tbuckley/cabot-search huggingface dataset:
Clinical immunogenicity outcomes from GENEr8-1, a phase 3 study of valoctocogene roxaparvovec, an AAV5-vectored gene therapy for hemophilia A
Authors: Brian R Long, Tara M Robinson, Jonathan R S Day, Hua Yu, Kelly Lau, Urooj Imtiaz, Kathryn S Patton, Greg de Hart, Joshua Henshaw, Suresh Agarwal, Christian Vettermann, Stephen J Zoog, Soumi Gupta
Journal: Molecular Therapy (2024)

Gene transfer therapies utilizing adeno-associated virus (AAV) vectors involve a complex drug design with multiple components that may impact immunogenicity. Valoctocogene roxaparvovec is an AAV serotype 5 (AAV5)-vectored gene therapy for the treatment of hemophilia A that encodes a B-domain-deleted human factor VIII (FVIII) protein controlled by a hepatocyte-selective promoter. Following previous results from the first-in-human phase 1/2 clinical trial, we assessed AAV5-capsid- and transgene-derived FVIII-specific immune responses with 2 years of follow-up data from GENEr8-1, a phase 3, single-arm, open-label study in 134 adult men with severe hemophilia A. No FVIII inhibitors were detected following administration of valoctocogene roxaparvovec. Immune responses were predominantly directed toward the AAV5 capsid, with all participants developing durable anti-AAV5 antibodies. Cellular immune responses specific for the AAV5 capsid were detected in most participants by interferon-γ enzyme-linked immunosorbent spot assay 2 weeks following dose administration and declined or reverted to negative over the first 52 weeks. These responses were weakly correlated with alanine aminotransferase elevations and showed no association with changes in FVIII activity. FVIII-specific cellular immune responses were less frequent and more sporadic compared with those specific for AAV5 and showed no association with safety or efficacy parameters.
3D printed PEDOT:PSS-based conducting and patternable eutectogel electrodes for machine learning on textiles
Authors: Ruben Ruiz-Mateos Serrano, Ana Aguzin, Eleni Mitoudi-Vagourdi, Xudong Tao, Tobias E. Naegele, Amy T. Jin, Naroa Lopez-Larrea, Matías L. Picchio, Marco Vinicio Alban-Paccha, Roque J. Minari, David Mecerreyes, Antonio Dominguez-Alfaro, George G. Malliaras
Journal: Biomaterials (2024)

The proliferation of medical wearables necessitates the development of novel electrodes for cutaneous electrophysiology. In this work, poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) is combined with a deep eutectic solvent (DES) and polyethylene glycol diacrylate (PEGDA) to develop printable and biocompatible electrodes for long-term cutaneous electrophysiology recordings. The impact of printing parameters on the conducting properties, morphological characteristics, mechanical stability and biocompatibility of the material were investigated. The optimised eutectogel formulations were fabricated in four different patterns —flat, pyramidal, striped and wavy— to explore the influence of electrode geometry on skin conformability and mechanical contact. These electrodes were employed for impedance and forearm EMG measurements. Furthermore, arrays of twenty electrodes were embedded into a textile and used to generate body surface potential maps (BSPMs) of the forearm, where different finger movements were recorded and analysed. Finally, BSPMs for three different letters (B, I, O) in sign-language were recorded and used to train a logistic regressor classifier able to reliably identify each letter. This novel cutaneous electrode fabrication approach offers new opportunities for long-term electrophysiological recordings, online sign-language translation and brain-machine interfaces.
Netrin-1 co-cross-linked hydrogel accelerates diabetic wound healing in situ by modulating macrophage heterogeneity and promoting angiogenesis
Authors: Futing Shu, Hongchao Huang, Shichu Xiao, Zhaofan Xia, Yongjun Zheng
Journal: Bioactive Materials (2024)

