tbuckley/cabot-search huggingface dataset:
Epidemiology, resistance genomics and susceptibility of Acinetobacter species: results from the 2020 Spanish nationwide surveillance study
Authors: Cristina Lasarte-Monterrubio, Paula Guijarro-Sánchez, Isaac Alonso-Garcia, Michelle Outeda, Romina Maceiras, Lucia González-Pinto, Marta Martínez-Guitián, Carlos Fernández-Lozano, Juan Carlos Vázquez-Ucha, German Bou, Jorge Arca-Suárez, Alejandro Beceiro
Journal: Eurosurveillance (2024)

Background As increasing antibiotic resistance in Acinetobacter baumannii poses a global healthcare challenge, understanding its evolution is crucial for effective control strategies. Aim We aimed to evaluate the epidemiology, antimicrobial susceptibility and main resistance mechanisms of Acinetobacter spp. in Spain in 2020, and to explore temporal trends of A. baumannii . Methods We collected 199 single-patient Acinetobacter spp. clinical isolates in 2020 from 18 Spanish tertiary hospitals. Minimum inhibitory concentrations (MICs) for nine antimicrobials were determined. Short-read sequencing was performed for all isolates, and targeted long-read sequencing for A. baumannii . Resistance mechanisms, phylogenetics and clonality were assessed. Findings on resistance rates and infection types were compared with data from 2000 and 2010. Results Cefiderocol and colistin exhibited the highest activity against A. baumannii , although colistin susceptibility has significantly declined over 2 decades. A. non- baumannii strains were highly susceptible to most tested antibiotics. Of the A. baumannii isolates, 47.5% (56/118) were multidrug-resistant (MDR). Phylogeny and clonal relationship analysis of A. baumannii revealed five prevalent international clones, notably IC2 (ST2, n = 52; ST745, n = 4) and IC1 (ST1, n = 14), and some episodes of clonal dissemination. Genes bla OXA-23 , bla OXA-58 and bla OXA-24/40 were identified in 49 (41.5%), eight (6.8%) and one (0.8%) A. baumannii isolates, respectively. IS Aba 1 was found upstream of the gene (a bla OXA-51 -like ) in 10 isolates. Conclusions The emergence of OXA-23-producing ST1 and ST2, the predominant MDR lineages, shows a pivotal shift in carbapenem-resistant A. baumannii (CRAB) epidemiology in Spain. Coupled with increased colistin resistance, these changes underscore notable alterations in regional antimicrobial resistance dynamics.
An oncolytic virus delivering tumor-irrelevant bystander T cell epitopes induces anti-tumor immunity and potentiates cancer immunotherapy
Authors: Xiangyu Chen, Jing Zhao, Shuai Yue, Ziyu Li, Xiang Duan, Yao Lin, Yang Yang, Junjian He, Leiqiong Gao, Zhiwei Pan, Xiaofan Yang, Xingxing Su, Min Huang, Xiao Li, Ye Zhao, Xuehui Zhang, Zhirong Li, Li Hu, Jianfang Tang, Yaxing Hao, Qin Tian, Yifei Wang, Lifan Xu, Qizhao Huang, Yingjiao Cao, Yaokai Chen, Bo Zhu, Yan Li, Fan Bai, Guozhong Zhang, Lilin Ye
Journal: Nature Cancer (2024)

