tbuckley/cabot-search huggingface dataset:
Uncovering Biological Factors That Regulate Hepatocellular Carcinoma Growth Using Patient‐Derived Xenograft Assays
Authors: Min Zhu, Lin Li, Tianshi Lu, Hyesun Yoo, Ji Zhu, Purva Gopal, Sam C. Wang, Matthew R. Porembka, Nicole E. Rich, Sofia Kagan, Mobolaji Odewole, Veronica Renteria, Akbar K. Waljee, Tao Wang, Amit G. Singal, Adam C. Yopp, Hao Zhu
Journal: Hepatology (2020)

Background and Aims Several major factors limit our understanding of hepatocellular carcinoma (HCC). First, human HCCs are infrequently biopsied for diagnosis and thus are not often biologically interrogated. Second, HCC initiation and progression are strongly influenced by the cirrhotic microenvironment, and the exact contributions of intrinsic and extrinsic tumor factors are unclear. A powerful approach to examine the personalized biology of liver cancers and the influence of host tissues is with patient‐derived xenograft (PDX) models. In Asia, HCCs from patients with hepatitis B virus have been efficiently converted into PDXs, but few parallel efforts from the west have been reported. Approach and Results In a large‐scale analysis, we implanted 93 HCCs and 8 cholangiocarcinomas (CCAs) to systematically analyze host factors and to define an optimized platform for PDX development from both surgical and biopsy samples. NOD Scid IL‐2Rγ−/− (NSG) mice that had undergone partial hepatectomy (PHx) represented the best combination of engraftability, growth, and passageability, but overall rates were low and indicative of a unique intrinsic biology for HCCs in the United States. PDX models preserved the histology and genetic features of parental tumors, and ultimately, eight models were usable for preclinical studies. Intriguingly, HCC PDXs were differentially sensitive to regorafenib and sorafenib, and CCA PDXs were also highly sensitive to regorafenib. Conclusions PDX models functionalize early and advanced stage HCCs and revealed unique biological features of liver cancers from the United States.
Schistosomiasis — Assessing Progress toward the 2020 and 2025 Global Goals
Authors: Arminder K Deol, Fiona M Fleming, Beatriz Calvo-Urbano, Martin Walker, Victor Bucumi, Issah Gnandou, Edridah M Tukahebwa, Samuel Jemu, Upendo J Mwingira, Abdulhakeem Alkohlani, Mahamadou Traoré, Eugene Ruberanziza, Seydou Touré, Maria-Gloria Basáñez, Michael D French, Joanne P Webster
Journal: New England Journal of Medicine (2019)

With the vision of "a world free of schistosomiasis," the World Health Organization (WHO) set ambitious goals of control of this debilitating disease and its elimination as a public health problem by 2020 and 2025, respectively. As these milestones become imminent, and if programs are to succeed, it is important to evaluate the WHO programmatic guidelines empirically.
The somatic mutation landscape of the human body
Authors: Pablo E. García-Nieto, Ashby J. Morrison, Hunter B. Fraser
Journal: Genome biology (2019)

Abstract Background Somatic mutations in healthy tissues contribute to aging, neurodegeneration, and cancer initiation, yet they remain largely uncharacterized. Results To gain a better understanding of the genome-wide distribution and functional impact of somatic mutations, we leverage the genomic information contained in the transcriptome to uniformly call somatic mutations from over 7500 tissue samples, representing 36 distinct tissues. This catalog, containing over 280,000 mutations, reveals a wide diversity of tissue-specific mutation profiles associated with gene expression levels and chromatin states. For example, lung samples with low expression of the mismatch-repair gene MLH1 show a mutation signature of deficient mismatch repair. In addition, we find pervasive negative selection acting on missense and nonsense mutations, except for mutations previously observed in cancer samples, which are under positive selection and are highly enriched in many healthy tissues. Conclusions These findings reveal fundamental patterns of tissue-specific somatic evolution and shed light on aging and the earliest stages of tumorigenesis.
Effect of antihypertensive medication reduction vs usual care on short-term blood pressure control in patients aged ≥ 80 years with hypertension The OPTiMISE randomized clinical trial
Authors: R Mcmanus, J Sheppard
Journal: JAMA (2020)

