tbuckley/cabot-search huggingface dataset:
Abstract PO-002: Pan-cancer integrative histology-genomic analysis via interpretable multimodal deep learning
Authors: Richard J. Chen, Ming Y. Lu, Maha Shady, Jana Lipkova, Tiffany Chen, Drew Fabrizio Williamson, Bumjin Joo, Faisal Mahmood
Journal: Clinical Cancer Research (2021)

Abstract Cancer prognostication and therapeutic response prediction is driven by prognostic markers in both histopathology slides and molecular profiles. The rapidly emerging field of deep learning-based computational pathology has demonstrated promise in developing objective prognostic models from histology whole slide images. Several studies have focused on predicting genomic and transcriptomic alterations from histology images. However, most prognostic models are either based on histology or genomics alone and do not address how histology and genomics can be integrated to develop joint image-omic assays and prognostic models. To overcome these challanges, we present a pan-cancer integrative platform for biomarker discovery in both histology slides and molecular profile data (http://pancancer.ai). We used corresponding gigapixel whole-slide images, RNA-Seq abundance, copy number variation, and mutation data from 5,720 patients across 14 cancer types to train a weakly supervised, interpretable, multimodal deep learning algorithm that is able to not only fuse these heterogenous modalities for survival analysis, but also discover prognostic features from these modalities that corroborate with poor and favorable survival outcomes using multimodal interpretability. In a 5-fold cross validation, we compared our model with unimodal deep learning models trained on histology slides and molecular profiles alone, and demonstrate performance increase in risk stratification on 9 out of 14 cancers, as well as shifts in feature importance when conditioned on more than one modality. To validate our setup as a platform for driving biomarker discovery, we analyzed both morphological and molecular features that were identified by high attribution regions in every patient, and discovered statistically significant associations between high tumor-infilitrating lymphocyte (TIL) presence in H&amp;E tissue and favorable survival outcomes made by our model. This indicates that our weakly supervised prognostic models are able to separate immune hot and immune cold patients while no pixel level annotations were used during training. Citation Format: Richard J. Chen, Ming Y. Lu, Maha Shady, Jana Lipkova, Tiffany Chen, Drew Fabrizio Williamson, Bumjin Joo, Faisal Mahmood. Pan-cancer integrative histology-genomic analysis via interpretable multimodal deep learning [abstract]. In: Proceedings of the AACR Virtual Special Conference on Artificial Intelligence, Diagnosis, and Imaging; 2021 Jan 13-14. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(5_Suppl):Abstract nr PO-002.
Abstract 17195: Differences in Cost of Care by Palliation Strategy for Infants With Ductal-Dependent Pulmonary Blood Flow: Results From a Multicenter Study of Patent Ductus Arteriosus Stent and Modified Blalock-Taussig Shunt
Authors: Bryan H Goldstein, Christopher J Petit, Athar M Qureshi, Dingwei Dai, Heather M Griffis, Michael S Kelleman, Courtney E McCracken, Michael L O'Byrne, Christopher E Mascio, Subi Shashidharan, R. Allen Ligon, Wendy Whiteside, W. Jack Wallen, Hitesh Agrawal, Varun Aggarwal, Andrew C Glatz
Journal: Circulation (2017)

Introduction: In infants with ductal-dependent pulmonary blood flow (PBF), initial palliation with patent ductus arteriosus stent (DAS) or modified Blalock-Taussig shunt (BTS) have comparable morta...
The Abiraterone Dosing Chess Match With Johnson &amp; Johnson—Back in Check
Authors: Russell Z. Szmulewitz, Walter M. Stadler, Mark J. Ratain
Journal: JAMA Oncology (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Military medical research on internal diseases in modern warfare: new concepts, demands, challenges, and opportunities
Authors: Guang-Dong Liu, Nan Wang, Hai-Ming Wang, Xin Li, Jun-Jie Shao, Zi-Fan Liu, Min Jiang, Lin Wang, Zi-Kai Wang, Meng Li, Xue-Ying Cao, Jiang Wang, Ran Zhang, Yun-Dai Chen
Journal: Military Medical Research (2021)

