tbuckley/cabot-search huggingface dataset:
Identifying COVID-19 Risk Through Observational Studies to Inform Control Measures
Authors: Mark W. Tenforde, Kiva A. Fisher, Manish M. Patel
Journal: JAMA (2021)

A year into the coronavirus disease 2019 (COVID-19) pandemic there remains an urgent need to limit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread and to curb the pandemic in the US through nonpharmaceutical interventions.Clear evidence supports the effectiveness of simple strategies in identifying risks and mitigating the spread of infection, with much of this evidence coming from observational studies.Community risk factors for infection can be identified by comparing recent behaviors and exposures among people who have been infected with those who are not infected using a traditional case-control approach.High-risk environments identified from these investigations need to be clearly communicated to the public to support public health measures and motivate individual behavior change to reduce the risk of infection.
Timing of Dialysis Initiation and End-Stage Kidney Disease Incidence—Reply
Authors: Chi-yuan Hsu, Alan S. Go
Journal: JAMA Internal Medicine (2021)

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Use of SNP chips to detect rare pathogenic variants: retrospective, population based diagnostic evaluation
Authors: Weedon MN, Jackson L, Harrison JW, Ruth KS, Tyrrell J, Hattersley AT, Wright CF
Journal: BMJ (2021)

To determine whether the sensitivity and specificity of SNP chips are adequate for detecting rare pathogenic variants in a clinically unselected population.Retrospective, population based diagnostic evaluation.49 908 people recruited to the UK Biobank with SNP chip and next generation sequencing data, and an additional 21 people who purchased consumer genetic tests and shared their data online via the Personal Genome Project.Genotyping (that is, identification of the correct DNA base at a specific genomic location) using SNP chips versus sequencing, with results split by frequency of that genotype in the population. Rare pathogenic variants in the BRCA1 and BRCA2 genes were selected as an exemplar for detailed analysis of clinically actionable variants in the UK Biobank, and BRCA related cancers (breast, ovarian, prostate, and pancreatic) were assessed in participants through use of cancer registry data.Overall, genotyping using SNP chips performed well compared with sequencing; sensitivity, specificity, positive predictive value, and negative predictive value were all above 99% for 108 574 common variants directly genotyped on the SNP chips and sequenced in the UK Biobank. However, the likelihood of a true positive result decreased dramatically with decreasing variant frequency; for variants that are very rare in the population, with a frequency below 0.001% in UK Biobank, the positive predictive value was very low and only 16% of 4757 heterozygous genotypes from the SNP chips were confirmed with sequencing data. Results were similar for SNP chip data from the Personal Genome Project, and 20/21 individuals analysed had at least one false positive rare pathogenic variant that had been incorrectly genotyped. For pathogenic variants in the BRCA1 and BRCA2 genes, which are individually very rare, the overall performance metrics for the SNP chips versus sequencing in the UK Biobank were: sensitivity 34.6%, specificity 98.3%, positive predictive value 4.2%, and negative predictive value 99.9%. Rates of BRCA related cancers in UK Biobank participants with a positive SNP chip result were similar to those for age matched controls (odds ratio 1.31, 95% confidence interval 0.99 to 1.71) because the vast majority of variants were false positives, whereas sequence positive participants had a significantly increased risk (odds ratio 4.05, 2.72 to 6.03).SNP chips are extremely unreliable for genotyping very rare pathogenic variants and should not be used to guide health decisions without validation.
Abstracts of the 27th Annual Conference of the International Society for Environmental Epidemiology (ISEE), 30 August–3 September 2015, Centro de Convenções Rebouças, São Paulo, Brazil
Authors: Ariane Guilbert, Koen Simons, Ann Packeu, Koen De Cremer, Lucie Hoebeke, Marijke Hendrickx, An Van Nieuwenhuyse
Journal: Environmental Health Perspectives (2015)

