tbuckley/cabot-search huggingface dataset:
A randomised trial of prednisolone <i>versus</i> prednisolone and itraconazole in acute-stage allergic bronchopulmonary aspergillosis complicating asthma
Authors: Ritesh Agarwal, Valliappan Muthu, Inderpaul Singh Sehgal, Sahajal Dhooria, Kuruswamy Thurai Prasad, Mandeep Garg, Ashutosh Nath Aggarwal, Arunaloke Chakrabarti
Journal: European Respiratory Journal (2021)

Whether a combination of glucocorticoid and antifungal triazole is superior to glucocorticoid alone in reducing exacerbations in patients with allergic bronchopulmonary aspergillosis (ABPA) remains unknown. We aimed to compare the efficacy and safety of prednisolone-itraconazole combination versus prednisolone monotherapy in ABPA.We randomised subjects with treatment-naïve acute-stage ABPA complicating asthma to receive either prednisolone alone (4 months) or a combination of prednisolone and itraconazole (4 and 6 months, respectively). The primary outcomes were exacerbation rates at 12 months and glucocorticoid-dependent ABPA within 24 months of initiating treatment. The key secondary outcomes were response rates, percentage decline in serum total IgE at 6 weeks, time to first ABPA exacerbation and treatment-emergent adverse events (TEAEs).We randomised 191 subjects to receive either prednisolone (n=94) or prednisolone-itraconazole combination (n=97). The 1-year exacerbation rate was 33% and 20.6% in the prednisolone monotherapy and prednisolone-itraconazole combination arms, respectively (p=0.054). None of the participants progressed to glucocorticoid-dependent ABPA. All of the subjects experienced a composite response at 6 weeks, along with a decline in serum total IgE (mean decline 47.6% versus 45.5%). The mean time to first ABPA exacerbation (417 days) was not different between the groups. None of the participants required modification of therapy due to TEAEs.There was a trend towards a decline in ABPA exacerbations at 1 year with the prednisolone-itraconazole combination versus prednisolone monotherapy. A three-arm trial comparing itraconazole and prednisolone monotherapies with their combination, preferably in a multicentric design, is required to define the best treatment strategy for acute-stage ABPA.
Predictors of COVID-19 epidemics in countries of the World Health Organization African Region
Authors: Feifei Zhang, Humphrey Karamagi, Ngoy Nsenga, Miriam Nanyunja, Miriam Karinja, Seth Amanfo, Margo Chase-Topping, Giles Calder-Gerver, Miles McGibbon, Alexandra Huber, Tara Wagner-Gamble, Chuan-Guo Guo, Samuel Haynes, Alistair Morrison, Miranda Ferguson, Gordon A. Awandare, Francisca Mutapi, Zabulon Yoti, Joseph Cabore, Matshidiso R. Moeti, Mark E. J. Woolhouse
Journal: Nature Medicine (2021)

Abstract Countries of the World Health Organization (WHO) African Region have experienced a wide range of coronavirus disease 2019 (COVID-19) epidemics. This study aimed to identify predictors of the timing of the first COVID-19 case and the per capita mortality in WHO African Region countries during the first and second pandemic waves and to test for associations with the preparedness of health systems and government pandemic responses. Using a region-wide, country-based observational study, we found that the first case was detected earlier in countries with more urban populations, higher international connectivity and greater COVID-19 test capacity but later in island nations. Predictors of a high first wave per capita mortality rate included a more urban population, higher pre-pandemic international connectivity and a higher prevalence of HIV. Countries rated as better prepared and having more resilient health systems were worst affected by the disease, the imposition of restrictions or both, making any benefit of more stringent countermeasures difficult to detect. Predictors for the second wave were similar to the first. Second wave per capita mortality could be predicted from that of the first wave. The COVID-19 pandemic highlights unanticipated vulnerabilities to infectious disease in Africa that should be taken into account in future pandemic preparedness planning.
A Definitive Answer to the Effect of Screen Time on Concussion Recovery
Authors: Sara P. D. Chrisman
Journal: JAMA Pediatrics (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
A phase 1b dose-escalation/expansion study of BET inhibitor RO6870810 in patients with advanced multiple myeloma
Authors: Karthik Ramasamy, Ajay Nooka, Hang Quach, Myo Htut, Rakesh Popat, Michaela Liedtke, Sascha A. Tuchman, Jacob Laubach, Cristina Gasparetto, Asher Chanan-Khan, Mark Hertzberg, Mark deMario, Eveline Nueesch, Evelyne Chesne, Izolda Franjkovic, Katharina Lechner, Martin Kornacker, Hearn Jay Cho
Journal: Blood Cancer Journal (2021)
Long Term Results of Patients with Acute Promyelocytic Leukemia of Recent Diagnosis Treated with Daunorubicin or Epirubicin in Induction Therapy
Authors: Luara Arana, Jose Alvarez, Martha Alvarado, Yayra Pichardo, M. Augusta Pacheco, Veronica Mena, Maricela Ortiz, Rosa Jimenez
Journal: Blood (2017)
Vaccine effectiveness against infection with the Delta (B.1.617.2) variant, Norway, April to August 2021
Authors: Elina Seppälä, Lamprini Veneti, Jostein Starrfelt, Anders Skyrud Danielsen, Karoline Bragstad, Olav Hungnes, Arne Michael Taxt, Sara Viksmoen Watle, Hinta Meijerink
Journal: Eurosurveillance (2021)