Battlefield internal medicine aims at the treatment of combatants and noncombatants with various internal diseases on the battlefield. The military medical research on battlefield internal diseases focuses on the pathogenesis, clinical management, and prevention of internal diseases under military war conditions. In both wartime and peacetime, the soldiers suffer from more internal diseases than surgical wounds. With the introduction of high-tech weapons, including chemical, physical, and biological agents, a large number of special internal illnesses and casualties will appear in future wars. The battles often occur in special environments, such as high or low temperatures, plateau or polar areas, and micro- or hyper-gravity. The current theories of battlefield internal medicine are mainly derived from wars decades ago and cannot meet the needs of military medical support under the conditions of modern warfare. Therefore, the military medical research on battlefield internal medicine should be based on contemporary military situations, focus on the purpose of treating battlefield internal diseases, and adhere to the actual needs of the troops in peacetime and wartime. We should investigate the pathogenesis of battlefield internal diseases and explore the threats that may arise in future wars to ensure the advancement of battlefield internal medicine. This review highlights new concepts, demands, challenges, and opportunities for the further development of military medical research on battlefield internal medicine.
In coronary artery disease, PCI increases all-cause and cause-specific mortality compared with CABG
Authors: Michael G. Nanna, L. Kristin Newby
Journal: Annals of Internal Medicine (2021)

Source Citation Gaudino M, Hameed I, Farkouh ME, et al. Overall and cause-specific mortality in randomized clinical trials comparing percutaneous interventions with coronary bypass surgery: a meta-analysis. JAMA Intern Med. 2020;180:1638-46. 33044497
The phytochemical hyperforin triggers thermogenesis in adipose tissue via a Dlat-AMPK signaling axis to curb obesity
Authors: Suzhen Chen, Xiaoxiao Liu, Chao Peng, Chang Tan, Honglin Sun, He Liu, Yao Zhang, Ping Wu, Can Cui, Chuchu Liu, Di Yang, Zhiqiang Li, Junxi Lu, Jian Guan, Xisong Ke, Renxiao Wang, Xiaohai Bo, Xiaojun Xu, Junfeng Han, Junli Liu
Journal: Cell Metabolism (2021)

Stimulation of adipose tissue thermogenesis is regarded as a promising avenue in the treatment of obesity. However, pharmacologic engagement of this process has proven difficult. Using the Connectivity Map (CMap) approach, we identified the phytochemical hyperforin (HPF) as an anti-obesity agent. We found that HPF efficiently promoted thermogenesis by stimulating AMPK and PGC-1α via a Ucp1-dependent pathway. Using LiP-SMap (limited proteolysis-mass spectrometry) combined with a microscale thermophoresis assay and molecular docking analysis, we confirmed dihydrolipoamide S-acetyltransferase (Dlat) as a direct molecular target of HPF. Ablation of Dlat significantly attenuated HPF-mediated adipose tissue browning both in vitro and in vivo. Furthermore, genome-wide association study analysis indicated that a variation in DLAT is significantly associated with obesity in humans. These findings suggest that HPF is a promising lead compound in the pursuit of a pharmacological approach to promote energy expenditure in the treatment of obesity.
Patterns of care and treatment outcomes in locoregional squamous cell carcinoma of the prostate.
Authors: Christopher Weil, Ryan Hutten, Jonathan David Tward, Shane Lloyd, Skyler B Johnson
Journal: Journal of Clinical Oncology (2021)

