tbuckley/cabot-search huggingface dataset:
Co-circulation of seasonal influenza A(H1N1)pdm09, A(H3N2) and B/Victoria lineage viruses with further genetic diversification, EU/EEA, 2022/23 influenza season
Authors: Eeva K Broberg, Olov Svartström, Maximilian Riess, Annette Kraus, Maja Vukovikj, Angeliki Melidou
Journal: Eurosurveillance (2024)

BackgroundInfluenza viruses can cause large seasonal epidemics with high healthcare impact and severity as they continually change their virological properties such as genetic makeup over time.AimWe aimed to monitor the characteristics of circulating influenza viruses over the 2022/23 influenza season in the EU/EEA countries. In addition, we wanted to compare how closely the circulating viruses resemble the viral components selected for seasonal influenza vaccines, and whether the circulating viruses had acquired resistance to commonly used antiviral drugs.MethodsWe performed a descriptive analysis of the influenza virus detections and characterisations reported by National Influenza Centres (NIC) from the 30 EU/EEA countries from week 40/2022 to week 39/2023 to The European Surveillance System (TESSy) as part of the Global Influenza Surveillance and Response System (GISRS).ResultsIn the EU/EEA countries, the 2022/23 influenza season was characterised by co-circulation of A(H1N1)pdm09, A(H3N2) and B/Victoria-lineage viruses. The genetic evolution of these viruses continued and clade 6B.1A.5a.2a of A(H1N1)pdm09, 3C.2a1b.2a.2b of A(H3N2) and V1A.3a.2 of B/Victoria viruses dominated. Influenza B/Yamagata-lineage viruses were not reported.DiscussionThe World Health Organization (WHO) vaccine composition recommendation for the northern hemisphere 2023/24 season reflects the European virus evolution, with a change of the A(H1N1)pdm09 component, while keeping the A(H3N2) and B/Victoria-lineage components unchanged.
The transmission risk of multidrug-resistant organisms between hospital patients and their pets – a case−control study, Germany, 2019 to 2022
Authors: Carolin Hackmann, Antonia Genath, Désirée Gruhl, Anna Weber, Friederike Maechler, Axel Kola, Frank Schwab, Stefan Schwarz, Antina Lübke-Becker, Thomas Schneider, Petra Gastmeier, Rasmus Leistner
Journal: Eurosurveillance (2024)

BackgroundCarriage of multidrug-resistant organisms (MDROs) in humans constitutes an important public health concern. Cross-transmission of bacteria between animals and humans has been demonstrated before.AimOur aim was to quantify the risk factor 'pet ownership' for MDRO colonisation in hospital patients.MethodsWe performed a matched case-control study from 2019 to 2022 in Berlin, Germany and compared MDRO-positive and MDRO-negative patients in terms of contact with pets and other risk factors for MDRO acquisition. Patients completed a questionnaire-based interview and provided nasal and rectal swabs. Pet owners provided swab samples from the throat and stool of their pets (dogs and cats). Phenotypically matching samples of owners and pets were analysed via whole genome sequencing.ResultsThe analyses included 2,891 patients. Reported pet ownership was 17.7% in MDRO-positives (154/871) and 23.4% in MDRO-negatives (472/2,020). Among 397 owner-pet pairs, we identified one pair sharing genotypically indistinguishable pathogens (0.3%). A risk factor analysis of pet ownership was performed for carriers of meticillin-resistant
A targeted gene expression biomarker predicts clinic low-risk meningioma recurrence
Authors: Minh P Nguyen, Ramin A Morshed, Mark W Youngblood, Haley K Perlow, Calixto-Hope G Lucas, Akash J Patel, Joshua D Palmer, Craig M Horbinski, Stephen T Magill, William C Chen, David R Raleigh
Journal: Neuro-Oncology (2024)