Abstract Tumor-specific T cells are crucial in anti-tumor immunity and act as targets for cancer immunotherapies. However, these cells are numerically scarce and functionally exhausted in the tumor microenvironment (TME), leading to inefficacious immunotherapies in most patients with cancer. By contrast, emerging evidence suggested that tumor-irrelevant bystander T (T BYS ) cells are abundant and preserve functional memory properties in the TME. To leverage T BYS cells in the TME to eliminate tumor cells, we engineered oncolytic virus (OV) encoding T BYS epitopes (OV-BYTE) to redirect the antigen specificity of tumor cells to pre-existing T BYS cells, leading to effective tumor inhibition in multiple preclinical models. Mechanistically, OV-BYTE induced epitope spreading of tumor antigens to elicit more diverse tumor-specific T cell responses. Remarkably, the OV-BYTE strategy targeting human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cell memory efficiently inhibited tumor progression in a human tumor cell-derived xenograft model, providing important insights into the improvement of cancer immunotherapies in a large population with a history of SARS-CoV-2 infection or coronavirus disease 2019 (COVID-19) vaccination.
Elucidation of genes enhancing natural product biosynthesis through co-evolution analysis
Authors: Xinran Wang, Ningxin Chen, Pablo Cruz-Morales, Biming Zhong, Yangming Zhang, Jian Wang, Yifan Xiao, Xinnan Fu, Yang Lin, Suneil Acharya, Zhibo Li, Huaxiang Deng, Yuhui Sun, Linquan Bai, Xiaoyu Tang, Jay D. Keasling, Xiaozhou Luo
Journal: Nature Metabolism (2024)
Emergence of OXA-48-like producing Citrobacter species, Germany, 2011 to 2022
Authors: Julian Sommer, Hannah Reiter, Janko Sattler, Elisabetta Cacace, Jessica Eisfeld, Sören Gatermann, Axel Hamprecht, Stephan Göttig
Journal: Eurosurveillance (2024)

BackgroundCarbapenemase-producing Enterobacterales are a public health threat worldwide and OXA-48 is the most prevalent carbapenemase in Germany and western Europe. However, the molecular epidemiology of OXA-48 in species other than
A lipidome landscape of aging in mice
Authors: Hiroshi Tsugawa, Tomoaki Ishihara, Kota Ogasa, Seigo Iwanami, Aya Hori, Mikiko Takahashi, Yutaka Yamada, Naoko Satoh-Takayama, Hiroshi Ohno, Aki Minoda, Makoto Arita
Journal: Nature Aging (2024)
Shear wave ultrasound elastography for estimating cartilage stiffness: implications for early detection of osteoarthritis
Authors: Elias Georgas, Adnan Rayes, Junhang Zhang, Qifa Zhou, Yi-Xian Qin
Journal: Med-X (2024)

Abstract Current osteoarthritis (OA) diagnosis relies on radiographic abnormalities found in later stages of the disease, posing a challenge to the treatment efficacy. Therefore, earlier detection of OA is essential for improving therapeutic outcomes. The aim of this study was to investigate the feasibility of shear wave ultrasound elastography (SWUE) to detect changes in cartilage mechanical properties under OA conditions ex-vivo. Bovine osteochondral units were harvested from femoral condyles and subjected to either trypsin degradation, cartilage surface roughness defect using varying degrees of sandpaper, or subchondral bone degeneration using formic acid (FA) injection. Shear waves were generated using a mechanical shaker, while a high-frequency ultrasound system operating at 18 MHz was employed to detect wave propagation along the samples. The elasticity of cartilage was estimated by the shear wave speed (SWS) through the auto-correlation method. Our results show that the estimated SWS of cartilage after 24, 48, and 72 hours of trypsin incubation significantly decreased by 37%, 43%, and 59%, respectively, compared to the control group. Surface roughness treatment using 150-grit sandpaper significantly decreased the SWS by 35% compared to the control. Samples treated with 7% FA showed a significant increase in SWS by 62%, 89%, and 53% compared to control, 1% FA, and 3% FA, respectively. Our findings demonstrate the feasibility of SWUE to differentiate the elastic properties of cartilage under different OA conditions. This study presents the potential of a noninvasive, nonionizing tool for early detection of OA, representing a significant step toward its clinical implementation. Graphical Abstract
Underwater endoscopic submucosal dissection performed under general anesthesia for the safe resection of superficial esophageal squamous cell carcinoma with ductal involvement
Authors: Yusuke Takahashi, Kotaro Shibagaki, Satoshi Kotani, Kenichi Kishimoto, Shinsaku Tanaka, Norihisa Ishimura, Shunji Ishihara
Journal: Endoscopy (2024)