Some variants of SARS-CoV-2 are associated with increased transmissibility, increased disease severity or decreased vaccine effectiveness (VE). In this population-based cohort study (n = 4,204,859), the Delta variant was identified in 5,430 (0.13%) individuals, of whom 84 were admitted to hospital. VE against laboratory confirmed infection with the Delta variant was 22.4% among partly vaccinated (95% confidence interval (CI): 17.0−27.4) and 64.6% (95% CI: 60.6−68.2) among fully vaccinated individuals, compared with 54.5% (95% CI: 50.4−58.3) and 84.4% (95%CI: 81.8−86.5) against the Alpha variant.
Actinomycosis associated with a permanently implanted duodenal over-the-scope clip
Authors: Carina Leal, Helene Dano, Leila Belkhir, Pierre H. Deprez
Journal: Endoscopy (2021)

The over-the-scope (OTS) clip system is a safe and effective endoscopic therapy for gastrointestinal bleeding, perforation, and leakage [1] [2]. A recent review reported an overall complication rate of 1.7 % [1]. We report the case of a 76-year-old woman with a complication that arose 11 years after the placement of two OTS clips (Ovesco Endoscopy AG, Tübingen, Germany).
Introgression among North American wild grapes (Vitis) fuels biotic and abiotic adaptation
Authors: Abraham Morales-Cruz, Jonas A. Aguirre-Liguori, Yongfeng Zhou, Andrea Minio, Summaira Riaz, Andrew M. Walker, Dario Cantu, Brandon S. Gaut
Journal: Genome biology (2021)