Diabetic wounds, characterized by prolonged inflammation and impaired vascularization, are a serious complication of diabetes. This study aimed to design a gelatin methacrylate (GelMA) hydrogel for the sustained release of netrin-1 and evaluate its potential as a scaffold to promote diabetic wound healing. The results showed that netrin-1 was highly expressed during the inflammation and proliferation phases of normal wounds, whereas it synchronously exhibited aberrantly low expression in diabetic wounds. Neutralization of netrin-1 inhibited normal wound healing, and the topical application of netrin-1 accelerated diabetic wound healing. Mechanistic studies demonstrated that netrin-1 regulated macrophage heterogeneity via the A2bR/STAT/PPARγ signaling pathway and promoted the function of endothelial cells, thus accelerating diabetic wound healing. These data suggest that netrin-1 is a potential therapeutic target for diabetic wounds.
Advanced nerve regeneration enabled by neural conformal electronic stimulators enhancing mitochondrial transport
Authors: Hao Bai, Siqi Zhang, Huiran Yang, Jing Wang, Hongli Chen, Jia Li, Lin Li, Qian Yang, Bo Peng, Ziyi Zhu, Siyuan Ni, Keyin Liu, Wei Lei, Tiger H. Tao, Yafei Feng
Journal: Bioactive Materials (2024)

Addressing peripheral nerve defects remains a significant challenge in regenerative neurobiology. Autografts emerged as the gold-standard management, however, are hindered by limited availability and potential neuroma formation. Numerous recent studies report the potential of wireless electronic system for nerve defects repair. Unfortunately, few has met clinical needs for inadequate electrode precision, poor nerve entrapment and insufficient bioactivity of the matrix material. Herein, we present an advanced wireless electrical nerve stimulator, based on water-responsive self-curling silk membrane with excellent bioabsorbable and biocompatible properties. We constructed a unique bilayer structure with an oriented pre-stretched inner layer and a general silk membrane as outer layer. After wetting, the simultaneous contraction of inner layer and expansion of outer layer achieved controllable super-contraction from 2D flat surface to 3D structural reconfiguration. It enables shape-adaptive wrapping to cover around nerves, overcomes the technical obstacle of preparing electrodes on the inner wall of the conduit, and prevents electrode breakage caused by material expansion in water. The use of fork capacitor-like metal interface increases the contact points between the metal and the regenerating nerve, solving the challenge of inefficient and rough electrical stimulation methods in the past. Newly developed electronic stimulator is effective in restoring 10 mm rat sciatic nerve defects comparable to autologous grafts. The underlying mechanism involves that electric stimulation enhances anterograde mitochondrial transport to match energy demands. This newly introduced device thereby demonstrated the potential as a viable and efficacious alternative to autografts for enhancing peripheral nerve repair and functional recovery.
Preterm and Early-Term Delivery After Heat Waves in 50 US Metropolitan Areas
Authors: Lyndsey A. Darrow, Mengjiao Huang, Joshua L. Warren, Matthew J. Strickland, Heather A. Holmes, Andrew J. Newman, Howard H. Chang
Journal: JAMA Network Open (2024)

Importance Heat waves are increasing in frequency, intensity, and duration and may be acutely associated with pregnancy outcomes. Objective To examine changes in daily rates of preterm and early-term birth after heat waves in a 25-year nationwide study. Design, Setting, and Participants This cohort study of singleton births used birth records from 1993 to 2017 from the 50 most populous US metropolitan statistical areas (MSAs). The study included 53 million births, covering 52.8% of US births over the period. Data were analyzed between October 2022 and March 2023 at the National Center for Health Statistics. Exposures Daily temperature data from Daymet at 1-km 2 resolution were averaged over each MSA using population weighting. Heat waves were defined in the 4 days (lag, 0-3 days) or 7 days (lag, 0-6 days) preceding birth. Main Outcomes and Measures Daily counts of preterm birth (28 to &amp;amp;lt;37 weeks), early-term birth (37 to &amp;amp;lt;39 weeks), and ongoing pregnancies in each gestational week on each day were enumerated in each MSA. Rate ratios for heat wave metrics were obtained from time-series models restricted to the warm season (May to September) adjusting for MSA, year, day of season, and day of week, and offset by pregnancies at risk. Results There were 53 154 816 eligible births in the 50 MSAs from 1993 to 2017; 2 153 609 preterm births and 5 795 313 early-term births occurring in the warm season were analyzed. A total of 30.0% of mothers were younger than 25 years, 53.8% were 25 to 34 years, and 16.3% were 35 years or older. Heat waves were positively associated with daily rates of preterm and early-term births, showing a dose-response association with heat wave duration and temperatures and stronger associations in the more acute 4-day window. After 4 consecutive days of mean temperatures exceeding the local 97.5th percentile, the rate ratio for preterm birth was 1.02 (95% CI, 1.00-1.03), and the rate ratio for early-term birth was 1.01 (95% CI, 1.01-1.02). For the same exposure, among those who were 29 years of age or younger, had a high school education or less, and belonged to a racial or ethnic minority group, the rate ratios were 1.04 (95% CI, 1.02-1.06) for preterm birth and 1.03 (95% CI, 1.02-1.05) for early-term birth. Results were robust to alternative heat wave definitions, excluding medically induced deliveries, and alternative statistical model specifications. Conclusions and Relevance In this cohort study, preterm and early-term birth rates increased after heat waves, particularly among socioeconomically disadvantaged subgroups. Extreme heat events have implications for perinatal health.
Addendum for Euro Surveill. 2024;29(18)
Journal: Eurosurveillance (2024)

