tbuckley/cabot-search huggingface dataset:
Clinician-Created Video Education for Patients With AF
Authors: Daniel McIntyre, Joshua G. Kovoor, Clara K. Chow, Desi Quintans, Simone Marschner, Stuart Thomas, Pramesh Kovoor, Aravinda Thiagalingam
Journal: JAMA Network Open (2023)

Importance Patient education is a critical aspect of atrial fibrillation (AF) management. However, there is limited time to provide effective patient education during routine care, and resources available online are of variable quality. Objective To determine whether clinician-led creation of video-based AF education is feasible and improves knowledge of AF. Design, Setting, and Participants This single-center randomized clinical trial was conducted between 2020 and 2022. Outcomes were assessed prior to their clinic visit and 2 and 90 days after the visit by blinded assessors. Participants included adults with AF and congestive heart failure, hypertension, age at least 75 years (doubled), diabetes, prior stroke or transient ischemic attack or thromboembolism (doubled), vascular disease, age 65 to 74 years, and sex category scores of 1 or greater presenting for routine care at publicly funded outpatient cardiology clinics within a tertiary teaching hospital. Individuals too unwell to participate or with limited English were excluded. Data were assessed as intention to treat and analyzed from December 2022 to October 2023. Intervention Intervention participants viewed a series of 4 videos designed and narrated by clinicians that aimed to improve understanding of AF pathophysiology, clinical presentation, diagnosis, and management. After viewing the videos, participants received weekly email links to review the videos. The control group received usual care. Main Outcomes and Measures The prospectively selected primary outcome was AF knowledge at 90 days, measured by the validated Jessa Atrial Fibrillation Knowledge Questionnaire (JAFKQ). Results Among 657 individuals screened, 208 adults with AF were randomized (mean [SD] age, 65.0 [12.2] years; 133 [65.2%] male) and included in analysis. Participants were randomized 1-to-1, with 104 participants in the control group and 104 participants in the video intervention group. At 90 days after the baseline clinic visit, intervention participants were more likely to correctly answer JAFKQ questions than control participants (odds ratio [OR], 1.23 [95% CI, 1.01-1.49]). The difference was greater in participants who remotely accessed videos on 3 or more occasions during the study (OR, 1.46 [95% CI, 1.14-1.88]). Conclusions and Relevance In this randomized clinical trial of patients with AF, remotely delivered, clinician-created video education improved medium-term AF knowledge beyond usual care of standard in-clinic education. The improvement demonstrated in this study provides support for the implementation of clinician-created educational resources across the care continuum. Further work is needed to assess for impact on clinical outcomes. Trial Registration anzctr.org.au Identifier: ANZCTRN12620000729921
When I use a word . . . Medicines regulation—chloroform
Authors: Jeffrey K Aronson
Journal: BMJ (2023)

Medicines are sometimes withdrawn from the market after having been used therapeutically. When that happens it is usually because of some adverse effects or adverse reactions that they have caused. Over the years the delay between marketing and withdrawal in such cases has fallen dramatically. One of the longest delays between the first clinical use of a compound and its withdrawal from the market was that experienced by chloroform, which was first used clinically in 1847 and, although it was known to have caused many deaths and was eventually superseded by better compounds, it was not withdrawn anywhere until 1976 and in the UK until 1979.
Metaproteomic assessment of gut microbial and host functional perturbations in <i>Helicobacter pylori</i> -infected patients subjected to an antimicrobial protocol
Authors: Marcello Abbondio, Alessandro Tanca, Laura De Diego, Rosangela Sau, Stefano Bibbò, Giovanni Mario Pes, Maria Pina Dore, Sergio Uzzau
Journal: Gut Microbes (2023)

