tbuckley/cabot-search huggingface dataset:
Neoadjuvant <i>In Situ</i> Immunomodulation Enhances Systemic Antitumor Immunity against Highly Metastatic Tumors
Authors: Takaaki Oba, Ryutaro Kajihara, Toshihiro Yokoi, Elizabeth A. Repasky, Fumito Ito
Journal: Cancer Research (2021)

Neoadjuvant immunotherapy, given before surgical resection, is a promising approach to develop systemic antitumor immunity for the treatment of high-risk resectable disease. Here, using syngeneic and orthotopic mouse models of triple-negative breast cancer, we have tested the hypothesis that generation of tumor-specific T-cell responses by induction and activation of tumor-residing Batf3-dependent conventional type 1 dendritic cells (cDC1) before resection improves control of distant metastatic disease and survival. Mice bearing highly metastatic orthotopic tumors were treated with a combinatorial in situ immunomodulation (ISIM) regimen comprised of intratumoral administration of Flt3L, local radiotherapy, and in situ TLR3/CD40 stimulations, followed by surgical resection. Neoadjuvant ISIM (neo-ISIM) generated tumor-specific CD8+ T cells that infiltrated into distant nonirradiated metastatic sites, which delayed the progression of lung metastases and improved survival after the resection of primary tumors. The efficacy of neo-ISIM was dependent on de novo adaptive T-cell immunity elicited by Batf3-dependent dendritic cells and was enhanced by increasing dose and fractionation of radiotherapy, and early surgical resection after the completion of neo-ISIM. Importantly, neo-ISIM synergized with programmed cell death protein-1 ligand-1 (PD-L1) blockade to improve control of distant metastases and prolong survival, while removal of tumor-draining lymph nodes abrogated the antimetastatic efficacy of neo-ISIM. Our findings illustrate the therapeutic potential of neoadjuvant multimodal intralesional therapy for the treatment of resectable tumors with high risk of relapse. SIGNIFICANCE: Neoadjuvant induction and activation of cDC1s in primary tumors enhances systemic antitumor immunity, suppresses metastatic progression, improves survival, and synergizes with anti-PD-L1 therapy.
Effectiveness of COVID-19 vaccines against SARS-CoV-2 infection with the Delta (B.1.617.2) variant: second interim results of a living systematic review and meta-analysis, 1 January to 25 August 2021
Authors: Thomas Harder, Wiebe Külper-Schiek, Sarah Reda, Marina Treskova-Schwarzbach, Judith Koch, Sabine Vygen-Bonnet, Ole Wichmann
Journal: Eurosurveillance (2021)

The Delta variant has become the dominant strain of SARS-CoV-2. We summarised the evidence on COVID-19 vaccine effectiveness (VE) identified in 17 studies that investigated VE against different endpoints. Pooled VE was 63.1% (95% confidence interval (CI): 40.9-76.9) against asymptomatic infection, 75.7% (95% CI: 69.3-80.8) against symptomatic infection and 90.9% (95% CI: 84.5-94.7) against hospitalisation. Compared with the Alpha variant, VE against mild outcomes was reduced by 10-20%, but fully maintained against severe COVID-19.
A quality assessment tool for artificial intelligence-centered diagnostic test accuracy studies: QUADAS-AI
Authors: Viknesh Sounderajah, Hutan Ashrafian, Sherri Rose, Nigam H. Shah, Marzyeh Ghassemi, Robert Golub, Charles E. Kahn, Andre Esteva, Alan Karthikesalingam, Bilal Mateen, Dale Webster, Dan Milea, Daniel Ting, Darren Treanor, Dominic Cushnan, Dominic King, Duncan McPherson, Ben Glocker, Felix Greaves, Leanne Harling, Johan Ordish, Jérémie F. Cohen, Jon Deeks, Mariska Leeflang, Matthew Diamond, Matthew D. F. McInnes, Melissa McCradden, Michael D. Abràmoff, Pasha Normahani, Sheraz R. Markar, Stephanie Chang, Xiaoxuan Liu, Susan Mallett, Shravya Shetty, Alastair Denniston, Gary S. Collins, David Moher, Penny Whiting, Patrick M. Bossuyt, Ara Darzi
Journal: Nature Medicine (2021)
Syphilis
Authors: Patrick O'Byrne, Paul MacPherson
Journal: BMJ (2019)

