tbuckley/cabot-search huggingface dataset:
Long-term gastrointestinal and hepatobiliary outcomes of COVID-19: A multinational population-based cohort study from South Korea, Japan, and the UK
Authors: Kwanjoo Lee, Jaeyu Park, Jinseok Lee, Myeongcheol Lee, Hyeon Jin Kim, Yejun Son, Sang Youl Rhee, Lee Smith, Masoud Rahmati, Jiseung Kang, Hayeon Lee, Yeonjung Ha, Dong Keon Yon
Journal: Clinical and Molecular Hepatology (2024)

Background/Aims: Considering emerging evidence on long COVID, comprehensive analyses of the post-acute complications of SARS-CoV-2 infection in the gastrointestinal and hepatobiliary systems are needed. We aimed to investigate the impact of COVID-19 on the long-term risk of gastrointestinal and hepatobiliary diseases and other digestive abnormalities.Methods: We used three large-scale population-based cohorts: the Korean cohort (discovery cohort), the Japanese cohort (validation cohort-A), and the UK Biobank (validation cohort-B). A total of 10,027,506 Korean, 12,218,680 Japanese, and 468,617 UK patients aged ≥20 years who had SARS-CoV-2 infection between 2020 and 2021 were matched to non-infected controls. Seventeen gastrointestinal and eight hepatobiliary outcomes as well as nine other digestive abnormalities following SARS-CoV-2 infection were identified and compared with controls.Results: The discovery cohort revealed heightened risks of gastrointestinal diseases (HR 1.15; 95% CI 1.08–1.22), hepatobiliary diseases (HR 1.30; 95% CI 1.09–1.55), and other digestive abnormalities (HR 1.05; 95% CI 1.01–1.10) beyond the first 30 days of infection, after exposure-driven propensity score-matching. The risk was pronounced according to the COVID-19 severity. The SARS-CoV-2 vaccination was found to lower the risk of gastrointestinal diseases but did not affect hepatobiliary diseases and other digestive disorders. The results derived from validation cohorts were consistent. The risk profile was most pronounced during the initial 3 months; however, it persisted for &gt;6 months in validation cohorts, but not in the discovery cohort.Conclusions: The incidence of gastrointestinal disease, hepatobiliary disease, and other digestive abnormalities increased in patients with SARS-CoV-2 infection during the post-acute phase.
Intraoperative Cavity Local Delivery System with NETs‐Specific Drug Release for Post‐Breast Cancer Surgery Recurrence Correction
Authors: Wan‐Fang Zhu, Wen‐Jing Ji, Qiu‐Yuan Wang, Wei Qu, Feng Feng, Ling‐Fei Han, Jing‐Wei Xue, Fu‐Lei Liu, Wen‐Yuan Liu
Journal: Advanced Healthcare Materials (2024)

Postoperative breast cancer recurrence is tricky due to the limited therapeutic options. Transforming growth factors-β (TGF-β) is vital in promoting postoperative tumor recurrence. However, conventional blocking strategies fail to satisfy both bio-safety and sufficient relapse correction. Neutrophil extracellular traps (NETs) are essential for the spatiotemporal dynamics of TGF-β at tumor-resection sites, whose unique mechanism for local TGF-β amplification could remarkably increase the risk of relapse after surgery. Herein, the principle of NETs formation is ingeniously utilized to construct a surgical residual cavity hydrogel that mimics NETs formation. The hydrogel is prepared based on the electrostatic interaction between histidine (His) and sodium alginate (Alg). Then, arginine deiminase 4 (PAD4) protein is released during NETs formation. Simultaneously, the electrical property of His in hydrogel changes automatically, which further lead to promising localized release of anti-TGF-β. The hydrogel system can realize specific and selective drug release at targeted NETs site over a prolonged period while exhibiting excellent biocompatibility. Superior breast cancer recurrence inhibition is achieved by suppressing TGF-β and related indicators, impeding epithelial-mesenchymal transition (EMT) progression, and rectifying the locally exacerbated immunosuppressive environment within NETs. The novel NETs local microenvironment drug release functional hydrogel will provide inspiration for postoperative recurrence correction strategies.
Analysis of Glucose Responsive Glucagon Therapeutics using Computational Models of the Glucoregulatory System
Authors: Ali A. Alizadehmojarad, Sungyun Yang, Xun Gong, Michael S. Strano
Journal: Advanced Healthcare Materials (2024)