The impact of therapeutic interventions on the human gut microbiota (GM) is a clinical issue of paramount interest given the strong interconnection between microbial dynamics and human health. Orally administered antibiotics are known to reduce GM biomass and modify GM taxonomic profile. However, the impact of antimicrobial therapies on GM functions and biochemical pathways has scarcely been studied. Here, we characterized the fecal metaproteome of 10 Helicobacter pylori-infected patients before (T0) and after 10 days (T1) of a successful quadruple therapy (bismuth, tetracycline, metronidazole, and rabeprazole) and 30 days after therapy cessation (T2), to investigate how GM and host functions change during the eradication and healing processes. At T1, the abundance ratio between microbial and host proteins was reversed compared with that at T0 and T2. Several pathobionts (including Klebsiella, Proteus, Enterococcus, Muribaculum, and Enterocloster) were increased at T1. Therapy reshaped the relative contributions of the functions required to produce acetate, propionate, and butyrate. Proteins related to the uptake and processing of complex glycans were increased. Microbial cross-feeding with sialic acid, fucose, and rhamnose was enhanced, whereas hydrogen sulfide production was reduced. Finally, microbial proteins involved in antibiotic resistance and inflammation were more abundant after therapy. Moreover, a reduction in host proteins with known roles in inflammation and H. pylori-mediated carcinogenesis was observed. In conclusion, our results support the use of metaproteomics to monitor drug-induced remodeling of GM and host functions, opening the way for investigating new antimicrobial therapies aimed at preserving gut environmental homeostasis.
Morphometric Analysis of Lateral Cervical Lymph Node Metastasis in Papillary Thyroid Carcinoma Using Digital Pathology
Authors: Chae A Kim, Hyeong Rok An, Jungmin Yoo, Yu-Mi Lee, Tae-Yon Sung, Won Gu Kim, Dong Eun Song
Journal: Endocrine Pathology (2023)
Cotadutide promotes glycogenolysis in people with overweight or obesity diagnosed with type 2 diabetes
Authors: Victoria E. R. Parker, Darren Robertson, Edmundo Erazo-Tapia, Bas Havekes, Esther Phielix, Marlies de Ligt, Kay H. M. Roumans, Julian Mevenkamp, Folke Sjoberg, Vera B. Schrauwen-Hinderling, Edvin Johansson, Yi-Ting Chang, Russell Esterline, Kenneth Smith, Daniel J. Wilkinson, Lars Hansen, Lars Johansson, Philip Ambery, Lutz Jermutus, Patrick Schrauwen
Journal: Nature Metabolism (2023)

Abstract Cotadutide is a dual glucagon-like peptide 1 and glucagon receptor agonist under development for the treatment of non-alcoholic steatohepatitis and type 2 diabetes mellitus (T2DM) and chronic kidney disease. Non-alcoholic steatohepatitis is a complex disease with no approved pharmacotherapies, arising from an underlying state of systemic metabolic dysfunction in association with T2DM and obesity. Cotadutide has been shown to improve glycaemic control, body weight, lipids, liver fat, inflammation and fibrosis. We conducted a two-part, randomized phase 2a trial in men and women with overweight or obesity diagnosed with T2DM to evaluate the efficacy and safety of cotadutide compared with placebo and liraglutide. The primary endpoints were change from baseline to day 28 of treatment in postprandial hepatic glycogen (part A) and to day 35 of treatment in fasting hepatic glycogen (part B) with cotadutide versus placebo. Secondary endpoints in part B were changes in fasting hepatic glycogen with cotadutide versus the mono glucagon-like peptide 1 receptor agonist, liraglutide, and change in hepatic fat fraction. The trial met its primary endpoint. We showed that cotadutide promotes greater reductions in liver glycogen and fat compared with placebo and liraglutide. Safety and tolerability findings with cotadutide were comparable to those of previous reports. Thus, this work provides evidence of additional benefits of cotadutide that could be attributed to glucagon receptor engagement. Our results suggest that cotadutide acts on the glucagon receptor in the human liver to promote glycogenolysis and improve the metabolic health of the liver. ClinicalTrials.gov registration: NCT03555994 .
Early lessons from the implementation of universal respiratory syncytial virus prophylaxis in infants with long-acting monoclonal antibodies, Galicia, Spain, September and October 2023
Authors: Federico Martinón-Torres, Susana Mirás-Carballal, Carmen Durán-Parrondo
Journal: Eurosurveillance (2023)

