tbuckley/cabot-search huggingface dataset:
Should the UK vaccinate children and adolescents against covid-19?
Authors: Sonia Saxena, Helen Skirrow, Kate Wighton
Journal: BMJ (2021)

The UK Joint Committee on Vaccination and Immunisation (JCVI) has now recommended covid-19 vaccination for select groups of adolescents.Those newly eligible comprise 12-15 year olds with underlying conditions that may place them at increased risk of serious covid-19 infection, 17 year olds who are within three months of turning 18, and adolescents living with someone who is immunosuppressed. 1 Young people aged 16 to 17 who are at higher risk of serious covid-19 were already eligible.The decision came after the Medicines and Healthcare Products Regulatory Agency approved Pfizer-BioNTech's covid-19 vaccine for use in children aged over 12 years. 2 The JCVI decision triggered public debate because unlike several other high income countries, including the United States 3 and Canada, 4 the UK will not offer covid-19 vaccines to all children aged over 12 years.The UK has vaccinated most of its high risk population against covid-19.Over two thirds of adults aged over 18 years have received two doses. 5However, breaking the chain of transmission needs close to 85% of the whole population to be immune. 6hildren and adolescents, whose lives have been disrupted by school closures, isolation, and social restrictions, 7 make up 21% of the population.As restrictions lift, cases are rising fast in this younger unvaccinated population.
Genetic Screens Identify a Context-Specific PI3K/p27Kip1 Node Driving Extrahepatic Biliary Cancer
Authors: Chiara Falcomatà, Stefanie Bärthel, Angelika Ulrich, Sandra Diersch, Christian Veltkamp, Lena Rad, Fabio Boniolo, Myriam Solar, Katja Steiger, Barbara Seidler, Magdalena Zukowska, Joanna Madej, Mingsong Wang, Rupert Öllinger, Roman Maresch, Maxim Barenboim, Stefan Eser, Markus Tschurtschenthaler, Arianeb Mehrabi, Stephanie Roessler, Benjamin Goeppert, Alexander Kind, Angelika Schnieke, Maria S. Robles, Allan Bradley, Roland M. Schmid, Marc Schmidt-Supprian, Maximilian Reichert, Wilko Weichert, Owen J. Sansom, Jennifer P. Morton, Roland Rad, Günter Schneider, Dieter Saur
Journal: Cancer Discovery (2021)

Biliary tract cancer ranks among the most lethal human malignancies, representing an unmet clinical need. Its abysmal prognosis is tied to an increasing incidence and a fundamental lack of mechanistic knowledge regarding the molecular basis of the disease. Here, we show that the Pdx1-positive extrahepatic biliary epithelium is highly susceptible toward transformation by activated PIK3CAH1047R but refractory to oncogenic KrasG12D. Using genome-wide transposon screens and genetic loss-of-function experiments, we discover context-dependent genetic interactions that drive extrahepatic cholangiocarcinoma (ECC) and show that PI3K signaling output strength and repression of the tumor suppressor p27Kip1 are critical context-specific determinants of tumor formation. This contrasts with the pancreas, where oncogenic Kras in concert with p53 loss is a key cancer driver. Notably, inactivation of p27Kip1 permits KrasG12D-driven ECC development. These studies provide a mechanistic link between PI3K signaling, tissue-specific tumor suppressor barriers, and ECC pathogenesis, and present a novel genetic model of autochthonous ECC and genes driving this highly lethal tumor subtype. We used the first genetically engineered mouse model for extrahepatic bile duct carcinoma to identify cancer genes by genome-wide transposon-based mutagenesis screening. Thereby, we show that PI3K signaling output strength and p27Kip1 function are critical determinants for context-specific ECC formation. This article is highlighted in the In This Issue feature, p. 2945.
A hop, skip, and a jump to evade USH2A deaf-blindness mutations
Authors: Stéphanie A. Mauriac, Gwenaëlle S.G. Géléoc
Journal: Molecular Therapy (2021)

