tbuckley/cabot-search huggingface dataset:
Cancer Incidence in World Trade Center Rescue and Recovery Workers: 14 Years of Follow-Up
Authors: Jiehui Li, Janette Yung, Baozhen Qiao, Erin Takemoto, David G Goldfarb, Rachel Zeig-Owens, James E Cone, Robert M Brackbill, Mark R Farfel, Amy R Kahn, Maria J Schymura, Moshe Z Shapiro, Christopher R Dasaro, Andrew C Todd, Dana Kristjansson, David J Prezant, Paolo Boffetta, Charles B Hall
Journal: JNCI Journal of the National Cancer Institute (2021)

Statistically significantly increased cancer incidence has been reported from 3 cohorts of World Trade Center (WTC) disaster rescue and recovery workers. We pooled data across these cohorts to address ongoing public concerns regarding cancer risk 14 years after WTC exposure.From a combined deduplicated cohort of 69 102 WTC rescue and recovery workers, a sample of 57 402 workers enrolled before 2009 and followed through 2015 was studied. Invasive cancers diagnosed in 2002-2015 were identified from 13 state cancer registries. Standardized incidence ratios (SIRs) were used to assess cancer incidence. Adjusted hazard ratios (aHRs) were estimated from Cox regression to examine associations between WTC exposures and cancer risk.Of the 3611 incident cancers identified, 3236 were reported as first-time primary (FP) cancers, with an accumulated 649 724 and 624 620 person-years of follow-up, respectively. Incidence for combined FP cancers was below expectation (SIR = 0.96, 95% confidence interval [CI] = 0.93 to 0.99). Statistically significantly elevated SIRs were observed for melanoma-skin (SIR = 1.43, 95% CI = 1.24 to 1.64), prostate (SIR = 1.19, 95% CI = 1.11 to 1.26), thyroid (SIR = 1.81, 95% CI = 1.57 to 2.09), and tonsil (SIR = 1.40, 95% CI = 1.00 to 1.91) cancer. Those arriving on September 11 had statistically significantly higher aHRs than those arriving after September 17, 2001, for prostate (aHR = 1.61, 95% CI = 1.33 to 1.95) and thyroid (aHR = 1.77, 95% CI = 1.11 to 2.81) cancers, with a statistically significant exposure-response trend for both.In the largest cohort of 9/11 rescue and recovery workers ever studied, overall cancer incidence was lower than expected, and intensity of WTC exposure was associated with increased risk for specific cancer sites, demonstrating the value of long-term follow-up studies after environmental disasters.
High Amount of Transcription Factor IRF8 Engages AP1-IRF Composite Elements in Enhancers to Direct Type 1 Conventional Dendritic Cell Identity
Authors: Sunkyung Kim, Prachi Bagadia, David A. Anderson, Tian-Tian Liu, Xiao Huang, Derek J. Theisen, Kevin W. O’Connor, Ray A. Ohara, Arifumi Iwata, Theresa L. Murphy, Kenneth M. Murphy
Journal: Immunity (2021)
Dynamics of antibody response to BNT162b2 vaccine after six months: a longitudinal prospective study
Authors: Paul Naaber, Liina Tserel, Kadri Kangro, Epp Sepp, Virge Jürjenson, Ainika Adamson, Liis Haljasmägi, Anna Pauliina Rumm, Regina Maruste, Jaanika Kärner, Joachim M. Gerhold, Anu Planken, Mart Ustav, Kai Kisand, Pärt Peterson
Journal: The Lancet Regional Health - Europe (2021)

SARS-CoV-2 mRNA vaccines have proven high efficacy, however, limited data exists on the duration of immune responses and their relation to age and side effects.We studied the antibody and memory T cell responses after the two-dose BNT162b2 vaccine in 122 volunteers up to 6 months and correlated the findings with age and side effects.We found a robust antibody response to Spike protein after the second dose. However, the antibody levels declined at 12 weeks and 6 months post-vaccination, indicating a waning of the immune response over time. At 6 months after the second dose, the Spike antibody levels were similar to the levels in persons vaccinated with one dose or in COVID-19 convalescent individuals. The antibodies efficiently blocked ACE2 receptor binding to SARS-CoV-2 Spike protein of five variants of concern at one week but this was decreased at three months. 87% of individuals developed Spike-specific memory T cell responses, which were lower in individuals with increased proportions of immunosenescent CD8+ TEMRA cells. We found antibody response to correlate negatively with age and positively with the total score of vaccination side effects.The mRNA vaccine induces a strong antibody response to SARS-CoV-2 and five VOCs at 1 week post-vaccination that decreases thereafter. T cell responses, although detectable in the majority, were lower in individuals with higher T cell immunosenescence. The deterioration of vaccine response suggests the need to monitor for the potential booster vaccination.
ADGRG1 enriches for functional human hematopoietic stem cells following ex vivo expansion–induced mitochondrial oxidative stress
Authors: Yandan Chen, Shuyi Fang, Qingwei Ding, Rongzhen Jiang, Jiefeng He, Qin Wang, Yuting Jin, Xinxin Huang, Sheng Liu, Maegan L. Capitano, Thao Trinh, Yincheng Teng, Qingyou Meng, Jun Wan, Hal E. Broxmeyer, Bin Guo
Journal: Journal of Clinical Investigation (2021)