This work received joint funding from the National Institute for Health Research (NIHR) Oxford Collaboration for Leadership in Applied Health Research and Care (CLAHRC) at Oxford Health NHS Foundation Trust (ref: P2-501) and the NIHR School for Primary Care Research (SPCR; ref 335).
Keyhole hysterectomy is effective for women with heavy menstrual bleeding
Authors: Rob Cook, Johnny Lyon-Maris, Peter Davidson
Journal: BMJ (2020)

The study Cooper K, Breeman S, Scott NW, et al. Laparoscopic supracervical hysterectomy versus endometrial ablation for women with heavy menstrual bleeding (HEALTH): a parallel-group, open-label, randomised controlled trial. Lancet 2019;394:1425-36. The study was funded by the NIHR Health Technology Assessment Programme (project number 12/35/23). To read the full NIHR Signal, go to: https://discover.dc.nihr.ac.uk/content/signal-000837/keyhole-hysterectomy-is-effective-for-women-with-heavy-menstrual-bleeding
FDG PET/CT of a Supraclavicular Silicone Granuloma at Follow-up of a Breast Carcinoma
Authors: Olivier Phan Sy, René-Charles Rouchy, Nicolas De Leiris, Eleni Nika, Loïc Djaileb
Journal: Clinical Nuclear Medicine (2019)

Abstract We report herein the case of a 33-year-old woman who was referred for FDG PET/CT staging prior to pregnancy after a 4-year lost to follow-up for a breast invasive ductal carcinoma (pT2N1 SBRII). FDG PET/CT revealed right supraclavicular lymphadenopathy potentially caused by breast carcinoma recurrence. No additional site was involved. Supraclavicular ultrasonography showed typical “snowstorm” appearance. MRI revealed signs of breast implant intracapsular rupture and signal intensity of silicone within a supraclavicular node. Fine-needle aspiration and microbiopsy of adenopathy finally confirmed silicone granuloma and ruled out breast cancer recurrence.
Abstract NT-097: QUANTITATIVE HIGH-THROUGHPUT SCREENING USING AN ORGANOTYPIC MODEL IDENTIFIES TWO KINASE INHIBITORS THAT INHIBIT OVARIAN CANCER METASTASIS
Authors: Hilary A. Kenny, Madhu Lal, Min Shen, Dominik Nahotko, Sarah Fazal, Siquan Chen, Chun-Yi Chiang, Betul Kara, S. Diane Yamada, Kyle Brimacombe, Juan Marugan, Marc Ferrer, Ernst Lengyel
Journal: Clinical Cancer Research (2019)

Abstract The cancer cells, stromal cells and stroma in the tumor microenvironment contribute to cancer metastasis and drug resistance. Therefore we applied an organotypic, robust and reliable assay for quantitative high throughput screening (qHTS) in drug discovery. This 1536-well HTS culture contains primary human mesothelial cells, fibroblasts, fibronectin and collagen type I and reproduces the human ovarian cancer (OvCa) metastatic microenvironment. The qHTS assay identifies small molecule compounds that inhibit OvCa adhesion/migration/invasion to the organotypic metastatic microenvironment. Over 44,000 small molecules were screened in the primary qHTS assay. A counter screen was performed to eliminate any compounds toxic to the mesothelial cells or fibroblasts within the metastatic microenvironment. The activity of hit compounds was confirmed using five OvCa cell lines, and validated in secondary in vitro and in vivo biological assays. The active compounds directly inhibit at least two of three OvCa functions: adhesion, invasion and growth. In vivo, these compounds prevent OvCa adhesion/invasion and metastasis, and improve survival in mouse models. Collectively, these data indicate that the three compounds, two tyrosine kinase inhibitors and one novel compound, identified using an complex organtoypic culture of the tumor microenvironment for qHTS are potential therapeutics for OvCa metastasis. Citation Format: Hilary A. Kenny, Madhu Lal, Min Shen, Dominik Nahotko, Sarah Fazal, Siquan Chen, Chun-Yi Chiang, Betul Kara, S. Diane Yamada, Kyle Brimacombe, Juan Marugan, Marc Ferrer and Ernst Lengyel. QUANTITATIVE HIGH-THROUGHPUT SCREENING USING AN ORGANOTYPIC MODEL IDENTIFIES TWO KINASE INHIBITORS THAT INHIBIT OVARIAN CANCER METASTASIS [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr NT-097.
High-resolution mycobiota analysis reveals dynamic intestinal translocation preceding invasive candidiasis
Authors: Bing Zhai, Mihaela Ola, Thierry Rolling, Nicholas L. Tosini, Sari Joshowitz, Eric R. Littmann, Luigi A. Amoretti, Emily Fontana, Roberta J. Wright, Edwin Miranda, Charlotte A. Veelken, Sejal M. Morjaria, Jonathan U. Peled, Marcel R. M. van den Brink, N. Esther Babady, Geraldine Butler, Ying Taur, Tobias M. Hohl
Journal: Nature Medicine (2020)
Chinese researcher who made CRISPR babies is sentenced to three years in prison
Authors: Owen Dyer
Journal: BMJ (2020)