Over the past decade, many gene therapy approaches have been designed to restore auditory and visual function lost due to Usher syndrome (USH).1 Among them, gene replacement therapy mediated by adeno-associated virus (AAV)-based vectors has been shown to be a safe and efficient strategy. However, this approach is not suitable for large genes, such as USH2A, which vastly exceed the cargo capacity of AAV vectors. In this issue of Molecular Therapy, Dulla et al.2 provide evidence that synthetic antisense oligonucleotides (ASO or AON) can mediate exon-skipping, which may be a viable approach for a subset of USH2A mutations.
Mesenchymal Stromal Cells (MSC) As Key Players in the Tumor Microenvironment Transformation from MGUS to Myeloma
Authors: Cesarina Giallongo, Daniele Tibullo, Nunziatina Laura Parrinello, Giuseppina Camiolo, Piera La Cava, Nunziatina Caporarello, Daniela Anfuso, Enrica Martino, Valeria Calafiore, Concetta Conticello, Giuseppe A Palumbo, Alessandra Romano, Francesco Di Raimondo
Journal: Blood (2017)
MO1-1 Lymphocyte-C-reactive protein ratio as a prognostic marker in rectal cancer patients with neoadjuvant chemoradiotherapy
Authors: Yoshinaga Okugawa, Hiroyuki Fujikawa, Yusuke Omura, Akira Yamamoto, Takahito Kitajima, Tadanobu Shimura, Hiroki Imaoka, Mikio Kawamura, Hiromi Yasuda, Yoshiki Okita, Takeshi Yokoe, Susumu Saigusa, Ikuyo Mochiki, Masaki Ohi, Kaname Nakatani, Yuji Toiyama
Journal: Annals of Oncology (2021)
Drug-eluting intraocular lens with sustained bromfenac release for conquering posterior capsular opacification
Authors: Xiaobo Zhang, Kairan Lai, Su Li, Jing Wang, Jiayong Li, Wei Wang, Shuang Ni, Bing Lu, Andrzej Grzybowski, Jian Ji, Haijie Han, Ke Yao
Journal: Bioactive Materials (2021)

Cataract is the leading cause of visual impairment, and posterior capsular opacification (PCO) is the most common long-term complication of modern cataract surgery, which can cause severe visual impairment after surgery. The proliferation, migration, and epithelial-mesenchymal transition (EMT) of residual lens epithelial cells (LECs) stimulated by growth factors and cytokines, are the key pathological mechanisms involved in the development of PCO. This study demonstrated that non-steroidal anti-inflammatory drug (NSAID), bromfenac, was capable of effectively inhibiting cell migration, overexpression of EMT markers, such as fibronectin (FN), matrix metalloproteinase 2 (MMP2), α-smooth muscle actin (α-SMA), and transcription factor Snail, and extracellular signal-regulated kinase (ERK)/glycogen synthase kinase-3β (GSK-3β) signaling induced by transforming growth factor-β2 (TGF-β2) in vitro. The inhibitory effect of bromfenac on TGF-β2-induced EMT was also verified on a primary lens epithelial cell model using human anterior capsules. Furthermore, based on ultrasonic spray technology, we developed a drug-eluting intraocular lens (IOL) using poly (lactic-co-glycolic acid) (PLGA) with sustained bromfenac release ability for the prevention of PCO development. In the rabbit models of cataract surgery, bromfenac-eluting IOL exhibited remarkable PCO prevention and inflammation suppression effects with excellent biocompatibility. In conclusion, bromfenac can inhibit TGF-β2-induced cell migration and the EMT of LECs via ERK/GSK-3β/Snail signaling. The present study offers a novel approach for preventing PCO through PLGA-based drug sustained-release IOLs.
Efficacy and safety of once-weekly semaglutide 2·0 mg versus 1·0 mg in patients with type 2 diabetes (SUSTAIN FORTE): a double-blind, randomised, phase 3B trial
Authors: Juan P Frías, Pernille Auerbach, Harpreet S Bajaj, Yasushi Fukushima, Ildiko Lingvay, Stanislava Macura, Anette L Søndergaard, Tsvetalina I Tankova, Nikolaos Tentolouris, John B Buse
Journal: The Lancet Diabetes & Endocrinology (2021)
Sexually Transmitted Infections Treatment Guidelines, 2021
Authors: Kimberly A. Workowski, Laura H. Bachmann, Philip A. Chan, Christine M. Johnston, Christina A. Muzny, Ina Park, Hilary Reno, Jonathan M. Zenilman, Gail A. Bolan
Journal: MMWR Recommendations and Reports (2021)

