tbuckley/cabot-search huggingface dataset:
The impact of the COVID-19 vaccination programme on symptomatic and severe SARS-CoV-2 infection during a period of Omicron variant dominance in Ireland, December 2021 to March 2023
Authors: Louise Marron, Alberto Mateo-Urdiales, Joan O’Donnell, Eve Robinson, Lisa Domegan
Journal: Eurosurveillance (2024)

Background As Ireland prepared for an autumn 2023 COVID-19 vaccination booster campaign, there was concern that vaccine fatigue would affect uptake, which has been abating. Aim This study aimed to quantify the direct impact of the COVID-19 vaccination programme in Ireland on averted COVID-19-related outcomes including symptomatic presentations to primary care/community testing centres, emergency department (ED) presentations, hospitalisations, intensive care unit (ICU) admissions and deaths, in individuals aged ≥ 50 years, during Omicron dominance. Methods We conducted a retrospective observational COVID-19 vaccine impact study in December 2021–March 2023 in Ireland. We used national data on notified outcomes and vaccine coverage, as well as vaccine effectiveness (VE) estimates, sourced from the World Health Organization’s live systematic review of VE, to estimate the count and prevented fraction of outcomes in ≥ 50-year-olds averted by the COVID-19 vaccination programme in this age group. Results The COVID-19 vaccination programme averted 48,551 symptomatic COVID-19 presentations to primary care/community testing centres (36% of cases expected in the absence of vaccination), 9,517 ED presentations (53% of expected), 102,160 hospitalisations (81% of expected), 3,303 ICU admissions (89% of expected) and 15,985 deaths (87% of expected). Conclusions When Omicron predominated, the COVID-19 vaccination programme averted symptomatic and severe COVID-19 cases, including deaths due to COVID-19. In line with other international vaccine impact studies, these findings emphasise the benefits of COVID-19 vaccination for population health and the healthcare system and are relevant for informing COVID-19 booster vaccination programmes, pandemic preparedness and communicating the reason for and importance of COVID-19 vaccination in Ireland and internationally.
Specific CD4+ T cell phenotypes associate with bacterial control in people who ‘resist’ infection with Mycobacterium tuberculosis
Authors: Meng Sun, Jolie M Phan, Nathan S Kieswetter, Huang Huang, Krystle K Q Yu, Malisa T Smith, Yiran E Liu, Chuanqi Wang, Sanjana Gupta, Gerlinde Obermoser, Holden Terry Maecker, Akshaya Krishnan, Sundari Suresh, Neha Gupta, Mary Rieck, Peter Acs, Mustafa Ghanizada, Shin-Heng Chiou, Purvesh Khatri, W Henry Boom, Thomas R Hawn, Catherine M Stein, Harriet Mayanja-Kizza, Mark M Davis, Chetan Seshadri
Journal: Nature Immunology (2024)

Abstract A subset of individuals exposed to Mycobacterium tuberculosis ( Mtb ) that we refer to as ‘resisters’ (RSTR) show evidence of IFN-γ − T cell responses to Mtb -specific antigens despite serially negative results on clinical testing. Here we found that Mtb -specific T cells in RSTR were clonally expanded, confirming the priming of adaptive immune responses following Mtb exposure. RSTR CD4 + T cells showed enrichment of T H 17 and regulatory T cell-like functional programs compared to Mtb -specific T cells from individuals with latent Mtb infection. Using public datasets, we showed that these T H 17 cell-like functional programs were associated with lack of progression to active tuberculosis among South African adolescents with latent Mtb infection and with bacterial control in nonhuman primates. Our findings suggested that RSTR may successfully control Mtb following exposure and immune priming and established a set of T cell biomarkers to facilitate further study of this clinical phenotype.
Pathogen prioritisation for wastewater surveillance ahead of the Paris 2024 Olympic and Paralympic Games, France
Authors: Laila Toro, Henriette de Valk, Laura Zanetti, Caroline Huot, Arnaud Tarantola, Nelly Fournet, Laurent Moulin, Ali Atoui, Benoît Gassilloud, Damien Mouly, Frédéric Jourdain
Journal: Eurosurveillance (2024)