### What you need to know Caused by the bacteria Treponema pallidum ,12 syphilis is transmitted through direct (usually sexual) contact with infected mucosal lesions. Other bodily fluids are also infectious when patients are bacteraemic. With infectivity up to 10-30% per sexual contact or 60% per relationship,3 syphilis rates have risen 300% since 2000 in many Western countries.4567 While most infections involve men who have sex with men, infections among people with opposite sex partners also occur.4567 In addition to increasing rates, syphilis can cause early complications such as irreversible loss of vision, so awareness of the infection is important for primary care clinicians.8910 While syphilis causes protean symptoms (box 1), the diagnosis should be considered in any sexually active patient with genital lesions or with rashes.161718 Box 1 ### Symptoms of syphilis by stage of infection (see fig 1) #### PrimaryRETURN TO TEXT
Enhanced national surveillance of severe acute respiratory infections (SARI) within COVID-19 surveillance, Slovenia, weeks 13 to 37 2021
Authors: Irena Klavs, Mojca Serdt, Veronika Učakar, Marta Grgič-Vitek, Mario Fafangel, Maja Mrzel, Lina Berlot, Uroš Glavan, Marjana Vrh, Tanja Kustec, Miha Simoniti, Božena Kotnik Kevorkijan, Tatjana Lejko Zupanc
Journal: Eurosurveillance (2021)

We monitored trends of severe COVID-19 morbidity in Slovenia during weeks 13 to 37 2021. National weekly rates of severe acute respiratory infections (SARI) cases testing positive for SARS-CoV-2 at admission in all hospitals varied between 0.2 and 16.3 cases per 100,000 population. Of those without previous COVID-19 diagnosis, SARI COVID-19 admission rates ranged between 0.3 and 17.5 per 100,000 unvaccinated, and 0.0 and 7.3 per 100,000 fully vaccinated individuals. National SARI COVID-19 surveillance is essential in informing COVID-19 response.
A Versatile Calcium Phosphate Nanogenerator for Tumor Microenvironment‐activated Cancer Synergistic Therapy
Authors: Lian‐Hua Fu, Chunying Li, Weimin Yin, Yan‐Ru Hu, Tuanwei Sun, Yilin Wan, Jing Lin, Zhiming Li, Peng Huang
Journal: Advanced Healthcare Materials (2021)

Gas therapy is an emerging "green" cancer treatment strategy; however, its outcome often restricted by the complexity, diversity, and heterogeneity of tumor. Herein, a tumor targeting and tumor microenvironment-activated calcium phosphate nanotheranostic system (denoted as GCAH) is constructed for effective synergistic cancer starvation/gas therapy. GCAH is obtained by a facile biomineralization strategy using glucose oxidase (GOx) as a biotemplate, followed by loading of l-Arginine (L-Arg) and modification of hyaluronic acid (HA) to allow special selectivity for glycoprotien CD44 overexpressed cancer cells. This nanotheranostic system not only exhausts the glucose nutrients in tumor region by the GOx-triggered glucose oxidation, the generated H2 O2 can oxidize L-Arg into NO under acidic tumor microenvironment for enhanced gas therapy. As such, there are significant enhancement effects of starvation therapy and gas therapy through the cascade reactions of GOx and L-Arg, which yields a remarkable synergistic therapeutic effect for 4T1 tumor-bearing mice without discernible toxic side effects.
Tricarboxylic acid cycle related-metabolites and risk of atrial fibrillation and heart failure
Authors: Mònica Bulló, Christopher Papandreou, Jesus García-Gavilán, Miguel Ruiz-Canela, Jun Li, Marta Guasch-Ferré, Estefanía Toledo, Clary Clish, Dolores Corella, Ramon Estruch, Emilio Ros, Montserrat Fitó, Chih-Hao Lee, Kerry Pierce, Cristina Razquin, Fernando Arós, Lluís Serra-Majem, Liming Liang, Miguel A. Martínez-González, Frank B. Hu, Jordi Salas-Salvadó
Journal: Metabolism (2021)