© This work is licensed under a Creative Commons Attribution 4.0 International License. Addendum This article is an addendum to the following content: A combined cross-sectional analysis and case-control study evaluating tick-borne encephalitis vaccination coverage, disease and vaccine effectiveness in children and adolescents, Switzerland, 2005 to 2022
Interruption of KLF5 acetylation promotes PTEN-deficient prostate cancer progression by reprogramming cancer-associated fibroblasts
Authors: Baotong Zhang, Mingcheng Liu, Fengyi Mai, Xiawei Li, Wenzhou Wang, Qingqing Huang, Xiancai Du, Weijian Ding, Yixiang Li, Benjamin G Barwick, Jianping Jenny Ni, Adeboye O Osunkoya, Yuanli Chen, Wei Zhou, Siyuan Xia, Jin-Tang Dong
Journal: Journal of Clinical Investigation (2024)

Inactivation of phosphatase and tensin homolog (PTEN) is prevalent in human prostate cancer and causes high-grade adenocarcinoma with a long latency. Cancer-associated fibroblasts (CAFs) play a pivotal role in tumor progression, but it remains elusive whether and how PTEN-deficient prostate cancers reprogram CAFs to overcome the barriers for tumor progression. Here, we report that PTEN deficiency induced Krüppel-like factor 5 (KLF5) acetylation and that interruption of KLF5 acetylation orchestrated intricate interactions between cancer cells and CAFs that enhance FGF receptor 1 (FGFR1) signaling and promote tumor growth. Deacetylated KLF5 promoted tumor cells to secrete TNF-α, which stimulated inflammatory CAFs to release FGF9. CX3CR1 inhibition blocked FGFR1 activation triggered by FGF9 and sensitized PTEN-deficient prostate cancer to the AKT inhibitor capivasertib. This study reveals the role of KLF5 acetylation in reprogramming CAFs and provides a rationale for combined therapies using inhibitors of AKT and CX3CR1.
Glycosylated nanoplatforms: From glycosylation strategies to implications and opportunities for cancer theranostics
Authors: Iman Zare, Shahrzad Zirak Hassan Kiadeh, Ayşegül Varol, Tuğba Ören Varol, Mehmet Varol, Serap Sezen, Atefeh Zarepour, Ebrahim Mostafavi, Shima Zahed Nasab, Amid Rahi, Arezoo Khosravi, Ali Zarrabi
Journal: Journal of Controlled Release (2024)
New atypical epidemiological profile of parvovirus B19 revealed by molecular screening of blood donations, France, winter 2023/24
Authors: Marlène Guillet, Ariane Bas, Marjorie Lacoste, Céline Ricard, Catherine Visse, Valérie Barlet, Lucile Malard, Sophie Le Cam, Pascal Morel, Xavier de Lamballerie, Syria Laperche, Pierre Gallian
Journal: Eurosurveillance (2024)

In France, blood donations are tested in pools of 96 samples for parvovirus B19 (B19V) DNA to discard plasma for fractionation when it contains high viral loads. Between January 2015 and March 2024, B19V-positive donations decreased during the COVID-19 pandemic, followed by a strong rebound in 2023 and unusually high circulation during winter 2023/24 (ca 10 times higher December 2023-March 2024 vs the pre-pandemic period). Variations over time are probably related to measures implemented to limit SARS-CoV-2 spread.
Ongoing outbreak of hepatitis A associated with sexual transmission among men who have sex with men, Portugal, October 2023 to April 2024
Authors: Ebba Rosendal, Sebastian von Schreeb, Alexandre Gomes, Sara Lino, Berta Grau-Pujol, Sara Magalhães, Vasco Ricoca Peixoto, Carla Roque, Joana Moreno, Fernando Maltez, Fernando Almeida, Rita Sá Machado, Rui Tato Marinho, Paula Vasconcelos, Rita de Sousa, João Vieira Martins
Journal: Eurosurveillance (2024)