BackgroundWastewater surveillance is an effective approach to monitor population health, as exemplified by its role throughout the COVID-19 pandemic.AimThis study explores the possibility of extending wastewater surveillance to the Paris 2024 Olympic and Paralympic Games, focusing on identifying priority pathogen targets that are relevant and feasible to monitor in wastewater for these events.MethodsA list of 60 pathogens of interest for general public health surveillance for the Games was compiled. Each pathogen was evaluated against three inclusion criteria: (A) analytical feasibility; (B) relevance, i.e. with regards to the specificities of the event and the characteristics of the pathogen; and (C) added value to inform public health decision-making. Analytical feasibility was assessed through evidence from peer-reviewed publications demonstrating the detectability of pathogens in sewage, refining the initial list to 25 pathogens. Criteria B and C were evaluated via expert opinion using the Delphi method. The panel consisting of some 30 experts proposed five additional pathogens meeting criterion A, totalling 30 pathogens assessed throughout the three-round iterative questionnaire. Pathogens failing to reach 70% group consensus threshold underwent further deliberation by a subgroup of experts.ResultsSix priority targets suitable for wastewater surveillance during the Games were successfully identified: poliovirus, influenza A virus, influenza B virus, mpox virus, SARS-CoV-2 and measles virus.ConclusionThis study introduced a model framework for identifying context-specific wastewater surveillance targets for a mass gathering. Successful implementation of a wastewater surveillance plan for Paris 2024 could incentivise similar monitoring efforts for other mass gatherings globally.
Lycium Barbarum Polysaccharide‐Derived Nanoparticles Protect Visual Function by Inhibiting RGC Ferroptosis and Microglial Activation in Retinal Ischemia‒Reperfusion Mice
Authors: Yueqi Ni, Yuanyuan Hu, Lijia Zhu, Xulin Jiang, Hong Zhang, Jia Liu, Yin Zhao
Journal: Advanced Healthcare Materials (2024)

Retinal ischemia‒reperfusion (IR) is a major contributor to vision impairment and irreversible vision loss due to retinal ganglion cell (RGC) injury or loss. Contemporary therapeutic approaches predominantly focus on the amelioration of symptoms rather than addressing the fundamental etiological factors. Oxidative stress is a notable feature and an important mediator of IR damage. Lycium barbarum polysaccharide (LBP), the main active ingredient of Lycium barbarum, has various pharmacological effects, including antioxidation, immunoregulation, and neuroprotective effects. In this study, the ROS-consumable moiety phenylboronic acid pinacol ester (PBA) is introduced to LBP molecules, which can self-assemble into nanoparticles in aqueous solution. This nanoparticle (termed PLBP) can reduce the cellular ROS levels and enhance the antioxidant capability of RGCs by activating the NRF2 pathway, thus protecting RGCs from ferroptosis and preserving visual function in response to IR injury. PLBP also reduces neuroinflammation by inhibiting the ability of microglia to phagocytose, migrate, secrete inflammatory cytokines, and activate the NF-κB pathway. In conclusion, this approach can be used as an inspiration for the future development of neuroprotective drugs.
Ambient Moisture‐Driven Self‐Powered Iontophoresis Patch for Enhanced Transdermal Drug Delivery
Authors: Zhenyou Ge, Wenshang Guo, Ye Tao, Shixin Li, Xiao Li, Weiyu Liu, Xiangyu Meng, Ruizhe Yang, Rui Xue, Yukun Ren
Journal: Advanced Healthcare Materials (2024)

