tbuckley/cabot-search huggingface dataset:
Food immunotherapy practice: Nation differences across Europe, the FIND project
Authors: Pablo Rodríguez del Río, Alberto Alvarez‐Perea, Katharina Blumchen, Davide Caimmi, Jean Christoph Caubet, Anastasios Panagiotis Konstantinopoulos, Carmen Riggioni, Filippo Fassio, Elif Karakoc‐Aydiner, Thuy May Le, Nandinee Patel, Johannes Savolainen, Marta Vazquez‐Ortiz, Montserrat Alvaro Lozano
Journal: Allergy (2021)

Food allergen immunotherapy (FA-AIT) practice is known to vary globally. This project aims to identify and characterize European centres performing FA-AIT.An EAACI task force conducted an online survey to gather relevant information regarding FA-AIT practice and setting-specific resources after reviewing the published literature and congress abstracts throughout Europe.We identified 102 FA-AIT centres in 18 countries; only Spain (n = 39) and France (n = 16) had ≥10 such centres. Overall, most facilities were hospital-based (77.5%), publicly funded (80.4%) and delivered FA-AIT as routine clinical care (80.4%). On average, departments had 3 allergists/paediatric allergists and 2 nurses. Surveyed centres had provided FA-AIT for a median of 9 years [1-24] to a median of 105 [5-2415] patients. The estimated total number of treated patients was 24875, of whom 41.3% received AIT for milk, 34.2% egg, 12.8% peanut and 11.7% other foods. Anaphylaxis to AIT doses requiring over 4-6 h of observation was reported by 70.6% of centres, ICU admissions by 10.8% and eosinophilic esophagitis by 45.1%. Quality of life and sustained unresponsiveness were evaluated in 20.6% and 54.9% of centres, respectively. The main contraindications for food AIT were severe asthma (57%-63%), eosinophilic esophagitis (56%-48%) and age below 5 years (47%-41%).In Europe, FA-AIT is provided mostly in clinical practice. Significant variation is seen in the number of centres per country, facility characteristics and inclusion/exclusion criteria, and in certain aspects of protocols. Potential inequality in access to AIT has been identified as well as the need for education and guidance for treatment standardization.
Enhancing the tropism of bacteria via genetically programmed biosensors
Authors: Tiffany Chien, Tetsuhiro Harimoto, Benjamin Kepecs, Kelsey Gray, Courtney Coker, Nicholas Hou, Kelly Pu, Tamjeed Azad, Andoni Nolasco, Martina Pavlicova, Tal Danino
Journal: Nature Biomedical Engineering (2021)
Comparison of Outcomes after Myeloablative Versus Reduced Intensity Conditioning Allogeneic Hematopoietic Cell Transplantation for Chronic Myeloid Leukemia
Authors: Saurabh Chhabra, Kwang Woo Ahn, Zhen-Huan Hu, Sandeep Jain, Robert K. Stuart, Matt Kalaycio, Uday Popat, Ronald Sobecks, Edwin Alyea, Wael Saber
Journal: Blood (2017)
The informed road map to prevention of Alzheimer Disease: A call to arms
Authors: Eric McDade, Jorge J. Llibre-Guerra, David M. Holtzman, John C. Morris, Randall J. Bateman
Journal: Molecular Neurodegeneration (2021)