A superficial esophageal squamous cell carcinoma (ESCC) will sometimes extend into the ducts of the submucosal esophageal glands (SEGs), so-called "ductal involvement," with the frequency of this reported to be 21.3%–37.1% [1] [2]. SEGs are generally ignored during an endoscopic submucosal dissection (ESD) procedure, although they should be considered because of the potential of ductal involvement. For digestive tumor cases, underwater endoscopic submucosal dissection (UESD) procedures can reportedly assist with the submucosal approach by raising the mucosa through buoyancy [3]; however, this is not usually applied for superficial ESCC cases owing to the severe risk of aspiration. The results presented of UESD for superficial ESCCs with ductal involvement being performed with the patient under general anesthesia indicate good safety and a high level of resectability.
Baroreflex activation therapy in patients with heart failure and a reduced ejection fraction: Long‐term outcomes
Authors: Michael R Zile, Joann Lindenfeld, Fred A Weaver, Faiez Zannad, Elizabeth Galle, Tyson Rogers, William T Abraham
Journal: European Journal of Heart Failure (2024)

Aims Carotid baroreflex activation therapy (BAT) restores baroreflex sensitivity and modulates the imbalance in cardiac autonomic function in patients with heart failure with reduced ejection fraction (HFrEF). We tested the hypothesis that treatment with BAT significantly reduces cardiovascular mortality and heart failure morbidity and provides long‐term safety and sustainable symptomatic improvement. Methods and results BeAT‐HF was a prospective, multicentre, randomized, two‐arm, parallel‐group, open‐label, non‐implanted control trial. New York Heart Association (NYHA) class III subjects, ejection fraction ≤35%, previous heart failure hospitalization or N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) &gt;400 pg/ml, no class I indication for cardiac resynchronization therapy and NT‐proBNP &lt;1600 pg/ml were randomized to BAT plus optimal medical management (BAT group) or optimal medical management alone (control). The primary endpoint was cardiovascular mortality and HF morbidity; additional pre‐specified endpoints included durability of safety, quality of life (QOL), exercise capacity (6‐min hall walk distance [6MHWD]), functional status (NYHA class), hierarchical composite win ratio, freedom from all‐cause death, left ventricular assists device (LVAD) implantation, heart transplant. Overall, 323 patients had 332 primary events, median follow‐up was 3.6 years/patient. Both primary endpoint (rate ratio 0.94, 95% confidence interval [CI] 0.57–1.57; p = 0.82) and components of the primary endpoints were not significantly different between BAT and control. The system‐ and procedure‐related major adverse neurological and cardiovascular event‐free rate remained 97% throughout the trial. Symptom improvement (QOL, 6MHWD, NYHA class, all nominal p &lt; 0.001) in the BAT group was durable in time, sustainable in extent. Win ratio (1.26, 95% CI 1.02–1.58) and freedom from all‐cause death, LVAD implantation, heart transplant (hazard ratio 0.66, 95% CI 0.43–1.01) favoured the BAT group but did not reach statistical significance. Conclusion The BeAT‐HF primary endpoint was neutral; however, BAT provided safe, effective, and sustainable improvements in HFrEF patient's functional status, 6MHWD and QOL.
Positive Vasoreactivity Testing in Pulmonary Arterial Hypertension: Therapeutic Consequences, Treatment Patterns, and Outcomes in the Modern Management Era
Authors: Felix Gerhardt, Eva Fiessler, Karen M. Olsson, Moritz Z. Kayser, Gabor Kovacs, Henning Gall, H. Ardeschir Ghofrani, Roza Badr Eslam, Irene M. Lang, Nicola Benjamin, Ekkehard Grünig, Michael Halank, Tobias J. Lange, Silvia Ulrich, Hanno Leuchte, Matthias Held, Hans Klose, Ralf Ewert, Heinrike Wilkens, Carmen Pizarro, Dirk Skowasch, Max Wissmüller, Martin Hellmich, Horst Olschewski, Marius M. Hoeper, Stephan Rosenkranz
Journal: Circulation (2024)

