tbuckley/cabot-search huggingface dataset:
EAACI guidelines: Anaphylaxis (2021 update)
Authors: Antonella Muraro, Margitta Worm, Cherry Alviani, Victoria Cardona, Audrey DunnGalvin, Lene Heise Garvey, Carmen Riggioni, Debra de Silva, Elizabeth Angier, Stefania Arasi, Abdelouahab Bellou, Kirsten Beyer, Diola Bijlhout, Maria Beatrice Bilò, Carsten Bindslev‐Jensen, Knut Brockow, Montserrat Fernandez‐Rivas, Susanne Halken, Britt Jensen, Ekaterina Khaleva, Louise J. Michaelis, Hanneke N. G. Oude Elberink, Lynne Regent, Angel Sanchez, Berber J. Vlieg‐Boerstra, Graham Roberts
Journal: Allergy (2021)

Abstract Anaphylaxis is a clinical emergency which all healthcare professionals need to be able to recognize and manage. The European Academy of Allergy and Clinical Immunology Anaphylaxis multidisciplinary Task Force has updated the 2014 guideline. The guideline was developed using the AGREE II framework and the GRADE approach. The evidence was systematically reviewed and recommendations were created by weighing up benefits and harms. The guideline was peer‐reviewed by external experts and reviewed in a public consultation. The use of clinical criteria to identify anaphylaxis is suggested with blood sampling for the later measurement of tryptase. The prompt use of intramuscular adrenaline as first‐line management is recommended with the availability of adrenaline autoinjectors to patients in the community. Pharmacokinetic data should be provided for adrenaline autoinjector devices. Structured, comprehensive training for people at risk of anaphylaxis is recommended. Simulation training and visual prompts for healthcare professionals are suggested to improve the management of anaphylaxis. It is suggested that school policies reflect anaphylaxis guidelines. The evidence for the management of anaphylaxis remains mostly at a very low level. There is an urgent need to prioritize clinical trials with the potential to improve the management of patients at risk of anaphylaxis.
P35.04 The Prognostic Value of Metastasis to Different Organs in EGFR-Mutated Stage IV NSCLC Patients Treated with First-Line Icotinib
Authors: Y. Wang, L. Wang, J. Zuo, L. Feng, Z. Fan, X. Zhang, J. Han, X. Zhou, B. Li, N. Su, H. Du, J. Zhou
Journal: Journal of Thoracic Oncology (2021)
Pan-Cancer Screening: A Dream or a Nightmare
Authors: Margaret Tempero
Journal: Journal of the National Comprehensive Cancer Network (2021)

Pan-Cancer Screening:A Dream or a Nightmare I t stands to reason that the earlier you can diagnose cancer, the better chance you have to cure it.This idea has certainly held up in some diseases, such as those in which screening has clear value, like colorectal and lung cancers.However, for some cancers, such as prostate cancer, early diagnosis sometimes just leads to "watchful waiting," with continued surveillance and repeated biopsies until a clear need to treat is found.This variability within and among cancers makes me concerned about new attempts to launch "pan-cancer" screening tests.On the surface, "one-stop shopping" seems good.And the test is easy.Forget surveillance radiology or endoscopy and physical examinations.Just a bit of blood, please.But what happens when during your annual checkup a simple blood test is performed and results come back positive for cancer?Now what?First, we need to look for the cancer, but where should we start?Should we look at risk factors like smoking, and start there?Maybe we should just rule out more common cancers first.Or maybe we look for the most lethal cancers first?What kind of decision tree do we use to avoid unnecessary and sometimes risky procedures and make this an efficient process?Also, don't forget that if these tests are very sensitive, we might be looking for a tumor so small that it falls below the level of detection of even the most advanced imaging modalities.What happens in that case?Do we just tell you that if it's that small, it's probably safe to wait and look again in a year?And now do you need a psychiatrist to deal with your anxiety?I know that scenario is oversimplified and perhaps a little ridiculous, but hopefully you get my point.If we can move toward a pan-cancer test, I think we also need a second tier of blood-based testing to narrow the possibilities, ideally to just one organ, before we wade into a full-blown cancer-finding exercise.I do recognize that having universal blood-based screening that allows for avoiding traditional screening modalities would be cheaper and would ease the strain on the healthcare system.Although this still doesn't solve the problem of tiny cancers that defy radiologic imaging, it would spawn renewed interest in research with respect to molecular and functional imaging where, increasingly, subcentimeter lesions can be identified.This research is particularly important for organs that can be difficult to image, such as the pancreas for pancreatic adenocarcinoma, or for highly lethal cancers, such as glioblastoma multiforme.To sum up, I do think pan-cancer screening could be a game changer.But we must remember the caveats, and approach this in a proper and orderly way to avoid doing more harm than good.
Exercise-induced angiogenesis is dependent on metabolically primed ATF3/4+ endothelial cells
Authors: Zheng Fan, Guillermo Turiel, Raphaela Ardicoglu, Moheb Ghobrial, Evi Masschelein, Tea Kocijan, Jing Zhang, Ge Tan, Gillian Fitzgerald, Tatiane Gorski, Abdiel Alvarado-Diaz, Paola Gilardoni, Christopher M. Adams, Bart Ghesquière, Katrien De Bock
Journal: Cell Metabolism (2021)