Abstract Glucose‐responsive glucagon (GRG) therapeutics are a promising technology for reducing the risk of severe hypoglycemia as a complication of diabetes mellitus. Herein, the performance of candidate GRGs in the literature by modeling the kinetics of activation and connecting them as input into physiological glucoregulatory models is evaluated and projected the two distinct GRG designs, experimental results reported in Wu et al. (GRG‐I) and Webber et al. (GRG‐II) is considered. Both are evaluated using a multi‐compartmental glucoregulatory model (IMPACT) and used to compare in‐vivo experimental data of therapeutic performance in rats and mice. For GRG‐I and GRG‐II, the total integrated glucose material balances are overestimated by 41.5% ± 14% and underestimated by 24.8% ± 16% compared to in‐vivo time‐course data, respectively. These large differences to the relatively simple computational descriptions of glucagon dynamics in the model, which underscores the urgent need for improved glucagon models is attributed. Additionally, therapeutic insulin and glucagon infusion pumps are modeled for type 1 diabetes mellitus (T1DM) human subjects to extend the results to additional datasets. These observations suggest that both the representative physiological and non‐physiological models considered in this work require additional refinement to successfully describe clinical data that involve simultaneous, coupled insulin, glucose, and glucagon dynamics.
Self‐Produced O<sub>2</sub> CNs‐Based Nanocarriers of DNA Hydrophobization Strategy Triggers Photodynamic and Mitochondrial‐Derived Ferroptosis for Hepatocellular Carcinoma Combined Treatment
Authors: Ming‐Xuan Liu, Yan‐Chao Liu, Yu‐Ting Cai, Ying‐Ying Gu, Ya‐Qi Zhu, Nan Zhang, Wei‐Zhong Zhu, Yong‐Hong Liu, Lei Yu, Qi‐Tao Zhang, Xiao‐Ling Zhang
Journal: Advanced Healthcare Materials (2024)

Abstract Hypoxia can aggravate tumor occurrence, development, invasion, and metastasis, and greatly inhibit the photodynamic therapy (PDT) effect. Herein, carbon nitride (CNs)‐based DNA and photosensitizer co‐delivery systems (BPSCNs) with oxygen‐producing functions are developed to address this problem. Selenide glucose (Seglu) is used as the dopant to prepare red/NIR‐active CNs (SegluCNs). The tumor‐targeting unit Bio‐PEG 2000 is utilized to construct BPSCNs nanoparticles through esterification reactions. Furthermore, DNA hydrophobization is realized via mixing P53 gene with a positively charged mitochondrial‐targeted near‐infrared (NIR) emitting photosensitizer (MTTPY), which is encapsulated in non‐cationic BPSCNs for synergistic delivery. Ester bonds in BPSCNs@MTTPY‐P53 complexes can be disrupted by lipase in the liver to facilitate P53 release, upregulated P53 expression, and promoted HIF‐1α degradation in mitochondria. In addition, the oxygen produced by the complexes improved the hypoxic microenvironment of hepatocellular carcinoma (HCC), synergistically downregulated HIF‐1α expression in mitochondria, promoted mitochondrial‐derived ferroptosis and enhanced the PDT effect of the MTTPY unit. Both in vivo and in vitro experiments indicated that the transfected P53‐DNA, produced O 2 and ROS by these complexes synergistically led to mitochondrial‐derived ferroptosis in hepatoma cells through the HIF‐1α/SLC7A11 pathway, and completely avoiding PDT resistance caused by hypoxia, exerting a significant therapeutic role in HCC treatment.
Selenium Nanoparticles Synergize with a KRAS Nanovaccine against Breast Cancer
Authors: Cláudio Ferro, Ana I. Matos, Luigia Serpico, Flavia Fontana, Jacopo Chiaro, Carmine D'Amico, Alexandra Correia, Risto Koivula, Marianna Kemell, Maria Manuela Gaspar, Rita C. Acúrcio, Vincenzo Cerullo, Hélder A. Santos, Helena F. Florindo
Journal: Advanced Healthcare Materials (2024)