These guidelines for the treatment of persons who have or are at risk for sexually transmitted infections (STIs) were updated by CDC after consultation with professionals knowledgeable in the field of STIs who met in Atlanta, Georgia, June 11-14, 2019. The information in this report updates the 2015 guidelines. These guidelines discuss 1) updated recommendations for treatment of Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis; 2) addition of metronidazole to the recommended treatment regimen for pelvic inflammatory disease; 3) alternative treatment options for bacterial vaginosis; 4) management of Mycoplasma genitalium; 5) human papillomavirus vaccine recommendations and counseling messages; 6) expanded risk factors for syphilis testing among pregnant women; 7) one-time testing for hepatitis C infection; 8) evaluation of men who have sex with men after sexual assault; and 9) two-step testing for serologic diagnosis of genital herpes simplex virus. Physicians and other health care providers can use these guidelines to assist in prevention and treatment of STIs.
Long-term solid fuel use and risks of major eye diseases in China: A population-based cohort study of 486,532 adults
Authors: Ka Hung Chan, Mingshu Yan, Derrick A. Bennett, Yu Guo, Yiping Chen, Ling Yang, Jun Lv, Canqing Yu, Pei Pei, Yan Lu, Liming Li, Huaidong Du, Kin Bong Hubert Lam, Zhengming Chen
Journal: PLoS Medicine (2021)

Over 3.5 billion individuals worldwide are exposed to household air pollution from solid fuel use. There is limited evidence from cohort studies on associations of solid fuel use with risks of major eye diseases, which cause substantial disease and economic burden globally.
Management of caustic injury: better to evaluate patient as a “whole” rather than only through a “hole”!
Authors: Mohan Ramchandani
Journal: Endoscopy (2021)

The prediction of outcome of caustic ingestion is traditionally based on endoscopic grading [1]. Endoscopic grading predicts short-term outcomes such as systemic complications, including respiratory failure and immediate mortality, and long-term outcomes such as nutritional autonomy and future stricture formation [2]. However, endoscopic grading is inaccurate in predicting depth of necrosis, which leads to both overestimation and underestimation of severity resulting in either inappropriate emergency surgery or nonoperative management, respectively, jeopardizing optimal outcomes. Other drawbacks of endoscopic severity assessment are interobserver variation, inability to perform endoscopy in all cases, and risk of overestimation beyond 48 hours of corrosive ingestion owing to the presence of edema and submucosal hemorrhage [2].
MO5-1 Characteristics of immune-related adverse events in patients with advanced esophageal cancer treated with nivolumab
Authors: Naokatsu Nakada, Takayuki Ando, Iori Motoo, Shinya Kajiura, Mayo Fuchino, Miho Sakumura, Sohachi Nanjo, Hiroshi Mihara, Haruka Fujinami, Kohei Ogawa, Kenichiro Tsukada, Koji Nakashima, Ayumu Hosokawa, Ichiro Yasuda
Journal: Annals of Oncology (2021)
Potential neurotoxicity of titanium implants: Prospective, in-vivo and in-vitro study
Authors: Shahar Shelly, Sigal Liraz Zaltsman, Ofir Ben-Gal, Avraham Dayan, Ithamar Ganmore, Chen Shemesh, Dana Atrakchi, Sharif Garra, Orly Ravid, Daniel Rand, Hila Israelov, Tayir Alon, Gabriel Lichtenstein, Shirley Sharabi, David Last, Fabien Gosselet, Vasiliy Rosen, Gideon Burstein, Alon Friedlander, Ran Harel, Guy Vogel, Michal Schnaider Beeri, Yael Mardor, Yair Lampl, Gideon Fleminger, Itzik Cooper
Journal: Biomaterials (2021)
Co-infections and superinfections complicating COVID-19 in cancer patients: A multicentre, international study
Authors: C. Gudiol, X. Durà-Miralles, J. Aguilar-Company, P. Hernández-Jiménez, M. Martínez-Cutillas, F. Fernandez-Avilés, M. Machado, L. Vázquez, P. Martín-Dávila, N. de Castro, E. Abdala, L. Sorli, T.M. Andermann, I. Márquez-Gómez, H. Morales, F. Gabilán, C.M. Ayaz, B. Kayaaslan, M. Aguilar-Guisado, F. Herrera, C. Royo-Cebrecos, M. Peghin, C. González-Rico, J. Goikoetxea, C. Salgueira, A. Silva-Pinto, B. Gutiérrez-Gutiérrez, S. Cuellar, G. Haidar, C. Maluquer, M. Marin, N. Pallarès, J. Carratalà
Journal: Journal of Infection (2021)