260 Background: Primary pure prostate squamous cell carcinoma (PSCC) is a rare, aggressive disease accounting for less than 0.5-1% of prostate cancer diagnoses. PSCC is a distinct entity from adenocarcinoma with historically poor outcomes, often presenting in younger patients with lower urinary tract symptoms and normal PSA. There are currently no established treatment guidelines. Case reports are limited but describe multiple treatment approaches including various combinations of surgery, platinum and non-platinum-based chemotherapy, radiotherapy and androgen deprivation therapy, with selected reports showing longer survival times with a combined modality approach. Methods: Seeking to identify practice patterns and treatment outcomes, we performed a retrospective analysis of the United States National Cancer Database to identify 66 males with locoregional, nonmetastatic primary pure squamous cell carcinoma of the prostate and treated with surgery, chemotherapy, and/or radiotherapy between 2004 and 2015. Clinical factors in analysis included pretreatment PSA, clinical T-stage, histology, treatment modality and demographic factors including age, comorbidity index, race, insurance status and treatment facility type. Patients were stratified into treatment groups consisting of local therapy alone (n = 40, 60%), local therapy and chemotherapy (n = 13, 20%), chemotherapy alone (n = 7, 11%), and observation (n = 6, 9%). Survival analysis was estimated using the Kaplan-Meier method and analyzed with log-rank testing. A Cox proportional hazards model was used to evaluate the association between patient characteristics and survival. Univariable and multivariable logistic regression was performed to identify covariates associated with receipt of each treatment modality. Results: With an overall median follow-up of 21.9 months, median survival was 19.7 months for patients treated with local therapy alone, 10.9 months with chemotherapy alone, and 36.5 months with combined local therapy and chemotherapy. Overall survival was not statistically significant between treatment groups. Statistically significant predictors of death included age (HR 1.1, 95% CI [1.03-1.17]) and clinical stage ≥T3a (HR 4.05, 95% CI [1.35-12.2]). Statistically significant predictors of receipt of chemotherapy were clinical stage T3a or greater (OR 34.6, 95% CI [2.65-364]) and age (OR 0.91, 95% CI [0.82-99]). Conclusions: This analysis represents the largest reported cohort analysis of locoregional pure PSCC. Unfortunately, due to the rarity of this disease, prospective or randomized trials to determine the optimal treatment strategy are not feasible. Despite limitations in sample size, and in the absence of prospective data, this analysis suggests the addition of chemotherapy to local therapy is a reasonable treatment approach in appropriately selected patients and may result in improved survival.
Prognostic significance of human papilloma virus (HPV) in penile cancer: A National Cancer Database (NCDB) study.
Authors: Adithya Chennamadhavuni, Josiah An, Sarah L. Mott, Rohan Garje
Journal: Journal of Clinical Oncology (2021)

5 Background: HPV is associated with 30 - 50% of penile cancers, with some studies showing improved outcomes in these patients. This study evaluated the effect of HPV infection on penile cancer outcomes. Methods: The national cancer database (NCDB) was utilized to identify HPV tested penile cancer patients at the time of diagnosis from 2004 – 2016. Chi-squared tests and Cox regression models were used in analysis. Results: Out of 486 patients with penile squamous cell cancer, 139 (29%) were HPV +ve, and 347 (71%) were HPV -ve. Greater than 50% of HPV +ve were &lt; 65 years old, Caucasian, from low-income areas ( &lt; $48,000), and had public or no insurance. Similar incidence patterns were noted in HPV- ve patients. 77% pts who were HPV +ve had a moderate to poorly differentiated tumor. Most HPV +ve presented with early-stage cancer, and 12% were stage IV at diagnosis. 5-year overall survival (OS) was better among HPV +ve 62% vs. 50% in HPV -ve patients. Multivariable analysis (MVA) shows superior survival among patients with age &lt; 65 years, low comorbidity score (0-1), and earlier stage at diagnosis. Patients with HPV +ve adjusted for age, comorbidities, stage, and treatment showed significantly improved survival. HPV -ve patients had 1.49 times increased risk of death compared to HPV +ve. Conclusions: HPV positive penile cancer is associated with significantly improved survival independent of age, comorbidities, stage, and treatment modality. This study reiterates the prognostic significance of HPV status and testing for HPV status at diagnosis should be a standard practice. [Table: see text]
TSUNAMI: Translational Bioinformatics Tool Suite for Network Analysis and Mining
Authors: Zhi Huang, Zhi Han, Tongxin Wang, Wei Shao, Shunian Xiang, Paul Salama, Maher Rizkalla, Kun Huang, Jie Zhang
Journal: Genomics Proteomics & Bioinformatics (2021)