Abstract Background Despite reassuring clinical and histological features, low grade meningiomas can recur after surgery. Targeted gene expression profiling improves risk stratification of meningiomas, but the utility of this approach for clinical low-risk meningiomas is incompletely understood. Methods This was a multicenter retrospective cohort study of meningiomas from patients who were treated at 4 institutions from 1992 to 2023. Adult patients with newly diagnosed or recurrent World Health Organization (WHO) grade 1 meningiomas that were treated with gross total resection (GTR) or subtotal resection (STR), or newly diagnosed WHO grade 2 meningiomas that were treated with GTR, were included. A 34-gene expression biomarker and gene expression risk score (continuous from 0 to 1) was evaluated in all samples. Results The study cohort was comprised of 723 patients, none of which were used for discovery or training of the gene expression biomarker and 265 of which were previously unreported. There were 626 WHO grade 1 meningiomas, 490 with GTR and 126 with STR, and 97 WHO grade 2 meningiomas with GTR. Targeted gene expression profiling classified 51.3% of clinical low-risk meningiomas as molecular intermediate-risk and 9.5% as molecular high-risk. Combining the gene expression biomarker with extent of resection revealed 19.8% of clinical low-risk meningiomas had unfavorable local freedom from recurrence (LFFR) and overall survival (OS), including 7.1% of newly diagnosed WHO grade 1 meningiomas with GTR. The risk score was prognostic for LFFR (HR per 0.1 increase in risk score 1.89, 95% CI 1.58-2.25) across all WHO grades, extents of resection, and newly diagnosed or recurrent presentations. Conclusions Targeted gene expression profiling can identify clinical low-risk meningiomas that are likely to recur after surgery
Obituary: Professor Marcus Maurer, Berlin, Germany
Authors: Ludger Klimek, Torsten Zuberbier, Frank Siebenhaar, Petra Staubach, Thilo Jakob, Andrea Bauer, Wolfgang Pfützner, Bettina Wedi, Stefano Del Giacco, Patrizia Bonadonna, Jolanta Walusiak‐Skorupa, André Morreira, Oscar Palomares, Oliver Pfaar, Ibon Eguíluz Gracia, Stefania Arasi, Jan Hagemann, Joachim Saloga, Roland Buhl, Jean Bousquet, Cezmi A. Akdis, Mohamed H. Shamji, Maria Jose Torres
Journal: Allergy (2024)
Clinical utility analysis of the Hoxb8 mast cell activation test for the diagnosis of peanut allergy
Authors: Noemi Bachmeier‐Zbären, Alper Celik, Robin van Brummelen, Nadine Roos, Melanie Steinmann, Jennifer A. Hoang, Xiaojun Yin, Christina M. Ditlof, Lucy Duan, Julia E. M. Upton, Thomas Kaufmann, Alexander Eggel, Thomas Eiwegger
Journal: Allergy (2024)

Abstract Background Peanut allergy is among the most severe and common food allergies. The diagnosis has a significant impact on the quality of life for patients and their families. An effective management approach depends on accurate, safe, and easily implementable diagnostic methods. We previously developed a cell‐based assay using Hoxb8 mast cells (Hoxb8 MCs) aimed at improving clinical allergy diagnosis. In this study, we assessed its diagnostic performance by measuring blinded sera from a prospectively enrolled and pre‐validated peanut allergy cohort. Methods Hoxb8 MCs were passively sensitized with sera from peanut‐allergic and peanut tolerant children and adolescents ( n = 112). Degranulation of Hoxb8 MCs was quantified upon stimulation with dose‐titrated peanut extract by means of flow cytometry, using CD107a as activation marker. The results from the Hoxb8 mast cell activation test (Hoxb8 MAT) were compared to established diagnostic assays such as the skin prick test (SPT), specific IgE (sIgE) levels, and the basophil activation test (BAT). Additionally, serum samples from BAT nonresponders were assessed with the Hoxb8 MAT. Results Hoxb8 MAT displayed a robust dose‐dependent activation to peanut extract, with a cutoff value of ≤5.2% CD107a positive cells. The diagnostic accuracy was highest at allergen concentrations ≥100 ng/mL, with an area under the receiver operating characteristic curve (AUROC) of 0.97, 93% sensitivity, and 96% specificity, outperforming traditional SPT and sIgE tests. When compared to BAT, Hoxb8 MAT exhibited comparable diagnostic efficacy. Moreover, sera from BAT nonresponders were accurately classified into allergics and nonallergics by the Hoxb8 MAT. Conclusions The Hoxb8 MAT demonstrated a very good diagnostic precision in patients prospectively assessed for peanut allergy comparable to the fresh whole blood‐based BAT. Additionally, it demonstrated its value for accurate classification of BAT nonresponders into allergic and nonallergic individuals. Further investigations into its utility in the routine clinical setting are warranted.