Abstract Iontophoretic transdermal drug delivery (TDD) devices are known to enhance the transdermal transport of drugs. However, conventional transdermal iontophoretic devices require external power sources, wired connections, or mechanical parts, which reduce the comfort level for patients during extended use. In this work, a self‐powered, wearable transdermal iontophoretic patch (TIP) is proposed by harvesting ambient humidity for energy generation, enabling controlled TDD. This patch primarily uses moist‐electric generators (MEGs) as its power source, thus obviating the need for complex power management modules and mechanical components. A single MEG unit can produce an open‐circuit voltage of 0.80 V and a short‐circuit current of 11.65 µA under the condition of 80% relative humidity. Amplification of the electrical output is feasible by connecting multiple generator units in series and parallel, facilitating the powering of certain commercial electronic devices. Subsequently, the MEG array is integrated with the TDD circuit to create the wearable TIP. After 20 min of application, the depth of drug penetration through the skin is observed to increase threefold. The effective promotion effect of TIP on the transdermal delivery of ionized drugs is corroborated by simulations and experiments. This wearable TIP offers a simple, noninvasive solution for TDD.
Injectable Gelled Multiple Emulsion for Glucose‐Responsive Insulin Delivery
Authors: Kofi Oti Boakye‐Yiadom, Qijing Chen, Yilong Teng, Chenshuang Zhang, Bin Hu, Xue‐Qing Zhang
Journal: Advanced Healthcare Materials (2024)

Abstract A glucose‐responsive insulin delivery system that sustains blood glucose equilibrium for an extended duration can address the low therapeutic window of insulin in diabetes treatment. Herein, insulin is loaded in a water‐in‐oil‐in‐water (W 1 /O/W 2 ) gelled multiple emulsion using poly (4‐vinylphenylboronic acid) (PVPBA) homopolymer as an effective emulsifier. The gelled multiple emulsion exhibits a high encapsulation efficiency (99%), enhanced stability and remarkable shear‐thinning behavior, making it easy to inject. Under hyperglycemic conditions, the gelled emulsion system instantly binds to glucose molecules and reduces the hydrogen bonds of the PVPBA homopolymer, resulting in insulin release. In a streptozotocin‐induced type 1 diabetic mouse model, a single subcutaneous injection of the gelled emulsion rapidly responds to high blood glucose concentration (BGC) and release insulin in a glucose dependent manner, thus prolonging the antihyperglycemic effect compared with free insulin.
Orchestration of antiviral responses within the infected central nervous system
Authors: Andreas Pavlou, Felix Mulenge, Olivia Luise Gern, Lena Mareike Busker, Elisabeth Greimel, Inken Waltl, Ulrich Kalinke
Journal: Cellular and Molecular Immunology (2024)

Abstract Many newly emerging and re-emerging viruses have neuroinvasive potential, underscoring viral encephalitis as a global research priority. Upon entry of the virus into the CNS, severe neurological life-threatening conditions may manifest that are associated with high morbidity and mortality. The currently available therapeutic arsenal against viral encephalitis is rather limited, emphasizing the need to better understand the conditions of local antiviral immunity within the infected CNS. In this review, we discuss new insights into the pathophysiology of viral encephalitis, with a focus on myeloid cells and CD8 + T cells, which critically contribute to protection against viral CNS infection. By illuminating the prerequisites of myeloid and T cell activation, discussing new discoveries regarding their transcriptional signatures, and dissecting the mechanisms of their recruitment to sites of viral replication within the CNS, we aim to further delineate the complexity of antiviral responses within the infected CNS. Moreover, we summarize the current knowledge in the field of virus infection and neurodegeneration and discuss the potential links of some neurotropic viruses with certain pathological hallmarks observed in neurodegeneration.
Children with eosinophilic esophagitis non‐responsive to combination therapy have distinct esophageal transcriptomic and microbiome profile
Authors: Girish Hiremath, Yash Choksi, Hernan Correa, Justin Jacobse, Suman R. Das, Siyuan Ma, Jeremy A. Goettel, Seesandra V. Rajagopala
Journal: Allergy (2024)

