tbuckley/cabot-search huggingface dataset:
Treatment Patterns and Healthcare Resource Utilization in Patients with Relapsed/Refractory Acute Myeloid Leukemia and a Subset with IDH1-Mutation: A United States Medical Chart Review Study
Authors: James D. Griffin, Mike Storm, Ken Wilhelm, Audra Boscoe, Dendy Macaulay, Zheng-Yi Zhou, Elizabeth Faust, Claudia Cheung
Journal: Blood (2018)
Alum impairs tolerogenic properties induced by allergoid‐mannan conjugates inhibiting mTOR and metabolic reprogramming in human DCs
Authors: Cristina Benito‐Villalvilla, Irene Soria, Mario Pérez‐Diego, Enrique Fernández‐Caldas, José Luis Subiza, Oscar Palomares
Journal: Allergy (2019)

Polymerized allergoids conjugated to mannan (PM) are suitable vaccines for allergen-specific immunotherapy (AIT). Alum remains the most widely used adjuvant in AIT, but its way of action is not completely elucidated. The better understanding of the mechanisms underlying alum adjuvanticity could help to improve AIT vaccine formulations.We sought to investigate the potential influence of alum in the tolerogenic properties imprinted by PM at the molecular level.Flow cytometry, ELISAs, cocultures, intracellular staining and suppression assays were performed to assess alum and PM effects in human dendritic cells (DCs). BALB/c mice were immunized with PM alone or adsorbed to alum. Allergen-specific antibodies, splenocyte cytokine production and splenic forkhead box P3 (FOXP3)+ regulatory T (Treg) cells were quantified. Metabolic and immune pathways were also studied in human DCs.Alum decreases PD-L1 expression and IL-10 production induced by PM in human DCs and increases pro-inflammatory cytokine production. Alum impairs PM-induced functional FOXP3+ Treg cells and promotes Th1/Th2/Th17 responses. Subcutaneous immunization of mice with PM plus alum inhibits in vivo induction of Treg cells promoted by PM without altering the capacity to induce functional allergen-specific blocking antibodies. Alum inhibits mTOR activation and alters metabolic reprogramming by shifting glycolytic pathways and inhibiting reactive oxygen species (ROS) production in PM-activated DCs, impairing their capacity to generate functional Treg cells.We uncover novel mechanisms by which alum impairs the tolerogenic properties induced by PM, which might well contribute to improve the formulation of novel vaccines for AIT.
Trump pledges to ban flavoured e-cigarettes
Authors: Janice Hopkins Tanne
Journal: BMJ (2019)

US president Donald Trump has pledged to ban the sale of most flavoured electronic cigarettes, after recent US cases of lung disease linked to vaping.1

At a press conference on Wednesday 11 September the president, with his wife, Melania, by his side, the president cited her concern for their son, Barron, and for young people made ill from e-cigarette use.

“We can’t allow people to get sick. And we can’t have our youth be so affected,” he said.

Norman Sharpless, acting commissioner of the Food and Drug Administration, and Alex Azar, the secretary of health and human services, also appeared at the press conference.

Many …
Molecular characterization and clinical relevance of m6A regulators across 33 cancer types
Authors: Yongsheng Li, Jun Xiao, Jing Bai, Yi Tian, Yinwei Qu, Xiang Chen, Qi Wang, Xinhui Li, Yunpeng Zhang, Juan Xu
Journal: Molecular Cancer (2019)

The methylation of N6 adenosine (m6A) plays a critical role in diverse biological processes. However, knowledge regarding the reconstitution of m6A across cancer types is still lacking. Here, we systematically analyzed the molecular alterations and clinical relevance of m6A regulators across > 10,000 subjects representing 33 cancer types. We found that there are widespread genetic alterations to m6A regulators, and that their expression levels are significantly correlated with the activity of cancer hallmark-related pathways. Moreover, m6A regulators were found to be potentially useful for prognostic stratification, and we identified IGF2BP3 as a potential oncogene across multiple cancer types. Our results provide a valuable resource that will guide both mechanistic and therapeutic analyses of the role of m6A regulators in cancer.
Neutrophil Extracellular Traps Drive Mitochondrial Homeostasis in Tumors to Augment Growth
Authors: Hamza O. Yazdani, Eva Roy, Alexander J. Comerci, Dirk J. van der Windt, Hongji Zhang, Hai Huang, Patricia Loughran, Sruti Shiva, David A. Geller, David L. Bartlett, Allan Tsung, Tai Sheng, Richard L. Simmons, Samer Tohme
Journal: Cancer Research (2019)

