tbuckley/cabot-search huggingface dataset:
Lysyl oxidase like 2 is increased in asthma and contributes to asthmatic airway remodelling
Authors: Jopeth Ramis, Robert Middlewick, Francesco Pappalardo, Jennifer T. Cairns, Iain D. Stewart, Alison E. John, Shams-Un-Nisa Naveed, Ramaswamy Krishnan, Suzanne Miller, Dominick E. Shaw, Christopher E. Brightling, Lee Buttery, Felicity Rose, Gisli Jenkins, Simon R. Johnson, Amanda L. Tatler
Journal: European Respiratory Journal (2022)

Background Airway smooth muscle (ASM) cells are fundamental to asthma pathogenesis, influencing bronchoconstriction, airway hyperresponsiveness and airway remodelling. The extracellular matrix (ECM) can influence tissue remodelling pathways; however, to date no study has investigated the effect of ASM ECM stiffness and cross-linking on the development of asthmatic airway remodelling. We hypothesised that transforming growth factor-β (TGF-β) activation by ASM cells is influenced by ECM in asthma and sought to investigate the mechanisms involved. Methods This study combines in vitro and in vivo approaches: human ASM cells were used in vitro to investigate basal TGF-β activation and expression of ECM cross-linking enzymes. Human bronchial biopsies from asthmatic and nonasthmatic donors were used to confirm lysyl oxidase like 2 (LOXL2) expression in ASM. A chronic ovalbumin (OVA) model of asthma was used to study the effect of LOXL2 inhibition on airway remodelling. Results We found that asthmatic ASM cells activated more TGF-β basally than nonasthmatic controls and that diseased cell-derived ECM influences levels of TGF-β activated. Our data demonstrate that the ECM cross-linking enzyme LOXL2 is increased in asthmatic ASM cells and in bronchial biopsies. Crucially, we show that LOXL2 inhibition reduces ECM stiffness and TGF-β activation in vitro , and can reduce subepithelial collagen deposition and ASM thickness, two features of airway remodelling, in an OVA mouse model of asthma. Conclusion These data are the first to highlight a role for LOXL2 in the development of asthmatic airway remodelling and suggest that LOXL2 inhibition warrants further investigation as a potential therapy to reduce remodelling of the airways in severe asthma.
Neuropilin-1 mediates lung tissue-specific control of ILC2 function in type 2 immunity
Authors: Jingjing Zhang, Jinxin Qiu, Wenyong Zhou, Jianping Cao, Xuefei Hu, Wenli Mi, Bing Su, Bin He, Ju Qiu, Lei Shen
Journal: Nature Immunology (2022)