The heterogeneity of human hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) under stress conditions such as ex vivo expansion is poorly understood. Here, we report that the frequencies of SCID-repopulating cells were greatly decreased in cord blood (CB) CD34+ HSCs and HPCs upon ex vivo culturing. Transcriptomic analysis and metabolic profiling demonstrated that mitochondrial oxidative stress of human CB HSCs and HPCs notably increased, along with loss of stemness. Limiting dilution analysis revealed that functional human HSCs were enriched in cell populations with low levels of mitochondrial ROS (mitoROS) during ex vivo culturing. Using single-cell RNA-Seq analysis of the mitoROS low cell population, we demonstrated that functional HSCs were substantially enriched in the adhesion GPCR G1-positive (ADGRG1+) population of CD34+CD133+ CB cells upon ex vivo expansion stress. Gene set enrichment analysis revealed that HSC signature genes including MSI2 and MLLT3 were enriched in CD34+CD133+ADGRG1+ CB HSCs. Our study reveals that ADGRG1 enriches for functional human HSCs under oxidative stress during ex vivo culturing, which can be a reliable target for drug screening of agonists of HSC expansion.
Atrial natriuretic peptide promotes uterine decidualization and a TRAIL-dependent mechanism in spiral artery remodeling
Authors: Wei Zhang, Shuo Li, Jinglei Lou, Hui Li, Meng Liu, Ningzheng Dong, Qingyu Wu
Journal: Journal of Clinical Investigation (2021)

Atrial natriuretic peptide (ANP) is an important hormone in cardiovascular biology. It is activated by the protease corin. In pregnancy, ANP and corin promote uterine spiral artery remodeling, but the underlying mechanism remains unknown. Here we report an ANP function in uterine decidualization and TNF-related apoptosis-inducing ligand–dependent (TRAIL-dependent) death in spiral arterial smooth muscle cells (SMCs) and endothelial cells (ECs). In ANP- or corin-deficient mice, uterine decidualization markers and TRAIL expression were decreased, whereas in cultured human endometrial stromal cells (HESCs), ANP increased decidualization and TRAIL expression. In uterine spiral arteries from pregnant wild-type mice, SMC and EC loss occurred sequentially before trophoblast invasion. In culture, TRAIL from decidualized HESCs induced apoptosis in uterine SMCs, but not in ECs with low TRAIL receptor expression. Subsequently, cyclophilin B was identified from apoptotic SMCs that upregulated endothelial TRAIL receptor and caused apoptosis in ECs. These results indicate that ANP promotes decidualization and TRAIL expression in endometrial stromal cells, contributing to sequential events in remodeling of spiral arteries, including SMC death and cyclophilin B release, which in turn induces TRAIL receptor expression and apoptosis in ECs.
White Blood Cell Membrane‐Coated Nanoparticles: Recent Development and Medical Applications
Authors: Dan Wang, Shuyan Wang, Zhidong Zhou, Dean Bai, Qiangzhe Zhang, Xiangzhao Ai, Weiwei Gao, Liangfang Zhang
Journal: Advanced Healthcare Materials (2021)

White blood cells (WBCs) are immune cells that play essential roles in critical diseases including cancers, infections, and inflammatory disorders. Their dynamic and diverse functions have inspired the development of WBC membrane-coated nanoparticles (denoted "WBC-NPs"), which are formed by fusing the plasma membranes of WBCs, such as macrophages, neutrophils, T cells, and natural killer cells, onto synthetic nanoparticle cores. Inheriting the entire source cell antigens, WBC-NPs act as source cell decoys and simulate their broad biointerfacing properties with intriguing therapeutic potentials. Herein, the recent development and medical applications of WBC-NPs focusing on four areas, including WBC-NPs as carriers for drug delivery, as countermeasures for biological neutralization, as nanovaccines for immune modulation, and as tools for the isolation of circulating tumor cells and fundamental research is reviewed. Overall, the recent development and studies of WBC-NPs have established the platform as versatile nanotherapeutics and tools with broad medical application potentials.
BCL-XL blockage in TNBC models confers vulnerability to inhibition of specific cell cycle regulators
Authors: Olivier Castellanet, Fahmida Ahmad, Yaron Vinik, Gordon B. Mills, Bianca Habermann, Jean-Paul Borg, Sima Lev, Fabienne Lamballe, Flavio Maina
Journal: Theranostics (2021)

