tbuckley/cabot-search huggingface dataset:
SCLC Subtypes Defined by ASCL1, NEUROD1, POU2F3, and YAP1: A Comprehensive Immunohistochemical and Histopathologic Characterization
Authors: Marina K Baine, Min-Shu Hsieh, W. Victoria Lai, Jacklynn V. Egger, Achim A. Jungbluth, Yahya Daneshbod, Amanda Beras, Rowanne Spencer, Jessica Lopardo, Francis Bodd, Joseph Montecalvo, Jennifer L. Sauter, Jason C. Chang, Darren J. Buonocore, William D. Travis, Triparna Sen, John T. Poirier, Charles M. Rudin, Natasha Rekhtman
Journal: Journal of Thoracic Oncology (2020)
Lactose-appended β-cyclodextrin as an effective nanocarrier for brain delivery
Authors: Ryoma Yokoyama, Toru Taharabaru, Takumi Nishida, Yoshitaka Ohno, Yuki Maeda, Masahiro Sato, Kandai Ishikura, Kazunori Yanagihara, Hiroki Takagi, Teruya Nakamura, Shingo Ito, Sumio Ohtsuki, Hidetoshi Arima, Risako Onodera, Taishi Higashi, Keiichi Motoyama
Journal: Journal of Controlled Release (2020)
Author Correction: L1CAM defines the regenerative origin of metastasis-initiating cells in colorectal cancer
Authors: Karuna Ganesh, Harihar Basnet, Yasemin Kaygusuz, Ashley M. Laughney, Lan He, Roshan Sharma, Kevin P. O’Rourke, Vincent P. Reuter, Yun-Han Huang, Mesruh Turkekul, Ekrem Emrah Er, Ignas Masilionis, Katia Manova-Todorova, Martin R. Weiser, Leonard B. Saltz, Julio Garcia-Aguilar, Richard Koche, Scott W. Lowe, Dana Pe’er, Jinru Shia, Joan Massagué
Journal: Nature Cancer (2020)
Electrodeposition of calcium phosphate onto polyethylene terephthalate artificial ligament enhances graft-bone integration after anterior cruciate ligament reconstruction
Authors: Jiangyu Cai, Qianqian Zhang, Jiebo Chen, Jia Jiang, Xiumei Mo, Chuanglong He, Jinzhong Zhao
Journal: Bioactive Materials (2020)

It is a big challenge to develop a polyethylene terephthalate (PET) artificial ligament with excellent osteogenetic activity to enhance graft-bone integration for ligament reconstruction. Herein, we evaluated the effect of biomineralization (BM) and electrodeposition (ED) method for depositing calcium-phosphate (CaP) on the PET artificial ligament in vitro and in vivo. Scanning electron microscopy and energy-dispersive X-Ray spectrometer mapping analysis revealed that the ED-CaP had more uniform particles and element distribution (Ca, P and O), and thermogravimetric analysis showed there were more CaP on the PET/ED-CaP than the PET/BM-CaP scaffold. Moreover, the hydrophilicity of PET scaffolds was significantly improved after CaP deposition. In vitro study showed that CaP coating via BM or ED method could improve the attachment and proliferation of MC3T3-E1 cells, and ED-CaP coating significantly increased osteogenic differentiation of the cells, in which the Wnt/β-catenin signaling pathway might be involved. In addition, radiological, histological and immunohistochemical results of in vivo study in a rabbit anterior cruciate ligament (ACL) reconstruction model demonstrated that the PET/BM-CaP and PET/ED-CaP scaffolds significantly improved graft-bone integration process compared to the PET scaffold. More importantly, larger areas of new bone ingrowth and the formation of fibrocartilage tissue were observed at 12 weeks in the PET/ED-CaP group, and the biomechanical tests showed increased ultimate failure load and stiffness in PET/ED-CaP group compared to PET/BM-CaP and PET group. Therefore, ED of CaP is an effective strategy for the modification of PET artificial ligament and can enhance graft-bone integration both in vitro and in vivo.
Recent Progress in the Development of Multifunctional Nanoplatform for Precise Tumor Phototherapy
Authors: Junjie Liu, Jinjin Shi, Weimin Nie, Sijie Wang, Genhua Liu, Kaiyong Cai
Journal: Advanced Healthcare Materials (2020)