Exercise is a powerful driver of physiological angiogenesis during adulthood, but the mechanisms of exercise-induced vascular expansion are poorly understood. We explored endothelial heterogeneity in skeletal muscle and identified two capillary muscle endothelial cell (mEC) populations that are characterized by differential expression of ATF3/4. Spatial mapping showed that ATF3/4+ mECs are enriched in red oxidative muscle areas while ATF3/4low ECs lie adjacent to white glycolytic fibers. In vitro and in vivo experiments revealed that red ATF3/4+ mECs are more angiogenic when compared with white ATF3/4low mECs. Mechanistically, ATF3/4 in mECs control genes involved in amino acid uptake and metabolism and metabolically prime red (ATF3/4+) mECs for angiogenesis. As a consequence, supplementation of non-essential amino acids and overexpression of ATF4 increased proliferation of white mECs. Finally, deleting Atf4 in ECs impaired exercise-induced angiogenesis. Our findings illustrate that spatial metabolic angiodiversity determines the angiogenic potential of muscle ECs.
Covid-19: CPAP reduces need for invasive mechanical ventilation in patients requiring oxygen, study finds
Authors: Elisabeth Mahase
Journal: BMJ (2021)

Covid-19: CPAP reduces need for invasive mechanical ventilation in patients requiring oxygen, study finds Elisabeth MahaseContinuous positive airway pressure (CPAP) reduced the need for invasive mechanical ventilation in adults admitted to hospital with acute respiratory failure due to covid-19, a trial has found. 1 1
Ample dietary fat reduced the risk of primary vesical calculi by inducing macrophages to engulf budding crystals in mice
Authors: Huiling Chen, Kaiqiang Hu, Yaru Liang, Yuqi Gao, Chenye Zeng, Kang Xu, Xiaojin Shi, Liyuan Li, Yuemiao Yin, Yi Qiao, Ying Qiu, Qingfei Liu, Zhao Wang
Journal: Acta Pharmaceutica Sinica B (2021)