Abstract Gene co-expression network (GCN) mining identifies gene modules with highly correlated expression profiles across samples/conditions. It enables researchers to discover latent gene/molecule interactions, identify novel gene functions, and extract molecular features from certain disease/condition groups, thus helping to identify disease biomarkers. However, there lacks an easy-to-use tool package for users to mine GCN modules that are relatively small in size with tightly connected genes that can be convenient for downstream gene set enrichment analysis, as well as modules that may share common members. To address this need, we developed an online GCN mining tool package: TSUNAMI (Tools SUite for Network Analysis and MIning). TSUNAMI incorporates our state-of-the-art lmQCM algorithm to mine GCN modules for both public and user-input data (microarray, RNA-seq, or any other numerical omics data), and then performs downstream gene set enrichment analysis for the identified modules. It has several features and advantages: 1) a user-friendly interface and real-time co-expression network mining through a web server; 2) direct access and search of NCBI Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases, as well as user-input gene expression matrices for GCN module mining; 3) multiple co-expression analysis tools to choose from, all of which are highly flexible in regards to parameter selection options; 4) identified GCN modules are summarized to eigengenes, which are convenient for users to check their correlation with other clinical traits; 5) integrated downstream Enrichr enrichment analysis and links to other gene set enrichment tools; and 6) visualization of gene loci by Circos plot in any step of the process. The web service is freely accessible through URL: https://biolearns.medicine.iu.edu/. Source code is available at https://github.com/huangzhii/TSUNAMI/.
Short-Course Antimicrobial Therapy for Pediatric Community-Acquired Pneumonia
Authors: Jeffrey M. Pernica, Stuart Harman, April J. Kam, Redjana Carciumaru, Thuva Vanniyasingam, Tyrus Crawford, Dale Dalgleish, Sarah Khan, Robert S. Slinger, Martha Fulford, Cheryl Main, Marek Smieja, Lehana Thabane, Mark Loeb
Journal: JAMA Pediatrics (2021)

Community-acquired pneumonia (CAP) is a common occurrence in childhood; consequently, evidence-based recommendations for its treatment are required.To determine whether 5 days of high-dose amoxicillin for CAP was associated with noninferior rates of clinical cure compared with 10 days of high-dose amoxicillin.The SAFER (Short-Course Antimicrobial Therapy for Pediatric Respiratory Infections) study was a 2-center, parallel-group, noninferiority randomized clinical trial consisting of a single-center pilot study from December 1, 2012, to March 31, 2014, and the follow-up main study from August 1, 2016, to December 31, 2019 at the emergency departments of McMaster Children's Hospital and the Children's Hospital of Eastern Ontario. Research staff, participants, and outcome assessors were blinded to treatment allocation. Eligible children were aged 6 months to 10 years and had fever within 48 hours, respiratory symptoms, chest radiography findings consistent with pneumonia as per the emergency department physician, and a primary diagnosis of pneumonia. Children were excluded if they required hospitalization, had comorbidities that would predispose them to severe disease and/or pneumonia of unusual origin, or had previous β-lactam antibiotic therapy. Data were analyzed from March 1 to July 8, 2020.Five days of high-dose amoxicillin therapy followed by 5 days of placebo (intervention group) vs 5 days of high-dose amoxicillin followed by a different formulation of 5 days of high-dose amoxicillin (control group).Clinical cure at 14 to 21 days.Among the 281 participants, the median age was 2.6 (interquartile range, 1.6-4.9) years (160 boys [57.7%] of 279 with sex listed). Clinical cure was observed in 101 of 114 children (88.6%) in the intervention group and in 99 of 109 (90.8%) in the control group in per-protocol analysis (risk difference, -0.016; 97.5% confidence limit, -0.087). Clinical cure at 14 to 21 days was observed in 108 of 126 (85.7%) in the intervention group and in 106 of 126 (84.1%) in the control group in the intention-to-treat analysis (risk difference, 0.023; 97.5% confidence limit, -0.061).Short-course antibiotic therapy appeared to be comparable to standard care for the treatment of previously healthy children with CAP not requiring hospitalization. Clinical practice guidelines should consider recommending 5 days of amoxicillin for pediatric pneumonia management in accordance with antimicrobial stewardship principles.ClinicalTrials.gov Identifier: NCT02380352.
Impact of treatment sequence on survival outcome in patients with a second treatment line for metastatic castration-resistant prostate cancer: A new user design in the French nationwide claims database.
Authors: Marine Gross-Goupil, Nicolas H. Thurin, Magali Rouyer, Thibaud Haaser, Xavier Rebillard, Michel Soulie, Gérard de Pouvourville, Fatiha Messaoudi, Camille Capone, Emmanuelle Bignon, Jérémy Jové, Stéphanie Lamarque, Cécile Droz-Perroteau, Nicholas Moore, Patrick Blin
Journal: Journal of Clinical Oncology (2021)