Abstract Background A combination of proton‐pump inhibitors (PPI) and topical steroids (TS) is used to treat children with eosinophilic esophagitis (EoE). However, a subset of children do not respond to this combination therapy. We aimed to identify the esophageal transcriptional, cell composition, and microbial differences between the non‐responders (EoE‐PPI‐TSnr; n = 7) and responders (EoE‐PPI‐TSr; n = 7) to the combination therapy for EoE and controls ( n = 9) using metatranscriptomics. Methods Differential gene expression analysis was used to identify transcriptional differences, validated using the EoE diagnostic panel (EDP). Deconvolution analysis was performed to identify differences in their cell type composition. Microbiome analysis was conducted from esophageal biopsies RNAseq data, and microbial abundance was correlated with esophageal gene expression. Results In all, 3164 upregulated and 3154 downregulated genes distinguished EoE‐PPI‐TSnr from EoE‐PPI‐TSr. Eosinophilic inflammatory response, cytokine signaling, and collagen formation pathways were significantly upregulated in EoE‐PPI‐TSnr. There was a 56% overlap in dysregulated genes between EoE‐PPI‐TSnr and EDP, with a perfect agreement in the directionality of modulation. Eosinophils, dendritic cells (DCs), immature DCs, megakaryocytic‐erythroid progenitors, and T helper type 1 cells were significantly higher in EoE‐PPI‐TSnr. There was no significant difference in microbiome diversity. The relative abundance of Fusobacterium sp. and Acinetobacter sp. notably differed in EoE‐PPI‐TSnr and correlated with the key pathways. Conclusion Our results provide critical insights into the molecular, cellular, and microbial factors associated with the lack of response to PPI and TS combination therapy in children with EoE. This study advances our understanding of the pathobiology of EoE while guiding personalized treatment strategies.
Prognostic and therapeutic implications of TP53 expression in chronic myelomonocytic leukemia
Authors: Yu-Hung Wang, Chien-Chin Lin, Kristian Gurashi, Chi-Yuan Yao, Andres Jerez, Hsin-An Hou, Wen-Chien Chou, Hwei-Fang Tien, Kiran Batta, Daniel H. Wiseman
Journal: Blood Cancer Journal (2024)
Biofabrication and Monitoring of a 3D Printed Skin Model for Melanoma
Authors: Paula Vázquez‐Aristizabal, Malou Henriksen‐Lacey, Clara García‐Astrain, Dorleta Jimenez de Aberasturi, Judith Langer, Claudia Epelde, Lucio Litti, Luis M. Liz‐Marzán, Ander Izeta
Journal: Advanced Healthcare Materials (2024)

Abstract There is an unmet need for in vitro cancer models that emulate the complexity of human tissues. 3D‐printed solid tumor micromodels based on decellularized extracellular matrices (dECMs) recreate the biomolecule‐rich matrix of native tissue. Herein a 3D in vitro metastatic melanoma model that is amenable for drug screening purposes and recapitulates features of both the tumor and the skin microenvironment is described. Epidermal, basement membrane, and dermal biocompatible inks are prepared by means of combined chemical, mechanical, and enzymatic processes. Bioink printability is confirmed by rheological assessment and bioprinting, and bioinks are subsequently combined with melanoma cells and dermal fibroblasts to build complex 3D melanoma models. Cells are tracked by confocal microscopy and surface‐enhanced Raman spectroscopy (SERS) mapping. Printed dECMs and cell tracking allow modeling of the initial steps of metastatic disease, and may be used to better understand melanoma cell behavior and response to drugs.
Prediction of melanoma metastasis using dermatoscopy deep features: an international multicentre cohort study
Authors: Konstantinos Lallas, Panagiota Spyridonos, Harald Kittler, Philipp Tschandl, Konstantinos Liopyris, Giuseppe Argenziano, Renato Bakos, Ralph Braun, Horacio Cabo, Emi Dika, Josep Malvehy, Ash Marghoob, Susana Puig, Alon Scope, Wilhelm Stolz, Tanaka Masaru, Luc Thomas, Zoe Apalla, Efstratios Vakirlis, Iris Zalaudek, Aimilios Lallas
Journal: British Journal of Dermatology (2024)