Although primary vesical calculi is an ancient disease, the mechanism of calculi formation remains unclear. In this study, we established a novel primary vesical calculi model with d,l-choline tartrate in mice. Compared with commonly used melamine and ethylene glycol models, our model was the only approach that induced vesical calculi without causing kidney injury. Previous studies suggest that proteins in the daily diet are the main contributors to the prevention of vesical calculi, yet the effect of fat is overlooked. To assay the relationship of dietary fat with the formation of primary vesical calculi, d,l-choline tartrate-treated mice were fed a high-fat, low-fat, or normal-fat diet. Genetic changes in the mouse bladder were detected with transcriptome analysis. A high-fat diet remarkably reduced the morbidity of primary vesical calculi. Higher fatty acid levels in serum and urine were observed in the high-fat diet group, and more intact epithelia in bladder were observed in the same group compared with the normal- and low-fat diet groups, suggesting the protective effect of fatty acids on bladder epithelia to maintain its normal histological structure. Transcriptome analysis revealed that the macrophage differentiation-related gene C-X-C motif chemokine ligand 14 (Cxcl14) was upregulated in the bladders of high-fat diet-fed mice compared with those of normal- or low-fat diet-fed mice, which was consistent with histological observations. The expression of CXCL14 significantly increased in the bladder in the high-fat diet group. CXCL14 enhanced the recruitment of macrophages to the crystal nucleus and induced the transformation of M2 macrophages, which led to phagocytosis of budding crystals and prevented accumulation of calculi. In human bladder epithelia (HCV-29) cells, high fatty acid supplementation significantly increased the expression of CXCL14. Dietary fat is essential for the maintenance of physiological functions of the bladder and for the prevention of primary vesical calculi, which provides new ideas for the reduction of morbidity of primary vesical calculi.
Perturbed BMP signaling and denervation promote muscle wasting in cancer cachexia
Authors: Roberta Sartori, Adam Hagg, Sandra Zampieri, Andrea Armani, Catherine E. Winbanks, Laís R. Viana, Mouna Haidar, Kevin I. Watt, Hongwei Qian, Camilla Pezzini, Pardis Zanganeh, Bradley J. Turner, Anna Larsson, Gianpietro Zanchettin, Elisa S. Pierobon, Lucia Moletta, Michele Valmasoni, Alberto Ponzoni, Shady Attar, Gianfranco Da Dalt, Cosimo Sperti, Monika Kustermann, Rachel E. Thomson, Lars Larsson, Kate L. Loveland, Paola Costelli, Aram Megighian, Stefano Merigliano, Fabio Penna, Paul Gregorevic, Marco Sandri
Journal: Science Translational Medicine (2021)

Neuromuscular junction remodeling and deterioration due to impaired BMP signaling are associated with cancer-induced muscle wasting.
25830 Wound healing outcomes in patients with concomitant autoimmune diseases prescribed disease-modifying anti-rheumatic drugs
Authors: Julianne Kiene, Suzanne Zhou, Jenna Bekeny, Ashley Rogers, Elizabeth Zolper, Paige Dekker, Kenneth Fan, Karen K. Evans, Carol Deane Benedict Mitnick, Helena Pasieka, Christopher E. Attinger
Journal: Journal of the American Academy of Dermatology (2021)
Mechanisms of Weight Loss After Obesity Surgery
Authors: Elina Akalestou, Alexander D Miras, Guy A Rutter, Carel W le Roux
Journal: Endocrine Reviews (2021)

Abstract Obesity surgery remains the most effective treatment for obesity and its complications. Weight loss was initially attributed to decreased energy absorption from the gut but has since been linked to reduced appetitive behavior and potentially increased energy expenditure. Implicated mechanisms associating rearrangement of the gastrointestinal tract with these metabolic outcomes include central appetite control, release of gut peptides, change in microbiota, and bile acids. However, the exact combination and timing of signals remain largely unknown. In this review, we survey recent research investigating these mechanisms, and seek to provide insights on unanswered questions over how weight loss is achieved following bariatric surgery which may eventually lead to safer, nonsurgical weight-loss interventions or combinations of medications with surgery.
Clinical outcomes of cancer patients with COVID-19: A systematic review and metaanalysis
Authors: M. Alasfour, S. Alawadi, M. AlMojel, P. A. Costa, P. B. Coelho, T. Plate, S. Ahn, G. Lopes
Journal: Journal of Clinical Oncology (2021)

