tbuckley/cabot-search huggingface dataset:
Assessing the unified airway hypothesis in children via transcriptional profiling of the airway epithelium
Authors: Anthony Kicic, Emma de Jong, Kak-Ming Ling, Kristy Nichol, Denise Anderson, Peter A.B. Wark, Darryl A. Knight, Anthony Bosco, Stephen M. Stick, Anthony Kicic, Stephen M. Stick, Darryl A. Knight, Elizabeth Kicic-Starcevich, Luke W. Garratt, Marc Padros-Goosen, Ee-Lyn Tan, Erika N. Sutanto, Kevin Looi, Jessica Hillas, Thomas Iosifidis, Nicole C. Shaw, Samuel T. Montgomery, Kak-Ming Ling, Kelly M. Martinovich, Francis J. Lannigan, Ricardo Bergesio, Bernard Lee, Shyan Vijaya-Sekeran, Paul Swan, Mairead Heaney, Ian Forsyth, Tobias Schoep, Alexander Larcombe, Monica Hunter, Kate McGee, Nyssa Millington, Anthony Kicic, Stephen M. Stick, Elizabeth Kicic-Starcevich, Luke W. Garratt, Erika N. Sutanto, Kevin Looi, Jessica Hillas, Thomas Iosifidis, Nicole C. Shaw, Samuel T. Montgomery, Kak-Ming Ling, Kelly M. Martinovich, Matthew W.-P. Poh, Daniel R. Laucirica, Craig Schofield, Samantha McLean, Katherine Landwehr, Emma de Jong, Nigel Farrow, Eugene Roscioli, David Parsons, Darryl A. Knight, Christopher Grainge, Andrew T. Reid, Su-Ling Loo, Punnam C. Veerati
Journal: Journal of Allergy and Clinical Immunology (2020)
Landscape of cyclin pathway genomic alterations across 7,207 non-prostate genitourinary tumors.
Authors: Denis Leonardo Fontes Jardim, Sherri Z. Millis, Michele Sue-Ann Woo, Jeffrey S. Ross, Siraj Mahamed Ali, Razelle Kurzrock
Journal: Journal of Clinical Oncology (2020)

549 Background: Cyclin pathway genomic alterations can be a possible therapeutic target as well as a resistance mechanism for therapy. We describe the landscape of cyclin alterations (alt) in non-prostate genitourinary (GU) cancers. Methods: Consecutive samples were analyzed in a CLIA-certified laboratory using comprehensive genomic profiling (CGP) performed by next-generation tissuesequencing (315 genes, &gt;500X coverage). We describe alterations in activating genes (Table) and co-alterations in resistant genes ( RB1 and CCNE1) (related to cyclin inhibition). Results: Alterations in any cyclin pathway genes were found in 37.9% of bladder/urothelial, 33.8% of testicular, 25.2% of penile and 24.6% of kidney cancers. Most alterations were copy number changes and frequencies varied substantially for each tumor type (Table). The high number of cases permitted identification of interesting patterns of outliers for each histology (examples: testis rhabdomyosarcoma and leydig tumor, 50% and 54.5% CDK4 alt; ureter urothelial, 17% CCND1 amp; bladder squamous, 41% CDKN2A del; kidney malignant rhabdoid, 90% SMARCB1 alt; urethra urothelial, 14.7% CCNE1 alt). Alterations in possible resistance genes RB1 and CCNE1 were more frequent in bladder cancers (especially with a neuroendocrine component). Co-occurrence analysis demonstrated a lower likelihood of concomitant vs. isolated alt in cyclin activating and resistance genes (odds ratio for bladder 0.17, p&lt;0.001; OR testis 0.49, p&lt;0.001 and OR kidney 0.45, p&lt;0.001). Conclusions: Cyclin pathway activating and resistance genomic alt are variable in non-prostate GU tumors. Activating alt often occur without simultaneous resistance alt. Our data may inform opportunities for targeted therapy, especially for rare subtypes.[Table: see text]
IgA deficiency Alters Systemic Immune Response to Commensal Gut Microbes
Authors: Peyton Conrey, Kaitlin O'Boyle, Lidiya Denu, Jean-Bernard Lubin, Tereza Duranova, Lauren Gianchetti, Brittany Haltzman, Laura Vella, Jonathan Spergel, E. John Wherry, Sarah Henrickson, Michael Silverman
Journal: Journal of Allergy and Clinical Immunology (2020)
Design biodegradable Zn alloys: Second phases and their significant influences on alloy properties
Authors: Zhang-Zhi Shi, Xi-Xian Gao, Hai-Jun Zhang, Xue-Feng Liu, Hui-Yan Li, Chao Zhou, Yu-Xia Yin, Lu-Ning Wang
Journal: Bioactive Materials (2020)