Abstract Alzheimer disease (AD) prevention trials hold the promise to delay or prevent cognitive decline and dementia onset by intervening before significant neuronal damage occurs. In recent years, the first AD prevention trials have launched and are yielding important findings on the biology of targeting asymptomatic AD pathology. However, there are limitations that impact the design of these prevention trials, including the translation of animal models that recapitulate key stages and multiple pathological aspects of the human disease, missing target validation in asymptomatic disease, uncertain causality of the association of pathophysiologic changes with cognitive and clinical symptoms, and limited biomarker validation for novel targets. The field is accelerating advancements in key areas including the development of highly specific and quantitative biomarker measures for AD pathology, increasing our understanding of the course and relationship of amyloid and tau pathology in asymptomatic through symptomatic stages, and the development of powerful interventions that can slow or reverse AD amyloid pathology. We review the current status of prevention trials and propose key areas of needed research as a call to basic and translational scientists to accelerate AD prevention. Specifically, we review (1) sporadic and dominantly inherited primary and secondary AD prevention trials, (2) proposed targets, mechanisms, and drugs including the amyloid, tau, and inflammatory pathways and combination treatments, (3) the need for more appropriate prevention animal models and experiments, and (4) biomarkers and outcome measures needed to design human asymptomatic prevention trials. We conclude with actions needed to effectively move prevention targets and trials forward.
Dermatomyositis on 68Ga-FAPI PET/CT in a Patient With Nasopharyngeal Carcinoma
Authors: Junhao Wu, Lin Qiu, Yingwei Wang, Chunyin Zhang
Journal: Clinical Nuclear Medicine (2021)

Dermatomyositis is an idiopathic inflammatory myopathy often associated with malignancies. 68Ga-FAPI PET/CT was performed on a 58-year-old man with newly diagnosed dermatomyositis. 68Ga-FAPI PET/CT showed multiple increased FAPI activity in whole-body muscles and nasopharyngeal lesion. A biopsy of the nasopharyngeal lesion confirmed nasopharyngeal carcinoma. 68Ga-FAPI PET/CT can provide a "1-stop" imaging method for patients with dermatomyositis.
MO27-1 Correlation between immune-related adverse events and prognosis in renal cell carcinoma patients treated with nivolumab
Authors: Taigo Kato, Akira Nagahara, Norihiko Kawamura, Wataru Nakata, Tetsuji Soda, Kyosuke Matsuzaki, Koji Hatano, Atsunari Kawashima, Takeshi Ujike, Ryoichi Imamura, Kensaku Nishimura, Shingo Takada, Masao Tsujihata, Seiji Yamaguchi, Tetsuya Takao, Kazuo Nishimura, Motohide Uemura, Norio Nonomura
Journal: Annals of Oncology (2021)
Improving Risk Stratification for Pediatric Patients with Rhabdomyosarcoma by Molecular Detection of Disseminated Disease
Authors: Nathalie S.M. Lak, Timon L. Voormanns, Lily Zappeij-Kannegieter, Lieke M.J. van Zogchel, Marta Fiocco, Max M. van Noesel, Johannes H.M. Merks, C. Ellen van der Schoot, Godelieve A.M. Tytgat, Janine Stutterheim
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Survival of children with rhabdomyosarcoma that suffer from recurrent or progressive disease is poor. Identifying these patients upfront remains challenging, indicating a need for improvement of risk stratification. Detection of tumor-derived mRNA in bone marrow (BM) and peripheral blood (PB) using reverse-transcriptase qPCR (RT-qPCR) is a more sensitive method to detect disseminated disease. We identified a panel of genes to optimize risk stratification by RT-qPCR. Experimental Design: Candidate genes were selected using gene expression data from rhabdomyosarcoma and healthy hematologic tissues, and a multiplexed RT-qPCR was developed. Significance of molecular disease was determined in a cohort of 99 Dutch patients with rhabdomyosarcoma (72 localized and 27 metastasized) treated according to the European pediatric Soft tissue sarcoma Study Group (EpSSG) RMS2005 protocol. Results: We identified the following 11 rhabdomyosarcoma markers: ZIC1, ACTC1, MEGF10, PDLIM3, SNAI2, CDH11, TMEM47, MYOD1, MYOG, and PAX3/7-FOXO1. RT-qPCR was performed for this 11-marker panel on BM and PB samples from the patient cohort. Five-year event-free survival (EFS) was 35.5% [95% confidence interval (CI), 17.5%–53.5%] for the 33/99 RNA-positive patients, versus 88.0% (95% CI, 78.9%–97.2%) for the 66/99 RNA-negative patients (P &amp;lt; 0.0001). Five-year overall survival (OS) was 54.8% (95% CI, 36.2%–73.4%) and 93.7% (95% CI, 86.6%–100.0%), respectively (P &amp;lt; 0.0001). RNA panel positivity was negatively associated with EFS (Hazard Ratio = 9.52; 95% CI, 3.23–28.02), whereas the RMS2005 risk group stratification was not, in the multivariate Cox regression model. Conclusions: This study shows a strong association between PCR-based detection of disseminated disease at diagnosis with clinical outcome in pediatric patients with rhabdomyosarcoma, also compared with conventional risk stratification. This warrants further validation in prospective trials as additional technique for risk stratification.
Enzymatically synthesized exopolysaccharide of a probiotic strain <i>Leuconostoc mesenteroides</i> NTM048 shows adjuvant activity to promote IgA antibody responses
Authors: Chiaki Matsuzaki, Yukari Nakashima, Ikuto Endo, Yusuke Tomabechi, Yasuki Higashimura, Saki Itonori, Koji Hosomi, Jun Kunisawa, Kenji Yamamoto, Keiko Hisa
Journal: Gut Microbes (2021)