Selenium (Se) is an element crucial for human health, known for its anticancer properties. Although selenium nanoparticles (SeNPs) have shown lower toxicity and higher biocompatibility than other Se compounds, bare SeNPs are unstable in aqueous solutions. In this study, several materials, including bovine serum albumin (BSA), chitosan, polymethyl vinyl ether-alt-maleic anhydride, and tocopherol polyethylene glycol succinate, are explored to develop stable SeNPs and further evaluate their potential as candidates for cancer treatment. All optimized SeNP are spherical, <100 nm, and with a narrow size distribution. BSA-stabilized SeNPs produced under acidic conditions present the highest stability in medium, plasma, and at physiological pH, maintaining their size ≈50-60 nm for an extended period. SeNPs demonstrate enhanced toxicity in cancer cell lines while sparing primary human dermal fibroblasts, underscoring their potential as effective anticancer agents. Moreover, the combination of BSA-SeNPs with a nanovaccine results in a strong tumor growth reduction in an EO771 breast cancer mouse model, demonstrating a three-fold decrease in tumor size. This synergistic anticancer effect not only highlights the role of SeNPs as effective anticancer agents but also offers valuable insights for developing innovative combinatorial approaches using SeNPs to improve the outcomes of cancer immunotherapy.
<i>Lactobacillus acidophilus</i> ameliorates cholestatic liver injury through inhibiting bile acid synthesis and promoting bile acid excretion
Authors: Lingyi Wu, Jianchun Zhou, An Zhou, Yuanyuan Lei, Li Tang, Shiping Hu, Sumin Wang, Xu Xiao, Qiao Chen, Dianji Tu, Cheng Lu, Yi Lai, Yiding Li, Xiao Zhang, Bo Tang, Shiming Yang
Journal: Gut Microbes (2024)

Gut microbiota dysbiosis is involved in cholestatic liver diseases. However, the mechanisms remain to be elucidated. The purpose of this study was to examine the effects and mechanisms of
Nanoplasmonic Rapid Antimicrobial‐Resistance Point‐of‐Care Identification Device: RAPIDx
Authors: Jong‐Hwan Lee, Jihwan Song, SoonGweon Hong, Yun Kim, Minsun Song, Byungrae Cho, Tiffany Wu, Lee W. Riley, Ulf Landegren, Luke P. Lee
Journal: Advanced Healthcare Materials (2024)

The emergence of antibiotic resistance has become a global health crisis, and everyone must arm themselves with wisdom to effectively combat the "silent tsunami" of infections that are no longer treatable with antibiotics. However, the overuse or inappropriate use of unnecessary antibiotics is still routine for administering them due to the unavailability of rapid, precise, and point-of-care assays. Here, a rapid antimicrobial-resistance point-of-care identification device (RAPIDx) is reported for the accurate and simultaneous identification of bacterial species (genotype) and target enzyme activity (phenotype). First, a contamination-free active target enzyme is extracted via the photothermal lysis of preconcentrated bacteria cells on a nanoplasmonic functional layer on-chip. Second, the rapid, precise identification of pathogens is achieved by the photonic rolling circle amplification of DNA on a chip. Third, the simultaneous identification of bacterial species (genotype) and target enzyme activity (phenotype) is demonstrated within a sample-to-answer 45 min operation via the RAPIDx. It is believed that the RAPIDx will be a valuable method for solving the bottleneck of employing on-chip nanotechnology for antibiotic-resistant bioassay and other infectious diseases.
Resting-State Functional Connectivity of the Amygdala in Autism: A Preregistered Large-Scale Study
Authors: Dorit Kliemann, Paola Galdi, Avery L. Van De Water, Brandon Egger, Dorota Jarecka, Ralph Adolphs, Satrajit S. Ghosh
Journal: American Journal of Psychiatry (2024)