Background: Patients with coronavirus disease 2019 (COVID-19) and cancer have worse clinical outcomes compared to those without cancer. Primary studies have examined this population, but most had small sample sizes and conflicting results. Prior meta-analyses exclude most US and European data or only examine mortality. The present meta-analysis evaluates the prevalence of several clinical outcomes in cancer patients with COVID-19, including new emerging data from Europe and the US. Methods: A systematic search of PubMED, medRxiv, JMIR and Embase by two independent investigators included peer-reviewed papers and preprints up to July 8, 2020. The primary outcome was mortality. Other outcomes were ICU and non-ICU admission, mild, moderate and severe complications, ARDS, invasive ventilation, stable, and clinically improved rates. Study quality was assessed through the Newcastle-Ottawa scale. Random effects model was used to derive prevalence rates, their 95% confidence intervals (CI) and 95% prediction intervals (PI). Results: Thirty-four studies (N = 4,371) were included in the analysis. The mortality prevalence rate was 25.2% (95% CI: 21.1-29.7;95% PI: 9.8-51.1;I2= 85.4), with 11.9% ICU admissions (95% CI: 9.2-15.4;95% PI: 4.3- 28.9;I2= 77.8) and 25.2% clinically stable (95% CI: 21.1-29.7;95% PI: 9.8-51.1;I2= 85.4). Furthermore, 42.5% developed severe complications (95% CI: 30.4-55.7;95% PI: 8.2- 85.9;I2= 94.3), with 22.7% developing ARDS (95% CI: 15.4-32.2;95% PI: 5.8-58.6;I2= 82.4), and 11.3% needing invasive ventilation (95% CI: 6.7-18.4;95% PI: 2.3-41.1;I2= 79.8). Post-follow up, 49% clinically improved (95% CI: 35.6-62.6;95% PI: 9.8-89.4;I2= 92.5). All outcomes had large I2 , suggesting high levels of heterogeneity among studies, and wide PIs indicating high variability within outcomes. Despite this variability, the mortality rate in cancer patients with COVID-19, even at the lower end of the PI (9.8%), is higher than the 2% mortality rate of the non-cancer with COVID-19 population, but not as high as what other meta-analyses conclude, which is around 25%. Conclusions: Patients with cancer who develop COVID-19 have a higher probability of mortality compared to the general population with COVID-19, but possibly not as high as previous studies have shown. A large proportion of them developed severe complications, but a larger proportion recovered. Prevalence of mortality and other outcomes published in prior meta-analyses did not report prediction intervals, which compromises the clinical utilization of such results.
Monogenic Diabetes in Youth With Presumed Type 2 Diabetes: Results From the Progress in Diabetes Genetics in Youth (ProDiGY) Collaboration
Authors: Jennifer N. Todd, Jeffrey W. Kleinberger, Haichen Zhang, Shylaja Srinivasan, Sherida E. Tollefsen, Lynne L. Levitsky, Lorraine E. Levitt Katz, Jeanie B. Tryggestad, Fida Bacha, Giuseppina Imperatore, Jean M. Lawrence, Catherine Pihoker, Jasmin Divers, Jason Flannick, Dana Dabelea, Jose C. Florez, Toni I. Pollin
Journal: Diabetes Care (2021)

OBJECTIVE Maturity-onset diabetes of the young (MODY) is frequently misdiagnosed as type 1 or type 2 diabetes. Correct diagnosis may result in a change in clinical treatment and impacts prediction of complications and familial risk. In this study, we aimed to assess the prevalence of MODY in multiethnic youth under age 20 years with a clinical diagnosis of type 2 diabetes. RESEARCH DESIGN AND METHODS We evaluated whole-exome sequence data of youth with a clinical diagnosis of type 2 diabetes. We considered participants to have MODY if they carried a MODY gene variant classified as likely pathogenic (LP) or pathogenic (P) according to current guidelines. RESULTS Of 3,333 participants, 93 (2.8%) carried an LP/P variant in HNF4A (16 participants), GCK (23), HNF1A (44), PDX1 (5), INS (4), and CEL (1). Compared with those with no LP/P variants, youth with MODY had a younger age at diagnosis (12.9 ± 2.5 vs. 13.6 ± 2.3 years, P = 0.002) and lower fasting C-peptide levels (3.0 ± 1.7 vs. 4.7 ± 3.5 ng/mL, P &amp;lt; 0.0001). Youth with MODY were less likely to have hypertension (6.9% vs. 19.5%, P = 0.007) and had higher HDL cholesterol (43.8 vs. 39.7 mg/dL, P = 0.006). CONCLUSIONS By comprehensively sequencing the coding regions of all MODY genes, we identified MODY in 2.8% of youth with clinically diagnosed type 2 diabetes; importantly, in 89% (n = 83) the specific diagnosis would have changed clinical management. No clinical criterion reliably separated the two groups. New tools are needed to find ideal criteria for selection of individuals for genetic testing.
Response to: Correspondence on “Update on the diagnosis and management of systemic lupus erythematosus” by Zhou<i>et al</i>
Authors: Antonis Fanouriakis, Nikolaos Tziolos, George Bertsias, Dimitrios T Boumpas
Journal: Annals of the Rheumatic Diseases (2021)