Cell cycle regulators are frequently altered in Triple-Negative Breast Cancer (TNBC). Emerging agents targeting these signals offer the possibility to design new combinatorial therapies. However, preclinical models that recapitulate TNBC primary resistance and heterogeneity are essential to evaluate the potency of these combined treatments. Methods: Bioinformatic processing of human breast cancer datasets was used to analyse correlations between expression levels of cell cycle regulators and patient survival outcome. The MMTV-R26Met mouse model of TNBC resistance and heterogeneity was employed to analyse expression and targeting vulnerability of cell cycle regulators in the presence of BCL-XL blockage. Robustness of outcomes and selectivity was further explored using a panel of human breast cancer cells. Orthotopic studies in nude mice were applied for preclinical evaluation of efficacy and toxicity. Alterations of protein expression, phosphorylation, and/or cellular localisation were analysed by western blots, reverse phase protein array, and immunocytochemistry. Bioinformatics was performed to highlight drug's mechanisms of action. Results: We report that high expression levels of the BCL2L1 gene encoding BCL-XL and of specific cell cycle regulators correlate with poor survival outcomes of TNBC patients. Blockage of BCL-XL confers vulnerability to drugs targeting CDK1/2/4, but not FOXM1, CDK4/6, Aurora A and Aurora B, to all MMTV-R26Met and human TNBC cell lines tested. Combined blockage of BCL-XL and CDK1/2/4 interfered with tumour growth in vivo. Mechanistically, we show that, co-targeting of BCL-XL and CDK1/2/4 synergistically inhibited cell viability by combinatorial depletion of survival and RTK/AKT signals, and concomitantly restoring FOXO3a tumour suppression actions. This was accompanied by an accumulation of DNA damage and consequently apoptosis. Conclusions: Our studies illustrate the possibility to exploit the vulnerability of TNBC cells to CDK1/2/4 inhibition by targeting BCL-XL. Moreover, they underline that specificity matters in targeting cell cycle regulators for combinatorial anticancer therapies.
An Updated Systematic Review on Focal Therapy in Localized Prostate Cancer: What Has Changed over the Past 5 Years?
Authors: Jana S. Hopstaken, Joyce G.R. Bomers, Michiel J.P. Sedelaar, Massimo Valerio, Jurgen J. Fütterer, Maroeska M. Rovers
Journal: European Urology (2021)

Focal therapy is a promising, minimally invasive strategy to selectively treat localized prostate cancer. A previous systematic review indicated that there is growing evidence for favorable functional outcomes, but that oncological effectiveness was yet to be defined.To assess the effectiveness of focal therapy in patients with localized prostate cancer in terms of functional and oncological outcomes.PubMed, Embase, and The Cochrane Library were searched for studies between October 2015 and December 31, 2020. In addition, the research stages were acquired according to the Idea, Development, Exploration, Assessment, Long-term study (IDEAL) recommendations. Ongoing studies were identified through clinical trial registries.Seventy-two studies were identified exploring eight different sources of energy to deliver focal therapy in 5827 patients. Twenty-seven studies reported on high-intensity focused ultrasound (HIFU), nine studies on irreversible electroporation, 11 on cryoablation, eight on focal laser ablation and focal brachytherapy, seven on photodynamic therapy (PDT), two on radiofrequency ablation, and one on prostatic artery embolization. The majority of studies were prospective development stage 2a studies (n = 357). PDT and HIFU, both in stage 3, showed promising results. Overall, HIFU studies reported a median of 95% pad-free patients and a median of 85% patients with no clinically significant cancer (CSC) in the treated area. For PDT, no changes in continence were reported and a median of 90% of patients were without CSC. Both treatments were well tolerated.Over the past 5 yr, focal therapy has been studied for eight different energy sources, mostly in single-arm stage 2 studies. Although a first randomized controlled trial in focal therapy has been performed, more high-quality evaluations are needed, preferably via multicenter randomized controlled trials with long-term follow-up and predefined assessment of oncological and functional outcomes and health-related quality-of-life measures.Focal treatment (FT) of prostate cancer has potential, considering that it has less impact on continence and potency than radical treatment. Our systematic review indicates that despite the method being studied extensively over the past half decade, the majority of studies remain in an early research stage. The techniques high-intensity focused ultrasound and photodynamic therapy have shown most progression toward advanced research stages and show favorable results. However, more high-quality evidence is required before FT can become available as a standard treatment.
Abstract 14307: Association of Piezo1 Variants With Hypertension in UK Biobank Participants
Authors: Chew Cheng, Vijayalakshmi Deivasikamani, David J Beech, Piruthivi Sukumar
Journal: Circulation (2019)