Leuconostoc mesenteroides strain NTM048 produces an exopolysaccharide (EPS; glucose polymers 94% and fructose polymers 6%) with adjuvanticity for mucosal vaccination. Strain NTM048 includes three putative EPS-synthesizing genes, gtf1 and gtf2 for synthesizing glucose polymers, and lvnS for synthesizing fructose polymer. To elucidate the key polymer structure for adjuvanticity, two genes, gtf1 and gtf2, which were annotated as glycoside hydrolase family 70 enzyme genes, were expressed in Escherichia coli. Glycosyl-linkage composition analysis and NMR analysis showed that the recombinant enzyme Gtf1 produced a soluble form of α-1,6-glucan, whereas the recombinant enzyme Gtf2 produced glucans with approximately equal percentages of α-1,6- and α-1,3-glucose residues both in the supernatant (S-glucan) and as a precipitate (P-glucan). Comparison of polysaccharides synthesized by Gtf1, Gtf2, and LvnS revealed that Gtf2-S-glucan, which was produced in the supernatant by Gtf2 and formed particles of 7.8 µm, possessed 1.8-fold higher ability to stimulate IgA production from murine Peyer's patch cells than native NTM048 EPS. Evaluation of adjuvanticity by intranasal administration of mice with an antigen (ovalbumin) and Gtf2-S-glucan or NTM048 EPS showed that Gtf2-S-glucan induced the production of higher antigen-specific antibodies in the airway mucosa and plasma, suggesting a pivotal role of Gtf2-S-glucan in the adjuvanticity of NTM048 EPS.
Tumor-Specific Major Histocompatibility-II Expression Predicts Benefit to Anti–PD-1/L1 Therapy in Patients With HER2-Negative Primary Breast Cancer
Authors: Paula I. Gonzalez-Ericsson, Julia D. Wulfkhule, Rosa I. Gallagher, Xiaopeng Sun, Margaret L. Axelrod, Quanhu Sheng, Na Luo, Henry Gomez, Violeta Sanchez, Melinda Sanders, Lajos Pusztai, Emanuel Petricoin, Kim R.M. Blenman, Justin M. Balko
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Immunotherapies targeting PD-1/L1 enhance pathologic complete response (pCR) rates when added to standard neoadjuvant chemotherapy (NAC) regimens in early-stage triple-negative, and possibly high-risk estrogen receptor–positive breast cancer. However, immunotherapy has been associated with significant toxicity, and most patients treated with NAC do not require immunotherapy to achieve pCR. Biomarkers discerning patients benefitting from the addition of immunotherapy from those who would achieve pCR to NAC alone are clearly needed. In this study, we tested the ability of MHC-II expression on tumor cells, to predict immunotherapy-specific benefit in the neoadjuvant breast cancer setting. Patients and Methods: This was a retrospective tissue-based analysis of 3 cohorts of patients with breast cancer: (i) primary nonimmunotherapy-treated breast cancers (n = 381), (ii) triple-negative breast cancers (TNBC) treated with durvalumab and standard NAC (n = 48), and (iii) HER2-negative patients treated with standard NAC (n = 87) or NAC and pembrolizumab (n = 66). Results: HLA-DR positivity on ≥5% of tumor cells, defined a priori, was observed in 10% and 15% of primary non-immunotherapy–treated hormone receptor–positive and triple-negative breast cancers, respectively. Quantitative assessment of MHC-II on tumor cells was predictive of durvalumab + NAC and pembrolizumab + NAC (ROC AUC, 0.71; P = 0.01 and AUC, 0.73; P = 0.001, respectively), but not NAC alone (AUC, 0.5; P = 0.99). Conclusions: Tumor-specific MHC-II has a strong candidacy as a specific biomarker of anti–PD-1/L1 immunotherapy benefit when added to standard NAC in HER2-negative breast cancer. Combined with previous studies in melanoma, MHC-II has the potential to be a pan-cancer biomarker. Validation is warranted in existing and future phase II/III clinical trials in this setting.
Genome-Wide SNPs Clarify a Complex Radiation and Support Recognition of an Additional Cat Species
Authors: Fernanda J Trindade, Maíra R Rodrigues, Henrique V Figueiró, Gang Li, William J Murphy, Eduardo Eizirik
Journal: Molecular Biology and Evolution (2021)