We thank Zhou et al for their interest in our manuscript and their insightful comments.1 In figure 4 of our manuscript (Diagnostic approach to a patient with suspected systemic lupus erythematosus and the use of classification criteria to aid clinical diagnosis), we propose an algorithm to aid clinical diagnosis, especially in patients not fulfilling the classification criteria.2 As opposed to classification, diagnosis by definition may include the notion of probability (ie, possible systemic lupus erythematosus (SLE)). Moreover, as …
The roles of Claspin and DNA repair proteins in DNA damage checkpoint response
Authors: Mette Praetorius-Ibba, Qi-En Wang, Gulzar Wani, Mohamed A. El-Mahdy, Qianzheng Zhu, Altaf A. Wani
Journal: Cancer Research (2006)

1069  The novel protein Claspin has recently been identified in mammalian cells as a mediator of replication checkpoint response. Localized at the replication fork, Claspin is also suggested to play a role in sensing DNA replication and DNA structures that may have evolved from genotoxic stress. To investigate whether Claspin would interact with upstream DNA repair proteins believed to sense UV-induced DNA lesions, protein-protein interaction experiments were carried out in the form of co-immunoprecipitations and co-purifications. Preliminary data suggest the ability of Claspin to physically interact with two upstream DNA repair proteins. Both of these factors, XPC and DDB1, are implicated in lesion recognition in nucleotide excision repair (NER). The interaction of XPC, a factor of the xeroderma pigmentosum group C protein complex, and of DDB1, one of two components of the UV-damage DNA binding protein complex (UV-DDB), was seen using nuclear extracts from UV-irradiated and non-irradiated cells. So far no association was detected between Claspin and the second factor of the UV-DDB complex, DDB2. On the other hand, DDB1 co-immunoprecipitation experiments demonstrate an association between DDB1 and XPC, which supports a recent finding that XPC interact with UV-DDB. Data will be presented examining the suggested protein-protein interactions as well as the functional relevance of such complexes. (Supported by NIH grants ES2388, ES12991 and CA93413)
Trends in Consumption of Ultraprocessed Foods Among US Youths Aged 2-19 Years, 1999-2018
Authors: Lu Wang, Euridice Martínez Steele, Mengxi Du, Jennifer L. Pomeranz, Lauren E. O’Connor, Kirsten A. Herrick, Hanqi Luo, Xuehong Zhang, Dariush Mozaffarian, Fang Fang Zhang
Journal: JAMA (2021)

The childhood obesity rate has been steadily rising among US youths during the past 2 decades. Increasing evidence links consumption of ultraprocessed foods to excessive calorie consumption and weight gain, but trends in the consumption of ultraprocessed foods among US youths have not been well characterized.
Multicenter Study of Endocarditis After Transcatheter Pulmonary Valve Replacement
Authors: Doff B. McElhinney, Yulin Zhang, Jamil A. Aboulhosn, Brian H. Morray, Elżbieta Katarzyna Biernacka, Athar M. Qureshi, Alejandro J. Torres, Shabana Shahanavaz, Bryan H. Goldstein, Allison K. Cabalka, Holly Bauser-Heaton, Stanimir Georgiev, Felix Berger, Oscar Millan-Iturbe, Lynn F. Peng, Aimee K. Armstrong, Daniel S. Levi, Aneta Fronczak-Jakubczyk, Lars Sondergaard, Jason H. Anderson, Dietmar Schranz, Thomas K. Jones, John P. Cheatham, Stephan Schubert, Peter Ewert
Journal: Journal of the American College of Cardiology (2021)
SCAPTURE: a deep learning-embedded pipeline that captures polyadenylation information from 3′ tag-based RNA-seq of single cells
Authors: Guo-Wei Li, Fang Nan, Guo-Hua Yuan, Chu-Xiao Liu, Xindong Liu, Ling-Ling Chen, Bin Tian, Li Yang
Journal: Genome biology (2021)

