With Radiotherapy in Oropharyngeal Cancer
Authors: James M. Price, Hitesh B. Mistry, Guy Betts, Eleanor J. Cheadle, Lynne Dixon, Kate Garcez, Tim Illidge, Zsuzsanna Iyizoba-Ebozue, Lip Wai Lee, Andrew McPartlin, Robin J.D. Prestwich, Savvas Papageorgiou, Dylan J. Pritchard, Andrew Sykes, Catharine M. West, David J. Thomson
Journal: Journal of Clinical Oncology (2022)

There is a need to refine the selection of patients with oropharyngeal squamous cell carcinoma (OPSCC) for treatment de-escalation. We investigated whether pretreatment absolute lymphocyte count (ALC) predicted overall survival (OS) benefit from the addition of concurrent chemotherapy to radical radiotherapy.
Population health outcomes in Nigeria compared with other west African countries, 1998–2019: a systematic analysis for the Global Burden of Disease Study
Authors: Blake Angell, Olutobi Sanuade, Ifedayo M O Adetifa, Iruka N Okeke, Aishatu Lawal Adamu, Muktar H Aliyu, Emmanuel A Ameh, Fatima Kyari, Muktar A Gadanya, Diana A Mabayoje, Adesola Yinka-Ogunleye, Tolu Oni, Rabiu Ibrahim Jalo, Fatimah I Tsiga-Ahmed, Sarah L Dalglish, Seye Abimbola, Tim Colbourn, Obinna Onwujekwe, Eme Theodora Owoaje, Gambo Aliyu, Sani H Aliyu, Belinda Archibong, Alex Ezeh, Chikwe Ihekweazu, Zubairu Iliyasu, Stephen Obaro, Ebenezer Babatunde Obadare, Friday Okonofua, Muhammed Pate, Babatunde L Salako, Fatima H Zanna, Scott Glenn, Ally Walker, Maha Ezalarab, Mohsen Naghavi, Ibrahim Abubakar
Journal: The Lancet (2022)

Population-level health and mortality data are crucial for evidence-informed policy but scarce in Nigeria. To fill this gap, we undertook a comprehensive assessment of the burden of disease in Nigeria and compared outcomes to other west African countries.