Group 2 innate lymphoid cells (ILC2s) are highly heterogeneous tissue-resident lymphocytes that regulate inflammation and tissue homeostasis in health and disease. However, how these cells integrate into the tissue microenvironment to perform tissue-specific functions is unclear. Here, we show neuropilin-1 (Nrp1), which is induced postnatally and sustained by lung-derived transforming growth factor beta-1 (TGFβ1), is a tissue-specific marker of lung ILC2s. Genetic ablation or pharmacological inhibition of Nrp1 suppresses IL-5 and IL-13 production by ILC2s and protects mice from the development of pulmonary fibrosis. Mechanistically, TGFβ1-Nrp1 signaling enhances ILC2 function and type 2 immunity by upregulating IL-33 receptor ST2 expression. These findings identify Nrp1 as a tissue-specific regulator of lung-resident ILC2s and highlight Nrp1 as a potential therapeutic target for pulmonary fibrosis.
Mutational Landscape and Outcomes of Conjunctival Melanoma in 101 Patients
Authors: Sara E. Lally, Tatyana Milman, Marlana Orloff, Lauren A. Dalvin, Charles G. Eberhart, Christopher M. Heaphy, Fausto J. Rodriguez, Chun-Chieh Lin, Philip W. Dockery, Jerry A. Shields, Carol L. Shields
Journal: Ophthalmology (2022)
A comparison among RIRS and MiniPerc for renal stones between 1-2 cm: A randomized controlled trial
Authors: L. Berti, M. Maltagliati, C. Buizza, U. Besana, A. Calori, D. Antonelli, M. Justich, P. Marcangeli, S. Micali, M.C. Sighinolfi, B. Rocco, G. Bozzini
Journal: European Urology (2021)
Individualized risk stratification of patients candidate to radical prostatectomy based on clinical and multi-parametric MRI parameters: Beyond the conventional clinical risk models
Authors: E. Mazzone, A. Stabile, F. Barletta, G. Cirulli, G. Ploussard, R.G. Rahota, M. Valerio, S. Serni, M. Gacci, A. Berni, R. Campi, A. Mari, G. Marra, A. Marquis, J.B. Beavaul, M.. Roumiguié, L. Afferi, M. Moschini, P. Gontero, J. Zhuang, H. Tuo, G. Gandaglia, N. Fossati, F. Montorsi, A. Briganti
Journal: European Urology (2021)
American Academy of Dermatology Guidelines: Awareness of comorbidities associated with atopic dermatitis in adults
Authors: Dawn M.R. Davis, Aaron M. Drucker, Ali Alikhan, Lionel Bercovitch, David E. Cohen, Jennifer M. Darr, Lawrence F. Eichenfield, Lindsy Frazer-Green, Amy S. Paller, Jonathan I. Silverberg, Anne Marie Singh, Robert Sidbury
Journal: Journal of the American Academy of Dermatology (2022)
Balancing efficacy and toxicity of docetaxel in patients with metastatic castration-resistant prostate cancer. Results from a pooled analysis of three prospective randomized trials
Authors: G.O. Cirulli, A. Martini, F. Pellegrino, S. Scuderi, A.B. Parikh, W.K. Oh, J.P. Sfakianos, P.I. Karakiewicz, M.D. Galsky, C. Tsao, V. Cucchiara, A. Stabile, G. Gandaglia, N. Fossati, A. Necchi, F. Montorsi, A. Briganti
Journal: European Urology (2021)
Early intestinal microbial features are associated with CD4 T-cell recovery after allogeneic hematopoietic transplant
Authors: Oriana Miltiadous, Nicholas R. Waters, Hana Andrlová, Anqi Dai, Chi L. Nguyen, Marina Burgos da Silva, Sarah Lindner, John Slingerland, Paul Giardina, Annelie Clurman, Gabriel K. Armijo, Antonio L. C. Gomes, Madhavi Lakkaraja, Peter Maslak, Michael Scordo, Roni Shouval, Anna Staffas, Richard O’Reilly, Ying Taur, Susan Prockop, Jaap Jan Boelens, Sergio Giralt, Miguel-Angel Perales, Sean M. Devlin, Jonathan U. Peled, Kate A. Markey, Marcel R. M. van den Brink
Journal: Blood (2022)
Neo-adjuvant 177Lu-PSMA-I&amp;T radionuclide in high-risk prostate cancer before radical prostatectomy: A feasibility trial
Authors: M. Frumer, E. Rosenbaum, D. Kedar, Y. Zohar, J. Baniel, A. Steinmetz, H. Bernstine, D. Groshar, S. Golan
Journal: European Urology (2021)
Treatment of hair loss caused by HSS with the antibiotic gentamicin
Journal: British Journal of Dermatology (2020)