Phototherapy, including photodynamic therapy and photothermal therapy, mainly relies on phototherapeutic agents (PAs) to produce heat or toxic reactive oxygen species (ROS) to kill tumors. It has attracted wide attention due to its merits of noninvasive properties and negligible drug resistance. However, the phototoxicity of conventional PAs is one of the main challenges for its potential clinical application. This is mainly caused by the uncontrolled distribution of PA in vivo, as well as the inevitable damage to healthy cells along the light path. Ensuring the generation of ROS or heat specific at tumor site is the key for precise tumor phototherapy. In this review, the progress of targeted delivery of PA and activatable phototherapy strategies based on nanocarriers for precise tumor therapy is summarized. The research progress of passive targeting, active targeting, and activatable targeting strategies in the delivery of PA is also described. Then, the switchable nanosystems for tumor precise phototherapy in response to tumor microenvironment, including pH, glutathione (GSH), protein, and nucleic acid, are highlighted. Finally, the challenges and opportunities of nanocarrier-based precise phototherapy are discussed for clinical application in the future.
Effects of fecal microbiota transplantation in subjects with irritable bowel syndrome are mirrored by changes in gut microbiome
Authors: Rasmus Goll, Peter Holger Johnsen, Erik Hjerde, Joseph Diab, Per Christian Valle, Frank Hilpusch, Jorunn Pauline Cavanagh
Journal: Gut Microbes (2020)

Irritable bowel syndrome (IBS) is a common disorder of the lower gastrointestinal tract. The pathophysiology is far from settled, but a gut microbial dysbiosis is hypothesized to be a contributing factor. We earlier published a randomized double-blind placebo-controlled clinical trial on fecal microbiota transplantation (FMT) for IBS – the REFIT trial. The present data set describes the engraftment and includes participants from the study who received active FMT; 14 participants with effect of FMT (Effect) and 8 without (No effect). Samples were collected at baseline, after 6 and 12 months. Samples from the transplants (Donor) served as a comparator. In total 66 recipient samples and 17 donor samples were subjected to deep metagenomic sequencing, and taxonomic and functional analyses were performed. Alpha diversity measures showed a significantly increased diversity and evenness in the IBS groups compared to the donors. Taxonomic profiles showed higher relative abundance of phylum Firmicutes, and lower relative abundance of phylum Bacteroidetes, compared to donors at baseline. This profile was shifted toward the donor profile following FMT. Imputed growth rates showed that the resulting growth pattern was a conglomerate of donor and recipient activity. Thirty-four functional subclasses showed distinct differences between baseline samples and donors, most of which were shifted toward a donor-like profile after FMT. All of these changes were less pronounced in the No effect group. We conclude that FMT induces long-term changes in gut microbiota, and these changes mirror the clinical effect of the treatment. The study was registered in ClinicalTrials.gov (NCT02154867).
Population-specific and trans-ancestry genome-wide analyses identify distinct and shared genetic risk loci for coronary artery disease
Authors: Satoshi Koyama, Kaoru Ito, Chikashi Terao, Masato Akiyama, Momoko Horikoshi, Yukihide Momozawa, Hiroshi Matsunaga, Hirotaka Ieki, Kouichi Ozaki, Yoshihiro Onouchi, Atsushi Takahashi, Seitaro Nomura, Hiroyuki Morita, Hiroshi Akazawa, Changhoon Kim, Jeong-sun Seo, Koichiro Higasa, Motoki Iwasaki, Taiki Yamaji, Norie Sawada, Shoichiro Tsugane, Teruhide Koyama, Hiroaki Ikezaki, Naoyuki Takashima, Keitaro Tanaka, Kokichi Arisawa, Kiyonori Kuriki, Mariko Naito, Kenji Wakai, Shinichiro Suna, Yasuhiko Sakata, Hiroshi Sato, Masatsugu Hori, Yasushi Sakata, Koichi Matsuda, Yoshinori Murakami, Hiroyuki Aburatani, Michiaki Kubo, Fumihiko Matsuda, Yoichiro Kamatani, Issei Komuro
Journal: Nature Genetics (2020)
Adjunctive rifampicin to reduce early mortality from Staphylococcus aureus bacteraemia (ARREST): a multi-centre, randomised, blinded, placebo controlled trial
Authors: G E Thwaites, M Scarborough, A J Szubert, E Nsutebu, R Tilley, J Greig, S A Wyllie, P Wilson, C Auckland, J Cairns, D Ward, P Lal, A Guleri, N Jenkins, J Sutton, M Wilselka, Armando G-R., C Graham, P R Chadwick, G Barlow, N C Gordon, B Young, S Meisner, P McWhinney, D A Price, D Harvey, D Nayar, D Jeyaratnam, T Planche, J Minton, F Hudson, S Hopkins, J Williams, M E Torok, M J Llewelyn, J D Edgeworth, A S Walker
Journal: The Lancet (2018)
Transluminal antegrade biopsy using a novel forceps biopsy device for hepaticojejunostomy stricture
Authors: Takeshi Ogura, Atsushi Okuda, Nobu Nishioka, Masanori Yamada, Kazuhide Higuchi
Journal: Endoscopy (2020)