91 Background: Abiraterone acetate in association with prednisone/prednisolone and docetaxel can both be used as first or second line treatments for metastatic castration-resistant prostate cancer (mCRPC). As a result, one may wonder if it is better to start with an abiraterone acetate first line followed by a docetaxel second line (ABI–DOCE sequence) or to use the inverse sequence DOCE-ABI. Methods: A new user cohort study design with a 3-year follow-up: patients initiating a first-line treatment for mCRPC in 2014 followed by a second treatment line were identified from the French nationwide claims database (SNDS), which covers about 86% of the population at the time of the study. Patients with sequence ABI–DOCE and those with DOCE-ABI were 1:1 matched on prostate cancer stage before mCRPC status, duration from prostate cancer diagnosis, and a high-dimensional propensity score. The 36-month overall survival and the 36-month survival time until treatment switch or death (proxy of progression-free survival) were compared using Cox proportional hazards risk model. Results: Out of the 3 949 mCRPC patients that initiated a first-line treatment in 2014, 1 162 died during this first line, and 2 283 had a second-line treatment. Among them, 693 received the sequence ABI–DOCE and 354 DOCE–ABI. A total of 159 patients per group were 1:1 matched. The median duration of the first treatment line was 8.4 months in the ABI–DOCE sequence and 6.6 months in the DOCE–ABI sequence. The median duration of the second line was 6.3 months and 6.5 months in the ABI–DOCE and DOCE–ABI sequences, respectively. Results are presented in the table below. Median survivals were similar in both groups with no significant differences observed in the 36-month survival probabilities. Around 60% of the patients received a third-line treatment in both groups. Conclusions: In real life settings, treatment sequences (ABI–DOCE versus DOCE–ABI) seem to have no differential impact on survival outcome in mCRPC patients sharing same characteristics. [Table: see text]
Human rights in domestic responses to the COVID-19 pandemic: preliminary findings from a media-coverage database to track human rights violations
Authors: Hanna E Huffstetler, Caitlin R Williams, Benjamin M Meier
Journal: The Lancet Global Health (2021)

BackgroundAs COVID-19 has spread throughout the world, domestic public health responses have neglected human rights. Human rights are crucial to public health promotion, yet there are significant gaps in how human rights are being monitored during the pandemic response. Existing efforts to track potential human rights violations in domestic responses to COVID-19 are neither comparative nor comprehensive. To fill this gap, we developed a novel, comparative database to systematically track media coverage of potential human rights violations. Using these data, we examine how public health policies impacted human rights realisation across countries during the first 3 months of the pandemic.MethodsWe used a systematic qualitative coding methodology to examine the extent and range of media coverage at the intersection of COVID-19, public health, and human rights. Using a structured key-term search strategy, we searched the NexisUni news database for English-language media reports. Results were screened based on pre-determined eligibility criteria, such as whether the report discussed a public health action (or inaction) in response to COVID-19 and described the human rights implications of that action (or inaction). Reports were coded by geographic location, type of public health response, human rights implications, and populations impacted. To guide the coding process, we developed a codebook based on WHO frameworks in public health and UN frameworks in human rights.FindingsIn the first 3 months of the pandemic, media coverage of domestic public health responses to COVID-19 increased rapidly as the crisis escalated. This coverage included a wide range of public health actions that impacted human rights across six geographic regions. We identified 17 public health actions that impact 24 distinct human rights, and noted that domestic public health responses were reported to have consequences for the range of civil, political, economic, and social rights that underlie public health. For example, domestic actions to implement lockdown measures were reported to have implications for the human rights to life, liberty and security of person, health, work, and education. These effects were reported to have been experienced differently across national contexts and disproportionately impacted the human rights of particular groups, including women and minority populations.InterpretationPublic health and human rights are inextricably linked in the COVID-19 pandemic. Ongoing data collection and comparative analysis can inform domestic best practices and future pandemic preparedness efforts. Our comparative database provides a foundation for future research that examines the public health impacts of human rights violations in the pandemic response.FundingNone.