Abstract Background Introgressive hybridization can reassort genetic variants into beneficial combinations, permitting adaptation to new ecological niches. To evaluate evolutionary patterns and dynamics that contribute to introgression, we investigate six wild Vitis species that are native to the Southwestern United States and useful for breeding grapevine ( V. vinifera ) rootstocks. Results By creating a reference genome assembly from one wild species, V. arizonica , and by resequencing 130 accessions, we focus on identifying putatively introgressed regions (pIRs) between species. We find six species pairs with signals of introgression between them, comprising up to ~ 8% of the extant genome for some pairs. The pIRs tend to be gene poor, located in regions of high recombination and enriched for genes implicated in disease resistance functions. To assess potential pIR function, we explore SNP associations to bioclimatic variables and to bacterial levels after infection with the causative agent of Pierce’s disease ( Xylella fastidiosa ). pIRs are enriched for SNPs associated with both climate and bacterial levels, suggesting that introgression is driven by adaptation to biotic and abiotic stressors. Conclusions Altogether, this study yields insights into the genomic extent of introgression, potential pressures that shape adaptive introgression, and the evolutionary history of economically important wild relatives of a critical crop.
CD4+ T cell and M2 macrophage infiltration predict dedifferentiated liposarcoma patient outcomes
Authors: Brett A Schroeder, Natalie A LaFranzo, Bonnie J LaFleur, Rachel M Gittelman, Marissa Vignali, Shihong Zhang, Kevin C Flanagan, Julie Rytlewski, Laura Riolobos, Brian C Schulte, Teresa S Kim, Eleanor Chen, Kimberly S Smythe, Michael J Wagner, Jose G Mantilla, Jean S Campbell, Robert H Pierce, Robin L Jones, Lee D Cranmer, Seth M Pollack
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Dedifferentiated liposarcoma (DDLPS) is one of the most common soft tissue sarcoma subtypes and is devastating in the advanced/metastatic stage. Despite the observation of clinical responses to PD-1 inhibitors, little is known about the immune microenvironment in relation to patient prognosis. Methods We performed a retrospective study of 61 patients with DDLPS. We completed deep sequencing of the T-cell receptor (TCR) β-chain and RNA sequencing for predictive modeling, evaluating both immune markers and tumor escape genes. Hierarchical clustering and recursive partitioning were employed to elucidate relationships of cellular infiltrates within the tumor microenvironment, while an immune score for single markers was created as a predictive tool. Results Although many DDLPS samples had low TCR clonality, high TCR clonality combined with low T-cell fraction predicted lower 3-year overall survival (p=0.05). Higher levels of CD14+ monocytes (p=0.02) inversely correlated with 3-year recurrence-free survival (RFS), while CD4+ T-cell infiltration (p=0.05) was associated with a higher RFS. Genes associated with longer RFS included PD-1 (p=0.003), ICOS (p=0.006), BTLA (p=0.033), and CTLA4 (p=0.02). In a composite immune score, CD4+ T cells had the strongest positive predictive value, while CD14+ monocytes and M2 macrophages had the strongest negative predictive values. Conclusions Immune cell infiltration predicts clinical outcome in DDLPS, with CD4+ cells associated with better outcomes; CD14+ cells and M2 macrophages are associated with worse outcomes. Future checkpoint inhibitor studies in DDLPS should incorporate immunosequencing and gene expression profiling techniques that can generate immune landscape profiles.
Patient-Derived Xenografts to Study Cancer Metabolism: When Does X Mark the Spot?
Authors: Christopher S. Nabel, Matthew G. Vander Heiden
Journal: Cancer Research (2021)

A major goal of cancer research is to understand the requirements for cancer growth and progression that can be exploited to treat patients. Model systems reduce the complexity and heterogeneity of human cancers to explore therapeutic hypotheses, however, some relevant aspects of human biology are not well represented by certain models, complicating the translation of preclinical findings to help patients. Here we discuss the advantages and limitations of patient-derived xenografts as a model system to study cancer metabolism, offering a framework to best use these models to address different types of metabolism-specific research questions.
NanoCaller for accurate detection of SNPs and indels in difficult-to-map regions from long-read sequencing by haplotype-aware deep neural networks
Authors: Mian Umair Ahsan, Qian Liu, Li Fang, Kai Wang
Journal: Genome biology (2021)

Long-read sequencing enables variant detection in genomic regions that are considered difficult-to-map by short-read sequencing. To fully exploit the benefits of longer reads, here we present a deep learning method NanoCaller, which detects SNPs using long-range haplotype information, then phases long reads with called SNPs and calls indels with local realignment. Evaluation on 8 human genomes demonstrates that NanoCaller generally achieves better performance than competing approaches. We experimentally validate 41 novel variants in a widely used benchmarking genome, which could not be reliably detected previously. In summary, NanoCaller facilitates the discovery of novel variants in complex genomic regions from long-read sequencing.
Clinical performance and accuracy of a qPCR-based SARS-CoV-2 mass-screening workflow for healthcare-worker surveillance using pooled self-sampled gargling solutions: A cross-sectional study
Authors: Flaminia Olearo, Dominik Nörz, Armin Hoffman, Moritz Grunwald, Kimani Gatzemeyer, Martin Christner, Anna Both, Cristina Elena Belmar Campos, Platon Braun, Gabriele Andersen, Susanne Pfefferle, Antonia Zapf, Martin Aepfelbacher, Johannes K.M. Knobloch, Marc Lütgehetmann
Journal: Journal of Infection (2021)
Butyrate and propionate restore interleukin 13‐compromised esophageal epithelial barrier function
Authors: Mirelle T.A. Kleuskens, Maria L. Haasnoot, Bart M. Herpers, Marleen T. J. van Ampting, Albert J. Bredenoord, Johan Garssen, Frank A. Redegeld, Betty C.A.M. van Esch
Journal: Allergy (2021)