A monoclonal antibody for universal respiratory syncytial virus prophylaxis in infants has recently been licensed. We share our experiences of integrating nirsevimab into the regional immunisation programme in Galicia, Spain. After a 3-week hospital-based immunisation campaign with flexible individualised appointments and educational activities, nirsevimab uptake was 97.5% in the high-risk group, 81.4% in the catch-up group and 92.6% in infants born during the campaign. This successful implementation strategy can serve as a model and may inform other countries’ programmatic deliberations.
Respiratory syncytial virus infections – recent developments providing promising new tools for disease prevention
Authors: Eeva K Broberg, Hanna Nohynek
Journal: Eurosurveillance (2023)

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Turnover of strain-level diversity modulates functional traits in the honeybee gut microbiome between nurses and foragers
Authors: Gilles L. C. Baud, Aiswarya Prasad, Kirsten M. Ellegaard, Philipp Engel
Journal: Genome biology (2023)

Strain-level diversity is widespread among bacterial species and can expand the functional potential of natural microbial communities. However, to what extent communities undergo consistent shifts in strain composition in response to environmental/host changes is less well understood.
Gut microbiota-derived 12-ketolithocholic acid suppresses the IL-17A secretion from colonic group 3 innate lymphoid cells to prevent the acute exacerbation of ulcerative colitis
Authors: Na Li, Peiguang Ma, Yalan Li, Xuekai Shang, Xinmei Nan, Lei Shi, Xiao Han, Jiajing Liu, Yanfei Hong, Qiuyi Li, Jiaqi Cui, Junxiang Li, Guiying Peng
Journal: Gut Microbes (2023)

Intestinal microbiota dysbiosis and metabolic disruption are well-known as the primary triggers of ulcerative colitis (UC). However, their role in regulating the group 3 innate lymphoid cells (ILC3s), which are essential for intestinal health, remains unexplored during the development of disease severity. Here, our results showed that the microbiota structure of patients with severe UC (SUCs) differed from those with mild UC (MiUCs), moderate UC (MoUCs), and healthy controls (HCs). Microbes producing secondary bile acids (SBAs) and SBAs decreased with the aggravation of UC, and a strong positive correlation existed between them. Next, fecal microbiota transfer was used to reproduce the human-derived microbiota in mice and decipher the microbiota-mediated inflammatory modulation during an increase in disease severity. Mice receiving SUC-derived microbiota exhibited enhancive inflammation, a lowered percentage of ILC3s, and the down-regulated expressions of bile acid receptors, including vitamin D receptor (VDR) and pregnane X receptor (PXR), in the colon. Similar to clinical results, SBA-producing microbes, deoxycholic acids (DCA), and 12-ketolithocholic acids (12-KLCA) were diminished in the intestine of these recipients. Finally, we compared the therapeutic potential of DCA and 12-KLCA in preventing colitis and the regulatory mechanisms mediated by ILC3s. 12-KLCA but not DCA represented a strong anti-inflammatory effect associated with the higher expression of VDR and the lower secretion of IL-17A from colonic ILC3s. Collectively, these findings provide new signatures for monitoring the acute deterioration of UC by targeting gut microbiota and bile acid metabolism and demonstrate the therapeutic and preventive potential of a novel microbiota-derived metabolite, 12-KLCA.
Prostacyclin Mitigates Renal Fibrosis by Activating Fibroblast Prostaglandin I2 Receptor
Authors: Jing Li, Yi Guan, Yunyu Xu, Yingxue Cao, Qionghong Xie, Raymond C. Harris, Matthew D. Breyer, Limin Lu, Chuan-Ming Hao
Journal: Journal of the American Society of Nephrology (2023)