Among patients with pulmonary arterial hypertension (PAH), acute vasoreactivity testing during right heart catheterization may identify acute vasoresponders, for whom treatment with high-dose calcium channel blockers (CCBs) is recommended. However, long-term outcomes in the current era remain largely unknown. We sought to evaluate the implications of acute vasoreactivity response for long-term response to CCBs and other outcomes.
Author Correction: Bridging the literacy gap for surgical consents: an AI-human expert collaborative approach
Authors: Rohaid Ali, Ian D. Connolly, Oliver Y. Tang, Fatima N. Mirza, Benjamin Johnston, Hael F. Abdulrazeq, Rachel K. Lim, Paul F. Galamaga, Tiffany J. Libby, Neel R. Sodha, Michael W. Groff, Ziya L. Gokaslan, Albert E. Telfeian, John H. Shin, Wael F. Asaad, James Zou, Curtis E. Doberstein
Journal: npj Digital Medicine (2024)
Recalcitrant rectal stricture following circumferential endoscopic mucosal resection: novel application of endoscopic stricturotomy
Authors: Julia L. Gauci, Renato Medas, Clarence Kerrison, Anthony Whitfield, Francesco V. Mandarino, Nicholas G. Burgess, Michael J. Bourke
Journal: Endoscopy (2024)

A 69-year-old woman underwent endoscopic mucosal resection (EMR) of a fully circumferential flat, homogeneous, granular lesion, abutting the anal verge and extending proximally for 6 cm ([Fig. 1]). Steroid enemas were prescribed for a 6-week period. Histopathology confirmed a low-grade tubulovillous adenoma. The procedure was complicated by delayed bleeding which was treated by the patient's local surgical team with extensive thermal coagulation.
Blockade of IL-13 signaling improves skin barrier function and biology in patients with moderate to severe atopic dermatitis
Authors: Nicole Sander, Dora Stölzl, Melina Fonfara, Jan Hartmann, Inken Harder, Ina Suhrkamp, Ivone Jakaša, Ellen van den Bogaard, Ivonne van Vlijmen-Willems, Silke Szymczak, Elke Rodriguez, Sascha Gerdes, Stephan Weidinger
Journal: British Journal of Dermatology (2024)

Abstract Background Interleukin (IL)-13 is a key driver of inflammation and barrier dysfunction in atopic dermatitis (AD). While there is robust evidence that tralokinumab – a monoclonal antibody that neutralizes IL-13 – reduces inflammation and clinical disease activity, less is known about its effects on barrier function. Objectives To characterize the effects of tralokinumab treatment on skin barrier function. Methods Transepidermal water loss (TEWL), stratum corneum hydration (SCH), natural moisturizing factor content, histopathological characteristics, biomarker expression and microbiome composition were evaluated in lesional, nonlesional and sodium lauryl sulfate-irritated skin of 16 patients with AD over the course of 16 weeks of tralokinumab treatment. Results All clinical severity scores decreased significantly over time. At week 16, mean TEWL in target lesions decreased by 33% (P = 0.01) and SCH increased by 58% (P = 0.004), along with a histological reduction in spongiosis (P = 0.003), keratin 16 expression and epidermal thickness (P = 0.001). In parallel, there was a significant decrease in several barrier dysfunction-associated and proinflammatory proteins such as fibronectin (P = 0.006), CCL17/TARC (P = 0.03) and IL-8 (P = 0.01), with significant changes seen as early as week 8. Total bacterial load and Staphylococcus aureus abundance were significantly reduced from week 2. Conclusions Tralokinumab treatment improved skin physiology, epidermal pathology and dysbiosis, further highlighting the pleiotropic role of IL-13 in AD pathogenesis.
Dual molecule targeting HDAC6 leads to intratumoral CD4+ cytotoxic lymphocytes recruitment through MHC-II upregulation on lung cancer cells
Authors: Sarah Ducellier, Mélanie Demeules, Boris Letribot, Massimiliano Gaetani, Chloé Michaudel, Harry Sokol, Abdallah Hamze, Mouad Alami, Mégane Nascimento, Sébastien Apcher
Journal: Journal for ImmunoTherapy of Cancer (2024)