The 27th annual conference of the International Society for Environmental Epidemiology was held 30 August-3 September 2015 in São Paulo, Brazil. The conference theme was "Addressing Environmental Health Inequalities." Sessions highlighted social determinants of health and how they can generate environmental health inequalities.
Abnormal dopamine receptor signaling allows selective therapeutic targeting of neoplastic progenitors in AML patients
Authors: Lili Aslostovar, Allison L. Boyd, Yannick D. Benoit, Justin Di Lu, Juan Luis Garcia Rodriguez, Mio Nakanishi, Deanna P. Porras, Jennifer C. Reid, Ryan R. Mitchell, Brian Leber, Anargyros Xenocostas, Ronan Foley, Mickie Bhatia
Journal: Cell Reports Medicine (2021)

The aberrant expression of dopamine receptors (DRDs) in acute myeloid leukemia (AML) cells has encouraged the repurposing of DRD antagonists such as thioridazine (TDZ) as anti-leukemic agents. Here, we access patient cells from a Phase I dose escalation trial to resolve the cellular and molecular bases of response to TDZ, and we extend these findings to an additional independent cohort of AML patient samples tested preclinically. We reveal that in DRD2+ AML patients, DRD signaling in leukemic progenitors provides leukemia-exclusive networks of sensitivity that spare healthy hematopoiesis. AML progenitor cell suppression can be increased by the isolation of the positive enantiomer from the racemic TDZ mixture (TDZ+), and this is accompanied by reduced cardiac liability. Our study indicates that the development of DRD-directed therapies provides a targeting strategy for a subset of AML patients and potentially other cancers that acquire DRD expression upon transformation from healthy tissue.
Clonal trajectories and cellular dynamics of myeloid neoplasms with SF3B1 mutations
Authors: Hassan Awada, Cassandra M. Kerr, Arda Durmaz, Vera Adema, Carmelo Gurnari, Simona Pagliuca, Misam Zawit, Sunisa Kongkiatkamon, Heesun J. Rogers, Yogen Saunthararajah, Mikkael A. Sekeres, Hetty Carraway, Jaroslaw P. Maciejewski, Valeria Visconte
Journal: Leukemia (2021)
Abstract PS1-50: Locoregional therapy in de novo metastatic breast cancer: Systemic review and meta-analysis
Authors: Daniel Jack Reinhorn, Raz Mutai, Rinat Yerushalmi, Assaf Moore, Eitan Amir, Hadar Goldvaser
Journal: Cancer Research (2021)

Abstract Background: De novo metastatic breast cancer represents around 6% of breast cancer diagnoses. Retrospective data suggest that locoregional therapy (LRT) for the primary breast cancer in metastatic disease may improve outcomes. Randomized control trials (RCTs) have evaluated the role of LRT in this setting with inconsistent results. Methods: We searched PubMed to identify RCTs that compared LRT and standard systemic therapy to standard therapy alone in de novo metastatic breast cancer. The search was supplemented by a review of abstracts from key conferences. Hazard ratios (HRs) and their associated 95% confidence intervals (CIs) were computed and pooled in a meta-analysis using generic inverse variance. Overall survival (OS) data were extracted for the intention to treat (ITT) population and for pre-specified subgroups defined by tumor subtype and by site of metastases. Subgroup analysis evaluated the effect of systemic treatment prior randomization to LRT. Results: Analyses included 4 trials comprising 970 patients. LRT included standard surgery to the primary breast tumor in all studies, and adjuvant radiation per standard of care was mandatory in 3 studies. Systemic treatment prior randomization showed similar results (HR=0.92 and HR=1.06 for upfront LRT and LRT following systemic treatment, respectively, p for the subgroup difference=0.72). LRT was not associated with improved OS in the ITT population (HR 0.97, 95% CI 0.72-1.29, p=0.81). LRT was not associated with improved OS in any tumor subtypes, including hormone receptor positive (HR for OS= 0.96, 95% CI 0.65-1.43, p=0.85), triple negative (HR 1.4, 95% CI 0.50-3.91, p=0.52) and human epidermal growth factor receptor 2 (HER2) positive disease (HR 0.93, 95% CI 0.68-1.28, p=0.67). Additionally, LRT did not improve OS in bone only disease (HR 0.97, 95% CI 0.58-1.62, p=0.92) and in visceral disease (HR=1.02, 95% CI 0.77-1.35, p=0.90). Conclusions: LRT in de novo metastatic breast cancer is not associated with improved OS. Results are consistent among different breast cancer subgroups. Citation Format: Daniel Jack Reinhorn, Raz Mutai, Rinat Yerushalmi, Assaf Moore, Eitan Amir, Hadar Goldvaser. Locoregional therapy in de novo metastatic breast cancer: Systemic review and meta-analysis [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-50.
Tabletized Supramolecular Assemblies for Sublingual Peptide Immunization
Authors: Sean H. Kelly, Emmanuel E. Opolot, Yaoying Wu, Benjamin Cossette, Ajay K. Varadhan, Joel H. Collier
Journal: Advanced Healthcare Materials (2021)