Significance Statement Renal fibrosis is a common pathologic process of progressive CKD. We have provided strong evidence that PGI 2 is an important component in the kidney injury/repairing process by reducing fibrosis and protecting renal function from declining. In our study, administration of a PGI 2 analog or selective PTGIR agonist after the acute injury ameliorated renal fibrosis. Our findings provide new insights into the role of PGI 2 in kidney biology and suggest that targeting PGI 2 /PTGIR may be a potential therapeutic strategy for CKD. Background Prostanoids have been demonstrated to be important modulators to maintain tissue homeostasis in response to physiologic or pathophysiologic stress. Prostacyclin (PGI 2 ) is a member of prostanoids. While limited studies have shown that PGI 2 is involved in the tissue injury/repairing process, its role in renal fibrosis and CKD progression requires further investigation. Methods Prostacyclin synthase ( Ptgis )-deficient mice, prostaglandin I 2 receptor ( Ptgir )-deficient mice, and an oral PGI 2 analog and selective PTGIR agonist were used to examine the role of PGI 2 in renal fibrosis in mouse models. We also analyzed the single-cell RNA-Seq data to examine the PTGIR -expressing cells in the kidneys of patients with CKD. Results Increased PTGIS expression has been observed in fibrotic kidneys in both humans and mice. Deletion of the PTGIS gene aggravated renal fibrosis and decline of renal function in murine models. A PGI 2 analog or PTGIR agonist that was administered after the acute injury ameliorated renal fibrosis. PTGIR, the PGI 2 receptor, deficiency blunted the protective effect of the PGI 2 analog. Fibroblasts and myofibroblasts were the major cell types expressing PTGIR in the kidneys of patients with CKD. Deletion of PTGIR in collagen-producing fibroblastic cells aggravated renal fibrosis. The protective effect of PGI 2 was associated with the inhibition of fibroblast activation through PTGIR-mediated signaling. Conclusions PGI 2 is an important component in the kidney injury/repairing process by preventing the overactivation of fibroblasts during the repairing process and protecting the kidney from fibrosis and decline of renal function. Our findings suggest that PGI 2 /PTGIR is a potential therapeutic target for CKD.
Bacterial Cellulose‐Based Bandages with Integrated Antibacteria and Electrical Stimulation for Advanced Wound Management
Authors: Xiaohao Liu, Zhuyun Cai, Manman Pei, Hua Zeng, Lijuan Yang, Wentao Cao, Xuhui Zhou, Feng Chen
Journal: Advanced Healthcare Materials (2023)

Abstract Bandages for daily wounds are the most common medical supplies, but there are still ingrained defects in their appearance, comfort, functions, as well as environmental pollution. Here, novel bandages based on bacterial cellulose (BC) membrane for wound monitoring and advanced wound management are developed. The BC membrane is combined with silver nanowires (AgNWs) by using vacuum filtration method to achieve transparent, ultrathin (≈7 µm), breathable (389.98–547.79 g m −2 d −1 ), and sandwich‐structured BC/AgNWs bandages with superior mechanical properties (108.45–202.35 MPa), antibacterial activities against Escherichia coli and Staphylococcus aureus, biocompatibility, and conductivity (9.8 × 10 3 –2.0 × 10 5 S m −1 ). Significantly, the BC/AgNWs bandage is used in the electrical stimulation (direct current, 600 microamperes for 1 h every other day) treatment of full‐thickness skin defect in rats, which obviously promotes wound healing by increasing the secretion of vascular endothelial growth factor (VEGF). The BC bandage is used for monitoring wounds and achieve a high accuracy of 94.7% in classifying wound healing stages of hemostasis, inflammation, proliferation, and remodeling, by using a convolutional neural network. The outcomes of this study not only provide two BC‐based bandages as multifunctional wound management, but also demonstrate a new strategy for the development of the next generation of smart bandage.
Aldehyde dehydrogenase 2-mediated aldehyde metabolism promotes tumor immune evasion by regulating the NOD/VISTA axis
Authors: Yuru Chen, Jiazheng Sun, Jiazhou Liu, Yuxian Wei, Xiaoyu Wang, Huiying Fang, Huimin Du, Jing Huang, Qin Li, Guosheng Ren, Xiaoyi Wang, Hongzhong Li
Journal: Journal for ImmunoTherapy of Cancer (2023)