Hair loss, also known as alopecia or baldness, is a loss of hair from the head or body.Hypotrichosis Simplex of the Scalp (HSS) is a rare hereditary disorder causing loss of scalp hair.Affected individuals, both males and females, suffer from a progressive loss of hair that starts in the middle of the first decade of life resulting in almost complete baldness by the third decade, which is associated with major psychological and sociological impacts on daily life.HSS is caused by a specific change in the genetic code of the gene CDSN encoding corneodesmosin protein, which is important for the normal function of the skin outer layers and human hair growth.The change in the genetic code results in the production of a short and defective product that accumulates around the hairs and prevents their growth.Despite major advances in medical genetics, there is no treatment for HSS.Gentamicin is a popular antibiotic therapy which is commonly used for the treatment of bacterial infections.In addition, gentamycin is known for its ability to bypass the genetic defect that results in abnormal protein production, and in the current study from Israel, the authors aimed to find out if gentamicin could be an effective treatment in HSS.First, the authors showed that gentamycin can lead to production of a normal protein in cell cultures.Then, the authors performed a clinical trial in which topical (to the skin) application of gentamycin twice daily for 6 months to the scalp of 4 HSS patients resulted in significant hair growth.In conclusion, the results of this study show that gentamycin is a potential treatment for patients with HSS.
Apixaban vs Rivaroxaban for Preventing Recurrent VTE
Authors: Anita Slomski
Journal: JAMA (2022)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Neoadjuvant programmed cell death 1 blockade combined with chemotherapy for resectable esophageal squamous cell carcinoma
Authors: Weixiong Yang, Xiangbin Xing, Sai-Ching Jim Yeung, Siyu Wang, Wenfang Chen, Yong Bao, Fang Wang, Shiting Feng, Fang Peng, Xiaoyan Wang, Shuling Chen, Minghui He, Ning Zhang, Honglei Wang, Bo Zeng, Zhenguo Liu, Biniam Kidane, Christopher W Seder, Kazuo Koyanagi, Yaron Shargall, Honghe Luo, Sui Peng, Chao Cheng
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background Programmed cell death 1 (PD-1) blockade induces tumor regression in patients with advanced esophageal squamous cell carcinoma (ESCC); however, little is known about the efficacy of PD-1 blockade as neoadjuvant therapy in resectable ESCC. We aim to assess the safety and feasibility of using the combination of neoadjuvant PD-1 blockade with chemotherapy in patients with ESCC. Methods Patients with previously untreated, resectable (stage II or III) ESCC were enrolled. Each patient received two 21-day cycles of neoadjuvant treatment with camrelizumab, nab-paclitaxel, and carboplatin before undergoing surgical resection approximately 6–9 weeks after the first cycle. Results Between January 2020 and September 2020, 37 patients were screened, of whom 23 were enrolled. The neoadjuvant therapeutic regimen had an acceptable side effect profile, and no delays in surgery were observed. Severe (grade 3–4) treatment-related adverse events included neutropenia (9 of 23, 39.1%) and leukopenia (2 of 23, 8.7%). The objective response and disease control rates were 90.5% and 100%, respectively. Twenty patients received surgery, and R0 resection was achieved in all cases. Five (25%) patients had a pathological complete response (PCR) and 10 (50%) patients had a major pathological response. The proportion of patients with a high tumor mutation burden and a high expression of programmed death-ligand 1 (PD-L1) in primary tumor was significantly higher in the PCR group than in the non-PCR group (p=0.044). The number of infiltrating PD-L1 + CD163 + cells was significantly lower in the PCR group than in the non-PCR group after treatment (p=0.017). Conclusions Neoadjuvant camrelizumab plus carboplatin and nab-paclitaxel had manageable treatment-related adverse effects and induced an objective response in 90.5% of patients, demonstrating its antitumor efficacy in resectable ESCC. Trial registration number ChiCTR2000028900.
Evaluation of a panel of preoperative blood-based systemic inflammatory response biomarkers for outcome prediction in patients treated with cytoreductive nephrectomy for metastatic renal cell carcinoma
Authors: E. Laukhtina, V.M. Schuettfort, D. D`andrea, B. Pradere, F. Quhal, K. Mori, R. Sari Motlagh, S. Katayama, H. Mostafaei, N.C. Grossmann, D. Enikeev, P.I. Karakiewicz, M. Schmidinger, S.F. Shariat
Journal: European Urology (2021)
Combined Varenicline With Nicotine Patch and Extended Duration of Therapy for Smoking Cessation—Reply
Authors: Timothy B. Baker, Michael C. Fiore
Journal: JAMA (2022)

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 HomeNew OnlineCurrent IssueFor Authors Publications 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Genome Resequencing Reveals Rapid, Repeated Evolution in the Colorado Potato Beetle
Authors: Benjamin Pélissié, Yolanda H Chen, Zachary P Cohen, Michael S Crossley, David J Hawthorne, Victor Izzo, Sean D Schoville
Journal: Molecular Biology and Evolution (2022)