We aimed to describe the epidemiology, risk factors, and clinical outcomes of co-infections and superinfections in onco-hematological patients with COVID-19.International, multicentre cohort study of cancer patients with COVID-19. All patients were included in the analysis of co-infections at diagnosis, while only patients admitted at least 48 h were included in the analysis of superinfections.684 patients were included (384 with solid tumors and 300 with hematological malignancies). Co-infections and superinfections were documented in 7.8% (54/684) and 19.1% (113/590) of patients, respectively. Lower respiratory tract infections were the most frequent infectious complications, most often caused by Streptococcus pneumoniae and Pseudomonas aeruginosa. Only seven patients developed opportunistic infections. Compared to patients without infectious complications, those with infections had worse outcomes, with high rates of acute respiratory distress syndrome, intensive care unit (ICU) admission, and case-fatality rates. Neutropenia, ICU admission and high levels of C-reactive protein (CRP) were independent risk factors for infections.Infectious complications in cancer patients with COVID-19 were lower than expected, affecting mainly neutropenic patients with high levels of CRP and/or ICU admission. The rate of opportunistic infections was unexpectedly low. The use of empiric antimicrobials in cancer patients with COVID-19 needs to be optimized.
Abstract 15586: GFAT2 Mediates Isoproterenol-Induced Cardiac Hypertrophy by Increasing Protein O-GlcNAcylation and Akt Activation
Authors: Akihito Ishikita, Shouji Matsushima, Masataka Ikeda, Soichiro Ikeda, Kosuke Okabe, Tomonori Tadokoro, Nobuyuki Enzan, Masashi Sada, Taishi Yamamoto, Hiroko Deguchi, Tomomi Ide, Hiroyuki Tsutsui
Journal: Circulation (2018)

Background: Cardiac hypertrophy is an independent risk factor for heart failure and cardiac death. The attachment of O-linked N-acetylglucosamine motif (O-GlcNAcylation) to proteins, a post-transla...
Heat-Related Emergency Department Visits During the Northwestern Heat Wave — United States, June 2021
Authors: Paul J. Schramm, Ambarish Vaidyanathan, Lakshmi Radhakrishnan, Abigail Gates, Kathleen Hartnett, Patrick Breysse
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

Record high temperatures are occurring more frequently in the United States, and climate change is causing heat waves to become more intense (1), directly impacting human health, including heat-related illnesses and deaths. On average, approximately 700 heat-related deaths occur in the United States each year (2). In the northwestern United States, increasing temperatures are projected to cause significant adverse health effects in the coming years (3). During June 25-30, 2021, most of Oregon and Washington were under a National Weather Service excessive heat warning.* Hot conditions persisted in parts of Oregon, Washington, or Idaho through at least July 14, 2021. The record-breaking heat had the largest impact in Oregon and Washington, especially the Portland metropolitan area, with temperatures reaching 116°F (46.7°C), which is 42°F (5.6°C) hotter than the average daily maximum June temperature.
Fructose-coated Ångstrom silver prevents sepsis by killing bacteria and attenuating bacterial toxin-induced injuries
Authors: Hao Yin, Mao Zhou, Xia Chen, Teng-Fei Wan, Ling Jin, Shan-Shan Rao, Yi-Juan Tan, Ran Duan, Yu Zhang, Zhen-Xing Wang, Yi-Yi Wang, Ze-Hui He, Ming-Jie Luo, Xiong-Ke Hu, Yang Wang, Wei-Yi Situ, Si-Yuan Tang, Wen-En Liu, Chun-Yuan Chen, Hui Xie
Journal: Theranostics (2021)