Background Aldehyde dehydrogenase 2 (ALDH2) is a crucial enzyme involved in endogenous aldehyde detoxification and has been implicated in tumor progression. However, its role in tumor immune evasion remains unclear. Methods Here, we analyzed the relationship between ALDH2 expression and antitumor immune features in multiple cancers. ALDH2 knockout tumor cells were then established using CRISPR/Cas9 system. In immunocompetent breast cancer EMT6 and melanoma B16-F10 mouse models, we investigated the impact of ALDH2 blockade on cytotoxic T lymphocyte function and tumor immune microenvironment by flow cytometry, mass cytometry, Luminex liquid suspension chip detection, and immunohistochemistry. Furthermore, RNA sequencing, flow cytometry, western blot, chromatin immunoprecipitation assay, and luciferase reporter assays were employed to explore the detailed mechanism of ALDH2 involved in tumor immune evasion. Lastly, the synergistic therapeutic efficacy of blocking ALDH2 by genetic depletion or its inhibitor disulfiram in combination with immune checkpoint blockade (ICB) was investigated in mouse models. Results In our study, we uncovered a positive correlation between the expression level of ALDH2 and T-cell dysfunction in multiple cancers. Furthermore, blocking ALDH2 significantly suppressed tumor growth by enhancing cytotoxic activity of CD8 + T cells and reshaping the immune landscape and cytokine milieu of tumors in vivo . Mechanistically, inhibiting ALDH2-mediated metabolism of aldehyde downregulated the expression of V-domain Ig suppressor of T-cell activation (VISTA) via inactivating the nucleotide oligomerization domain (NOD)/nuclear factor kappa-B (NF-κB) signaling pathway. As a result, the cytotoxic function of CD8 + T cells was revitalized. Importantly, ALDH2 blockade markedly reinforced the efficacy of ICB treatment. Conclusions Our data delineate that ALDH2-mediated aldehyde metabolism drives tumor immune evasion by activating the NOD/NF-κB/VISTA axis. Targeting ALDH2 provides an effective combinatorial therapeutic strategy for immunotherapy.
Real world data on outcomes of anti-CD38 antibody treated, including triple class refractory, patients with multiple myeloma: a multi-institutional report from the Canadian Myeloma Research Group (CMRG) Database
Authors: A. Visram, A. De La Torre, D. White, J. Su, E. Masih-Khan, M. Chu, V. Jimenez-Zepeda, A. McCurdy, R. LeBlanc, K. Song, H. Mian, M. Louzada, M. Sebag, D. Bergstrom, J. Stakiw, A. Reiman, R. Kotb, M. Aslam, C. Venner, R. Kaedbey, E. Gul, D. Reece
Journal: Blood Cancer Journal (2023)