Eosinophilic esophagitis (EoE) is a food allergen driven disease that is accompanied by interleukin (IL) 13 overexpression and esophageal barrier dysfunction allowing transepithelial food allergen permeation. Nutraceuticals, such as short-chain fatty acids (SCFAs) that restore barrier function and increase immune fitness may be a promising tool in the management of EoE. Here, we investigated the effects of the SCFAs acetate, propionate, and butyrate on an IL-13-compromised human esophageal epithelial barrier, including the mechanisms involved.An air-liquid interface culture model of differentiated human EPC2-hTERT (EPC2) was used to study whether SCFAs could restore barrier function after IL-13-induced impairment. Esophageal epithelial barrier function was monitored by transepithelial electrical resistance (TEER) and FITC-dextran paracellular flux, and was further examined by qPCR and immunohistochemical analysis. G protein-coupled receptor (GPR) GPR41, GPR43, GPR109a, or histone deacetylase (HDAC) (ant)agonists were used to assess mechanisms of action of SCFAs.IL-13 stimulation decreased TEER and increased FITC flux, which was counteracted by butyrate and propionate, but not acetate treatment. Barrier proteins FLG and DSG1 mRNA expression was upregulated following butyrate and propionate treatment, whereas expression of eosinophil chemoattractant CCL26 and protease CAPN14 was downregulated. Similarly, butyrate and propionate restored FLG and DSG1 protein expression. Similar effects were observed with an HDAC antagonist but not with GPR agonists.Nutraceuticals butyrate and propionate restore the barrier function of esophageal epithelial cells after an inflammatory insult and may be of therapeutic benefit in the management of EoE.
P-178 Rego-Nivo II-III: Proof-of-concept phase II trial for the treatment of HCC refractory to chemotherapy after the 2nd line
Authors: Y. Ben Merabet, M. Lewin, A. Pascale, C. Guettier, A. Laurent-Bellue, E. Goldschmidt, J. Duclos-Vallée, J. Morere, A. Coilly, D. Samuel, O. Rosmorduc
Journal: Annals of Oncology (2021)
Covid-19: JCVI opts not to recommend universal vaccination of 12-15 year olds
Authors: Gareth Iacobucci
Journal: BMJ (2021)

The UK's Joint Committee on Vaccination and Immunisation (JCVI) has not recommended that all young people aged 12-15 are given the covid-19 vaccination, and it has instead asked ministers to seek further advice from the UK's chief medical officers on the wider potential benefits of vaccination.
Call for Emergency Action to Limit Global Temperature Increases, Restore Biodiversity, and Protect Health
Authors: Lukoye Atwoli, Abdullah H Baqui, Thomas Benfield, Raffaella Bosurgi, Fiona Godlee, Stephen Hancocks, Richard Horton, Laurie Laybourn-Langton, Carlos Augusto Monteiro, Ian Norman, Kirsten Patrick, Nigel Praities, Marcel G M Olde Rikkert, Eric J Rubin, Peush Sahni, Richard Smith, Nick Talley, Sue Turale, Damián Vázquez
Journal: JNCI Journal of the National Cancer Institute (2021)

> Wealthy nations must do much more, much faster.

The United Nations General Assembly in September 2021 will bring countries together at a critical time for marshalling collective action to tackle the global environmental crisis. They will meet again at the biodiversity summit in Kunming, China, and the climate conference (Conference of the Parties (COP)26) in Glasgow, UK. Ahead of these pivotal meetings, we—the editors of health journals worldwide—call for urgent action to keep average global temperature increases below 1.5°C, halt the destruction of nature and protect health.

Health is already being harmed by global temperature increases and the destruction of the natural world, a state of affairs health professionals have been bringing attention to for decades.1 The science is unequivocal; a global increase of 1.5°C above the preindustrial average and the continued loss of biodiversity risk catastrophic harm to health that will be impossible to reverse.2 3 Despite the world’s necessary preoccupation with COVID-19, we cannot wait for the pandemic to pass to rapidly reduce emissions.

Reflecting the severity of the moment, this editorial appears in health journals across the world. We are united in recognising that only fundamental and equitable changes to societies will reverse our current trajectory.