Hypertension is a major risk factor for cardiovascular diseases worldwide. Piezo1 is a mechanosensitive ion channel that plays vital roles in multiple homeostatic process including in volume regula...
Should women with Lynch syndrome be offered gynaecological cancer surveillance?
Authors: NAJ Ryan, T Snowsill, E McKenzie, KJ Monahan, D Nebgen
Journal: BMJ (2021)

### What you need to know

Guidelines published in 2020 by the National Institute for Health and Care Excellence (NICE) recommend testing for Lynch syndrome in women with endometrial cancer at the time of diagnosis.1 Lynch syndrome is an inherited autosomal dominant condition. It is associated with an increased risk of colorectal, endometrial, and ovarian cancers. It is caused by harmful mutations in the DNA mismatch repair genes MLH1 , MSH2 (EPCAM) , MSH6 , or PMS2 .2 One in 440 individuals has Lynch syndrome according to US data, and one in 278 individuals based on a study from Denmark.2 The lifetime risk of someone with Lynch syndrome developing any cancer is estimated to be greater than 60% (unless caused by a PMS2 mutation), according to data from the Prospective Lynch Syndrome database (http://www.plsd.eu). For a woman with Lynch syndrome, the lifetime risk of endometrial or ovarian cancer is 40-60% and 10-17%, respectively, the incidence increasing with age beyond 40 years.2

### Data sources and selection strategy

We searched CENTRAL, Medline, Embase, and the Cochrane Database of Systematic Reviews for articles in English from the database inception to February 2021. Our search yielded 974 records. After removal of duplicates, 719 were available to screen. Screening was done by two independent reviewers using the Rayyan platform (https://www.rayyan.ai). Of …
Decoding the pharmacogenetics of nonsteroidal anti‐inflammatory drug hypersensitivity
Authors: C. Flores
Journal: British Journal of Dermatology (2021)

Journal Article Decoding the pharmacogenetics of nonsteroidal anti‐inflammatory drug hypersensitivity Get access C. Flores C. Flores Research Unit, Hospital Universitario N. S. de Candelaria Santa Cruz de Tenerife 38010 SpainGenomics Division Instituto Tecnológico y de Energías Renovables Santa Cruz de Tenerife 38600 SpainCIBER de Enfermedades Respiratorias Instituto de Salud Carlos III Madrid 28029 Spain https://orcid.org/0000-0001-5352-069X Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 185, Issue 4, 1 October 2021, Pages 697–698, https://doi.org/10.1111/bjd.20693 Published: 01 October 2021
Periodontitis and rheumatoid arthritis: What have we learned about their connection and their treatment?
Authors: Jerián González‐Febles, Mariano Sanz
Journal: Periodontology 2000 (2021)

Abstract Rheumatoid arthritis and periodontitis are chronic inflammatory diseases defined respectively by the destruction of the articular cartilage and tooth‐supporting periodontal tissues. Although the epidemiologic evidence for an association between these two diseases is still scarce, there is emerging scientific information linking specific bacterial periodontal pathogens, such as Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, in the citrullination process, leading to autoantibody formation and compromised immunotolerance of the susceptible patient to rheumatoid arthritis. In this review, we update the existing information on the evidence, not only regarding the epidemiologic association, but also the biologic mechanisms linking these two diseases. Finally, we review information emerging from intervention studies evaluating whether periodontal treatment could influence the initiation and progression of rheumatoid arthritis.
Allergic Reactions After COVID-19 Vaccination—Putting Risk Into Perspective
Authors: Elizabeth J. Phillips
Journal: JAMA Network Open (2021)

Ronen Shavit, MD; Ramit Maoz-Segal, MD; Mona Iancovici-Kidon, MD; Irena Offengenden, MD; Soad Haj Yahia, MD; Diti Machnes Maayan, MD; Yulia Lifshitz-Tunitsky, MD; Stanley Niznik, MD; Shirly Frizinsky, MD; Michal Deutch, BSN; Eti Elbaz, BSN; Hosney Genaim, BSN; Galia Rahav, MD, PhD; Itzchak Levy, MD; Anna Belkin, MD; Gili Regev-Yochay, MD; Arnon Afek, MD, MHA; Nancy Agmon-Levin, MD
Two Genomic Loci Control Three Eye Colors in the Domestic Pigeon (<i>Columba livia</i>)
Authors: Emily T Maclary, Bridget Phillips, Ryan Wauer, Elena F Boer, Rebecca Bruders, Tyler Gilvarry, Carson Holt, Mark Yandell, Michael D Shapiro
Journal: Molecular Biology and Evolution (2021)