Neutrophil infiltration and neutrophil extracellular traps (NET) in solid cancers are associated with poorer prognosis, but the mechanisms are incompletely understood. We hypothesized that NETs enhance mitochondrial function in tumor cells, providing extra energy for accelerated growth. Metastatic colorectal cancer tissue showed increased intratumoral NETs and supranormal preoperative serum MPO-DNA, a NET marker. Higher MPO-DNA correlated with shorter survival. In mice, subcutaneous tumor implants and hepatic metastases grew slowly in PAD4-KO mice, genetically incapable of NETosis. In parallel experiments, human cancer cell lines grew slower in nu/nu mice treated with DNAse, which disassembles NETs. PAD4-KO tumors manifested decreased proliferation, increased apoptosis, and increased evidence of oxidative stress. PAD4-KO tumors had decreased mitochondrial density, mitochondrial DNA, a lesser degree of ATP production, along with significantly decreased mitochondrial biogenesis proteins PGC1α, TFAM, and NRF-1.
Principal component analysis of seven skin‐ageing features identifies three main types of skin ageing
Authors: L.M. Pardo, M.A. Hamer, F. Liu, P. Velthuis, M. Kayser, D.A. Gunn, T. Nijsten
Journal: British Journal of Dermatology (2019)

The underlying phenotypic correlations between wrinkles, pigmented spots (PS), telangiectasia and other related facial‐ageing subphenotypes are not well understood. To analyse the underlying phenotypic correlation structure between seven features for facial ageing: global wrinkling, perceived age (PA), Griffiths photodamage grading, PS, telangiectasia, actinic keratosis (AK) and keratinocyte cancer (KC). This was a cross‐sectional study. Facial photographs and a full‐body skin examination were used. We used principal component analysis (PCA) to derive principal components (PCs) of common variation between the features. We performed multivariable linear regressions between age, sex, body mass index, smoking and ultraviolet radiation exposure and the PC scores derived from PCA. We also tested the association between the main PC scores and 140 single‐nucleotide polymorphisms (SNPs) previously associated with skin‐ageing phenotypes. We analysed data from 1790 individuals with complete data on seven features of skin ageing. Three main PCs explained 73% of the total variance of the ageing phenotypes: a hypertrophic/wrinkling component (PC1: global wrinkling, PA and Griffiths grading), an atrophic/skin colour component (PC2: PS and telangiectasia) and a cancerous component (PC3: AK and KC). The associations between lifestyle and host factors differed per PC. The strength of SNP associations also differed per component with the most SNP associations found with the atrophic component [e.g. the IRF4 SNP (rs12203592); P‐value = 1·84 × 10–22]. Using a hypothesis‐free approach, we identified three major underlying phenotypes associated with extrinsic ageing. Associations between determinants for skin ageing differed in magnitude and direction per component. What's already known about this topic? Facial ageing is a complex phenotype consisting of different features including wrinkles, pigmented changes, telangiectasia and cancerous‐related growths; it is not clear how these phenotypes are related to each other and to other phenotypes. A few studies have described two main clinical phenotypes for photoageing, namely hypertrophic ageing and atrophic ageing, which have been based solely on the clinical assessment of photoageing characteristics. What does this study add? We are the first to use epidemiology data to identify three main components associated with photoageing, namely a hypertrophic component (global wrinkling; perceived age; Griffiths grading) and atrophic component (pigmented spots; telangiectasia) and a cancer component (actinic keratosis; keratinocyte cancer). Association analysis showed different effects and direction of environmental determinants and genetic associations with the three components, with the most significant gene variants associations found for the atrophic component.
Optimism in unconscious, intuitive morality
Authors: Cory J Clark, Bo M Winegard
Journal: Behavioral and Brain Sciences (2019)