Abstract Phylogenetic reconstruction and species delimitation are often challenging in the case of recent evolutionary radiations, especially when postspeciation gene flow is present. Leopardus is a Neotropical cat genus that has a long history of recalcitrant taxonomic problems, along with both ancient and current episodes of interspecies admixture. Here, we employ genome-wide SNP data from all presently recognized Leopardus species, including several individuals from the tigrina complex (representing Leopardus guttulus and two distinct populations of Leopardus tigrinus), to investigate the evolutionary history of this genus. Our results reveal that the tigrina complex is paraphyletic, containing at least three distinct species. While one can be assigned to L. guttulus, the other two remain uncertain regarding their taxonomic assignment. Our findings indicate that the “tigrina” morphology may be plesiomorphic within this group, which has led to a longstanding taxonomic trend of lumping these poorly known felids into a single species.
Open letter to the prime minister and secretary of state on the second anniversary of England’s announcement that it would be smoke-free by 2030
Authors: Nicholas S Hopkinson, Helen Stokes-Lampard, Jennifer Dixon, Maggie Rae, Linda Bauld, Sarah Woolnough, Andrew Goddard, Jeanelle de Gruchy, Charmaine Griffiths, Ian Walker, Jon Bennett
Journal: BMJ (2021)

Smoking prevalence projections for England, Scotland, Wales, and Northern Ireland
MO23-1 Detection of hematological malignancies using N-NOSE (Nematode-NOSE)
Authors: Shingen Nakamura, Yoshihisa Ueno, Sumiko Yoshida, Masafumi Nakamura, Makiko Mizuguchi, Ryohei Sumitani, Masahiro Oura, Kimiko Sogabe, Mamiko Takahashi, Tomoko Maruhashi, Takeshi Harada, Shiro Fujii, Hirokazu Miki, Kumiko Kagawa, Takaaki Hirotsu, Masahiro Abe
Journal: Annals of Oncology (2021)
Abstract 14408: Inferior QRS Fragmentation Pattern on Surface Electrocardiogram- A Marker of Right Ventricular Out Flow Tract Aneurysm in Operated Tetralogy of Fallot
Authors: Nesan Shanmugam
Journal: Circulation (2011)

Introduction: Fragmented QRS complexes (fQRS) on 12-lead ECG have been shown to correlate with myocardial scar. Some have also postulated a link with LV aneurysm. No studies have reported the preva...
Disability-Adjusted Life-Years Associated With Intracerebral Hemorrhage and Secondary Injury
Authors: David Haupenthal, Joji B. Kuramatsu, Bastian Volbers, Jochen A. Sembill, Anne Mrochen, Stefanie Balk, Philip Hoelter, Hannes Lücking, Tobias Engelhorn, Arnd Dörfler, Stefan Schwab, Hagen B. Huttner, Maximilian I. Sprügel
Journal: JAMA Network Open (2021)