Alloying combined with plastic deformation processing is widely used to improve mechanical properties of pure Zn. As-cast Zn and its alloys are brittle. Beside plastic deformation processing, no effective method has yet been found to eliminate the brittleness and even endow room temperature super-ductility. Second phase, induced by alloying, not only largely determines the ability of plastic deformation, but also influences strength, corrosion rate and cytotoxicity. Controlling second phase is important for designing biodegradable Zn alloys. In this review, knowledge related to second phases in biodegradable Zn alloys has been analyzed and summarized, including characteristics of binary phase diagrams, volume fraction of second phase in function of atomic percentage of an alloying element, and so on. Controversies about second phases in Zn–Li, Zn–Cu and Zn–Fe systems have been settled down, which benefits future studies. The effects of alloying elements and second phases on microstructure, strength, ductility, corrosion rate and cytotoxicity have been neatly summarized. Mg, Mn, Li, Cu and Ag are recommended as the major alloying elements, owing to their prominent beneficial effects on at least one of the above properties. In future, synergistic effects of these elements should be more thoroughly investigated. For other nutritional elements, such as Fe and Ca, refining second phase is a matter of vital concern.
Notes from the Field: Syndromic Surveillance Used To Monitor Emergency Department Visits During a Synthetic Cannabinoid Overdose Outbreak — Connecticut, August 2018
Authors: Sydney A. Jones, Kristen Soto, Erin Grogan, Alexander Senetcky, Susan Logan, Matthew Cartter
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

In 2018, the Connecticut Department of Public Health was able to use syndromic surveillance to rapidly understand the magnitude of an outbreak of synthetic cannabinoid overdoses and provide timely information to state and local health departments.
Using high-resolution magic angle spinning magnetic resonance spectroscopy to characterize the metabolomic profile of renal cell carcinoma.
Authors: Melissa Jessica Huynh, Andrew Gusev, Francesco Palmas, Lindsey Vandergrift, Chin-Lee Wu, Leo Cheng, Adam S. Feldman
Journal: Journal of Clinical Oncology (2020)

710 Background: Renal cell carcinoma (RCC) is a metabolic disease, with the various subtypes exhibiting aberrations in different metabolic pathways. Metabolomics may offer greater sensitivity for revealing disease biology than evaluation of tissue morphology. In this study, we investigate the metabolomic profile of RCC using high resolution magic angle spinning (HRMAS) magnetic resonance spectroscopy (MRS). Methods: Tissue samples were obtained from radical or partial nephrectomy specimens that were fresh frozen &amp; stored at -80ºC. Tissue HRMAS MRS was performed by a Bruker AVANCE spectrometer. Metabolomic profiles of RCC &amp; adjacent benign renal tissue were compared, and false discovery rates (FDR) were used to account for multiple testing. Regions of interest (ROI) with FDR &lt; 0.05 were selected as potential predictors of malignancy. The Wilcoxon rank sum test was used to compare median MRS relative intensities for the candidate predictors. Logistic regression was used to determine odds ratios for risk of malignancy based on abundance of each metabolite. Results: There were 38 RCC (16 clear cell, 11 papillary, 11 chromophobe) &amp; 13 adjacent normal tissue specimens (matched pairs). Metabolic predictors of malignancy based on FDR include histidine, phenylalanine, phosphocholine, serine, phosphocreatine, creatine, glycerophosphocholine, valine, glycine, myo-inositol, scylla-inositol, taurine, glutamine, spermine, acetoacetate &amp; lactate. Higher levels of spermine, histidine &amp; phenylalanine at 3.15-3.13 ppm were associated with a decreased risk of RCC (OR 4x10 −5 , 95% CI 7.42x10 −8 , 0.02), while 2.84-2.82 ppm increased the risk of malignant pathology (OR 7158.67, 95% CI 6.3, 8.3x10 6 ), and the specific metabolites characterizing this region remain to be identified. Tumor stage did not appear to affect the metabolomics of malignant tumors, suggesting that metabolites are more dependent on histologic subtype. Conclusions: HRMAS-MRS identified many metabolites that may predict RCC. We demonstrated that those in the 3.14-3.13 ppm ROI were present in lower levels in RCC, while higher levels of metabolites in the 2.84-2.82 ppm ROI substantially increased the risk of RCC.