Serious infection caused by multi-drug-resistant bacteria is a major threat to human health. Bacteria can invade the host tissue and produce various toxins to damage or kill host cells, which may induce life-threatening sepsis. Here, we aimed to explore whether fructose-coated Ångstrom-scale silver particles (F-AgÅPs), which were prepared by our self-developed evaporation-condensation system and optimized coating approach, could kill bacteria and sequester bacterial toxins to attenuate fatal bacterial infections. Methods: A series of in vitro assays were conducted to test the anti-bacterial efficacy of F-AgÅPs, and to investigate whether F-AgÅPs could protect against multi-drug resistant Staphylococcus aureus (S. aureus)- and Escherichia coli (E. coli)-induced cell death, and suppress their toxins (S. aureus hemolysin and E. coli lipopolysaccharide)-induced cell injury or inflammation. The mouse models of cecal ligation and puncture (CLP)- or E. coli bloodstream infection-induced lethal sepsis were established to assess whether the intravenous administration of F-AgÅPs could decrease bacterial burden, inhibit inflammation, and improve the survival rates of mice. The levels of silver in urine and feces of mice were examined to evaluate the excretion of F-AgÅPs. Results: F-AgÅPs efficiently killed various bacteria that can cause lethal infections and also competed with host cells to bind with S. aureus α-hemolysin, thus blocking its cytotoxic activity. F-AgÅPs inhibited E. coli lipopolysaccharide-induced endothelial injury and macrophage inflammation, but not by directly binding to lipopolysaccharide. F-AgÅPs potently reduced bacterial burden, reversed dysregulated inflammation, and enhanced survival in mice with CLP- or E. coli bloodstream infection-induced sepsis, either alone or combined with antibiotic therapy. After three times injections within 48 h, 79.18% of F-AgÅPs were excreted via feces at the end of the 14-day observation period. Conclusion: This study suggests the prospect of F-AgÅPs as a promising intravenous agent for treating severe bacterial infections.
MO25-3 Long time follow-up data of first-line pembrolizumab for advanced NSCLC patients with PD-L1 TPS of 50% or greater
Authors: Yuichi Tambo, Takashi Sone, Kazuhiko Shibata, Kouichi Nishi, Hiroki Shirasaki, Taro Yoneda, Tomoyuki Araya, Kazumasa Kase, Shingo Nishikawa, Hideharu Kimura, Kazuo Kasahara
Journal: Annals of Oncology (2021)
Real‐Time PCR Test: All‐in‐One DNA Extraction Tube for Facilitated Real‐Time Detection of Infectious Pathogens (Adv. Healthcare Mater. 14/2021)
Authors: Younseong Song, Yong Tae Kim, Yunho Choi, Hogi Kim, Min Hee Yeom, Yesol Kim, Tae Jae Lee, Kyoung G. Lee, Sung Gap Im
Journal: Advanced Healthcare Materials (2021)

In article number 2100430 by Sung Gap Im, Kyoung G. Lee, and co-workers, an “all-in-one tube” is devised by coating poly-(2-dimethylaminomethyl styrene) (pDMAMS) on a polymerase chain reaction (PCR) tube via initiated chemical vapor deposition (iCVD) to extract, amplify, and detect pathogens within a single tube. The all-in-one tube can capture the DNA of the pathogens by charge interaction and directly perform real-time PCR, reducing the labor-intensive pathogen detection steps.
Supporting Real-Time Ethical Deliberation in Contingency Capacity During the COVID-19 Pandemic
Authors: Catherine R. Butler, Mark R. Tonelli
Journal: The American Journal of Bioethics (2021)