Whether dermatoscopy deep features could serve as biomarker for the prediction of melanoma metastasis remains an underexplored area in medical research. In this cohort of 712 patients from 10 centres in 3 continents, a support vector machine classifier that analysed deep features on dermatoscopic images demonstrated similar prognostic performance for metastasis in terms of AUC and true positive rate to current benchmarks of melanoma staging, namely Breslow thickness and ulceration. Deep features derived from dermatoscopy could predict early-stage melanomas with high metastatic potential, tailoring further treatment strategies.
ERBB2 amplification in gastric cancer: a genomic insight into ethnic disparities
Authors: Muhammad Bilal Mirza, Jungyoon Choi, Paula Marincola Smith, Jordan J Baechle, Chandrasekhar Padmanabhan, Andreana N Holowatyj, Shailja C Shah, Xingyi Guo, Kamran Idrees
Journal: JNCI Journal of the National Cancer Institute (2024)

Abstract Overall, gastric adenocarcinoma (GC) incidence rates have declined in recent years, but racial and ethnic disparities persist. Individuals who identify as Hispanic/Spanish/Latino are diagnosed with GC at younger ages and have poorer outcomes than non-Hispanic individuals. However, our understanding of GC biology across racial/ethnic groups remains limited. We assessed tumor genomic patterns by race/ethnicity among 1019 patients with primary GC in the American Association for Cancer Research (AACR) Project GENIE Consortium. Hispanic individuals presented with significantly higher rates of ERBB2/HER2 amplification vs other racial/ethnic groups (Hispanic: 13.9% vs 9.8% non-Hispanic White, 8.1% non-Hispanic Asian, and 11.0% non-Hispanic Black; P &amp;lt; .001, FDR adjusted q &amp;lt; 0.001). Hispanic patients also had higher odds of an ERBB2 amplification vs non-Hispanic Whites in adjusted models (OR = 2.52, 95%CI = 1.20 to 5.33, P = .015). These findings underscore the important role of genomic factors in GC disparities. Ensuring equitable access to genomic profiling and targeted therapies, such as trastuzumab for HER2-overexpressing GC, is a promising avenue to mitigate GC disparities and improve outcomes.
Cerebellum in Alzheimer's disease and other neurodegenerative diseases: an emerging research frontier
Authors: Cui Yang, Guangdong Liu, Xi Chen, Weidong Le
Journal: MedComm (2024)

Abstract The cerebellum is crucial for both motor and nonmotor functions. Alzheimer's disease (AD), alongside other dementias such as vascular dementia (VaD), Lewy body dementia (DLB), and frontotemporal dementia (FTD), as well as other neurodegenerative diseases (NDs) like Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and spinocerebellar ataxias (SCA), are characterized by specific and non‐specific neurodegenerations in central nervous system. Previously, the cerebellum's significance in these conditions was underestimated. However, advancing research has elevated its profile as a critical node in disease pathology. We comprehensively review the existing evidence to elucidate the relationship between cerebellum and the aforementioned diseases. Our findings reveal a growing body of research unequivocally establishing a link between the cerebellum and AD, other forms of dementia, and other NDs, supported by clinical evidence, pathological and biochemical profiles, structural and functional neuroimaging data, and electrophysiological findings. By contrasting cerebellar observations with those from the cerebral cortex and hippocampus, we highlight the cerebellum's distinct role in the disease processes. Furthermore, we also explore the emerging therapeutic potential of targeting cerebellum for the treatment of these diseases. This review underscores the importance of the cerebellum in these diseases, offering new insights into the disease mechanisms and novel therapeutic strategies.
An Orphan Gene Enhances Male Reproductive Success in <i>Plutella xylostella</i>
Authors: Qian Zhao, Yahong Zheng, Yiying Li, Lingping Shi, Jing Zhang, Dongna Ma, Minsheng You
Journal: Molecular Biology and Evolution (2024)