The risks to health of increases above 1.5°C are now well established.2 Indeed, no temperature rise is ‘safe’. In the past 20 years, heat-related mortality among people aged over 65 has increased by more than 50%.4 Higher temperatures have brought increased dehydration and renal function loss, dermatological malignancies, tropical infections, adverse mental health outcomes, pregnancy complications, allergies, and cardiovascular and pulmonary morbidity and mortality.5 6 Harms disproportionately affect the most vulnerable, including children, older populations, ethnic minorities, poorer communities and those with underlying health problems.2 4 

Global heating is also contributing to the decline in …
Functional microRNA targetome undergoes degeneration-induced shift in the retina
Authors: Joshua A. Chu-Tan, Adrian V. Cioanca, Zhi-Ping Feng, Yvette Wooff, Ulrike Schumann, Riemke Aggio-Bruce, Hardip Patel, Matt Rutar, Katherine Hannan, Konstantin Panov, Jan Provis, Riccardo Natoli
Journal: Molecular Neurodegeneration (2021)

Abstract Background MicroRNA (miRNA) play a significant role in the pathogenesis of complex neurodegenerative diseases including age-related macular degeneration (AMD), acting as post-transcriptional gene suppressors through their association with argonaute 2 (AGO2) - a key member of the RNA Induced Silencing Complex (RISC). Identifying the retinal miRNA/mRNA interactions in health and disease will provide important insight into the key pathways miRNA regulate in disease pathogenesis and may lead to potential therapeutic targets to mediate retinal degeneration. Methods To identify the active miRnome targetome interactions in the healthy and degenerating retina, AGO2 HITS-CLIP was performed using a rodent model of photoreceptor degeneration. Analysis of publicly available single-cell RNA sequencing (scRNAseq) data was performed to identify the cellular location of AGO2 and key members of the microRNA targetome in the retina. AGO2 findings were verified by in situ hybridization (RNA) and immunohistochemistry (protein). Results Analysis revealed a similar miRnome between healthy and damaged retinas, however, a shift in the active targetome was observed with an enrichment of miRNA involvement in inflammatory pathways. This shift was further demonstrated by a change in the seed binding regions of miR-124-3p, the most abundant retinal AGO2-bound miRNA, and has known roles in regulating retinal inflammation. Additionally, photoreceptor cluster miR-183/96/182 were all among the most highly abundant miRNA bound to AGO2. Following damage, AGO2 expression was localized to the inner retinal layers and more in the OLM than in healthy retinas, indicating a locational miRNA response to retinal damage. Conclusions This study provides important insight into the alteration of miRNA regulatory activity that occurs as a response to retinal degeneration and explores the miRNA-mRNA targetome as a consequence of retinal degenerations. Further characterisation of these miRNA/mRNA interactions in the context of the degenerating retina may provide an important insight into the active role these miRNA may play in diseases such as AMD.
Dendritic cells in cancer immunology
Authors: Theresa L. Murphy, Kenneth M. Murphy
Journal: Cellular and Molecular Immunology (2021)

Abstract The clinical success of immune checkpoint therapy (ICT) has produced explosive growth in tumor immunology research because ICT was discovered through basic studies of immune regulation. Much of the current translational efforts are aimed at enhancing ICT by identifying therapeutic targets that synergize with CTLA4 or PD1/PD-L1 blockade and are solidly developed on the basis of currently accepted principles. Expanding these principles through continuous basic research may help broaden translational efforts. With this mindset, we focused this review on three threads of basic research directly relating to mechanisms underlying ICT. Specifically, this review covers three aspects of dendritic cell (DC) biology connected with antitumor immune responses but are not specifically oriented toward therapeutic use. First, we review recent advances in the development of the cDC1 subset of DCs, identifying important features distinguishing these cells from other types of DCs. Second, we review the antigen-processing pathway called cross-presentation, which was discovered in the mid-1970s and remains an enigma. This pathway serves an essential in vivo function unique to cDC1s and may be both a physiologic bottleneck and therapeutic target. Finally, we review the longstanding field of helper cells and the related area of DC licensing, in which CD4 T cells influence the strength or quality of CD8 T cell responses. Each topic is connected with ICT in some manner but is also a fundamental aspect of cell-mediated immunity directed toward intracellular pathogens.