He Jiankui, the researcher and entrepreneur who in 2018 announced the birth of the world’s first gene edited babies, has been sentenced to three years’ imprisonment and fined 3m yuan (£329 000; €386 000; $430 000) by a Chinese court.

Two researchers who worked with him received lesser sentences and fines. The three were convicted of practising medicine without a licence. He Jiankui also fabricated an ethics review certificate, the District People’s Court in Shenzhen found. All three men pleaded guilty.

“The three accused did not have the proper certification to practise medicine, and, in seeking fame and wealth, deliberately violated national regulations in scientific research and medical treatment,” the court said, according to China’s official news agency Xinhua.

The court also confirmed reports of the birth of a …
Refining the bigger picture: On the integrative memory model
Authors: John P Aggleton
Journal: Behavioral and Brain Sciences (2019)

The integrative memory model contains multiple subsystems. In this commentary, the processes within these subsystems are questioned. First, the assumption that familiarity largely reflects perceptual fluency is examined. Next, the distinction between "process" and "representational" models of temporal lobe function is challenged. Finally, the "relational representation core system" (or "extended hippocampal system"), which is central to the model, is especially sketchy. Here, I highlight key questions to be addressed in order to understand this system's role in trace formation.
Disparities between high-impact clinical trials in oncology and disease burden.
Authors: Nicklas Pfanzelter, Neha Jeurkar, Brian S. Finkelman, Ronac Mamtani
Journal: Journal of Clinical Oncology (2013)

e17591 Background: Recent research has identified a discrepancy between NIH funding in oncology and various measures of disease burden by tumor type. We sought to identify whether this disparity exists in recent high impact publications. Methods: 833 clinical trials published in five high impact general medicine and clinical oncology journals between January, 2009 and October, 2012 were reviewed. 692 trials were included in this analysis after excluding those that studied &gt;1 tumor type. Disease burden was measured as person-years of life lost (YLLs), reported in the Surveillance, Epidemiology, and End Results database, and disability adjusted life years (DALYs), reported by the World Health Organization. We used a chi square goodness of fit test to compare the overall distribution of trials by tumor type to the distribution of annual YLLs and DALYs. Results: Breast cancer was the most published tumor, accounting for 14% of all trials, followed by lung (13%) and colorectal (7%) cancers. More than half of the trials (56%) were for patients with metastatic disease, and most (81%) were phase 2 and 3 clinical trials. Nearly half of all publications studied targeted therapies (45%), and the majority received industry support (61%). 67% of trials with a comparator arm met their primary endpoint. The distribution of trials by cancer site differed significantly from the distribution of both measures of disease burden (YLLs and DALYs) (both p&lt;0.001). The findings were unchanged in analyses that accounted for the total number of subjects enrolled in the trials (both p&lt;0.001). The most underrepresented malignancies based on burden of disease were lung and pancreatic cancers, while the most overrepresented were breast cancer, leukemia, and melanoma. Conclusions: The number of trials published by tumor type does not directly reflect the burden of these diseases in the population as assessed by YLL or DALY. Future studies examining potential confounders such as funding availability by cancer type or number of unpublished clinical trials may further clarify the observed disparities.
Abstract 15874: Next Generation Sequencing Reveals Intra-Cardiac/Extra-Cardiac Circulating MicroRNA Transcriptomes in Atrial Fibrillation
Authors: Masahide Harada, Daisuke Okuzaki, Jun Takeda, Yuji Motoike, Masayuki Koshikawa, Eiichi Watanabe, Yukio Ozaki
Journal: Circulation (2018)