Abstract Single-cell RNA-seq (scRNA-seq) profiles gene expression with high resolution. Here, we develop a stepwise computational method-called SCAPTURE to identify, evaluate, and quantify cleavage and polyadenylation sites (PASs) from 3′ tag-based scRNA-seq. SCAPTURE detects PASs de novo in single cells with high sensitivity and accuracy, enabling detection of previously unannotated PASs. Quantified alternative PAS transcripts refine cell identity analysis beyond gene expression, enriching information extracted from scRNA-seq data. Using SCAPTURE, we show changes of PAS usage in PBMCs from infected versus healthy individuals at single-cell resolution.
アトピー性湿疹における乳児腸マイクロビオームとメタボロームの妥協的発達軌跡【JST・京大機械翻訳】
Authors: Ta Le Duc Huy, Chan James Chun Yip, Yap Gaik Chin, W Purbojati Rikky, I Drautz-Moses Daniela, Koh Yanqing Michelle, Tay Carina Jing Xuan, Huang Chiung-Hui, Kioh Dorinda Yan Qin, Woon Jia Yun, Tham Elizabeth Huiwen, Loo Evelyn Xiu Ling, P C Shek Lynette, Karnani Neerja, Goh Anne, P S Van Bever Hugo, Teoh Oon Hoe, Chan Yiong Huak, Lay Christophe, Knol Jan, Yap Fabian, Tan Kok Hian, Chong Yap-Seng, M Godfrey Keith, Kjelleberg Staffan, C Schuster Stephan, Chan Eric Chun Yong, Lee Bee Wah
Journal: Gut Microbes (2020)
Early nasal type I IFN immunity against SARS-CoV-2 is compromised in patients with autoantibodies against type I IFNs
Authors: Jonathan Lopez, Marine Mommert, William Mouton, Andrés Pizzorno, Karen Brengel-Pesce, Mehdi Mezidi, Marine Villard, Bruno Lina, Jean-Christophe Richard, Jean-Baptiste Fassier, Valérie Cheynet, Blandine Padey, Victoria Duliere, Thomas Julien, Stéphane Paul, Paul Bastard, Alexandre Belot, Antonin Bal, Jean-Laurent Casanova, Manuel Rosa-Calatrava, Florence Morfin, Thierry Walzer, Sophie Trouillet-Assant
Journal: The Journal of Experimental Medicine (2021)

IFN-I and IFN-III immunity in the nasal mucosa is poorly characterized during SARS-CoV-2 infection. We analyze the nasal IFN-I/III signature, namely the expression of ISGF-3-dependent IFN-stimulated genes, in mildly symptomatic COVID-19 patients and show its correlation with serum IFN-α2 levels, which peak at symptom onset and return to baseline from day 10 onward. Moreover, the nasal IFN-I/III signature correlates with the nasopharyngeal viral load and is associated with the presence of infectious viruses. By contrast, we observe low nasal IFN-I/III scores despite high nasal viral loads in a subset of critically ill COVID-19 patients, which correlates with the presence of autoantibodies (auto-Abs) against IFN-I in both blood and nasopharyngeal mucosa. In addition, functional assays in a reconstituted human airway epithelium model of SARS-CoV-2 infection confirm the role of such auto-Abs in abrogating the antiviral effects of IFN-I, but not those of IFN-III. Thus, IFN-I auto-Abs may compromise not only systemic but also local antiviral IFN-I immunity at the early stages of SARS-CoV-2 infection.