Moral cognition, by its very nature, stems from intuitions about what is good and bad, and these intuitions influence moral assessments outside of conscious awareness. However, because humans evolved a shared set of moral intuitions, and are compelled to justify their moral assessments as good and rational (even erroneously) to others, moral virtue and moral progress are still possible.
Is serum tryptase level a novel biomarker in colorectal cancer patients?
Authors: Mario Brandi, Gennaro Gadaleta-Caldarola, Eustachio Ruggieri, Michele Ammendola, Rosa Patruno, Veronica Goffredo, Andrea Misino, Severino Montemurro, Cosmo Damiano Gadaleta, Girolamo Ranieri
Journal: Journal of Clinical Oncology (2012)

e21134 Background: Tryptase is a serin protease stored in mast cell granules that plays a role in tumour angiogenesis. Mast cells (MCs) can release tryptase following c-Kit receptor activation. On the other hand colo-rectal cancer (CRC) is a well-established angiogenesis dependent tumour and anti-angiogenic based therapy is a standard treatment in metastatic CRC. This preliminary study aims to assess tryptase serum levels in 51 CRC patients before and after radical surgery. Methods: In this study patients with stage B and C CRC (according to Astler e Coller staging system) were selected. Samples of blood were taken from CRC patients between 7 and 9 a.m.1 day before and 1 day after curative surgery. Venous blood was dispensed into a tube for serum (Becton Dickinson Hemogard Vacutainer Systems, Plymouth, UK). Tryptase levels were measured using the UniCAP Tryptase Fluoroenzymeimmunoassay (Pharmacia,Uppsala, Sweden). Primary tumour tissue were also evaluated in terms of MCs positive to tryptase by immunohistochemistry utilizing an anti-tryptase primary antibody (clone AA1; Dako, Glostrup, Denmark). Results: Mean ± s.d. tryptase level pre-tumour surgical resection was 6.37 ± 4.57 μg/L, and mean ± s.d. tryptase level post tumour surgical resection was 5.15 ± 3.82 μg/L. A statistically significant difference between pre-tumour surgical resection and post-tumour surgical resection tryptase level concentrations was found: p=0.000 by t-test. A statistically significant correlation between MCs positive to trypase and serum tryptase levels pre-surgical resection was also found (r=086; p=0.000) by Pearson’s analysis. Conclusions: This pilot report analyzes the possible significance of serum tryptase levels changes in CRC patients who underwent curative surgery. Our results demonstrated higher serum tryptase levels CRC patients suggesting the release of tryptase from MCs of primary CRC tissue. As expected, after radical surgical resection, serum tryptase levels had decreased. We suggest that tryptase may play a role as a new predictive biomarker in CRC patients. In this context several tryptase inhibitors such as gabexate mesilate and nafamostat mesilate might be evaluated as adjuvant treatment in clinical trials.
Malaria could be eradicated by 2050, say global experts
Authors: Elisabeth Mahase
Journal: BMJ (2019)

Malaria could be eradicated as early as 2050, according to a group of 41 leading experts including malariologists, biomedical scientists, economists, and health policy experts.1

They advocated for a number of actions including increased funding, creating a single global data hub to track and respond to pockets of transmission, and a global training programme to produce a network of malaria eradication professionals.

The report, published in the Lancet , combined existing evidence with new epidemiological and financial analyses to show that with the right strategy and action, malaria could be eliminated within a generation.

The authors used modelling to determine the likely distribution and intensity of malaria in 2030 and 2050. They found …
Lack of Robust Prognostic Biomarkers for Immunotherapy in Breast Cancer—Adverse Events—In Reply
Authors: Sylvia Adams, Elizabeth A. Mittendorf
Journal: JAMA Oncology (2019)

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
Clinical and immune profiling for cancer of unknown primary site
Authors: Koji Haratani, Hidetoshi Hayashi, Takayuki Takahama, Yasushi Nakamura, Shuta Tomida, Takeshi Yoshida, Yasutaka Chiba, Takahiro Sawada, Kazuko Sakai, Yoshihiko Fujita, Yosuke Togashi, Junko Tanizaki, Hisato Kawakami, Akihiko Ito, Kazuto Nishio, Kazuhiko Nakagawa
Journal: Journal for ImmunoTherapy of Cancer (2019)