Abstract Insecticide resistance and rapid pest evolution threatens food security and the development of sustainable agricultural practices, yet the evolutionary mechanisms that allow pests to rapidly adapt to control tactics remains unclear. Here, we examine how a global super-pest, the Colorado potato beetle (CPB), Leptinotarsa decemlineata, rapidly evolves resistance to insecticides. Using whole-genome resequencing and transcriptomic data focused on its ancestral and pest range in North America, we assess evidence for three, nonmutually exclusive models of rapid evolution: pervasive selection on novel mutations, rapid regulatory evolution, and repeated selection on standing genetic variation. Population genomic analysis demonstrates that CPB is geographically structured, even among recently established pest populations. Pest populations exhibit similar levels of nucleotide diversity, relative to nonpest populations, and show evidence of recent expansion. Genome scans provide clear signatures of repeated adaptation across CPB populations, with especially strong evidence of selection on insecticide resistance genes in different populations. Analyses of gene expression show that constitutive upregulation of candidate insecticide resistance genes drives distinctive population patterns. CPB evolves insecticide resistance repeatedly across agricultural regions, leveraging similar genetic pathways but different genes, demonstrating a polygenic trait architecture for insecticide resistance that can evolve from standing genetic variation. Despite expectations, we do not find support for strong selection on novel mutations, or rapid evolution from selection on regulatory genes. These results suggest that integrated pest management practices must mitigate the evolution of polygenic resistance phenotypes among local pest populations, in order to maintain the efficacy and sustainability of novel control techniques.
Mitigating climate change must be a priority for public health
Authors: None The Lancet Public Health
Journal: The Lancet Public Health (2021)

On Aug 9, the Intergovernmental Panel on Climate Change (IPCC) published its latest report, Climate Change 2021: The Physical Science Basis—the contribution of the Working Group I to the Sixth Assessment Report. The IPCC has three working groups: Working Group I, focused on the most updated physical understanding of the climate system and climate change; Working Group II, detailing impacts, adaptation, and vulnerability; and Working Group III, dealing with the mitigation of climate change. The next two working groups will report in 2022.
A Machine Learning Model Based on Tumor and Immune Biomarkers to Predict Undetectable MRD and Survival Outcomes in Multiple Myeloma
Authors: Camila Guerrero, Noemi Puig, Maria-Teresa Cedena, Ibai Goicoechea, Cristina Perez, Juan-José Garcés, Cirino Botta, Maria-Jose Calasanz, Norma C. Gutierrez, Maria-Luisa Martin-Ramos, Albert Oriol, Rafael Rios, Miguel-Teodoro Hernandez, Rafael Martinez-Martinez, Joan Bargay, Felipe de Arriba, Luis Palomera, Ana Pilar Gonzalez-Rodriguez, Adrian Mosquera-Orgueira, Marta-Sonia Gonzalez-Perez, Joaquin Martinez-Lopez, Juan-José Lahuerta, Laura Rosiñol, Joan Blade, Maria-Victoria Mateos, Jesus F. San-Miguel, Bruno Paiva
Journal: Clinical Cancer Research (2022)