Abstract Plutella xylostella exhibits exceptional reproduction ability, yet the genetic basis underlying the high reproductive capacity remains unknown. Here, we demonstrate that an orphan gene, lushu, which encodes a sperm protein, plays a crucial role in male reproductive success. Lushu is located on the Z chromosome and is prevalent across different P. xylostella populations worldwide. We subsequently generated lushu mutants using transgenic CRISPR/Cas9 system. Knockout of Lushu results in reduced male mating efficiency and accelerated death in adult males. Furthermore, our findings highlight that the deficiency of lushu reduced the transfer of sperms from males to females, potentially resulting in hindered sperm competition. Additionally, the knockout of Lushu results in disrupted gene expression in energy-related pathways and elevated insulin levels in adult males. Our findings reveal that male reproductive performance has evolved through the birth of a newly evolved, lineage-specific gene with enormous potentiality in fecundity success. These insights hold valuable implications for identifying the target for genetic control, particularly in relation to species-specific traits that are pivotal in determining high levels of fecundity.
Lipid-coated gold nanorods for photoimmunotherapy of primary breast cancer and the prevention of metastasis
Authors: So-Jung Kim, Hae-Bin Park, Eun-Koung An, Dayoung Ryu, Wei Zhang, Chan-Gi Pack, HyunCheol Kim, Minseok Kwak, Wonpil Im, Ja-Hyoung Ryu, Peter C.W. Lee, Jun-O Jin
Journal: Journal of Controlled Release (2024)
Automated segmentation of brain metastases with deep learning: A multi-center, randomized crossover, multi-reader evaluation study
Authors: Xiao Luo, Yadi Yang, Shaohan Yin, Hui Li, Ying Shao, Dechun Zheng, Xinchun Li, Jianpeng Li, Weixiong Fan, Jing Li, Xiaohua Ban, Shanshan Lian, Yun Zhang, Qiuxia Yang, Weijing Zhang, Cheng Zhang, Lidi Ma, Yingwei Luo, Fan Zhou, Shiyuan Wang, Cuiping Lin, Jiao Li, Ma Luo, Jianxun He, Guixiao Xu, Yaozong Gao, Dinggang Shen, Ying Sun, Yonggao Mou, Rong Zhang, Chuanmiao Xie
Journal: Neuro-Oncology (2024)

Abstract Background Artificial intelligence has been proposed for brain metastasis (BM) segmentation but it has not been fully clinically validated. The aim of this study was to develop and evaluate a system for BM segmentation. Methods A deep-learning-based BM segmentation system (BMSS) was developed using contrast-enhanced MR images from 488 patients with 10338 brain metastases. A randomized crossover, multi-reader study was then conducted to evaluate the performance of the BMSS for BM segmentation using data prospectively collected from 50 patients with 203 metastases at 5 centers. Five radiology residents and 5 attending radiologists were randomly assigned to contour the same prospective set in assisted and unassisted modes. Aided and unaided Dice similarity coefficients (DSCs) and contouring times per lesion were compared. Results The BMSS alone yielded a median DSC of 0.91 (95% confidence interval, 0.90–0.92) in the multi-center set and showed comparable performance between the internal and external sets (P = .67). With BMSS assistance, the readers increased the median DSC from 0.87 (0.87–0.88) to 0.92 (0.92–0.92) (P &amp;lt; .001) with a median time saving of 42% (40–45%) per lesion. Resident readers showed a greater improvement than attending readers in contouring accuracy (improved median DSC, 0.05 [0.05–0.05] vs 0.03 [0.03–0.03]; P &amp;lt; .001), but a similar time reduction (reduced median time, 44% [40–47%] vs 40% [37–44%]; P = .92) with BMSS assistance. Conclusions The BMSS can be optimally applied to improve the efficiency of brain metastasis delineation in clinical practice.