Epicutaneous immunotherapy for the treatment of peanut allergy
Authors: Mayuran Ravindran, Hugh A. Sampson, Edwin H. Kim, Katharine J. Bee, Todd D. Green, A. Wesley Burks
Journal: Allergy (2024)

Abstract Peanut allergy treatment options remain limited, but novel approaches are being studied, including epicutaneous immunotherapy (EPIT). EPIT uses the cutaneous immune system to promote tolerance to food allergens. Viaskin™ Peanut, an approach to EPIT in late‐stage clinical development uses an occlusive patch with a condensation chamber that enables natural epidermal water loss to solubilize dry antigen on the patch, which is then absorbed and captured by skin Langerhans cells. This form of EPIT does not require disruption of the skin barrier, thus avoiding a proinflammatory cytokine response by targeting the nonvascularized epidermis and limiting systemic allergen exposure. Extensive preclinical research suggests that Viaskin Peanut has a distinct mechanism of desensitization, including the potential for disease modification, driven by a unique population of regulatory T cells. Numerous clinical studies of Viaskin Peanut have demonstrated desensitization and reductions in reaction severity, particularly in children aged 1 through 11 years, as well as a favorable safety profile with mostly mild‐to‐moderate skin reactions that were observed to decrease over time. EPIT with Viaskin Peanut may be a potential therapeutic option for peanut allergy that is clinically practical with long‐term efficacy and tolerability.
E3 ubiquitin ligase DTX2 fosters ferroptosis resistance via suppressing NCOA4-mediated ferritinophagy in non-small cell lung cancer
Authors: Zhuang Liu, Chang Liu, Caihong Fan, Runze Li, Shiqi Zhang, Jia Liu, Bo Li, Shengzheng Zhang, Lihong Guo, Xudong Wang, Zhi Qi, Yanna Shen
Journal: Drug Resistance Updates (2024)
Association of metabolic signatures of air pollution with MASLD: Observational and Mendelian randomization study
Authors: Shanshan Ran, Jingyi Zhang, Fei Tian, Zhengmin Min Qian, Shengtao Wei, Yuhua Wang, Ge Chen, Junguo Zhang, Lauren D Arnold, Stephen Edward McMillin, Hualiang Lin
Journal: Journal of Hepatology (2024)
Effects of the Non-Steroidal MRA Finerenone with and without Concomitant SGLT2 Inhibitor Use in Heart Failure
Authors: Muthiah Vaduganathan, Brian L. Claggett, Ian J. Kulac, Zi Michael Miao, Akshay S. Desai, Pardeep S. Jhund, Alasdair D. Henderson, Meike Brinker, James Lay-Flurrie, Prabhakar Viswanathan, Markus Florian Scheerer, Andrea Lage, Carolyn S.P. Lam, Michele Senni, Sanjiv J. Shah, Adriaan A. Voors, Faiez Zannad, Bertram Pitt, John J.V. McMurray, Scott D. Solomon
Journal: Circulation (2024)

BACKGROUND: Patients with heart failure (HF) with mildly reduced or preserved ejection fraction face heightened long-term risks of morbidity and mortality. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and the nonsteroidal mineralocorticoid receptor antagonist finerenone have both been shown to reduce the risk of cardiovascular events in this population, but the effects of their combined use are not known. METHODS: FINEARTS-HF (Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients With Heart Failure) was a randomized, double-blind, placebo-controlled trial of finerenone in patients with HF and left ventricular ejection fraction ≥40%. Baseline SGLT2i use was a prespecified subgroup. The primary outcome was a composite of total (first and recurrent) worsening HF events and cardiovascular death. We first assessed for evidence of treatment heterogeneity on the basis of baseline SGLT2i use. We further examined SGLT2i uptake during the trial and evaluated the treatment effects of finerenone accounting for baseline and during-trial use of SGLT2i in time-varying analyses. RESULTS: Among 6001 participants, 817 (13.6%) were treated with an SGLT2i at baseline. During 2.6 years median follow-up, treatment with finerenone similarly reduced the risk of the primary outcome in participants treated with an SGLT2i (rate ratio, 0.83 [95% CI, 0.60–1.16]) and without an SGLT2i at baseline (rate ratio, 0.85 [95% CI, 0.74–0.98]; P interaction =0.76). In follow-up, 980 participants initiated SGLT2i, which was less frequent in the finerenone arm compared with placebo (17.7% versus 20.1%; hazard ratio, 0.86 [95% CI, 0.76–0.97]). Time-updated analyses accounting for baseline and subsequent use of SGLT2i did not meaningfully alter the treatment effects of finerenone on the primary end point. CONCLUSIONS: The treatment benefits of the nonsteroidal mineralocorticoid receptor antagonist finerenone were observed irrespective of concomitant use of an SGLT2i. These data suggest that the combined use of SGLT2i and a nonsteroidal mineralocorticoid receptor antagonist may provide additive protection against cardiovascular events in patients with HF with mildly reduced or preserved ejection fraction. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04435626.