Abstract The iris of the eye shows striking color variation across vertebrate species, and may play important roles in crypsis and communication. The domestic pigeon (Columba livia) has three common iris colors, orange, pearl (white), and bull (dark brown), segregating in a single species, thereby providing a unique opportunity to identify the genetic basis of iris coloration. We used comparative genomics and genetic mapping in laboratory crosses to identify two candidate genes that control variation in iris color in domestic pigeons. We identified a nonsense mutation in the solute carrier SLC2A11B that is shared among all pigeons with pearl eye color, and a locus associated with bull eye color that includes EDNRB2, a gene involved in neural crest migration and pigment development. However, bull eye is likely controlled by a heterogeneous collection of alleles across pigeon breeds. We also found that the EDNRB2 region is associated with regionalized plumage depigmentation (piebalding). Our study identifies two candidate genes for eye colors variation, and establishes a genetic link between iris and plumage color, two traits that vary widely in the evolution of birds and other vertebrates.
TAZ is indispensable for c-MYC-induced hepatocarcinogenesis
Authors: Haichuan Wang, Shanshan Zhang, Yi Zhang, Jiaoyuan Jia, Jingxiao Wang, Xianqiong Liu, Jie Zhang, Xinhua Song, Silvia Ribback, Antonio Cigliano, Matthias Evert, Bingyong Liang, Hong Wu, Diego F Calvisi, Yong Zeng, Xin Chen
Journal: Journal of Hepatology (2021)
Comparison of SARS-CoV-2 Antibody Response by Age Among Recipients of the BNT162b2 vs the mRNA-1273 Vaccine
Authors: Nathan E. Richards, Behnam Keshavarz, Lisa J. Workman, Michael R. Nelson, Thomas A. E. Platts-Mills, Jeffrey M. Wilson
Journal: JAMA Network Open (2021)

μg/mL [95% CI, 48.8-71.4μg/mL]) and age-similar peers who received mRNA-1273 (71.8 μg/mL [95% CI, 58.1-88.8μg/mL]) (Figure). DiscussionIn this cohort study, we used a quantitative assay and found that BNT162b2 elicited relatively lower antibody levels in older adults vs younger adults, which is consistent with emerging reports. 4,5By contrast, there was no difference in postboost antibody levels in older adults vs younger adults who received mRNA-1273.One explanation for the difference in immunogenicity observed in older adults could relate to the amount of mRNA used in the respective vaccines, with 30 μg contained in BNT162b2 and 100 μg in mRNA-1273. 1,2A limitation of this study is that the neutralizing antibodies were not measured; however, several groups have reported a strong correlation between SARS-CoV-2 binding and neutralizing antibodies. 6Additional studies are warranted to determine whether binding antibodies to SARS-CoV-2 can be used to predict clinical protection against COVID-19.
A selective HDAC8 inhibitor potentiates antitumor immunity and efficacy of immune checkpoint blockade in hepatocellular carcinoma
Authors: Weiqin Yang, Yu Feng, Jingying Zhou, Otto Ka-Wing Cheung, Jianquan Cao, Jing Wang, Wenshu Tang, Yalin Tu, Liangliang Xu, Feng Wu, Zhiwu Tan, Hanyong Sun, Yuan Tian, John Wong, Paul Bo-San Lai, Stephen Lam Chan, Anthony Wing-Hung Chan, Patrick Boon-Ooi Tan, Zhiwei Chen, Joseph Jao-Yiu Sung, Kevin Yuk-Lap Yip, Ka-Fai To, Alfred Sze-Lok Cheng
Journal: Science Translational Medicine (2021)

HDAC8 inhibition elicits durable responses to immune checkpoint blockade by improving adaptive immune responses through enhancer reprogramming.
Moving beyond AUC: decision curve analysis for quantifying net benefit of risk prediction models
Authors: Mohsen Sadatsafavi, Amin Adibi, Milo Puhan, Andrea Gershon, Shawn D. Aaron, Don D. Sin
Journal: European Respiratory Journal (2021)

<b>Statistical constructs such as ROC/AUC do not answer the critical question of how much clinical utility a risk prediction model confers. This paper overviews decision curve analysis, a novel method for quantifying net benefit of a risk prediction model.</b>https://bit.ly/3h1rraX