Immune checkpoint inhibitors (ICIs) confer a survival benefit in many cancer types. Given that the survival outcome for cancer of unknown primary site (CUP) remains poor, we investigated the potential of CUP for immunotherapy.A total of 164 patients with CUP (favorable subset, 34 patients; unfavorable subset, 130 patients) who were treated between January 2009 and March 2017 was identified from a review of medical records at Kindai University Hospital. They included 92 patients for whom pretreatment tumor tissue was available both for determination of programmed cell death-ligand 1 expression and tumor-infiltrating lymphocyte (TIL) density by immunohistochemistry (IHC) and for immune-related gene expression profiling (irGEP). The results of irGEP for CUP were compared with published data for ICI-treated solid cancers classified into progressive disease (PD) and non-PD subsets according to their best response to ICIs.The median overall survival of all CUP patients was 29.3 months (95% confidence interval [CI], 15.7-not reached) and 7.1 months (95% CI, 5.0-9.4) for favorable and unfavorable subsets, respectively. IHC and irGEP revealed that pretreatment immune activity-including expression of immune checkpoint molecules-for CUP was similar to that for ICI-responsive malignancies (antitumor immune cell signatures: CUP versus PD, P = 0.002-0.067; CUP versus non-PD, P = 0.591-0.999), although VEGFA expression was associated with suppression of antitumor immunity in CUP (P = 0.008, false discovery rate = 0.010). In addition, one case of CUP in the unfavorable subset that was associated with prominent PD-L1 expression on TILs and showed a durable response to nivolumab is presented.The survival outcome of CUP remains unsatisfactory. However, our clinical and immune profiling of CUP has revealed a potential to benefit from immunotherapy, with ICIs thus being a potential option for CUP treatment.
Revealing the molecular signaling pathways of mucus stasis in cystic fibrosis
Authors: Susan E. Birket, Steven M. Rowe
Journal: Journal of Clinical Investigation (2019)

Mucus obstruction is a hallmark of cystic fibrosis (CF) airway disease, leading to chronic infection, dysregulated inflammation, and progressive lung disease. As mucus hyperexpression is a key component in the initiation and perpetuation of airway obstruction, the triggers underlying mucin release must be identified and understood. In this issue of the JCI, Chen et al. sought to delineate the mechanisms that allow IL-1α/IL-1β to perpetuate the mucoinflammatory environment characteristic of the CF airway. The authors demonstrated that IL-1α and IL-1β stimulated non-CF human bronchial epithelial (HBE) cells to upregulate and secrete both MUC5B and MUC5AC in a dose-dependent manner, an effect that was neutralized by the inhibition of the IL-1α/IL-1β receptor (IL-1R1). Further experiments using mouse models and excised lung tissue identified contributors that drive a vicious feedback cycle of hyperconcentrated mucus secretions and persistent inflammation in the CF airway, factors that are likely at the nidus of progressive lung disease.
Subcutaneously engineered autologous extracellular matrix scaffolds with aligned microchannels for enhanced tendon regeneration
Authors: Wen Li, Adam C. Midgley, Yanli Bai, Meifeng Zhu, Hong Chang, Wenying Zhu, Lina Wang, Yuhao Wang, Hongjun Wang, Deling Kong
Journal: Biomaterials (2019)
Electrolyte Studies in Heart Failure
Authors: LLOYD T. ISERI, IVAN J. MADER, ALBERT J. BOYLE
Journal: Circulation (1955)