The incidence of hepaticojejunostomy strictures may increase in the future with the expansion of the operative indications. Differentiating between a hepaticojejunostomy stricture and a recurrence of primary disease, such as bile duct cancer, is clinically important. A hepaticojejunostomy stricture is usually treated using an endoscopic approach, although technical success is not always achieved with this technique [1]. Hence, endoscopic ultrasound-guided biliary drainage (EUS-BD) has been developed as an alternative method [2] [3] [4]. However, obtaining histological evidence of a hepaticojejunostomy stricture is sometimes difficult because transluminal insertion of the biopsy forceps is sometimes challenging due to the acute angle between the left hepatic bile duct and the B3 liver segment. Recently, a forceps biopsy device that can be inserted over the guidewire became available in Japan (Histoguide; STERIS Endoscopy, Mentor, Ohio, USA) ([Fig. 1]). We herein describe a successful diagnosis made by obtaining histological tissue of a hepaticojejunostomy stricture through EUS-guided hepaticogastrostomy (EUS-HPG) using the novel forceps biopsy device.
Abstract IA05: Distinct immune and molecular features of melanoma brain metastases
Authors: Michael A. Davies
Journal: Cancer Research (2020)

Abstract Brain metastases are a common and devastating complication of metastatic melanoma. Clinical trials have shown that targeted and immune therapies frequently achieve less favorable results in melanoma brain metastases than in other metastatic sites, and the central nervous system (CNS) is a common initial site of systemic treatment failure in this disease. Several previous focused studies demonstrated significant differences between melanoma brain metastases (MBMs) and extracranial metastases (ECMs) that may contribute to therapeutic resistance. However, very little data are currently available about the global features of MBMs, particularly in comparison to patient-matched ECMs. Thus, we performed RNA sequencing (RNAseq) on a large cohort of resected MBMs, and resected ECMs, from metastatic melanoma patients treated at our institution. Parallel studies were performed on preclinical models of MBMs to further and functionally characterize these tumors. These studies have identified unique immune and metabolic features of MBMs. These differences provide new insights into possible mechanisms of therapeutic resistance among MBMs and suggest rational approaches to improve the efficacy of treatments for them. Citation Format: Michael A. Davies. Distinct immune and molecular features of melanoma brain metastases [abstract]. In: Proceedings of the AACR Special Conference on Melanoma: From Biology to Target; 2019 Jan 15-18; Houston, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(19 Suppl):Abstract nr IA05.
<i>Mycobacterium genavense</i> Infection Presenting as an Endobronchial Polyp and Upper Lobe Atelectasis
Authors: Chiaki Hosoda, Takashi Ishiguro, Yoshihiko Shimizu, Hirokazu Kanegane, Noboru Takayanagi
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

