tbuckley/cabot-search huggingface dataset:
The importance of patient characteristics, operators, and image quality for the accuracy of heart failure diagnosis by general practitioners using handheld ultrasound devices
Authors: Malgorzata Izabela Magelssen, Anna Katarina Hjorth-Hansen, Garrett Newton Andersen, Torbjørn Graven, Jens Olaf Kleinau, Kyrre Skjetne, Lasse Lovstakken, Havard Dalen, Ole Christian Mjølstad
Journal:  (2023)

Abstract Aims To evaluate whether the characteristics of patients, operators, and image quality could explain the accuracy of heart failure (HF) diagnostics by general practitioners (GPs) using handheld ultrasound devices (HUDs) with automatic decision-support software and telemedical support. Methods and results Patients referred to an outpatient cardiac clinic due to symptoms indicating HF were examined by one of five GPs after dedicated training. In total, 166 patients were included [median (inter-quartile range) age 73 (63–78) years; mean ± standard deviation ejection fraction 53 ± 10%]. The GPs considered whether the patients had HF in four diagnostic steps: (i) clinical examination, (ii) adding focused cardiac HUD examination, (iii) adding automatic decision-support software measuring mitral annular plane systolic excursion (autoMAPSE) and ejection fraction (autoEF), and (iv) adding telemedical support. Overall, the characteristics of patients, operators, and image quality explained little of the diagnostic accuracy. Except for atrial fibrillation [lower accuracy for HUD alone and after adding autoEF (P &amp;lt; 0.05)], no patient characteristics influenced the accuracy. Some differences between operators were found after adding autoMAPSE (P &amp;lt; 0.05). Acquisition errors of the four-chamber view and a poor visualization of the mitral plane were associated with reduced accuracy after telemedical support (P &amp;lt; 0.05). Conclusion The characteristics of patients, operators, and image quality explained just minor parts of the modest accuracy of GPs’ HF diagnostics using HUDs with and without decision-support software. Atrial fibrillation and not well-standardized recordings challenged the diagnostic accuracy. However, the accuracy was only modest in well-recorded images, indicating a need for refinement of the technology.
Targeting myeloid cells for cancer immunotherapy: Siglec-7/9/10/15 and their ligands
Authors: Kelly Boelaars, Yvette van Kooyk
Journal: Trends in cancer (2023)

Advances in immunotherapy have revolutionized cancer treatment, yet many patients do not show clinical responses. While most immunotherapies target T cells, myeloid cells are the most abundant cell type in solid tumors and are key orchestrators of the immunosuppressive tumor microenvironment (TME), hampering effective T cell responses. Therefore, unraveling the immune suppressive pathways within myeloid cells could unveil new avenues for cancer immunotherapy. Over the past decade, Siglec receptors and their ligand, sialic acids, have emerged as a novel immune checkpoint on myeloid cells. In this review, we highlight key findings on how sialic acids modify immunity in the TME through engagement of Siglec-7/9/10/15 expressed on myeloid cells, and how the sialic acid–Siglec axis can be targeted for future cancer immunotherapies.
Incorporation of quantitative imaging data using artificial intelligence improves risk prediction in veterans with liver disease
Authors: Grace L. Su, Peng Zhang, Patrick X. Belancourt, Bradley Youles, Binu Enchakalody, Ponni Perumalswami, Akbar Waljee, Sameer Saini
Journal: Hepatology (2023)

Utilization of electronic health records data to derive predictive indexes such as the electronic Child-Turcotte-Pugh (eCTP) Score can have significant utility in health care delivery. Within the records, CT scans contain phenotypic data which have significant prognostic value. However, data extractions have not traditionally been applied to imaging data. In this study, we used artificial intelligence to automate biomarker extraction from CT scans and examined the value of these features in improving risk prediction in patients with liver disease.
Mitofusin-2 Regulates Platelet Mitochondria and Function
Authors: Shancy Jacob, Yasuhiro Kosaka, Seema Bhatlekar, Frederik Denorme, Haley Benzon, Alexandra Moody, Victoria Moody, Emilia A. Tugolukova, Grayson Hull, Nina Kishimoto, Bhanu K. Manne, Li Guo, Rhonda Souvenir, Brayden J. Seliger, Alicia S. Eustes, Kelly Hoerger, Neal D. Tolley, Amir N. Fatahian, Sihem Boudina, David C. Christiani, Yongyue Wei, Can Ju, Robert A. Campbell, Matthew T. Rondina, E. Dale Abel, Paul F. Bray, Andrew S. Weyrich, Jesse W. Rowley
Journal: Circulation Research (2023)