BackgroundTricarboxylic acid (TCA) cycle deregulation may predispose to cardiovascular diseases, but the role of TCA cycle-related metabolites in the development of atrial fibrillation (AF) and heart failure (HF) remains unexplored. This study sought to investigate the association of TCA cycle-related metabolites with risk of AF and HF.MethodsWe used two nested case-control studies within the PREDIMED study. During a mean follow-up for about 10 years, 512 AF and 334 HF incident cases matched by age (±5 years), sex and recruitment center to 616 controls and 433 controls, respectively, were included in this study. Baseline plasma levels of citrate, aconitate, isocitrate, succinate, malate and d/l-2-hydroxyglutarate were measured with liquid chromatography-tandem mass spectrometry. Multivariable conditional logistic regression models were fitted to estimate odds ratios (OR) and 95% confidence intervals (95% CI) for metabolites and the risk of AF or HF. Potential confounders included smoking, family history of premature coronary heart disease, physical activity, alcohol intake, body mass index, intervention groups, dyslipidemia, hypertension, type 2 diabetes and medication use.ResultsComparing extreme quartiles of metabolites, elevated levels of succinate, malate, citrate and d/l-2-hydroxyglutarate were associated with a higher risk of AF [ORQ4 vs. Q1 (95% CI): 1.80 (1.21–2.67), 2.13 (1.45–3.13), 1.87 (1.25–2.81) and 1.95 (1.31–2.90), respectively]. One SD increase in aconitate was directly associated with AF risk [OR (95% CI): 1.16 (1.01–1.34)]. The corresponding ORs (95% CI) for HF comparing extreme quartiles of malate, aconitate, isocitrate and d/l-2-hydroxyglutarate were 2.15 (1.29–3.56), 2.16 (1.25–3.72), 2.63 (1.56–4.44) and 1.82 (1.10–3.04), respectively. These associations were confirmed in an internal validation, except for aconitate and AF.ConclusionThese findings underscore the potential role of the TCA cycle in the pathogenesis of cardiac outcomes.
P36.01 Primary Acinic Cell Carcinoma of Bronchial Ground Origin: A Case Report
Authors: K. Hirano, H. Harada, S. Shibata, E. Chou, Y. Naka, K. Kawaguchi, Y. Nishimura, K. Akayama, K. Miyazaki, K. Mandai
Journal: Journal of Thoracic Oncology (2021)
Two Pituitary Neuroendocrine Tumors (PitNETs) with Very High Proliferation and TP53 Mutation — High-Grade PitNET or PitNEC?
Authors: Wolfgang Saeger, Christian Mawrin, Matthias Meinhardt, Annika K. Wefers, Frank Jacobsen
Journal: Endocrine Pathology (2021)

We report two pituitary neuroendocrine tumors (PitNETs) with very high Ki67 labeling indices, many mitoses and TP53 mutation (nearly all tumor cell nuclei were positive for p53). One of the tumors had bone and liver metastases. One was a corticotroph cell tumor; the other was a lactotroph tumor. The classification of these tumors is the subject of this discussion. Traditionally, pituitary carcinomas are only diagnosed by demonstration of metastases according to the 2017 WHO classification. In contrast, neuroendocrine neoplasms of the gastrointestinal tract and pancreas are classified as either well differentiated NETs that are graded as G1, G2, and G3 based on proliferation as determined by Ki67 indices of ≤ 3, 3-20 and > 20%, and/or < 2, 2-20, and > 20 mitoses per 10 high-power field respectively, or as neuroendocrine carcinomas (NECs) that are poorly differentiated neoplasms with mitoses > 20/HPF and/or a Ki67 index > 20%. With the reclassificiation of PitNETs, in our opinion, the adequate term for the well-differentiated corticotroph tumor that we report is a PitNET G3, whereas the undifferentiated prolactin tumor should be classified as PitNEC. This report expands the spectrum of pituitary neuroendocrine neoplasms.
US taskforce advises against low dose aspirin for primary prevention of cardiovascular disease
Authors: Elisabeth Mahase
Journal: BMJ (2021)