Three leading neurobiological hypotheses about autism spectrum disorder (ASD) propose underconnectivity between brain regions, atypical function of the amygdala, and generally higher variability between individuals with ASD than between neurotypical individuals. Past work has often failed to generalize, because of small sample sizes, unquantified data quality, and analytic flexibility. This study addressed these limitations while testing the above three hypotheses, applied to amygdala functional connectivity.
Clinical and pathological characterization of Tebentafusp-associated skin toxicity – a cohort study with 33 patients.
Authors: Dirk Tomsitz, Katrin Kerl, Lars Einar French, Lucie Heinzerling
Journal: Journal of the American Academy of Dermatology (2024)

Tebentafusp is a novel treatment for patients with metastatic uveal melanoma and often causes cutaneous side effects.
Favipiravir for COVID-19 in adults in the community in PRINCIPLE, an open-label, randomised, controlled, adaptive platform trial of short- and longer-term outcomes
Authors: FD Richard Hobbs, Oghenekome A. Gbinigie-Thompson, Milensu Shanyinde, Ly-Mee Yu, Victoria Harris, Jienchi Dorward, Gail Hayward, Benjamin R. Saville, Nicholas S. Berry, Philip H. Evans, Nicholas PB Thomas, Mahendra G. Patel, Duncan Richards, Oliver Van Hecke, Michelle A. Detry, Christina T. Saunders, Mark Fitzgerald, Jared Robinson, Charlotte Latimer-Bell, Julie Allen, Emma Ogburn, Jenna Grabey, Simon de Lusignan, Monique Andersson, Paul Little, Christopher C. Butler
Journal: Journal of Infection (2024)

Evidence for the effect of favipiravir treatment of acute COVID-19 on recovery, hospital admissions and longer-term outcomes in community settings is limited.
Adenovirus vaccine targeting kinases induces potent antitumor immunity in solid tumors
Authors: Fei Zhu, Zheng Lu, Wenjing Tang, Guangya Zhao, Yingxiang Shao, Bowen Lu, Jiage Ding, Yanyan Zheng, Lin Fang, Huizhong Li, Gang Wang, Renjin Chen, Junnian Zheng, Dafei Chai
Journal: Journal for ImmunoTherapy of Cancer (2024)

Targeting kinases presents a potential strategy for treating solid tumors; however, the therapeutic potential of vaccines targeting kinases remains uncertain.
Nanoparticles targeting immune checkpoint protein VISTA induce potent antitumor immunity
Authors: Taylor J Moon, Hieu Minh Ta, Anubhuti Bhalotia, Kai E Paulsen, Diarmuid W Hutchinson, Gabrielle M Arkema, Andrew S Choi, Michiko G Haynie, Laolu Ogunnaike, Margee Dever, Li Lily Wang, Efstathios Karathanasis
Journal: Journal for ImmunoTherapy of Cancer (2024)