Despite the current therapeutic treatments including surgery, chemotherapy, radiotherapy and more recently immunotherapy, the mortality rate of lung cancer stays high. Regarding lung cancer, epigenetic modifications altering cell cycle, angiogenesis and programmed cancer cell death are therapeutic targets to combine with immunotherapy to improve treatment success. In a recent study, we uncovered that a molecule called QAPHA ((E)-3-(5-((2-cyanoquinolin-4-yl)(methyl)amino)-2-methoxyphenyl)-N-hydroxyacrylamide) has a dual function as both a tubulin polymerization and HDAC inhibitors. Here, we investigate the impact of this novel dual inhibitor on the immune response to lung cancer.
NHS and the whole of society must act on social determinants of health for a healthier future
Authors: Lucinda Hiam, Bob Klaber, Annabel Sowemimo, Michael Marmot
Journal: BMJ (2024)

The UK is facing a prolonged and serious health crisis.At a time when the future of the NHS is in jeopardy after over a decade of austerity, and with public satisfaction at an all time low, 1 it must pick up the pieces of failures across government.Attaining good health requires more than healthcare, and improvements in the provision of healthcare by the NHS alone is inadequate to address the health crisis-action is needed on the social determinants of health 2 (box 1). Box 1: Definition of social determinants of health 3The social determinants of health are defined by the World Health Organization as: "the conditions in which people are born, grow, live, work, and age, and the wider set of forces and systems shaping the conditions of daily life.These forces and systems include economic policies and systems, development agendas, social norms, social policies, and political systems.
Sustainability is critical for future proofing the NHS
Authors: Rita Issa, Callum Forbes, Catherine Baker, Matt Morgan, Kate Womersley, Bob Klaber, Elaine Mulcahy, Rachel Stancliffe
Journal: BMJ (2024)

Interventions that consider climate change, sustainability, and nature should be integral to health system functioning. Placing sustainability at the core of the NHS's future offers opportunities to deliver better services, support healthier populations, and save costs.
OMA1 competitively binds to HSPA9 to promote mitophagy and activate the cGAS–STING pathway to mediate GBM immune escape
Authors: Wen de Zhu, Jin Rao, Li hua Zhang, Ka ming Xue, Lin Li, Jun jun Li, Qian zhi Chen, Rong Fu
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background Immunotherapy with checkpoint inhibitors, especially those targeting programmed death receptor 1 (PD-1)/PD-1 ligand (PD-L1), is increasingly recognized as a highly promising therapeutic modality for malignancies. Nevertheless, the efficiency of immune checkpoint blockade therapy in treating glioblastoma (GBM) is constrained. Hence, it is imperative to expand our comprehension of the molecular mechanisms behind GBM immune escape (IE). Methods Protein chip analysis was performed to screen aberrantly expressed OMA1 protein in PD-1 inhibitor sensitive or resistant GBM. Herein, public databases and bioinformatics analysis were employed to investigate the OMA1 and PD-L1 relation. Then, this predicted relation was verified in primary GBM cell lines through distinct experimental methods. To investigate the molecular mechanism behind OMA1 in immunosuppression, a series of experimental methods were employed, including Western blotting, co-immunoprecipitation (Co-IP), mass spectrometry (MS), immunofluorescence, immunohistochemistry, and qRT-PCR. Results Our findings revealed that OMA1 competitively binds to HSPA9 to induce mitophagy and mediates the IE of GBM. Data from TCGA indicated a significant correlation between OMA1 and immunosuppression. OMA1 promoted PD-L1 levels in primary cells from patients with GBM. Next, the results of Co-IP and MS conducted on GBM primary cells revealed that OMA1 interacts with HSPA9 and induces mitophagy. OMA1 promoted not only cGAS–STING activity by increasing mitochondrial DNA release but also PD-L1 transcription by activating cGAS–STING. Eventually, OMA1 has been found to induce immune evasion in GBM through its regulation of PD-1 binding and PD-L1 mediated T cell cytotoxicity. Conclusions The OMA1/HSPA9/cGAS/PD-L1 axis is elucidated in our study as a newly identified immune therapeutic target in GBM.
Simulated lateral tunneling for treating a huge submucosal tumor at the cervical esophagus
Authors: Yue Zhao, Huige Wang, Dan Liu
Journal: Endoscopy (2024)