Intracerebral hemorrhage (ICH) contributes significantly to the global burden of disease.
Myelofibrosis Pattern in 68Ga-PSMA PET/CT of a Patient With Recurrence Prostate Cancer
Authors: Jolanta Kunikowska, Kacper Pełka
Journal: Clinical Nuclear Medicine (2021)

Abstract We present the case of a 64-year-old man with prostate adenocarcinoma, Gleason score 7, after radical prostatectomy and adjuvant radiotherapy in 2015. Because of high risk and perineural invasion, hormonotherapy was indicated. PSA levels began to rise, and at PSA level of 0.9 ng/mL, he was referred for 68 Ga-PSMAPET/CT. It showed focal uptake in the right femur and diffuse tracer accumulation in bone marrow. The patient was previously diagnosed with macrocytic anemia. He underwent bone marrow biopsy. Based on clinical, laboratory, and histopathology results, myelodysplastic fibrosis was diagnosed. Diffuse uptake of 68 Ga-PSMA was the sign of the bone marrow stimulation.
ABC of AIDS: Development of the epidemic
Authors: M. W Adler
Journal: BMJ (2001)

The first recognised cases of the acquired immune deficiency syndrome (AIDS) occurred in the summer of 1981 in America. Reports began to appear of Pneumocystis carinii pneumonia and Kaposi's sarcoma in young men, who it was subsequently realised were both homosexual and immunocompromised. Even though the condition became known early on as AIDS, its cause and modes of transmission were not immediately obvious. The virus now known to cause AIDS in a proportion of those infected was discovered in 1983 and given various names. The internationally accepted term is now the human immunodeficiency virus (HIV). subsequently a new variant has been isolated in patients with West African connections—HIV-2.

This article has been adapted from the forthcoming 5th edition of ABC of AIDS . The book will be available from the BMJ bookshop and at www.bmjbooks.com

#### AIDS defining conditions without laboratory evidence of HIV

The definition of AIDS has changed over the years as a result of an increasing appreciation of the wide spectrum of clinical manifestations of infection with HIV. Currently, AIDS is defined as an illness characterised by one or more indicator diseases. In the absence of another cause of immune deficiency and without laboratory evidence of HIV infection (if the patient has not been tested or the results are inconclusive), certain diseases when definitively diagnosed are indicative of AIDS. Also, regardless of the presence of other …
Defective Satellite DNA Clustering into Chromocenters Underlies Hybrid Incompatibility in <i>Drosophila</i>
Authors: Madhav Jagannathan, Yukiko M Yamashita
Journal: Molecular Biology and Evolution (2021)

Although rapid evolution of pericentromeric satellite DNA repeats is theorized to promote hybrid incompatibility (HI) (Yunis and Yasmineh 1971; Henikoff et al. 2001; Ferree and Barbash 2009; Sawamura 2012; Jagannathan and Yamashita 2017), how divergent repeats affect hybrid cells remains poorly understood. Recently, we demonstrated that sequence-specific DNA-binding proteins cluster satellite DNA from multiple chromosomes into "chromocenters," thereby bundling chromosomes to maintain the entire genome in a single nucleus (Jagannathan et al. 2018, 2019). Here, we show that ineffective clustering of divergent satellite DNA in the cells of Drosophila hybrids results in chromocenter disruption, associated micronuclei formation, and tissue atrophy. We further demonstrate that previously identified HI factors trigger chromocenter disruption and micronuclei in hybrids, linking their function to a conserved cellular process. Together, we propose a unifying framework that explains how the widely observed satellite DNA divergence between closely related species can cause reproductive isolation.
p38 MAPK signaling in M1 macrophages results in selective elimination of M2 macrophages by MEK inhibition
Authors: Daniel Baumann, Jennifer Drebant, Tanja Hägele, Luisa Burger, Clara Serger, Claudia Lauenstein, Przemyslaw Dudys, Gerrit Erdmann, Rienk Offringa
Journal: Journal for ImmunoTherapy of Cancer (2021)