"Mycobacterium genavense Infection Presenting as an Endobronchial Polyp and Upper Lobe Atelectasis." American Journal of Respiratory and Critical Care Medicine, 202(11), pp. e144–e145
RIPK1 gene variants associate with obesity in humans and can be therapeutically silenced to reduce obesity in mice
Authors: Denuja Karunakaran, Adam W. Turner, Anne-Claire Duchez, Sebastien Soubeyrand, Adil Rasheed, David Smyth, David P. Cook, Majid Nikpay, Joshua W. Kandiah, Calvin Pan, Michele Geoffrion, Richard Lee, Ludovic Boytard, Hailey Wyatt, My-Anh Nguyen, Paulina Lau, Markku Laakso, Bhama Ramkhelawon, Marcus Alvarez, Kirsi H. Pietiläinen, Päivi Pajukanta, Barbara C. Vanderhyden, Peter Liu, Scott B. Berger, Peter J. Gough, John Bertin, Mary-Ellen Harper, Aldons J. Lusis, Ruth McPherson, Katey J. Rayner
Journal: Nature Metabolism (2020)
A Functional Genomic Screen Identifies the Deubiquitinase USP11 as a Novel Transcriptional Regulator of ERα in Breast Cancer
Authors: Lisa Dwane, Aisling E. O'Connor, Sudipto Das, Bruce Moran, Laoighse Mulrane, Adan Pinto-Fernandez, Elspeth Ward, Anna M. Blümel, Brenton L. Cavanagh, Brian Mooney, Annette M. Dirac, Karin Jirström, Benedikt M. Kessler, Tríona Ní Chonghaile, René Bernards, William M. Gallagher, Darran P. O'Connor
Journal: Cancer Research (2020)

Approximately 70% of breast cancers express estrogen receptor α (ERα) and depend on this key transcriptional regulator for proliferation and differentiation. While patients with this disease can be treated with targeted antiendocrine agents, drug resistance remains a significant issue, with almost half of patients ultimately relapsing. Elucidating the mechanisms that control ERα function may further our understanding of breast carcinogenesis and reveal new therapeutic opportunities. Here, we investigated the role of deubiquitinases (DUB) in regulating ERα in breast cancer. An RNAi loss-of-function screen in breast cancer cells targeting all DUBs identified USP11 as a regulator of ERα transcriptional activity, which was further validated by assessment of direct transcriptional targets of ERα. USP11 expression was induced by estradiol, an effect that was blocked by tamoxifen and not observed in ERα-negative cells. Mass spectrometry revealed a significant change to the proteome and ubiquitinome in USP11-knockdown (KD) cells in the presence of estradiol. RNA sequencing in LCC1 USP11-KD cells revealed significant suppression of cell-cycle-associated and ERα target genes, phenotypes that were not observed in LCC9 USP11-KD, antiendocrine-resistant cells. In a breast cancer patient cohort coupled with in silico analysis of publicly available cohorts, high expression of USP11 was significantly associated with poor survival in ERα-positive (ERα+) patients. Overall, this study highlights a novel role for USP11 in the regulation of ERα activity, where USP11 may represent a prognostic marker in ERα+ breast cancer. SIGNIFICANCE: A newly identified role for USP11 in ERα transcriptional activity represents a novel mechanism of ERα regulation and a pathway to be exploited for the management of ER-positive breast cancer.
Nociceptors protect sickle cell disease mice from vaso-occlusive episodes and chronic organ damage
Authors: Chunliang Xu, Maria Gulinello, Paul S. Frenette
Journal: The Journal of Experimental Medicine (2020)