Background: Atrial fibrillation (AF) evolves from a paroxysmal to a persistent form with a process attributed to atrial remodeling. MicroRNAs (miRNAs) play a critical role in AF pathophysiology and...
The role of interventional bronchoscopy in the management of post-intubation tracheal stenosis: A 20-year experience
Authors: C. Freitas, N. Martins, H. Novais-Bastos, A. Morais, G. Fernandes, A. Magalhães
Journal: Pulmonology (2019)

Benign tracheal stenosis management is still controversial, and there is no international consensus on the best treatment option. Thus, we aimed to look into the history of PITS and the different strategies used in its treatment. The importance of bronchoscopic treatment was also defined, and its effectiveness and safety were assessed.Retrospective study of patients diagnosed with PITS, who were referred to the Bronchology Department between January 1996 and December 2016.Of 115 patients enrolled (mean age 48.5±17.6 years, 53% males), 66.1% had complex stenosis. The most common causes of intubation were respiratory (29.9%), neurological (26.8%) and surgical (19.6%). Complex stenosis was caused by longer intubation, and was more frequent among previously tracheostomized patients. The most common location was the upper third of trachea (60.9%). Most cases were initially treated by interventional bronchoscopy, and although serial dilations were effective in some complex PITS, a higher proportion of simple stenosis was successfully managed with this treatment option. Long-term recurrence after serial dilation was observed in 25.0% of cases. Stent placement was required (19.1%) only for complex PITS. Stent-related complications were frequent (61.9%) and linked to the stenting time (p<0.001). Overall, there were no procedure-related complications. Surgical intervention was also performed (30.0%), always with complex PITS. Post-surgical recurrences were observed in 24.2% of cases.Interventional bronchoscopy is an efficient and safe modality in PITS management. Further studies are needed for better classification and improved knowledge of PITS pathogenesis, and to achieve international consensus of definition to guide clinicians in their practice.
Association Between Exposure to Pyrethroid Insecticides and Risk of All-Cause and Cause-Specific Mortality in the General US Adult Population
Authors: Wei Bao, Buyun Liu, Derek W. Simonsen, Hans-Joachim Lehmler
Journal: JAMA Internal Medicine (2019)

<h3>Importance</h3> Widespread exposure to pyrethroid insecticides has been reported among the general population in the United States and worldwide. However, little is known about the association of pyrethroid exposure with long-term health outcomes in adults. <h3>Objective</h3> To examine the association of pyrethroid exposure with all-cause and cause-specific mortality among adults in the United States. <h3>Design, Setting, and Participants</h3> The nationally representative cohort included 2116 adults aged 20 years and older who participated in the US National Health and Nutrition Examination Survey conducted from 1999 to 2002 and provided urine samples for pyrethroid metabolite measurements. Participants were linked to mortality data from the survey date through December 31, 2015. Data were analyzed from May to August 2019. <h3>Exposures</h3> Urinary levels of 3-phenoxybenzoic acid, a general pyrethroid metabolite and commonly used biomarker for pyrethroid exposure, were determined by using high-performance liquid chromatography coupled with electrospray chemical ionization and tandem mass spectrometry. <h3>Main Outcomes and Measures</h3> Mortality from all causes, cardiovascular disease, and cancer. <h3>Results</h3> This cohort study of 2116 adults comprised 1145 women (weighted proportion, 51.6%) and 971 men (weighted, 48.4%), with a weighted mean (SE) age of 42.6 (0.5) years; 958 participants (weighted, 68.4%) were of non-Hispanic white ancestry, 646 (weighted, 14.7%) of Hispanic ancestry, 419 (weighted, 11.3%) of non-Hispanic black ancestry, and 93 (weighted, 5.6%) of other ancestry. During a median of 14.4 years (range, 0.1-16.8 years) of observation, 246 deaths occurred, including 41 associated with cardiovascular disease and 52 associated with cancer. Participants with higher urinary 3-phenoxybenzoic acid levels were at a higher risk of death during the follow-up period, with death occurring in 8.5% (unweighted, 75 of 709), 10.2% (unweighted, 81 of 701), and 11.9% (unweighted, 90 of 706) of participants across increasing tertiles of urinary 3-phenoxybenzoic acid levels. After adjustment for age, sex, race/ethnicity, socioeconomic status, dietary and lifestyle factors, body mass index, and urinary creatinine levels, the hazard ratios for all-cause mortality, cardiovascular disease mortality, and cancer mortality among participants with the highest tertile compared with those with the lowest tertile of urinary 3-phenoxybenzoic acid levels were 1.56 (95% CI, 1.08-2.26), 3.00 (95% CI, 1.02-8.80), and 0.91 (95% CI, 0.31-2.72), respectively. <h3>Conclusions and Relevance</h3> In this nationally representative sample of US adults, environmental exposure to pyrethroid insecticides was associated with an increased risk of all-cause and cardiovascular disease mortality. Further studies are needed to replicate the findings and determine the underlying mechanisms.
Quality and Safety in Healthcare, Part LX
Authors: Jay A. Harolds
Journal: Clinical Nuclear Medicine (2019)