Immune checkpoint protein V-domain immunoglobulin suppressor of T cell activation (VISTA) controls antitumor immunity and is a valuable target for cancer immunotherapy. Previous mechanistic studies have indicated that VISTA impairs the toll-like receptor (TLR)-mediated activation of myeloid antigen-presenting cells, promoting the expansion of myeloid-derived suppressor cells, and suppressing tumor-reactive cytotoxic T cell function.
Tumor microenvironment biomarkers predicting pathological response to neoadjuvant chemoimmunotherapy in locally advanced esophageal squamous cell carcinoma: post-hoc analysis of a single center, phase 2 study
Authors: Tingting Feng, Qian Li, Rui Zhu, Chang Yu, Liwei Xu, Lisha Ying, Canming Wang, Weiming Xu, Jinchao Wang, Jing Zhu, Minran Huang, Chenyang Xu, Jiaoyue Jin, Xiaotian Zhang, Tingting Lu, Ying Yang, Changbin Zhu, Qixun Chen, Dan Su
Journal: Journal for ImmunoTherapy of Cancer (2024)

Neoadjuvant chemoimmunotherapy has a promising effect on locally advanced esophageal squamous cell carcinoma (ESCC). However, reliable biomarkers robustly predicting therapeutic response are still lacking.
Identification of Siglec-10 as a new dendritic cell checkpoint for cervical cancer immunotherapy
Authors: Congwen Wang, Lewei He, Jing Peng, Chong Lu, Meng Zhang, Xingling Qi, Mingxing Zhang, Yumeng Wang
Journal: Journal for ImmunoTherapy of Cancer (2024)

The occurrence of chronic inflammation resulting from infection with human papillomaviruses is an important factor in the development of cervical cancer (CC); thus, deciphering the crosstalk between the tumor microenvironment and innate immune cells during the establishment of immune tolerance is vital for identifying potential treatment strategies.
Chronic endothelial dopamine receptor stimulation improves endothelial function and hemodynamics in autosomal dominant polycystic kidney disease
Authors: Audrey Dumont, Mouad Hamzaoui, Déborah Groussard, Michèle Iacob, Dominique Bertrand, Isabelle Remy-Jouet, Mélanie Hanoy, Frank Le Roy, Laurence Chevalier, Christoph Enzensperger, Hans-Dieter Arndt, Sylvanie Renet, Anaïs Dumesnil, Emilie Lévêque, Thomas Duflot, Valéry Brunel, Aurore Michel-Després, Marie-Pierre Audrézet, Vincent Richard, Robinson Joannidès, Dominique Guerrot, Jérémy Bellien
Journal: Kidney International (2024)
Immune checkpoint blockade: timing is everything
Authors: Frank A Sinicrope, Mary Jo Turk
Journal: Journal for ImmunoTherapy of Cancer (2024)

Neoadjuvant immunotherapy effectively uses the in situ tumor as a reservoir of tumor antigens to promote systemic antitumor immunity. Studies indicate that intratumoral responses to immune checkpoint inhibitors (ICIs) are mediated by resident memory T cells cells that are sequestered in tumors and have specificity for a wide range of tumor antigens ICI treatment produces de novo priming of CD8
Inclusion, characteristics, and reporting of older adults in FDA registration studies of immunotherapy, 2018–2022
Authors: Colm Mac Eochagain, Robert Power, Christine Sam, Nicolas M Gonzalez-Senac, Darren Walsh, Mukul Roy, Nicolò Matteo Luca Battisti
Journal: Journal for ImmunoTherapy of Cancer (2024)