An outbreak of hepatitis A is ongoing in Portugal, with 71 confirmed cases from 7 October 2023 to 24 April 2024. Most cases are male, aged 18-44 years, with many identifying as men who have sex with men (MSM) and reported as suspected sexual transmission. Phylogenetic analysis identified the subgenotype IA, VRD 521-2016 strain, last observed in an MSM-associated multi-country outbreak in 2016 to 2018. We wish to alert colleagues in other countries to investigate potential similar spread.
Factors potentially contributing to the decline of the mpox outbreak in the Netherlands, 2022 and 2023
Authors: Manon R Haverkate, Inge JM Willemstein, Catharina E van Ewijk, Philippe CG Adam, Susan J Lanooij, Petra Jonker-Jorna, Colette van Bokhoven, Gini GC van Rijckevorsel, Elske Hoornenborg, Silke David, Liesbeth Mollema, Margreet J te Wierik, Jente Lange, Eelco Franz, Hester E de Melker, Eline LM Op de Coul, Susan JM Hahné
Journal: Eurosurveillance (2024)

BackgroundIn 2022 and 2023, a global outbreak of mpox affected mostly gay, bisexual and other men having sex with men (GBMSM). Outbreak control in the Netherlands included isolation, quarantine, post-exposure prophylaxis vaccination and primary preventive vaccination (PPV).AimWe describe the course of the outbreak, the vaccination programme, vaccine effectiveness (VE) of full vaccination against symptomatic disease, and trends in behaviour to generate hypotheses about factors that influenced the outbreak's decline.MethodsIn this observational study, we collected data from public health services on notified cases, number of PPV invitations and PPV doses administered. We calculated PPV uptake and coverage. Trends in behavioural data of GBMSM visiting sexual health centres were analysed for all consultations in 2022. We estimated VE using the screening method.ResultsUntil 31 December 2023, 1,294 mpox cases were reported. The outbreak peaked in early July 2022 and then declined sharply. PPV started on 25 July 2022; in total 29,851 doses were administered, 45.8% received at least one dose, 35.4% were fully vaccinated. The estimated VE was 68.2% (95% CI 4.3-89.5%). We did not observe an evident decrease in high-risk behaviour.DiscussionIt is unlikely that PPV was a driver of the outbreak's decline, as incidence started to decline well before the start of the PPV programme. The possible impact of behavioural change could not be demonstrated with the available indicators, however, the data had limitations, hampering interpretation. We hypothesise that infection-induced immunity in high-risk groups was an important factor explaining the decline.
Mpox in children and adolescents and contact follow-up in school settings in greater Paris, France, May 2022 to July 2023
Authors: Laura Reques, Lilas Mercuriali, Yassoungo Silué, Emilie Chazelle, Guillaume Spaccaferri, Annie Velter, Alexandra Mailles, Pierre Frange, Arnaud Tarantola
Journal: Eurosurveillance (2024)

BackgroundDuring the 2022 mpox outbreak in Europe, primarily affecting men who have sex with men, a limited number of cases among children and adolescents were identified. Paediatric cases from outbreaks in endemic countries have been associated with a higher likelihood of severe illness. Detailed clinical case descriptions and interventions in school settings before 2022 are limited.AimTo describe clinical characteristics of mpox cases among children (< 15 years) and adolescents (15-17 years) in the greater Paris area in France, and infection control measures in schools.MethodsWe describe all notified laboratory-confirmed and non-laboratory-confirmed cases among children and adolescents identified from May 2022 to July 2023, including demographic and clinical characterisation and infection control measures in school settings, i.e. contact tracing, contact vaccination, secondary attack rate and post-exposure vaccination uptake.ResultsNineteen cases were notified (13 children, 6 adolescents). Four adolescent cases reported sexual contact before symptom onset. Ten child cases were secondary cases of adult patients; three cases were cryptic, with vesicles on hands, arms and/or legs and one case additionally presented with genitoanal lesions. Five cases attended school during their infectious period, with 160 at-risk contacts identified, and one secondary case. Five at-risk contacts were vaccinated following exposure.ConclusionCases among children and adolescents are infrequent but require a careful approach to identify the source of infection and ensure infection control measures. We advocate a 'contact warning' strategy vs 'contact tracing' in order to prevent alarm and stigma. Low post-exposure vaccination rates are expected.
Evaluation of glomerular hemodynamic changes by sodium-glucose-transporter 2 inhibition in type 2 diabetic rats using in vivo imaging
Authors: Yoshihisa Wada, Kengo Kidokoro, Megumi Kondo, Atsuyuki Tokuyama, Hiroyuki Kadoya, Hajime Nagasu, Eiichiro Kanda, Tamaki Sasaki, David Z.I. Cherney, Naoki Kashihara
Journal: Kidney International (2024)