(NZW×BXSB)F 1 マウス 自然発生的血小板減少性紫斑病の新しい動物モデル
Authors: Oyaizu N, Yasumizu R, Miyama-Inaba M, Nomura S, Miyawaki S, Mitsuoka S, Morii S, Good R A, Ikehara S
Journal: The Journal of Experimental Medicine (1988)
Early epidemiological analysis of the coronavirus disease 2019 outbreak based on crowdsourced data: a population-level observational study
Authors: Kaiyuan Sun, Jenny Chen, Cécile Viboud
Journal: The Lancet Digital Health (2020)

SummaryBackgroundAs the outbreak of coronavirus disease 2019 (COVID-19) progresses, epidemiological data are needed to guide situational awareness and intervention strategies. Here we describe efforts to compile and disseminate epidemiological information on COVID-19 from news media and social networks.MethodsIn this population-level observational study, we searched DXY.cn, a health-care-oriented social network that is currently streaming news reports on COVID-19 from local and national Chinese health agencies. We compiled a list of individual patients with COVID-19 and daily province-level case counts between Jan 13 and Jan 31, 2020, in China. We also compiled a list of internationally exported cases of COVID-19 from global news media sources (Kyodo News, The Straits Times, and CNN), national governments, and health authorities. We assessed trends in the epidemiology of COVID-19 and studied the outbreak progression across China, assessing delays between symptom onset, seeking care at a hospital or clinic, and reporting, before and after Jan 18, 2020, as awareness of the outbreak increased. All data were made publicly available in real time.FindingsWe collected data for 507 patients with COVID-19 reported between Jan 13 and Jan 31, 2020, including 364 from mainland China and 143 from outside of China. 281 (55%) patients were male and the median age was 46 years (IQR 35–60). Few patients (13 [3%]) were younger than 15 years and the age profile of Chinese patients adjusted for baseline demographics confirmed a deficit of infections among children. Across the analysed period, delays between symptom onset and seeking care at a hospital or clinic were longer in Hubei province than in other provinces in mainland China and internationally. In mainland China, these delays decreased from 5 days before Jan 18, 2020, to 2 days thereafter until Jan 31, 2020 (p=0·0009). Although our sample captures only 507 (5·2%) of 9826 patients with COVID-19 reported by official sources during the analysed period, our data align with an official report published by Chinese authorities on Jan 28, 2020.InterpretationNews reports and social media can help reconstruct the progression of an outbreak and provide detailed patient-level data in the context of a health emergency. The availability of a central physician-oriented social network facilitated the compilation of publicly available COVID-19 data in China. As the outbreak progresses, social media and news reports will probably capture a diminishing fraction of COVID-19 cases globally due to reporting fatigue and overwhelmed health-care systems. In the early stages of an outbreak, availability of public datasets is important to encourage analytical efforts by independent teams and provide robust evidence to guide interventions.FundingFogarty International Center, US National Institutes of Health.