Abstract Multiple myeloma (MM) remains incurable despite the availability of novel agents. This multi-center retrospective cohort study used the Canadian Myeloma Research Group Database to describe real-world outcomes of patients withanti-CD38 monoclonal antibody (mAb) refractory MM subsequently treated with standard of care (SoC) regimens. Patients with triple class refractory (TCR) disease (refractory to a proteasome inhibitor, immunomodulatory drug, and anti-CD38 mAb) were examined as a distinct cohort. Overall, 663 patients had disease progression on anti-CD38 mAb therapy, 466 received further treatment (346 with SoC regimens were included, 120 with investigational agents on clinical trial and were excluded). The median age at initiation of subsequent SoC therapy of 67.9 (range 39.6–89.6) years with a median of 3 prior lines (range 1–9). The median PFS and OS from the start of subsequent therapy was 4.6 (95% CI 4.1–5.6) months and 13.3 (95% CI 10.6–16.6) months, respectively. The median PFS and OS of patients with TCR disease ( n = 199) was 4.4 (95% CI 3.6–5.3) months and 10.5 (95% CI 8.5–13.8) months. Our results reinforce that real-world patients with relapsed MM, particularly those with TCR disease, have dismal outcomes. There remains an urgent unmet need for the development of and access to effective therapeutics for these patients.
Strengthening the Combinational Immunotherapy from Modulating the Tumor Inflammatory Environment via Hypoxia‐Responsive Nanogels
Authors: Wenhe Luo, Yanqiao Zeng, Qingle Song, Yu Wang, Feng Yuan, Qi Li, Yingnan Liu, Su Li, Nahar Jannatun, Guofang Zhang, Yang Li
Journal: Advanced Healthcare Materials (2023)

Despite the success of immuno-oncology in clinical settings, the therapeutic efficacy is lower than the expectation due to the immunosuppressive inflammatory tumor microenvironment (TME) and the lack of functional lymphocytes caused by exhaustion. To enhance the efficacy of immuno-oncotherapy, a synergistic strategy should be used that can effectively improve the inflammatory TME and increase the tumor infiltration of cytotoxic T lymphocytes (CTLs). Herein, a TME hypoxia-responsive nanogel (NG) is developed to enhance the delivery and penetration of diacerein and (-)-epigallocatechin gallate (EGCG) in tumors. After systemic administration, diacerein effectively improves the tumor immunosuppressive condition through a reduction of MDSCs and Tregs in TME, and induces tumor cell apoptosis via the inhibition of IL-6/STAT3 signal pathway, realizing a strong antitumor effect. Additionally, EGCG can effectively inhibit the expression of PD-L1, restoring the tumor-killing function of CTLs. The infiltration of CTLs increases at the tumor site with activation of systemic immunity after the combination of TIM3 blockade therapy, ultimately resulting in a strong antitumor immune response. This study provides valuable insights for future research on eliciting effective antitumor immunity by suppressing adverse tumor inflammation. The feasible strategy proposed in this work may solve the urgent clinical concerns of the dissatisfactory checkpoint-based immuno-oncotherapy.
Cotton Fibers with a Lactic Acid‐Like Surface for Re‐establishment of Protective <i>Lactobacillus</i> Microbiota by Selectively Inhibiting Vaginal Pathogens
Authors: Yuzheng Wu, Pei Liu, Qing Liao, Tao Jin, Zhengwei Wu, Guomin Wang, Huaiyu Wang, Paul K. Chu
Journal: Advanced Healthcare Materials (2023)

Abstract Failure to reconstruct the Lactobacillus microbiota is the major reason for the recurrence of vaginal infection. However, most empiric therapies focus on the efficacy of pathogen elimination but do not sufficiently consider the viability of Lactobacillus . Herein, cotton fibers with a lactic acid‐like surface (LC) are fabricated by NaIO 4 oxidation and L ‐isoserine grafting. The lactic acid analog chain ends and imine structure of LC can penetrate cell walls to cause protein cleavage in Escherichia coli and Candida albicans and inhibit vaginal pathogens. Meanwhile, the viability of Lactobacillus acidophilus is unaffected by the LC treatment, thus revealing a selective way to suppress pathogens as well as provide a positive route to re‐establish protective microbiota in the vaginal tract. Moreover, LC has excellent properties such as good biosafety, antiadhesion, water absorption, and weight retention. The strategy proposed here not only is practical, but also provides insights into the treatment of vaginal infections.