Sickle cell disease (SCD) is a common hereditary hematologic disorder. SCD patients suffer from acute vaso-occlusive episodes (VOEs), chronic organ damage, and premature death, with few therapeutic options. Although severe pain is a major clinical manifestation of SCD, it remains unknown whether nociception plays a role in SCD pathogenesis. To address this question, we generated nociceptor-deficient SCD mice and found, unexpectedly, that the absence of nociception led to more severe and more lethal VOE, indicating that somatosensory nerves protect SCD mice from VOE. Mechanistically, the beneficial effects of sensory nerves were induced by the neuropeptide calcitonin gene-related peptide (CGRP), which acted on hematopoietic cells. Additionally, oral capsaicin consumption, which can activate somatosensory nerves by binding to TRPV1, dramatically alleviated acute VOE and significantly prevented chronic liver and kidney damage in SCD mice. Thus, the manipulation of nociception may provide a promising approach to treat SCD.
Effect of a single day of increased as-needed budesonide–formoterol use on short-term risk of severe exacerbations in patients with mild asthma: a post-hoc analysis of the SYGMA 1 study
Authors: Paul M O'Byrne, J Mark FitzGerald, Eric D Bateman, Peter J Barnes, Jinping Zheng, Per Gustafson, Rosa Lamarca, Margareta Puu, Christina Keen, Vijay K T Alagappan, Helen K Reddel
Journal: The Lancet Respiratory Medicine (2020)
Trends in the Age of Cigarette Smoking Initiation Among Young Adults in the US From 2002 to 2018
Authors: Jessica L. Barrington-Trimis, Jessica L. Braymiller, Jennifer B. Unger, Rob McConnell, Andrew Stokes, Adam M. Leventhal, James D. Sargent, Jonathan M. Samet, Renee D. Goodwin
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Success in reducing the prevalence of adolescent smoking could reflect complete prevention of smoking initiation or a shift in the age of cigarette smoking initiation from adolescence into early adulthood. <h3>Objective</h3> To assess trends in early adult (ages 18-23 years) vs adolescent (age &lt;18 years) cigarette smoking initiation and transition to daily cigarette smoking from 2002 to 2018. <h3>Design, Setting, and Participants</h3> Ages at initiation of smoking and the transition to daily smoking were ascertained from the National Survey on Drug Use and Health (2002-2018), an annual, population-based, repeated cross-sectional study representative of the US population. This cross-sectional analysis was restricted to young adults who completed the survey at ages 22 to 23 years during survey years 2002 to 2018 to limit potential age-related recall bias. Retrospectively collected age of cigarette smoking initiation was assessed among ever cigarette smokers; age of transition to daily smoking was assessed among ever daily cigarette smokers. Data analysis was performed from June 2019 to July 2020. <h3>Exposures</h3> Calendar year of survey (2002 to 2018). <h3>Main Outcomes and Measures</h3> The main outcomes were population-weighted cigarette smoking prevalence and cigarette smoking initiation and transition to daily smoking in adolescence (age &lt;18 years) vs early adulthood (ages 18-23 years). <h3>Results</h3> Among 71 756 young adults aged 22 to 23 years (38 226 women [50.5%]), ever cigarette smoking prevalence decreased from a population-weighted estimate of 74.6% (95% CI, 73.1%-75.9%) in 2002 to 51.4% (95% CI, 49.3%-53.5%) in 2018 (<i>P</i> &lt; .001). Daily smoking prevalence rates similarly decreased from 41.1% (95% CI, 39.1%-43.1%) in 2002 to 20.2% (95% CI, 18.6%-21.8%) in 2018 (<i>P</i> &lt; .001). However, among 48 015 ever smokers, the proportion initiating smoking in early adulthood (ages 18-23 years) increased over this time, from 20.6% (95% CI, 18.5%-22.8%) in 2002 to 42.6% (95% CI, 39.6%-45.7%) in 2018 (<i>P</i> &lt; .001). Similarly, among 24 490 daily cigarette smokers, the proportion who transitioned to daily smoking in early adulthood increased from 38.7% (95% CI, 35.9%-41.6%) in 2002 to 55.9% (95% CI, 52.0%-59.8%) in 2018 (<i>P</i> &lt; .001). <h3>Conclusions and Relevance</h3> A substantial proportion of beginning smokers and most new daily smokers are now young adults, reflecting a shift from adolescence to early adulthood, a population segment once considered beyond the critical risk period for cigarette smoking onset. Expanding the long-standing emphasis on adolescent surveillance and prevention in adolescence to include the young adult population is warranted.
Plasminogen Activator Inhibitor-1 as a Marker of Esophageal Functional Changes in Pediatric Eosinophilic Esophagitis
Authors: Prerana Williamson, James Proudfoot, Armen Gharibans, Lucas Dohil, Robert Newbury, Jacqueline Barsamian, Maheen Hassan, Renee Rawson, David Katzka, Richard Kurten, Ranjan Dohil, Hayat Mousa, Seema Aceves
Journal: Clinical Gastroenterology and Hepatology (2020)
Faecal immunochemical test after negative colonoscopy may reduce the risk of incident colorectal cancer in a population-based screening programme
Authors: Szu-Min Peng, Wen-Feng Hsu, Ying-Wei Wang, Li-Ju Lin, Amy Ming-Fang Yen, Li-Sheng Chen, Yi-Chia Lee, Ming-Shiang Wu, Tony Hsiu-Hsi Chen, Han-Mo Chiu
Journal: Gut (2020)