Surgical management versus combination radiotherapy in Gleason score 9-10 prostate cancer.
Authors: Edward Christopher Dee, Martin T. King, Santino Butler, Zizi Yu, Sybil Sha, David Dewei Yang, Brandon Arvin Virgil Mahal, Kent William Mouw, Anthony Victor D'Amico, Paul L. Nguyen, Vinayak Muralidhar
Journal: Journal of Clinical Oncology (2020)

135 Background: For men with Gleason score 9-10 prostate cancer, studies have demonstrated conflicting results on the outcomes from combination radiation therapy (ComboRT) with external beam radiation therapy plus brachytherapy boost versus radical prostatectomy (RP), with or without adjuvant radiation therapy (ART). Differences in patient selection and management may explain some of the disparate outcomes of prior reports. Methods: The Surveillance, Epidemiology, and End Results database identified 10,396 men managed with ComboRT versus RP (+/-ART). Competing-risks regression analysis with treatment propensity adjustment defined hazard ratios (aHR) for prostate cancer-specific mortality (PCSM), controlling for patient-specific demographic factors. To explore the possible effect of patient selection, analyses were conducted before and after excluding men from analysis if they had evidence-based indications for ART (adverse pathology, i.e. pT3-T4 or positive margins) but did not receive it. Results: Median age was 64 years; median follow-up was 69 months. Five-year PCSM was similar between patients treated with RP (with or without ART, regardless of pathologic features, N=8,934) and ComboRT (N=1,462) (6.9% vs 8.1%, aHR=0.94, 95% confidence interval [CI] 0.78–1.13, P=0.51). After excluding RP-treated men with adverse pathology who did not receive ART (N=4,527 excluded), patients treated with RP+/-ART (N=4,407) had improved 5-year PCSM compared with those treated with ComboRT (5.3% vs 8.1%, aHR=0.74, 95% CI 0.60–0.91, P=0.004). Conclusions: For Gleason 9-10 prostate cancer, ComboRT was associated with similar PCSM compared to RP, but risk-tailored surgical management may be associated with superior PCSM.
89P A Feedback Regulatory Loop Between Mir-125B and Brms1 Linked to Breast Tumor Progression
Authors: D. Allard, M. Lacroix-Triki, G. Maillot, L. Mhamdi, S. Pierredon, F. Obrist, A. Goubar, H. Roche, F. Andr纯, S. Vagner
Journal: Annals of Oncology (2012)
Association of PI-RADS categories and PSA density with active surveillance progression in patients with prostate cancer.
Authors: Alex Z. Wang, Luke P. O'Connor, Nitin Yerram, Johnathan Zeng, Sherif Mehralivand, Stephanie Harmon, Sandeep Gurram, Heather Chalfin, Siobhan Telfer, Amir H. Lebastchi, Michael Ahdoot, Patrick H. Gomella, Maria J. Merino, Baris Turkbey, Bradford J. Wood, Peter L. Choyke, Peter A. Pinto
Journal: Journal of Clinical Oncology (2020)

293 Background: Active surveillance (AS) is now considered a well-accepted alternative for low-favorable intermediate risk prostate cancer over definitive therapy. Few studies have incorporated the use of multi-parametric MRI (mpMRI) into the treatment paradigm. In this study we investigate imaging findings that are predictive of a patient dropping off AS. Methods: Our institutional database was queried for all patients who met criteria for active surveillance from 11/2003 to 5/2017. Criteria for inclusion included ≥ 2 mpMRIs, ≥ 2 prostate biopsies, and a diagnosis of Gleason Grade group (GG) 1 or higher. Patients were excluded if they received any other therapy for the treatment of their prostate cancer such as radiation, chemotherapy, focal therapy, or immunologic therapy. Patient demographics, mpMRI, biopsy and most recent follow-up data were recorded. Factors, including PSA density (PSAD), PSA, lesion size, and PI-RADS category, associated with AS progression were evaluated in Cox Proportional Hazards Model. Results: An analysis of a total of 212 patients were performed during the study time interval. 88 patients were dropped from AS during this time and of those patients the median amount of time before removal was 4.70 years (range, 0.7-10.5). On univariable analysis, PI-RADS category (HR, 1.302 for every increase in 1 unit of the PI-RADS category; 95% CI, 1.046-1.62, p = 0.01) and PSAD (HR, 4.98 for every increase in 0.001 ng/mL/cc; 95% CI, 2.127-11.66; p &lt; 0.001) were found to be associated with being removed from AS. On multivariable analysis, both PI-RADS score (HR, 1.281 for every increase in 1 unit of the PI-RADS category; 95% CI, 1.025-1.6; p = 0.003) and PSAD (HR, 4.188 for every increase in 0.001 ng/mL/cc; 95% CI, 1.640-10.7; p &lt; 0.001) remained associated with being removed from AS. Conclusions: PI-RADS categories and PSAD predict the risk of a patient to drop off active surveillance. AS. Patients with these criteria should be considered high risk in any current AS protocol.[Table: see text]