The US Preventive Services Task Force (USPSTF) will no longer recommend routine prescribing of low dose aspirin for preventing a first heart attack or stroke, or for the prevention of colorectal cancer, according to new draft guidelines.1

The move has been widely reported in the media as a big shift in advice, however both the US Food and Drug Administration (in 2014)2 and the 2019 joint guidelines from the American College of Cardiology (ACC) and American Heart Association (AHA) have already published this advice.3

As such, The BMJ understands that many US doctors already do not recommend aspirin routinely for primary prevention of cardiovascular disease.

UK …
P60.13 MYLUNG Consortium: Molecularly Informed Lung Cancer Treatment in a Community Cancer Network. Pragmatic Prospective RWR Study
Authors: M. Evangelist, R. Jotte, A. Spira, D. Waterhouse, K. Ali, S. Alwardt, S. Bullock, J. Butrynski, J. Espirito, C. Fitzgerald, D. Hakimian, T. Larson, M. Meshad, M. Neubauer, J. Paschold, N. Robert, J. Walberg, R. Coleman
Journal: Journal of Thoracic Oncology (2021)
Kidney single-cell transcriptome profile reveals distinct response of proximal tubule cells to SGLT2i and ARB treatment in diabetic mice
Authors: Jinshan Wu, Zeguo Sun, Shumin Yang, Jia Fu, Ying Fan, Niansong Wang, Jinbo Hu, Linqiang Ma, Chuan Peng, Zhihong Wang, Kyung Lee, John Cijiang He, Qifu Li
Journal: Molecular Therapy (2021)

Angiotensin receptor blockers (ARBs) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been used as the standard therapy for patients with diabetic kidney disease (DKD). However, how these two drugs possess additive renoprotective effects remains unclear. Here, we conducted single-cell RNA sequencing to profile the kidney cell transcriptome of db/db mice treated with vehicle, ARBs, SGLT2i, or ARBs plus SGLT2i, using db/m mice as control. We identified 10 distinct clusters of kidney cells with predominant proximal tubular (PT) cells. We found that ARBs had more anti-inflammatory and anti-fibrotic effects, while SGLT2i affected more mitochondrial function in PT. We also identified a new PT subcluster, was increased in DKD, but reversed by the treatments. This new subcluster was also confirmed by immunostaining of mouse and human kidneys with DKD. Together, our study reveals kidney cell-specific gene signatures in response to ARBs and SGLT2i and identifies a new PT subcluster, which provides new insight into the pathogenesis of DKD.
Development and validation of a novel online calculator for estimating survival benefit of adjuvant transcatheter arterial chemoembolization in patients undergoing surgery for hepatocellular carcinoma
Authors: Lei Liang, Chao Li, Ming-Da Wang, Hong Wang, Ya-Hao Zhou, Yong-Yi Zeng, Wan-Guang Zhang, Ting-Hao Chen, Nan-Ya Wang, Jie Li, Yao-Ming Zhang, Yu Wang, Wei-Min Gu, Hao Xing, Yong-Kang Diao, Wan Yee Lau, Cheng-Wu Zhang, Timothy M. Pawlik, Feng Shen, Dong-Sheng Huang, Tian Yang
Journal: Journal of Hematology & Oncology (2021)