Abstract Purpose: Undetectable measurable residual disease (MRD) is a surrogate of prolonged survival in multiple myeloma. Thus, treatment individualization based on the probability of a patient achieving undetectable MRD with a singular regimen could represent a new concept toward personalized treatment, with fast assessment of its success. This has never been investigated; therefore, we sought to define a machine learning model to predict undetectable MRD at the onset of multiple myeloma. Experimental Design: This study included 487 newly diagnosed patients with multiple myeloma. The training (n = 152) and internal validation cohorts (n = 149) consisted of 301 transplant-eligible patients with active multiple myeloma enrolled in the GEM2012MENOS65 trial. Two external validation cohorts were defined by 76 high-risk transplant-eligible patients with smoldering multiple myeloma enrolled in the Grupo Español de Mieloma(GEM)-CESAR trial, and 110 transplant-ineligible elderly patients enrolled in the GEM-CLARIDEX trial. Results: The most effective model to predict MRD status resulted from integrating cytogenetic [t(4;14) and/or del(17p13)], tumor burden (bone marrow plasma cell clonality and circulating tumor cells), and immune-related biomarkers. Accurate predictions of MRD outcomes were achieved in 71% of cases in the GEM2012MENOS65 trial (n = 214/301) and 72% in the external validation cohorts (n = 134/186). The model also predicted sustained MRD negativity from consolidation onto 2 years maintenance (GEM2014MAIN). High-confidence prediction of undetectable MRD at diagnosis identified a subgroup of patients with active multiple myeloma with 80% and 93% progression-free and overall survival rates at 5 years. Conclusions: It is possible to accurately predict MRD outcomes using an integrative, weighted model defined by machine learning algorithms. This is a new concept toward individualized treatment in multiple myeloma. See related commentary by Pawlyn and Davies, p. 2482
An analysis of public sunscreen distribution in the United States during the COVID-19 pandemic
Authors: Mindy D. Szeto, Ryan E. Kokoska, Jalal Maghfour, Chandler W. Rundle, Colby L. Presley, Taylor Harp, Austin Hamp, Victoria Wegener, Jeremy Hugh, Robert P. Dellavalle
Journal: Journal of the American Academy of Dermatology (2022)
KVD900, an oral on-demand treatment for hereditary angioedema: Phase 1 study results
Authors: Andreas Maetzel, Michael D. Smith, Edward J. Duckworth, Sally L. Hampton, Gian Marco De Donatis, Nivetha Murugesan, Louise J. Rushbrooke, Lily Li, Danielle Francombe, Edward P. Feener, Christopher M. Yea
Journal: Journal of Allergy and Clinical Immunology (2022)

Attacks of hereditary angioedema are attributed to excessive plasma kallikrein (PKa) activity, which cleaves high-molecular-weight kininogen to generate the proinflammatory hormone bradykinin.We evaluated the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of KVD900, an orally administered inhibitor of PKa in healthy adults.KVD900 was administered in 2 clinical studies. In the first study, healthy adult men received single ascending doses (5-600 mg) of KVD900 capsule or placebo, single 100 mg doses of KVD900 tablet and KVD900 capsule (crossover), and single 600 mg doses of KVD900 (6 × 100 mg tablets) under fed and fasting conditions (crossover). In a second study, 3 cohorts of healthy adults were provided 600 mg of KVD900 tablets at 8-, 4-, and 2-hour intervals.Overall, 98 healthy participants received KVD900. All adverse events (AEs) were mild, except for a single moderate AE (headache). Exposure to KVD900 was proportional to dose. The PK parameters for KVD900 600 mg in tablet form under fasted conditions were mean (coefficient of variation) maximum plasma concentration of 6460 (22.0) ng/mL, mean (coefficient of variation) area under the curve (AUC0-24) of 18,600 (22.5) h⋅ng/mL, and median (range) time to maximum plasma concentration of 0.5 (0.33-1.5) hours. Mean PKa inhibition was essentially complete (>98%) between 20 minutes and 3 hours, and >90% inhibition was maintained for at least 8 hours after dosing. High-molecular-weight kininogen cleavage protection at the 600 mg dose was attained within 20 minutes and maintained for 8 to 10 hours.These phase 1 studies evaluated the PK/PD profile of KVD900, showing that KVD900 rapidly achieves near-complete PKa inhibition and is generally safe and well tolerated.NCT04349800.
Presumptive Guillain-Barré Syndrome Associated With Receipt of the Ad26.COV2.2.S COVID-19 Vaccine—Reply
Authors: Emily Jane Woo, Rositsa B. Dimova, Adamma Mba-Jonas
Journal: JAMA (2022)

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 HomeNew OnlineCurrent IssueFor Authors Publications 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Covid-19: CoronaVac immunity is strongest after boosting with a different vaccine
Authors: Luke Taylor
Journal: BMJ (2022)

Covid-19: CoronaVac immunity is strongest after boosting with a different vaccine Luke TaylorA booster dose of a covid-19 jab other than CoronaVac significantly increased antibodies in those who had received two doses of the Chinese vaccine, a study funded by Brazil's Ministry of Health has found.