BACKGROUND: Single-nucleotide polymorphisms linked with the rs1474868 T allele ( MFN2 [mitofusin-2] T/T) in the human mitochondrial fusion protein MFN2 gene are associated with reduced platelet MFN2 RNA expression and platelet counts. This study investigates the impact of MFN2 on megakaryocyte and platelet biology. METHODS: Mice with megakaryocyte/platelet deletion of Mfn2 ( Mfn2 −/− [ Mfn2 conditional knockout]) were generated using Pf4-Cre crossed with floxed Mfn2 mice. Human megakaryocytes were generated from cord blood and platelets isolated from healthy subjects genotyped for rs1474868. Ex vivo approaches assessed mitochondrial morphology, function, and platelet activation responses. In vivo measurements included endogenous/transfused platelet life span, tail bleed time, transient middle cerebral artery occlusion, and pulmonary vascular permeability/hemorrhage following lipopolysaccharide-induced acute lung injury. RESULTS: Mitochondria was more fragmented in megakaryocytes derived from Mfn2 −/− mice and from human cord blood with MFN2 T/T genotype compared with control megakaryocytes. Human resting platelets of MFN2 T/T genotype had reduced MFN2 protein, diminished mitochondrial membrane potential, and an increased rate of phosphatidylserine exposure during ex vivo culture. Platelet counts and platelet life span were reduced in Mfn2 −/− mice accompanied by an increased rate of phosphatidylserine exposure in resting platelets, especially aged platelets, during ex vivo culture. Mfn2 −/− also decreased platelet mitochondrial membrane potential (basal) and activated mitochondrial oxygen consumption rate, reactive oxygen species generation, calcium flux, platelet-neutrophil aggregate formation, and phosphatidylserine exposure following dual agonist activation. Ultimately, Mfn2 −/− mice showed prolonged tail bleed times, decreased ischemic stroke infarct size after cerebral ischemia-reperfusion, and exacerbated pulmonary inflammatory hemorrhage following lipopolysaccharide-induced acute lung injury. Analysis of MFN2 SNPs in the iSPAAR study (Identification of SNPs Predisposing to Altered ALI Risk) identified a significant association between MFN2 and 28-day mortality in patients with acute respiratory distress syndrome. CONCLUSIONS: Mfn2 preserves mitochondrial phenotypes in megakaryocytes and platelets and influences platelet life span, function, and outcomes of stroke and lung injury.
Renal macrophages monitor and remove particles from urine to prevent tubule obstruction
Authors: Jian He, Yangyang Cao, Qian Zhu, Xinge Wang, Guo Cheng, Qiang Wang, Rukun He, Haoran Lu, Yuancheng Weng, Genxiang Mao, Yizhong Bao, Jing Wang, Xiaoli Liu, Fei Han, Peng Shi, Xiao Z. Shen
Journal: Immunity (2023)
Novel Discoveries and Clinical Advancements for Treating Onychomycosis: A Mechanistic Insight
Authors: Jitesh Kumar Behera, Samarth Kumar, Rajeev Sharma, Ashay Jain, Neeraj Kumar Garg, Ajay Khopade, Krutika K. Sawant, Ranjit Singh, Pradip Nirbhavane
Journal: Advanced Drug Delivery Reviews (2023)
In search of critical dsRNA targets of ADAR1
Authors: Erez Y. Levanon, Roni Cohen-Fultheim, Eli Eisenberg
Journal: Trends in Genetics (2023)