Corrigendum to “Mitochondria-engine with self-regulation to restore degenerated intervertebral disc cells via bioenergetic robust hydrogel design” [Bioact. Mater. 40C (2024) 1–18]
Authors: Juehan Wang, Yulin Jiang, Ce Zhu, Zheng Liu, Lin Qi, Hong Ding, Jing Wang, Yong Huang, Yubao Li, Yueming Song, Ganjun Feng, Li Zhang, Limin Liu
Journal: Bioactive Materials (2024)
Time to Significant Benefit of Finerenone in Patients With Heart Failure
Authors: Muthiah Vaduganathan, Brian L. Claggett, Akshay S. Desai, Pardeep S. Jhund, Carolyn S.P. Lam, Michele Senni, Sanjiv J. Shah, Adriaan A. Voors, Faiez Zannad, Bertram Pitt, John J.V. McMurray, Scott D. Solomon
Journal: Journal of the American College of Cardiology (2024)
Deep learning for identifying personal and family history of suicidal thoughts and behaviors from EHRs
Authors: Prakash Adekkanattu, Al'ona Furmanchuk, Yonghui Wu, Aman Pathak, Braja Gopal Patra, Sarah Bost, Destinee Morrow, Grace Hsin-Min Wang, Yuyang Yang, Noah James Forrest, Yuan Luo, Theresa L Walunas, Weihsuan Lo-Ciganic, Walid Gelad, Jiang Bian, Yuhua Bao, Mark Weiner, David Oslin, Jyotishman Pathak
Journal: npj Digital Medicine (2024)
Circulating monocytes as a marker of response to adalimumab in patients with hidradenitis suppurativa: A single institution, real-world cohort study
Authors: Nessr Abu Rached, Jana Herbst, Thilo Gambichler, Schapoor Hessam, Lennart Ocker, Marina Skrygan, Eggert Stockfleth, Falk G Bechara
Journal: Journal of the American Academy of Dermatology (2024)
Accelerated hypofractionated radiotherapy for locally-advanced non-small cell lung cancer: A systematic review from the International Association for the Study of Lung Cancer (IASLC) Advanced Radiation Technology (ART) Subcommittee
Authors: Badr Id Said, Yimin Geng, Shahed N Badiyan, Andrew Bang, Andrea Bezjak, Kevin L M Chua, Corinne Faivre-Finn, Feng-Ming Kong, Daniel Przybysz, Paul M Putora, Pablo Munoz-Schuffenegger, Shankar Siva, Meng Xu-Welliver, Fiona McDonald, Alexander Louie, Stephen G Chun
Journal: Journal of Thoracic Oncology (2024)
Tailored polysaccharide entrapping metal-organic framework for RNAi therapeutics and diagnostics in atherosclerosis
Authors: Sen Li, Han Gao, Haoji Wang, Xiaolin Zhao, Da Pan, Idaira Pacheco-Fernández, Ming Ma, Jianjun Liu, Jouni Hirvonen, Zehua Liu, Hélder A Santos
Journal: Bioactive Materials (2024)
Long term outcomes in patients with advanced intrahepatic cholangiocarcinoma treated with hepatic arterial infusion chemotherapy
Authors: Darren Cowzer, Kevin Soares, Henry Walch, Mithat Gönen, Taryn M Boucher, Richard K G Do, James J Harding, Anna M Varghese, Diane Reidy-Lagunes, Leonard Saltz, Louise C Connell, Ghassan K Abou-Alfa, Alice C Wei, Nikolaus Schultz, T Peter Kingham, Michael I D’Angelica, Jeffrey A Drebin, Vinod Balachandran, Francisco Sanchez-Vega, Nancy E Kemeny, William R Jarnagin, Andrea Cercek
Journal: JNCI Journal of the National Cancer Institute (2024)

Abstract Introduction Hepatic artery infusion (HAI) of chemotherapy has demonstrated disease control and suggested improvement in overall survival (OS) in intrahepatic cholangiocarcinoma (IHC). We report herein the long-term results and role of molecular alterations of a phase II clinical trial of HAI chemotherapy plus systemic chemotherapy, with a retrospective cohort of patients treated with HAI at Memorial Sloan Kettering Cancer Center. Methods This secondary analysis of a single-institution, phase 2 trial and retrospective cohort of unresectable