Abstract Widespread vaccination is essential to global health. Significant barriers exist to improving vaccine coverage in lower‐ and middle‐income countries, including the costly requirements for cold‐chain distribution and trained medical personnel to administer the vaccines. A heat‐stable and highly porous tablet vaccine that can be administered sublingually via simple dissolution under the tongue is described. SIMPL tablet vaccines (Supramolecular IMmunization with Peptides subLingually) are produced by freeze‐drying a mixture of self‐assembling peptide‐polymer nanofibers, sugars, and adjuvant. Sublingual immunization with SIMPL tablets raises antibody responses against both a model epitope from ovalbumin and a clinically relevant epitope from Mycobacterium tuberculosis . Further, sublingual antibody responses are not diminished after heating the tablets for 1 week at 45 °C, in contrast to a more conventional carrier vaccine (KLH). This approach directly addresses the need for a heat‐stable and easily deliverable vaccine to improve equity in global vaccine coverage.
Assessment of Outcomes Associated With the Use of Newly Approved Oncology Drugs in Medicare Beneficiaries
Authors: Angela K. Green, Michael Curry, Niti Trivedi, Peter B. Bach, Sham Mailankody
Journal: JAMA Network Open (2021)

A lack of generalizability of pivotal cancer clinical trial data to treatment of older adults with Medicare could affect therapeutic decision-making in clinical practice.To evaluate the differences in survival, duration of therapy, and treatment patterns between clinical trial patients and older adults with Medicare receiving cancer drugs for metastatic solid cancers in usual practice.This retrospective cohort study, performed from May 1, 2018, to August 30, 2020, used the linked Surveillance, Epidemiology, and End Results (SEER) program and Medicare database to examine sequential US Food and Drug Administration (FDA)-approved cancer drug indications (2008-2013) for locally advanced or metastatic solid tumors to assess whether pivotal trials reflect the outcomes of Medicare patients with cancer treated in usual practice.Treatment with FDA-approved cancer drugs for metastatic solid cancers in pivotal clinical trials and in the SEER-Medicare database.Overall survival, duration of treatment, and dose reductions among trial participants and treated Medicare patients.A total of 11 828 trial participants (mean age, 61.8 years; 6718 [56.8%] male; and 7605 [64.3%] White) and 9178 SEER-Medicare patients (mean age, 72.7 years; 4800 [52.3%] male; and 7437 [81.0% White]) were compared. Twenty-nine indications for 22 cancer drugs were included. Median overall survival among Medicare patients was shorter than among patients in the clinical trial intervention arm for 28 of 29 indications (median difference, -6.3 months; range, -28.7 to 2.7 months). Median duration of therapy among Medicare patients was shorter for 23 of the 27 indications with data available (median difference, -1.9 months; range, -12.4 to 1.4 months). For 9 indications, there was information available regarding dose reductions in the package insert or trial publication. In all but 1 instance, dose reductions or single prescriptions were more common in the Medicare population compared with dose reductions among the clinical trial patients; for example, in the Medicare patients, 600 of 1032 (58.1%) received dose reduction or a single prescription and 172 of 1032 (16.7%) received a single prescription vs 734 of 3416 (21.5%) in the trial intervention arm. The exception was afatinib for non-small cell lung cancer: 34 of 71 (47.9%) received dose reduction or a single prescription and 15 of 71 (21.1%) received a single prescription among the Medicare patients vs 120 of 230 (52.2%) receiving dose reductions among the trial intervention group.In this cohort study, patients receiving Medicare who were treated with FDA-approved cancer drugs did not live as long as treated clinical trial participants and commonly received treatment modifications. This study suggests that cancer clinical data relevant to newly approved drugs lack generalizability to Medicare beneficiaries with cancer; therefore, these agents should be used with caution.
Abstract PS16-34: Phenotype and prognosis of patients with breast cancer and pathogenic <i>TP53</i> variants
Authors: Vanessa Petry
Journal: Cancer Research (2021)