Progress, opportunity, and perspective on exosome isolation - efforts for efficient exosome-based theranostics
Authors: Dongbin Yang, Weihong Zhang, Huanyun Zhang, Fengqiu Zhang, Lanmei Chen, Lixia Ma, Leon M. Larcher, Suxiang Chen, Nan Liu, Qingxia Zhao, Phuong H.L. Tran, Changying Chen, Rakesh N Veedu, Tao Wang
Journal: Theranostics (2020)

Exosomes are small extracellular vesicles with diameters of 30-150 nm.In both physiological and pathological conditions, nearly all types of cells can release exosomes, which play important roles in cell communication and epigenetic regulation by transporting crucial protein and genetic materials such as miRNA, mRNA, and DNA.Consequently, exosome-based disease diagnosis and therapeutic methods have been intensively investigated.However, as in any natural science field, the in-depth investigation of exosomes relies heavily on technological advances.Historically, the two main technical hindrances that have restricted the basic and applied researches of exosomes include, first, how to simplify the extraction and improve the yield of exosomes and, second, how to effectively distinguish exosomes from other extracellular vesicles, especially functional microvesicles.Over the past few decades, although a standardized exosome isolation method has still not become available, a number of techniques have been established through exploration of the biochemical and physicochemical features of exosomes.In this work, by comprehensively analyzing the progresses in exosome separation strategies, we provide a panoramic view of current exosome isolation techniques, providing perspectives toward the development of novel approaches for high-efficient exosome isolation from various types of biological matrices.In addition, from the perspective of exosome-based diagnosis and therapeutics, we emphasize the issue of quantitative exosome and microvesicle separation.
A highly sensitive and specific workflow for detecting rare copy-number variants from exome sequencing data
Authors: Ramakrishnan Rajagopalan, Jill R. Murrell, Minjie Luo, Laura K. Conlin
Journal: Genome Medicine (2020)

Exome sequencing (ES) is a first-tier diagnostic test for many suspected Mendelian disorders. While it is routine to detect small sequence variants, it is not a standard practice in clinical settings to detect germline copy-number variants (CNVs) from ES data due to several reasons relating to performance. In this work, we comprehensively characterized one of the most sensitive ES-based CNV tools, ExomeDepth, against SNP array, a standard of care test in clinical settings to detect genome-wide CNVs. We propose a modified ExomeDepth workflow by excluding exons with low mappability prior to variant calling to drastically reduce the false positives originating from the repetitive regions of the genome, and an iterative variant calling framework to assess the reproducibility. We used a cohort of 307 individuals with clinical ES data and clinical SNP array to estimate the sensitivity and false discovery rate of the CNV detection using exome sequencing. Further, we performed targeted testing of the STRC gene in 1972 individuals. To reduce the number of variants for downstream analysis, we performed a large-scale iterative variant calling process with random control cohorts to assess the reproducibility of the CNVs. The modified workflow presented in this paper reduced the number of total variants identified by one third while retaining a higher sensitivity of 97% and resulted in an improved false discovery rate of 11.4% compared to the default ExomeDepth pipeline. The exclusion of exons with low mappability removes 4.5% of the exons, including a subset of exons (0.6%) in disease-associated genes which are intractable by short-read next-generation sequencing (NGS). Results from the reproducibility analysis showed that the clinically reported variants were reproducible 100% of the time and that the modified workflow can be used to rank variants from high to low confidence. Targeted testing of 30 CNVs identified in STRC, a challenging gene to ascertain by NGS, showed a 100% validation rate. In summary, we introduced a modification to the default ExomeDepth workflow to reduce the false positives originating from the repetitive regions of the genome, created a large-scale iterative variant calling framework for reproducibility, and provided recommendations for implementation in clinical settings.