IHC treated with HAI floxuridine (FUDR) plus systemic gemcitabine and oxaliplatin. The primary aim was to assess long-term oncologic outcomes. A subset underwent tissue-based genomic sequencing, and molecular alterations were correlated with progression-free survival (PFS) and OS. Results Thirty-eight patients were treated on trial with a median follow up of 76.9 months. Median PFS was 11.8 months (95% CI11-15.1). The median OS was 26.8 months (95% CI20.9-40.6). The 1-, 2- and 5-year OS rate was 89.5%, 55%, and 21% respectively. Nine (24%) received HAI with mitomycin C post FUDR progression with an objective response rate of 44% and a median PFS of 3.93 (2.33-NR) months. One-hundred and seventy patients not treated on the clinical trial were included in a retrospective analysis. Median PFS and OS was 7.93 (95%CI: 7.27-10.07) and 22.5 (95%CI : 19.5-28.3) months, respectively. Alterations in the TP53 and cell-cycle pathway had a worse PFS to HAI based therapy compared to wildtype disease. Conclusion In locally advanced IHC, HAI with FUDR in combination with systemic therapy can offer long term durable disease control. Molecular alterations may predict for response.
Changes in intestinal permeability and gut microbiota following diet-induced weight loss in patients with metabolic dysfunction-associated steatohepatitis and liver fibrosis
Authors: Dimitrios A. Koutoukidis, Sandi Yen, Paula Gomez Castro, Mariya Misheva, Susan A. Jebb, Paul Aveyard, Jeremy W. Tomlinson, Ferenc E. Mozes, Jeremy F. Cobbold, Jethro S. Johnson, Julian R. Marchesi
Journal: Gut Microbes (2024)

Weight loss improves metabolic dysfunction-associated steatohepatitis (MASH). We investigated whether there were associated changes in intestinal permeability, short-chain fatty acids (SCFAs), and gut microbiota, which are implicated in the pathophysiology of MASH. Sixteen adults with MASH, moderate fibrosis, and obesity received a low-energy total diet replacement program for 12 weeks and stepped food re-introduction over the following 12 weeks (ISRCTN12900952). Intestinal permeability, fecal SCFAs, and fecal microbiota were assessed at 0, 12, and 24 weeks. Data were analyzed using mixed-effects linear regression and sparse partial least-squares regression. Fourteen participants completed the trial, lost 15% (95% CI: 11.2-18.6%) of their weight, and 93% had clinically relevant reductions in liver disease severity markers. Serum zonulin concentrations were reduced at both 12 and 24 weeks (152.0 ng/ml, 95% CI: 88.0-217.4,
Yap methylation‐induced FGL1 expression suppresses anti‐tumor immunity and promotes tumor progression in <i>KRAS</i>‐driven lung adenocarcinoma
Authors: Ji Jiang, Pengfei Ye, Ningning Sun, Weihua Zhu, Mei Yang, Manman Yu, Jingjing Yu, Hui Zhang, Zijie Gao, Ningjie Zhang, Shijie Guo, Yuru Ji, Siqi Li, Cuncun Zhang, Sainan Miao, Mengqi Chai, Wenmin Liu, Yue An, Jian Hong, Wei Wei, Shihao Zhang, Huan Qiu
Journal: Cancer Communications (2024)

Abstract Background Despite significant strides in lung cancer immunotherapy, the response rates for Kirsten rat sarcoma viral oncogene homolog ( KRAS )‐driven lung adenocarcinoma (LUAD) patients remain limited. Fibrinogen‐like protein 1 (FGL1) is a newly identified immune checkpoint target, and the study of related resistance mechanisms is crucial for improving the treatment outcomes of LUAD patients. This study aimed to elucidate the potential mechanism by which FGL1 regulates the tumor microenvironment in KRAS ‐mutated cancer. Methods