Abstract Background: The lifetime risk of cancer in individuals with Li Fraumeni syndrome (LFS) is more than 70% for men and more than 90% for women. Breast cancer (BC) is the most common type of cancer in premenopause women with pathogenic allelic TP53 variants (PVs). However, little is known about the BC response to systemic therapy and the prognosis in these patients. We aim to analyze the phenotype and the outcomes of patients with LFS and BC. Methods: We evaluated a cohort of patients with PVs or likely PVs of TP53 with BC diagnosis treated from December 1999 to June 2020 from a single tertiary cancer center. Our primary objective is to evaluate the outcomes of these patients. Secondary objective is to describe the BC phenotype, characterizing the clinical and the pathological features.Results: Among 56 patients with PVs or likely PVs of TP53, 25 were diagnosed with BC. Median age at BC diagnosis was 39.2 years (range 23.4-57.4 years). The majority (N= 18, 72%) harbored a germline PV TP53 p.R337H in heterozygosity status. The most common histology type was an invasive carcinoma of no special subtype, 73% were hormone receptor-positive, and 32% were HER2-positive. Three (12%) patients were metastatic at diagnosis. Seven (28%) of the patients with localized disease at diagnosis received neoadjuvant chemotherapy, and other 7 (28%) received adjuvant chemotherapy. Among patients treated with neoadjuvant chemotherapy, 5 (71%) had a tumor response, while 2 (29%) presented with disease progression. No pathologic complete response was achieved. After a median follow-up of 52.6 months, no deaths secondary to breast cancer occurred. Only 1 patient died due to another neoplasm (jaw osteosarcoma), and 3 (12%) patients developed radiotherapy-induced malignancies in the irradiated field. Conclusions: BC in patients with LFS is mainly the invasive carcinoma of no special subtype, enriched in hormone receptor and HER2 positivity. Although response to neoadjuvant chemotherapy is high, no pathologic complete response occurred in this cohort. Favorable outcomes were observed, with a high BC specific survival. Secondary malignancies remain a major concern. Larger cohorts should test whether new genes act as modifiers of p53 function and breast cancer susceptibility. Citation Format: Vanessa Petry. Phenotype and prognosis of patients with breast cancer and pathogenic TP53 variants [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS16-34.
Call to action: how can the US Ending the HIV Epidemic initiative succeed?
Authors: Chris Beyrer, Adaora A Adimora, Sally L Hodder, Ernest Hopkins, Greg Millett, Sandra Hsu Hnin Mon, Patrick S Sullivan, Rochelle P Walensky, Anton Pozniak, Mitchell Warren, Bruce Richman, Raniyah Copeland, Kenneth H Mayer
Journal: The Lancet (2021)
SARS-CoV-2 infections in children following the full re-opening of schools and the impact of national lockdown: Prospective, national observational cohort surveillance, July-December 2020, England
Authors: Anna A Mensah, Mary Sinnathamby, Asad Zaidi, Laura Coughlan, Ruth Simmons, Sharif A Ismail, Mary E Ramsay, Vanessa Saliba, Shamez N Ladhani
Journal: Journal of Infection (2021)
Abstract PS11-31: Survival among female breast cancer patients who have survived a previous cancer
Authors: Sandi L Pruitt, Hong Zhu, Daniel Heitjan, David E Gerber, Bhumika Maddineni, Danyi Xiong, Ethan Halm, Caitlin Murphy
Journal: Cancer Research (2021)