A 43-year-old man was referred to our hospital for treatment of a huge submucosal tumor adjacent to introitus esophagus identified by surveillance endoscopy ([Fig. 1] a). An enhanced computed tomography demonstrated a marked submucosal tumor measuring 2.6 × 8 cm, protruding intra- and extraluminally ([Fig. 1] b). After multidisciplinary team discussion and sufficient informed consent, endoscopic resection with simulated lateral tunneling was scheduled to remove this mass ([Video 1]).
<i>TP53</i>-associated early breast cancer: new observations from a large cohort
Authors: Renata L Sandoval, Michele Bottosso, Li Tianyu, Natalia Polidorio, Brittany L Bychkovsky, Benjamin Verret, Alessandra Gennari, Sophie Cahill, Maria Isabel Achatz, Olivier Caron, Marion Imbert-Bouteille, Catherine Noguès, Kara N Mawell, Cristina Fortuno, Amanda B Spurdle, Nabihah Tayob, Fabrice Andre, Judy E Garber
Journal: JNCI Journal of the National Cancer Institute (2024)

A recent large, well-annotated international cohort of patients with Li-Fraumeni syndrome and early-stage breast cancer was examined for shared features.
Benralizumab does not elicit therapeutic effect in patients with chronic spontaneous urticaria: results from the phase IIb multinational randomized double-blind placebo-controlled ARROYO trial
Authors: Sabine Altrichter, Ana Maria Giménez-Arnau, Jonathan A Bernstein, Martin Metz, Lila Bahadori, Maria Bergquist, Laura Brooks, Calvin N Ho, Priya Jain, Pradeep B Lukka, Eva Rodriguez-Suárez, Claire Walton, Catherine J Datto, Kamelia Vekovska, Jeffrey Leflein, Sonya Stoyanova Genova, Mariana Mandazhieva - Pepelanova, Marita Nittner Marszalska, Anna Hofman, Ana Maria Gimenez Arnau, Ricardo Tan, Hiromitsu Noguchi, Yoshiko Oda, Akihiro Kume, Seong Jun Seo, Elzbieta Szymanska, Juan Francisco Silvestre Salvador, Jonathan Bernstein, Aisaku Yamamoto, Warner Carr, Grisha Mateev, Regina Treudler, Ryan Klein, Jill Waibel, Beata Imko Walczuk, Rositsa Dencheva, Young Min Park, Shunsuke Takahagi, Grazyna Pulka, Plamen Stanev, Andrea Bauer, Irida Vasileva, Tae Gyun Kim, Eduardo Lopez Bran, Martin Metz, Juan Alberto Ruano Ruiz, Antonio Martorell Calatayud, Blakely Richardson, Kenneth Steil, Yaohan Lam, Robert Cartwright, Lon Lynn, Amal Assaad
Journal: British Journal of Dermatology (2024)

Chronic spontaneous urticaria (CSU) is a relatively common skin disease associated with hives and angio-oedema. Eosinophils play a role in CSU pathogenesis. Benralizumab, an anti-interleukin-5 receptor-α monoclonal antibody, has been shown to induce nearly complete depletion of eosinophils.