Subjects with a positive faecal immunochemical test (FIT) have a much higher likelihood of advanced neoplasms than the general population. Whether FIT-positive subjects with negative colonoscopy should receive subsequent FIT screening remain unclear.Subjects with a negative colonoscopy after positive FIT in the first screening in the Taiwanese Colorectal Cancer (CRC) Screening Program 2004-2009 were followed until the end of 2014. CRC incidence was compared between those who did and did not receive subsequent FIT screening. Cox regression analysis was conducted, adjusting for major confounders to investigate whether subsequent FIT was associated with lower risk of incident CRC.The study cohort was comprised of 9179 subjects who had negative diagnostic colonoscopy after positive FIT in 2004-2009, of whom 6195 received subsequent FIT during the study period. The CRC incidence (per 1000 person years) was 1.34 in those who received subsequent FIT and 2.69 in those who did not, with corresponding adjusted HR (aHR) of 0.47 (95% CI 0.31 to 0.71). Lower adenoma detection rate of diagnostic colonoscopy was associated with higher risk of incident CRC but became non-significant in multivariable analysis after adjustment for subsequent FIT. Higher baseline faecal haemoglobin concentration (FHbC, μg haemoglobin/g faeces) was associated with increased risk of incident CRC (reference: FHbC=20-39; aHR=1.93 (1.04-3.56), 0.95 (0.45-2.00), 2.26 (1.16-4.43) and 2.44 (1.44-4.12) for FHbC=40-59, 60-99, 100-149 and ≥150, respectively).Subsequent FIT should be scheduled after negative colonoscopy to detect missed neoplasms and reduce the risk of incident CRC in a national FIT screening programme.
Tumor genotype dictates radiosensitization after Atm deletion in primary brainstem glioma models
Authors: Katherine Deland, Bryce F. Starr, Joshua S. Mercer, Jovita Byemerwa, Donna M. Crabtree, Nerissa T. Williams, Lixia Luo, Yan Ma, Mark Chen, Oren J. Becher, David G. Kirsch
Journal: Journal of Clinical Investigation (2020)

Diffuse intrinsic pontine glioma (DIPG) kills more children than any other type of brain tumor. Despite clinical trials testing many chemotherapeutic agents, palliative radiotherapy remains the standard treatment. Here, we utilized Cre/loxP technology to show that deleting Ataxia telangiectasia mutated (Atm) in primary mouse models of DIPG can enhance tumor radiosensitivity. Genetic deletion of Atm improved survival of mice with p53-deficient but not p53 wild-type gliomas after radiotherapy. Similar to patients with DIPG, mice with p53 wild-type tumors had improved survival after radiotherapy independent of Atm deletion. Primary p53 wild-type tumor cell lines induced proapoptotic genes after radiation and repressed the NRF2 target, NAD(P)H quinone dehydrogenase 1 (Nqo1). Tumors lacking p53 and Ink4a/Arf expressed the highest level of Nqo1 and were most resistant to radiation, but deletion of Atm enhanced the radiation response. These results suggest that tumor genotype may determine whether inhibition of ATM during radiotherapy will be an effective clinical approach to treat DIPGs.
COVID-19: opacification score is higher in the right lung and right lung involvement is a better predictor of ICU admission
Authors: Deepak Nagra, Mark Russell, Mark Yates, James Galloway, Richard Barker, Sujal R. Desai, Sam Norton
Journal: European Respiratory Journal (2020)

<b>In COVID-19 the right lung has higher degree of opacification on plain radiograph than the left lung. Right lung opacificiation is a stronger predictor for critical care admission and death.</b>https://bit.ly/36dig2N
The mutational signature profile of known and suspected human carcinogens in mice
Authors: Laura Riva, Arun R. Pandiri, Yun Rose Li, Alastair Droop, James Hewinson, Michael A. Quail, Vivek Iyer, Rebecca Shepherd, Ronald A. Herbert, Peter J. Campbell, Robert C. Sills, Ludmil B. Alexandrov, Allan Balmain, David J. Adams
Journal: Nature Genetics (2020)