Abstract Improving the culture of the community the physician encounters at work is very important to combat burnout and improve joyfulness and wellness. This includes better relationships between doctors, and between doctors and other healthcare professionals and administrators. Engaging the physicians in their clinical work and other meaningful activities such as research, teaching, and important administrative activities is also important. Wellness in its broadest sense is not merely the absence of burnout or other maladies; it is also about achieving the individual's full potential for a successful life.
The Indian cobra reference genome and transcriptome enables comprehensive identification of venom toxins
Authors: Kushal Suryamohan, Sajesh P. Krishnankutty, Joseph Guillory, Matthew Jevit, Markus S. Schröder, Meng Wu, Boney Kuriakose, Oommen K. Mathew, Rajadurai C. Perumal, Ivan Koludarov, Leonard D. Goldstein, Kate Senger, Mandumpala Davis Dixon, Dinesh Velayutham, Derek Vargas, Subhra Chaudhuri, Megha Muraleedharan, Ridhi Goel, Ying-Jiun J. Chen, Aakrosh Ratan, Peter Liu, Brendan Faherty, Guillermo de la Rosa, Hiroki Shibata, Miriam Baca, Meredith Sagolla, James Ziai, Gus A. Wright, Domagoj Vucic, Sangeetha Mohan, Aju Antony, Jeremy Stinson, Donald S. Kirkpatrick, Rami N. Hannoush, Steffen Durinck, Zora Modrusan, Eric W. Stawiski, Kristen Wiley, Terje Raudsepp, R. Manjunatha Kini, Arun Zachariah, Somasekar Seshagiri
Journal: Nature Genetics (2020)

Snakebite envenoming is a serious and neglected tropical disease that kills ~100,000 people annually. High-quality, genome-enabled comprehensive characterization of toxin genes will facilitate development of effective humanized recombinant antivenom. We report a de novo near-chromosomal genome assembly of Naja naja, the Indian cobra, a highly venomous, medically important snake. Our assembly has a scaffold N50 of 223.35 Mb, with 19 scaffolds containing 95% of the genome. Of the 23,248 predicted protein-coding genes, 12,346 venom-gland-expressed genes constitute the 'venom-ome' and this included 139 genes from 33 toxin families. Among the 139 toxin genes were 19 'venom-ome-specific toxins' (VSTs) that showed venom-gland-specific expression, and these probably encode the minimal core venom effector proteins. Synthetic venom reconstituted through recombinant VST expression will aid in the rapid development of safe and effective synthetic antivenom. Additionally, our genome could serve as a reference for snake genomes, support evolutionary studies and enable venom-driven drug discovery.
Association Between Maternal Fluoride Exposure and Child IQ
Authors: Stuart J. Ritchie, Alexander J. Morris, Kevin McConway
Journal: JAMA Pediatrics (2019)

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Abstract 10611: Association Between Ultra-Processed Food Intake and Cardiovascular Health Among US Adults: NHANES 2011-2016
Authors: Zefeng Zhang, Sandra Jackson, Euridice Martinez, Cathleen Gillespie, Quanhe Yang
Journal: Circulation (2019)

Introduction: Studies have suggested that higher intake of ultra-processed foods (UPF) is associated with increased risk for cardiovascular disease. The American Heart Association’s “Life’s Simple ...