M2 macrophages promote tumor progression and therapy resistance, whereas proimmunogenic M1 macrophages can contribute to the efficacy of cytostatic and immunotherapeutic strategies. The abundance of M2 macrophages in the immune infiltrate of many cancer types has prompted the search for strategies to target and eliminate this subset. From our prior experiments in syngeneic mouse tumor models, we learned that pharmacological inhibition of mitogen-activated protein kinase kinase (MEK) did not merely result in tumor cell death, but also in the modulation of the tumor immune infiltrate. This included a prominent decrease in the numbers of macrophages as well as an increase in the M1/M2 macrophage ratio. Investigation of the mechanism underlying this finding in primary murine macrophage cultures revealed that M2 macrophages are significantly more sensitive to MEK inhibition-induced cell death than their M1 counterparts. Further analyses showed that the p38 MAPK pathway, which is activated in M1 macrophages only, renders these cells resistant to death by MEK inhibition. In conclusion, the dependency of M2 macrophages on the MEK/extracellular-signal regulated kinase (ERK) pathway empowers MEK inhibitors to selectively eliminate this subset from the tumor microenvironment.
P1-6 Preoperative docetaxel, cisplatin, and 5-FU for resectable esophagogastric junction adenocarcinoma: Retrospective study
Authors: Toshiharu Hirose, Shun Yamamoto, Kotoe Oshima, Hidekazu Hirano, Natsuko Okita, Hirokazu Shoji, Satoru Iwasa, Yoshitaka Honma, Atsuo Takashima, Narikazu Boku, Koshiro Ishiyama, Junya Oguma, Hiroyuki Daiko, Ken Kato
Journal: Annals of Oncology (2021)
Ficolin A exacerbates severe H1N1 influenza virus infection-induced acute lung immunopathological injury via excessive complement activation
Authors: Xu Wu, Linlin Bao, Ziqi Hu, Duoduo Yao, Fengdi Li, Hui Li, Xiaoxue Xu, Yunqing An, Xi Wang, Bin Cao, Xulong Zhang
Journal: Cellular and Molecular Immunology (2021)
Abstract 13630: Catheter Ablation Lesion Mapping With Intracardiac Echocardiography in Canines and Humans
Authors: Vincent Sayseng, Julien Grondin, Christopher Grubb, Maryam Basij, Mohammad Mehrmohammadi, Vivek Iyer, Daniel Y Wang, Hasan Garan, Elaine Wan, Elisa Konofagou
Journal: Circulation (2019)

Introduction: Arrhythmia recurrence following catheter ablations is associated with lesion gaps or non-transmurality. Lesion visualization could increase procedural success and avoid repeat treatme...
Emerging strategies to target RAS signaling in human cancer therapy
Authors: Kun Chen, Yalei Zhang, Ling Qian, Peng Wang
Journal: Journal of Hematology & Oncology (2021)

RAS mutations (HRAS, NRAS, and KRAS) are among the most common oncogenes, and around 19% of patients with cancer harbor RAS mutations. Cells harboring RAS mutations tend to undergo malignant transformation and exhibit malignant phenotypes. The mutational status of RAS correlates with the clinicopathological features of patients, such as mucinous type and poor differentiation, as well as response to anti-EGFR therapies in certain types of human cancers. Although RAS protein had been considered as a potential target for tumors with RAS mutations, it was once referred to as a undruggable target due to the consecutive failure in the discovery of RAS protein inhibitors. However, recent studies on the structure, signaling, and function of RAS have shed light on the development of RAS-targeting drugs, especially with the approval of Lumakras (sotorasib, AMG510) in treatment of KRAS
Multi-omics reveal microbial determinants impacting responses to biologic therapies in inflammatory bowel disease
Authors: Jonathan Wei Jie Lee, Damian Plichta, Larson Hogstrom, Nynke Z. Borren, Helena Lau, Sara M. Gregory, William Tan, Hamed Khalili, Clary Clish, Hera Vlamakis, Ramnik J. Xavier, Ashwin N. Ananthakrishnan
Journal: Cell Host & Microbe (2021)