Abstract Background and aims Although adjuvant transcatheter arterial chemoembolization (TACE) for resected hepatocellular carcinoma (HCC) may improve survival for some patients, identifying which patients can benefit remains challenging. The present study aimed to construct a survival prediction calculator for individualized estimating the net survival benefit of adjuvant TACE for patients with resected HCC. Methods From a multicenter database, consecutive patients undergoing curative resection for HCC were enrolled and divided into the developing and validation cohorts. Using the independent survival predictors in the developing cohort, two nomogram models were constructed for patients with and without adjuvant TACE, respectively, which predictive performance was validated internally and externally by measuring concordance index (C-index) and calibration. The difference between two estimates of the prediction models was the expected survival benefit of adjuvant TACE. Results A total of 2514 patients met the inclusion criteria for the study. The nomogram prediction models for patients with and without adjuvant TACE were, respectively, built by incorporating the same eight independent survival predictors, including portal hypertension, Child–Pugh score, alpha-fetoprotein level, tumor size and number, macrovascular and microvascular invasion, and resection margin. These two prediction models demonstrated good calibration and discrimination, with all the C-indexes of greater than 0.75 in the developing and validation cohorts. A browser-based calculator was generated for individualized estimating the net survival benefit of adjuvant TACE. Conclusions Based on large-scale real-world data, an easy-to-use online calculator can be adopted as a decision aid to predict which patients with resected HCC can benefit from adjuvant TACE.
Abstract 9785: Comparing Emergency Department Risk Stratification Tools for Chest Pain in African Americans
Authors: Olusayo Fadiran, Vishnu Priya Mallipeddi, Emmanuel Mbey, Henry Janna, Adebayo Atanda, Sumon Mahbubur, Julius Ngwa, Daniel A Larbi
Journal: Circulation (2019)

Introduction: Several risk stratification tools exist in the emergency department (ED) for assessing patients presenting with chest pain – the most common of which are the HEART and the TIMI scores...
One dose does not fit all: revising the WHO paediatric dosing tool to include the non-linear effect of body size and maturation
Authors: Paolo Denti, Roeland E Wasmann, Jose Francis, Helen McIlleron, Nandita Sugandhi, Tim R Cressey, Mark Mirochnick, Edmund V Capparelli, Martina Penazzato
Journal: The Lancet Child & Adolescent Health (2021)
A genetic risk score and diabetes predict development of alcohol-related cirrhosis in drinkers
Authors: John B. Whitfield, Tae-Hwi Schwantes-An, Rebecca Darlay, Guruprasad P. Aithal, Stephen R. Atkinson, Ramon Bataller, Greg Botwin, Naga P. Chalasani, Heather J. Cordell, Ann K. Daly, Christopher P. Day, Florian Eyer, Tatiana Foroud, Dermot Gleeson, David Goldman, Paul S. Haber, Jean-Marc Jacquet, Tiebing Liang, Suthat Liangpunsakul, Steven Masson, Philippe Mathurin, Romain Moirand, Andrew McQuillin, Christophe Moreno, Marsha Y. Morgan, Sebastian Mueller, Beat Müllhaupt, Laura E. Nagy, Pierre Nahon, Bertrand Nalpas, Sylvie Naveau, Pascal Perney, Munir Pirmohamed, Helmut K. Seitz, Michael Soyka, Felix Stickel, Andrew Thompson, Mark R. Thursz, Eric Trépo, Timothy R. Morgan, Devanshi Seth
Journal: Journal of Hepatology (2021)
A global effort to dissect the human genetic basis of resistance to SARS-CoV-2 infection
Authors: Evangelos Andreakos, Laurent Abel, Donald C. Vinh, Elżbieta Kaja, Beth A. Drolet, Qian Zhang, Cliona O’Farrelly, Giuseppe Novelli, Carlos Rodríguez-Gallego, Filomeen Haerynck, Carolina Prando, Aurora Pujol, Paul Bastard, Catherine M. Biggs, Benedetta Bigio, Bertrand Boisson, Alexandre Bolze, Anastasiia Bondarenko, Petter Brodin, Samya Chakravorty, John Christodoulou, Aurelié Cobat, Antonio Condino-Neto, Stefan N. Constantinescu, Hagit Baris Feldman, Jacques Fellay, Carlos Flores, Rabih Halwani, Emmanuelle Jouanguy, Yu-Lung Lau, Isabelle Meyts, Trine H. Mogensen, Satoshi Okada, Keisuke Okamoto, Tayfun Ozcelik, Qiang Pan-Hammarström, Rebeca Pérez de Diego, Anna M. Planas, Anne Puel, Lluis Quintana-Murci, Laurent Renia, Igor Resnick, Anna Sediva, Anna Shcherbina, Ondrej Slaby, Ivan Tancevski, Stuart E. Turvey, K. M. Furkan Uddin, Diederik van de Beek, Mayana Zatz, Pawel Zawadzki, Shen-Ying Zhang, Helen C. Su, Jean-Laurent Casanova, András N. Spaan
Journal: Nature Immunology (2021)