The mechanisms responsible for glomerular hemodynamic regulation with sodium-glucose co-transporter 2 (SGLT2) inhibitors in kidney disease due to type 2 diabetes remain unclear. Therefore, we investigated changes in glomerular hemodynamic function using an animal model of type 2 diabetes, treated with an SGLT2 inhibitor alone or in combination with a renin-angiotensin-aldosterone system inhibitor using male Zucker lean (ZL) and Zucker diabetic fatty (ZDF) rats. Afferent and efferent arteriolar diameter and single-nephron glomerular filtration rate (SNGFR) were evaluated in ZDF rats measured at 0, 30, 60, 90, and 120 minutes after the administration of a SGLT2 inhibitor (luseogliflozin). Additionally, we assessed these changes under the administration of the adenosine A1 receptor (A1aR) antagonist (8-cyclopentyl-1,3-dipropylxanthine), along with coadministration of luseogliflozin and an angiotensin II receptor blocker (ARB), telmisartan. ZDF rats had significantly increased SNGFR, and afferent and efferent arteriolar diameters compared to ZL rats, indicating glomerular hyperfiltration. Administration of luseogliflozin significantly reduced afferent vasodilatation and glomerular hyperfiltration, with no impact on efferent arteriolar diameter. Urinary adenosine levels were increased significantly in the SGLT2 inhibitor group compared to the vehicle group. A1aR antagonism blocked the effect of luseogliflozin on kidney function. Co-administration of the SGLT2 inhibitor and ARB decreased the abnormal expansion of glomerular afferent arterioles, whereas the efferent arteriolar diameter was not affected. Thus, regulation of afferent arteriolar vascular tone via the A1aR pathway is associated with glomerular hyperfiltration in type 2 diabetic kidney disease.
Timing and co-occurrence of symptoms prior to a diagnosis of light chain (AL) amyloidosis
Authors: Ashima Singh, Aniko Szabo, Qinghua Lian, Liliana Pezzin, Rodney Sparapani, Anita D’Souza
Journal: Blood Cancer Journal (2024)

Abstract It is well-established that most patients with systemic light chain (AL) amyloidosis have multi-organ involvement and are often diagnosed after a lag period of increasing symptoms. We leverage electronic health record (EHR) data from the TriNetX research network to describe the incidence, timing, and co-occurrence of precursor conditions of interests in a cohort of AL amyloidosis patients identified between October 2015-December 2020. Nineteen precursor diagnoses of interest representing features of AL amyloidosis were identified using ICD codes up to 36 months prior to AL amyloidosis diagnosis. Among 1,401 patients with at least 36 months of EHR data prior to AL amyloidosis diagnosis, 46% were females, 16% were non-Hispanic Black, and 6% were Hispanic. The median age was 71 (range, 21–91) years. The median number of precursor diagnoses was 5 with dyspnea and fatigue being the most prevalent. The time from the first occurrence of a precursor to AL diagnosis ranged from 3.2 to 21.4 months. Analyses of pairwise co-occurrence of specific diagnoses indicated a high association (Cole’s coefficient &gt;0.6) among the examined precursor diagnoses. These findings provide novel information about the timing and co-occurrence of key precursor conditions and could be used to develop algorithms for early identification of AL amyloidosis.
Autophagy inhibition mediated via an injectable and NO-releasing hydrogel for amplifying the antitumor efficacy of mild magnetic hyperthermia
Authors: Yaoben Wang, Xiaobin Chen, Zhiyong Chen, Xin Wang, Hancheng Wang, Huajuan Zhai, Jiandong Ding, Lin Yu
Journal: Bioactive Materials (2024)

While mild hyperthermia holds great potential in the treatment of solid tumors, the thermal stress-triggered self-repairing autophagy significantly compromises its efficacy. To circumvent this obstacle, an injectable hydrogel (NO-Gel) composed of thermosensitive poly(ethylene glycol)-polypeptide copolymers modified with abundant NO donors on their side chains is developed. Meanwhile, ferrimagnetic Zn