The expression levels of FGL1 and SET1 histone methyltransferase (SET1A) in lung cancer were assessed using public databases and clinical samples. Lentiviruses were constructed for transduction to overexpress or silence FGL1 in lung cancer cells and mouse models. The effects of FGL1 and Yes‐associated protein (Yap) on the immunoreactivity of cytotoxic T cells in tumor tissues were evaluated using immunofluorescence staining and flow cytometry. Chromatin immunoprecipitation and dual luciferase reporter assays were used to study the SET1A‐directed transcriptional program. Results Upregulation of FGL1 expression in KRAS ‐mutated cancer was inversely correlated with the infiltration of CD8 + T cells. Mechanistically, KRAS activated extracellular signal‐regulated kinase 1/2 (ERK1/2), which subsequently phosphorylated SET1A and increased its stability and nuclear localization. SET1A‐mediated methylation of Yap led to Yap sequestration in the nucleus, thereby promoting Yap‐induced transcription of FGL1 and immune evasion in KRAS ‐driven LUAD. Notably, dual blockade of programmed cell death‐1 (PD‐1) and FGL1 further increased the therapeutic efficacy of anti‐PD‐1 immunotherapy in LUAD patients. Conclusion FGL1 could be used as a diagnostic biomarker of KRAS ‐mutated lung cancer, and targeting the Yap‐FGL1 axis could increase the efficacy of anti‐PD‐1 immunotherapy.
Dietary fiber intake impacts gut bacterial and viral populations in a hypertensive mouse model
Authors: Laura Avellaneda-Franco, Liang Xie, Michael Nakai, Jeremy J. Barr, Francine Z. Marques
Journal: Gut Microbes (2024)

The gut microbiome is an emerging factor in preventing hypertension, yet the influence of gut bacteriophages, viruses infecting bacteria, on this condition remains unclear. Bacteriophage-bacteria interactions, which impact the gut microbiome, are influenced differentially by temperate and virulent bacteriophages. However, the standard technique for studying viral populations, viral-like particles (VLPs)-metagenomes, often overlook prophages, the intracellular stage of temperate bacteriophages, creating a knowledge gap. To address this, we investigated alterations in extracellular and intracellular bacteriophages, alongside bacterial populations, in the angiotensin II-hypertension model. We sequenced VLPs and bulk DNA from cecal-colonic samples collected from male C57BL/6J mice implanted with minipumps containing saline or angiotensin II. We assembled 106 bacterial and 816 viral genomes and found that gut viral and bacterial populations remained stable between hypertensive and normotensive mice. A higher number of temperate viruses were observed across all treatments. Although temperate viruses outnumbered virulent viruses, sequencing of both VLPs and bulk revealed that virions from virulent viruses were more abundant in the murine gut. We then evaluated the impact of low- and high-fiber intake on gut microbiome composition in the angiotensin II model. Fiber intake significantly influenced the gut microbiome composition and hypertension development. Mice receiving high-fiber had lower blood pressure, a higher bacterial-encoded carbohydrate-associated enzyme, and a higher total relative abundance of temperate viruses than those receiving low-fiber. Our findings suggest that phages are not associated with hypertension development in the angiotensin II model. However, they support a complex diet-bacteria/phage interaction that may be involved in blood pressure regulation.