A novel water-soluble budesonide nasal spray (Budesolv 10) improves asthmatic symptoms promptly in patients suffering from grass pollen allergic symptoms induced in an allergen exposure chamber
Authors: Petra Zieglmayer, Patrick Lemell, Nicole Unger- Manhart, Andreas Goessl, René Zieglmayer, Eva Prieschl- Grassauer
Journal: Journal of Allergy and Clinical Immunology (2020)
Genetic alterations of early-stage breast cancers by next-generation sequencing (NGS)
Authors: Y. Xu, M. Zhang, R. Chen, X. Xia
Journal: Annals of Oncology (2018)

Background: Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death in women. Patients diagnosed with early stage generally have better survival. However, disease free survival differed significantly for different molecular subtypes. Understanding the genetic alterations of early-stage breast cancer may help to identify patients at high risk for relapse. Methods: We retrospectively reviewed genetic profiling of 53 early-stage breast cancer samples in our institute. Surgical specimens were analyzed using hybridization capture-based NGS ER-seq method, white blood cells as control, which enables simultaneously assess single-nucleotide variants (SNV), insertions/deletions (indel), rearrangements and somatic copy-number variation(CNV) of 1021 genes. Results: Fifty-three surgical specimens from 51 female patients with early-stage breast cancer were analyzed, including two bilateral primary breast cancers with different molecular subtypes. There were 29 HR+/HER2-, 6 HER2+, 6 HR+/HER2+ and 12 TNBC. The median diagnosis age was 43(range 31-67). In addition to TP53, there were 16 genes carried actionable mutations identified (details in table). The most frequently mutant genes were TP53 and PIK3CA, in all molecular subtypes. Among PIK3CA mutations, the H1047R/L were tested in all subtypes. Other gene alterations were highly heterogeneous in different molecular subtypes. HRAS or KRAS mutation was always identified with other genes. For instance, HRAS/PIK3CA and KRAS/AKT1 concurrent in 2 HR+/HER2-, KRAS/PIK3CA concurrent in 1 TNBC. Interestingly, for the two bilateral primary breast cancers, one patient had no overlapping mutation in 2 samples within total 6 variants, the other one only had common HER2 CNV in 2 samples within total 13 variants.Table: 210PSignaling PathwaysGenetic AlterationsHR+/HER2-(29)HER2 + (6)HR+/HER2 + (6)TNBC(12)p53TP53145411PI3K/AKT/mTORPIK3CA12313AKT16---PTEN3---NF11---FLCN1---Homologous recombination repairBRCA1(gm)---1BRCA1(sc)-1--BRCA2(gm)2---BRCA2(sc)-1--ATM(gm)--1-Ras/Raf/MAPKHRAS1---KRAS1--1Cell cycleRB11---CDKN2A1---CCND11---RTKsFGFR11-1-HER2 CNV-45-EGFR CNV---1sc, somatic mutation; gm, germline mutation. Open table in a new tab sc, somatic mutation; gm, germline mutation. Conclusions: Genetic alterations were highly heterogeneous in different molecular subtypes of early-stage breast cancers. And this may contribute to the different relapse risk. Legal entity responsible for the study: Geneplus-Beijing. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.