Click to increase image sizeClick to decrease image sizeThis article refers to:Between Usual and Crisis Phases of a Public Health Emergency: The Mediating Role of Contingency MeasuresThis article is referred to by:Ethics Frameworks and Beyond—Advancing Our Understanding of the Contingency Phase to Improve Health Care Quality During Public Health Emergencies
SO-14 The prognostic impact of KRAS G12C mutation in patients with metastatic colorectal cancer: A multicenter retrospective observational study
Authors: Y. Matsubara, T. Masuishi, K. Fushiki, K. Sawada, K. Chida, R. Kumanishi, H. Shirasu, Y. Kawamoto, D. Kotani, K. Kato, T. Kawakami, S. Yuki, K. Yamazaki, Y. Komatsu, T. Yoshino
Journal: Annals of Oncology (2021)
Edward de Bono: physician, psychologist, and inventor who coined the term “lateral thinking”
Authors: Rebecca Wallersteiner
Journal: BMJ (2021)

Credit: Roy Zhao

One of five children, Edward Charles Francis Publius de Bono was born in Malta, to Joseph de Bono, a seventh generation Maltese physician, and Josephine (nee O’Byrne), an Anglo-Irish journalist, who campaigned for women’s rights. From the age of 7, de Bono attended St Edward’s College, a Maltese boarding school run along English lines. Inventive from an early age, he ingeniously figured out a way to escape from the school and the citadel of Mdina through an underground network of tunnels. When older boys wanted to sneak out for a beer, they had to come to him for the map. During de Bono’s childhood, Malta was severely bombed by Germany and Italy on account of its strategic importance. He spent many nights sleeping in an air raid shelter in the garden of his family home, as bombs flattened many of the houses in the square.

At the age of 15 he entered the Royal University of Malta to read medicine. In 1955 he went to Christ Church, Oxford, on a Rhodes scholarship and read psychology and physiology. He stayed on to do a doctorate in medicine, which he completed in 1961. A talented athlete, at Oxford he played polo and canoed Canadian style from Oxford to London. After graduating he taught at the University of London and lectured in medicine at Cambridge (1976-83), where he did another doctorate and was assistant director …
Metabolomic analyses reveal new stage-specific features of COVID-19
Authors: Hongling Jia, Chaowu Liu, Dantong Li, Qingsheng Huang, Dong Liu, Ying Zhang, Chang Ye, Di Zhou, Yang Wang, Yanlian Tan, Kuibiao Li, Fangqin Lin, Haiqing Zhang, Jingchao Lin, Yang Xu, Jingwen Liu, Qing Zeng, Jian Hong, Guobing Chen, Hao Zhang, Lingling Zheng, Xilong Deng, Changwen Ke, Yunfei Gao, Jun Fan, Biao Di, Huiying Liang
Journal: European Respiratory Journal (2021)

The current pandemic of coronavirus disease 2019 (COVID-19) has affected &gt;160 million individuals to date, and has caused millions of deaths worldwide, at least in part due to the unclarified pathophysiology of this disease. Identifying the underlying molecular mechanisms of COVID-19 is critical to overcome this pandemic. Metabolites mirror the disease progression of an individual and can provide extensive insights into their pathophysiological significance at each stage of disease. We provide a comprehensive view of metabolic characterisation of sera from COVID-19 patients at all stages using untargeted and targeted metabolomic analysis. As compared with the healthy controls, we observed different alteration patterns of circulating metabolites from the mild, severe and recovery stages, in both the discovery cohort and the validation cohort, which suggests that metabolic reprogramming of glucose metabolism and the urea cycle are potential pathological mechanisms for COVID-19 progression. Our findings suggest that targeting glucose metabolism and the urea cycle may be a viable approach to fight COVID-19 at various stages along the disease course.
The chemerin-CMKLR1 axis limits thermogenesis by controlling a beige adipocyte/IL-33/type 2 innate immunity circuit
Authors: Yuli Lin, Liuling Xiao, Qian Cai, Cuisong Zhu, Shufen Li, Bingji Li, Ting Liu, Qiongyue Zhang, Yi Wang, Yiming Li, Xing He, Dongning Pan, Qiqun Tang, Xiaohui Wu, Weiqing Pan, Jiqiu Wang, Xi Li, Rui He
Journal: Science Immunology (2021)

Chemerin restricts cold-induced IL-33 production by beige adipocytes, impairing beige fat’s ability to dissipate excess energy stores.