SARS-CoV-2 infections display tremendous interindividual variability, ranging from asymptomatic infections to life-threatening disease. Inborn errors of, and autoantibodies directed against, type I interferons (IFNs) account for about 20% of critical COVID-19 cases among SARS-CoV-2-infected individuals. By contrast, the genetic and immunological determinants of resistance to infection per se remain unknown. Following the discovery that autosomal recessive deficiency in the DARC chemokine receptor confers resistance to Plasmodium vivax, autosomal recessive deficiencies of chemokine receptor 5 (CCR5) and the enzyme FUT2 were shown to underlie resistance to HIV-1 and noroviruses, respectively. Along the same lines, we propose a strategy for identifying, recruiting, and genetically analyzing individuals who are naturally resistant to SARS-CoV-2 infection.
心不全患者における肺炎の発生率と転帰【JST・京大機械翻訳】
Authors: Shen Li, S Jhund Pardeep, S Anand Inder, S Bhatt Ankeet, S Desai Akshay, P Maggioni Aldo, A Martinez Felipe, A Pfeffer Marc, R Rizkala Adel, L Rouleau Jean, Swedberg Karl, Vaduganathan Muthiah, Vardeny Orly, J van Veldhuisen Dirk, Zannad Faiez, R Zile Michael, Packer Milton, D Solomon Scott, J V McMurray John
Journal: Journal of the American College of Cardiology (2021)
P57.04 Predicting Treatment Response to 1st- line Pembrolizumab in Advanced Non-Small Cell Lung Cancer (NSCLC) Patients with High PDL1 Expression
Authors: I. Janzen, R. Abraham, S. Seyyedi, C. Ho, B. Melosky, M. Martin, S. Lam, R. Yuan, C. Macaulay
Journal: Journal of Thoracic Oncology (2021)
Addressing the post-acute sequelae of SARS-CoV-2 infection: a multidisciplinary model of care
Authors: Ann M Parker, Emily Brigham, Bronwen Connolly, Joanne McPeake, Anna V Agranovich, Michael T Kenes, Kelly Casey, Cynthia Reynolds, Konrad F R Schmidt, Soo Yeon Kim, Adam Kaplin, Carla M Sevin, Martin B Brodsky, Alison E Turnbull
Journal: The Lancet Respiratory Medicine (2021)
Mitochondrial complex II in intestinal epithelial cells regulates T cell-mediated immunopathology
Authors: Hideaki Fujiwara, Keisuke Seike, Michael D. Brooks, Anna V. Mathew, Ilya Kovalenko, Anupama Pal, Ho-Joon Lee, Daniel Peltier, Stephanie Kim, Chen Liu, Katherine Oravecz-Wilson, Lu Li, Yaping Sun, Jaeman Byun, Yoshinobu Maeda, Max S. Wicha, Thomas L. Saunders, Alnawaz Rehemtulla, Costas A. Lyssiotis, Subramaniam Pennathur, Pavan Reddy
Journal: Nature Immunology (2021)
Approaches to quantifying hepatitis B virus covalently closed circular DNA
Authors: Henrik Zhang, Thomas Tu
Journal: Clinical and Molecular Hepatology (2021)

Chronic hepatitis B is a major cause of liver disease worldwide and is currently incurable. Hepatitis B virus (HBV) covalently closed circular (ccc) DNA is a key form of the virus responsible for its persistence and is the transcriptional template for all viral transcripts. The field is focussed on methods to clear HBV cccDNA but this been limited by technical difficulties in its quantification due to: identical sequence to other forms of HBV DNA; low copy number per cell; and high resistance to denaturation by heat, leading to difficulty using polymerase chain reaction or hybridization methods for detection. A number of assays have been developed in order to overcome these hurdles either directly or detecting cccDNA levels indirectly via its transcriptional products. In this review, we summarize the approaches to cccDNA quantification that are currently used, and outline key open questions in the cccDNA biology field which remain to be answered due to the limitations of current methods.