Immune checkpoint inhibitors (ICI) have transformed the management of cancer, particularly for older adults, who constitute a majority of the global cancer patient population. This study aimed to assess the inclusion, characteristics, and reporting of older adults enrolled in Food and Drug Administration (FDA) registration clinical trials of ICI between 2018 and 2022. Clinical trials of ICI leading to an FDA approval in solid tumor oncology between 2018 and 2022 were included. Primary study reports and all available secondary publications were assessed. The availability and completeness of older subgroup data for protocol-defined clinical efficacy endpoints, health-related quality of life (HRQOL) and toxicity outcomes, and baseline characteristics were assessed according to predefined criteria which categorized reporting completeness hierarchically in relation to the availability of published data, including effect size, sample size, and measures of precision. 53 registration trials were included, involving a total of 37,094 participants. Most trials (64.2%) were of ICI combination therapy. 42.3% of patients were aged≥65 years; 11.1% were aged≥75. No trials specified an upper age limit for eligibility. 98.1% of trials excluded patients with European Cooperative Oncology Group performance status>1. 87.2% of primary efficacy endpoints and 17.9% of secondary efficacy endpoints were reported completely for older adults. Five studies (9.4%) reported baseline characteristics, three (6.1%) reported HRQOL assessments, and four (7.5%) reported toxicity outcomes completely among older subgroups. No trials conducted baseline geriatric assessments or reported geriatric-specific symptoms or quality of life scales. This analysis highlights significant deficits in the enrollment and reporting of older subgroups in pivotal trials of ICI therapy. The findings highlight an urgent need for improved reporting and inclusion standards in clinical trials of ICI to better inform treatment decisions for older adults.
Neutralizing IL-38 activates γδ T cell-dependent antitumor immunity and sensitizes for chemotherapy
Authors: Priscila da Silva, Javier Mora, Xin You, Svenja Wiechmann, Mateusz Putyrski, Javier Garcia-Pardo, Aimo Kannt, Andreas Ernst, Bernhard Bruene, Andreas Weigert
Journal: Journal for ImmunoTherapy of Cancer (2024)

The interleukin (IL)-1-family receptor antagonist IL-38 has emerged as a negative regulator of auto-inflammation. Given the intricate interplay between antitumor immunity and auto-inflammation, we hypothesized that blocking IL-38 may enhance tumor immune control.
Nivolumab maintenance improves overall survival of patients with advanced melanoma who experience severe immune-related adverse events on nivolumab plus ipilimumab
Authors: Anna K Maloney, Anita Giobbie-Hurder, Nikita Katukota, Miklos C Fogarasi, Patrick A Ott, F Stephen Hodi, Tamara A Sussman, Ann W Silk, Rizwan Haq, David Liu, Megan Insco, Elizabeth I Buchbinder
Journal: Journal for ImmunoTherapy of Cancer (2024)

The combination of ipilimumab and nivolumab is a highly effective treatment for metastatic cutaneous melanoma. However, immune-related adverse events (irAEs) are common, often necessitating treatment interruption and the use of immunosuppressive agents. There is no data on the impact of resuming nivolumab on survival following recovery from the irAE and completion of immunosuppressive treatment.
SGLT-2 inhibitors and dementia
Authors: Sung-Yun Tu, Shih-Chieh Shao, Ching-Hui Loh, Huei-Kai Huang
Journal: BMJ (2024)

Dementia remains a profound global health challenge.According to a report from the World Health Organization, more than 55 million people worldwide currently have dementia, and each year the disease is diagnosed in around 10 million people. 1 This neurological disorder, characterised by the progressive deterioration of cognitive function, continues to elude effective treatment.Notably, type 2 diabetes is recognised as an important modifiable risk factor for dementia, contributing to both Alzheimer's disease and vascular dementia. 2 Recent evidence suggests that certain antidiabetic drugs, specifically sodium-glucose cotransporter-2 (SGLT-2) inhibitors, may offer neuroprotective benefits beyond their glucose lowering effects, thereby adding a promising dimension to dementia prevention strategies.
Risk of dementia after initiation of sodium-glucose cotransporter-2 inhibitors versus dipeptidyl peptidase-4 inhibitors in adults aged 40-69 years with type 2 diabetes: population based cohort study
Authors: Anna Shin, Bo Kyung Koo, Jun Young Lee, Eun Ha Kang
Journal: BMJ (2024)

To compare the risk of dementia associated with sodium-glucose cotransporter-2 (SGLT-2) inhibitors versus dipeptidyl peptidase-4 (DPP-4) inhibitors in adults aged 40-69 years with type 2 diabetes.