Indirect metabolic studies and direct muscle biopsy studies have indicated diminution of intracellular electrolyte concentration during congestive heart failure explainable by extrusion of these electrolytes due to increase in osmolarity within the cells. Acute and chronic physical and circulatory stress in cardiac patients produced an elevation of plasma sodium concentration indicative of a concomittant increase in osmolarity of the extracellular fluid.
Outcome of Patients with Gamma Delta T Cell Lymphomas: Analysis of 1429 Cases Registered in the Prospective T-Cell Project
Authors: Francine M Foss, Steven M. Horwitz, Monica Bellei, Martina Manni, Vittoria Tarantino, Andrei R. Shustov, Ivan Dlouhy, Maria Elena Cabrera, Won Seog Kim, Felicitas Hitz, Raul Gabus, Antonio Gutierrez, Sabela Bobillo Varela, Umberto Vitolo, Francesco Merli, Veronika Ballova, Andrew Davies, Maria Giuseppina Cabras, Francesco Di Raimondo, Massimo Federico
Journal: Blood (2017)
CCR9-CCL25 interaction mediates breast cancer cell survival via Akt activation
Authors: Crystal Johnson-Holiday, Erica Johnson, Shailesh Singh, James Lillard
Journal: Cancer Research (2007)

457  Breast cancer (BrCa) is one of the most frequently diagnosed cancers and the second leading cause of cancer-related deaths in North American women. Most cancer-related deaths are due to metastasis. In addition, BrCa cells readily become resistant to a wide variety of chemotherapeutic agents, which is a major obstacle in the treatment of BrCa. Tumor cell migration and metastasis share similarities with leukocyte trafficking, which is regulated, in part, by chemokines and their receptors. We have previously shown that CCR9 is functionally expressed by BrCa cells and its expression is enhanced by the presence of its ligand, CCL25. We show that CCR9-CCL25 interaction increases BrCa cell migration, invasion, and matrix metalloproteinase expression, when compared to normal breast epithelial cells. However, this study characterizes the role of CCL25-CCR9 cell-signaling cascades involved in BrCa cell resistance to cisplatin. This drug is often ineffective due to cancer cell resistance and the development of anti-apoptotic mechanisms. In this regard, CCR9-CCL25 interaction plays a role in immature T-cell survival through PI3K and Gαi protein-dependent activation of Akt/protein kinase B. Activated Akt phosphorylates multiple downstream targets that are involved in cell survival signaling, which include glycogen synthase kinase 3β (GSK-3β), forkhead transcriptional factor (FKHR), and caspase-9. We examined the effect of CCR9-CCL25 interactions on BrCa cell lines MDA-MB-231 and MDA-435, with or without cisplatin treatment. CCR9-CCL25 interactions decreased cisplatin-induced apoptosis. These interactions also modulated the activation of cell signaling cascades involved in cell survival. These studies provide important new information regarding the cellular and molecular mechanisms that mediate BrCa cell survival.
Don’t vape, CDC says, as US lung disease epidemic grows
Authors: Janice Hopkins Tanne
Journal: BMJ (2019)

The Centers for Disease Control and Prevention has advised Americans to stop using e-cigarettes as a multi-state epidemic of a mysterious lung disease spreads.

More than 450 possible cases of the lung illness have been reported from 33 states and the US Virgin Islands. The first case appeared in April. There have been five deaths so far.

There has been no evidence of infection, but all those affected had used e-cigarettes. Chemical exposure to a contaminant is suspected as the cause.

Electronic cigarettes, known as e-cigarettes, are battery operated devices that heat a liquid and deliver an aerosol that the user inhales (called vaping). The liquid usually contains nicotine, flavouring, and other chemicals. Marijuana products may be included. Medical and recreational marijuana is legally available in some US states. However, e-cigarette users may also purchase liquids or “pods” for their devices on the street or may make their own vaping products.

Use of e-cigarettes has increased rapidly among US high school students; last year 20.8% reported using e-cigarettes.1 …
scBFA: modeling detection patterns to mitigate technical noise in large-scale single-cell genomics data
Authors: Ruoxin Li, Gerald Quon
Journal: Genome biology (2019)

Technical variation in feature measurements, such as gene expression and locus accessibility, is a key challenge of large-scale single-cell genomic datasets. We show that this technical variation in both scRNA-seq and scATAC-seq datasets can be mitigated by analyzing feature detection patterns alone and ignoring feature quantification measurements. This result holds when datasets have low detection noise relative to quantification noise. We demonstrate state-of-the-art performance of detection pattern models using our new framework, scBFA, for both cell type identification and trajectory inference. Performance gains can also be realized in one line of R code in existing pipelines.