Abstract Background A growing number of women newly diagnosed with breast cancer have survived a previous cancer. Although little is known about their prognosis, this population is frequently excluded from clinical trials. Additional evidence about the survival of this population is needed, so that trial sponsors and investigators can create evidence-based trial eligibility criteria. Among women newly diagnosed with breast cancer, we examined the impact of previous cancer on overall and cancer-specific survival. Methods This population-based cohort study included patients age ≥66 years and diagnosed with breast cancer between 2005-2015 in linked SEER-Medicare data. Separately by breast cancer stage, we estimated overall survival using Cox regression and cause-specific survival using competing risk regression for women with and without previous cancer, adjusting for numerous covariates and competing risk of death from previous cancer, other causes, or the incident breast cancer. Results Of 138,576 women diagnosed with incident breast cancer, 10,822 (8%) had a previous cancer of another organ site. Many of these (n=5,014, 46.3%) were diagnosed ≤5 years of breast cancer. For all breast cancer stages except IV in which there was no significant survival difference, women with vs. without previous cancer had worse overall survival. This survival disadvantage was driven by deaths due to the previous cancer and other causes. In contrast, women with previous cancer generally had favorable breast-cancer specific survival; however this varied somewhat by stage and over time. Conclusions Many women newly diagnosed with breast cancer are already cancer survivors. These women had generally worse overall survival, worse survival from other causes, but their disease-specific survival varied depending on their breast cancer stage and over time. Citation Format: Sandi L Pruitt, Hong Zhu, Daniel Heitjan, David E Gerber, Bhumika Maddineni, Danyi Xiong, Ethan Halm, Caitlin Murphy. Survival among female breast cancer patients who have survived a previous cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS11-31.
Photochemical internalization (PCI)-mediated activation of CD8 T cells involves antigen uptake and CCR7-mediated transport by migratory dendritic cells to draining lymph nodes
Authors: Philipp Schineis, Zuzanna K. Kotkowska, Sarah Vogel-Kindgen, Mona C. Friess, Martine Theisen, David Schwyter, Lucy Hausammann, Saurav Subedi, Eleni M. Varypataki, Ying Waeckerle-Men, Isabel Kolm, Thomas M. Kündig, Anders Høgset, Bruno Gander, Cornelia Halin, Pål Johansen
Journal: Journal of Controlled Release (2021)
Three heads are better than two: Hepatitis B core-related antigen as a new predictor of hepatitis B virus-related hepatocellular carcinoma
Authors: Jer-Wei Wu, Jia-Horng Kao, Tai-Chung Tseng
Journal: Clinical and Molecular Hepatology (2021)

Patients with chronic hepatitis B virus (HBV) infection are at risk of developing hepatocellular carcinoma (HCC), and serum markers reflecting viral replication are potential predictors for HCC development. Besides the levels of serum HBV DNA and hepatitis B surface antigen (HBsAg), hepatitis B core-related antigen (HBcrAg) quantification is an emerging serological marker for viral replication. Unlike HBV DNA and HBsAg, HBcrAg is a covalently closed circular DNA-derived protein marker, consisting of hepatitis B e antigen (HBeAg), p22cr, and hepatitis B core antigen. In treatment-naïve HBV patients, higher HBcrAg levels are shown to be associated with an increased risk of HCC in several studies. More importantly, HBcrAg may complement HBV DNA level to predict HCC development. For example, an Asian treatmentnaïve cohort study’s data showed that HBcrAg level of 4 log U/mL was effective to stratify HCC risk in HBeAg-negative patients with intermediate viral loads, who may not need antiviral therapy because of the low to moderate risk of HCC. In patients receiving prolonged nucleos(t)ide analogue with profound viral suppression, most data indicated that HBV DNA and HBsAg levels no longer serve as HCC predictors. However, several studies suggested on-treatment HBcrAg levels may remain as an HCC predictor. In summary, HBcrAg level can be a useful biomarker for treatment-naïve patients, but its value in on-treatment patients needs validation. The next challenge is how to combine HBcrAg with the other viral markers to construct a better HCC prediction model, optimizing the management of HBV patients.