Recent studies have underscored the pivotal role of adenosine-to-inosine RNA editing, catalyzed by ADAR1, in suppressing innate immune interferon responses triggered by cellular double-stranded RNA (dsRNA). However, the specific ADAR1 editing targets crucial for this regulatory function remain elusive. We review analyses of transcriptome-wide ADAR1 editing patterns and their evolutionary dynamics, which offer valuable insights into this unresolved query. The growing appreciation of the significance of immunogenic dsRNAs and their editing in inflammatory and autoimmune diseases and cancer calls for a more comprehensive understanding of dsRNA immunogenicity, which may promote our understanding of these diseases and open doors to therapeutic avenues.
Cardiovascular comorbidities are associated with dermatomyositis: A cross-sectional study in the All of Us Research Program
Authors: Jill T. Shah, Keya T. Shah, Daniel R. Mazori, Avrom S. Caplan, Emily Hejazi, Michael S. Garshick, Alisa N. Femia
Journal: Journal of the American Academy of Dermatology (2023)
Risk of alcohol-associated liver disease in the offspring of parents with alcohol-associated liver disease: A nationwide cohort study
Authors: Peter Jepsen, Joe West, Anna Emilie Kann, Frederik Kraglund, Joanne Morling, Colin Crooks, Gro Askgaard
Journal: Hepatology (2023)

Offspring of patients with alcohol-associated liver disease (ALD) may have a higher risk of ALD. We examined their risk of ALD and survival with ALD.
Association of tea and coffee consumption and biliary tract cancer risk: The Biliary Tract Cancers Pooling Project
Authors: Yu-Han Huang, Erikka Loftfield, Ilona Argirion, Hans-Olov Adami, Demetrius Albanes, Andrew T. Chan, Veronika Fedirko, Gary E. Fraser, Neal D. Freedman, Graham G. Giles, Patricia Hartge, Verena Katzke, Synnove F. Knutsen, James Lacey, Linda M. Liao, Juhua Luo, Roger L. Milne, Katie M. O’Brien, Ulrike Peters, Jenny N. Poynter, Mark P. Purdue, Kim Robien, Sven Sandin, Dale P. Sandler, Veronica W. Setiawan, Jae H. Kang, Tracey G. Simon, Rashmi Sinha, Trang VoPham, Stephanie J. Weinstein, Emily White, Xuehong Zhang, Bin Zhu, Katherine A. McGlynn, Peter T. Campbell, Mei-Hsuan Lee, Jill Koshiol
Journal: Hepatology (2023)

Background and Aims: Tea and coffee are widely consumed beverages worldwide. We evaluated their association with biliary tract cancer (BTC) incidence. Approach and Results: We pooled data from 15 studies in the Biliary Tract Cancers Pooling Project to evaluate associations between tea and coffee consumption and biliary tract cancer development. We categorized participants as nondrinkers (0 cup/day), moderate drinkers (&gt;0 and &lt;3 cups/day), and heavy drinkers (≥3 cups/day). We estimated multivariable HRs and 95% CIs using Cox models. During 29,911,744 person-years of follow-up, 851 gallbladder, 588 intrahepatic bile duct, 753 extrahepatic bile duct, and 458 ampulla of Vater cancer cases were diagnosed. Individuals who drank tea showed a statistically significantly lower incidence rate of gallbladder cancer (GBC) relative to tea nondrinkers (HR=0.77; 95% CI, 0.64–0.91), and intrahepatic bile duct cancer (IHBDC) had an inverse association (HR=0.81; 95% CI, 0.66–1.00). However, no associations were observed for extrahepatic bile duct cancer (EHBDC) or ampulla of Vater cancer (AVC). In contrast, coffee consumption was positively associated with GBC, with a higher incidence rate for individuals consuming more coffee (HR &lt;3 cups/day =1.29; 95% CI, 1.01–1.66; HR ≥3 cups/day =1.49; 95% CI, 1.11–1.99, P trend =0.01) relative to coffee nondrinkers. However, there was no association between coffee consumption and GBC when restricted to coffee drinkers. There was little evidence of associations between coffee consumption and other biliary tract cancers. Conclusions: Tea consumption was associated with a lower incidence of GBC and possibly IHBDC. Further research is warranted to replicate the observed positive association between coffee and GBC.
Clinical phenogroup diversity and multiplicity: Impact on mechanisms of exercise intolerance in heart failure with preserved ejection fraction
Authors: Kathryn Larson, Massar Omar, Hidemi Sorimachi, Kazunori Omote, Alessio Alogna, Dejana Popovic, Atsushi Tada, Shunichi Doi, Jwan Naser, Yogesh N.V. Reddy, Margaret M. Redfield, Barry A. Borlaug
Journal: European Journal of Heart Failure (2023)
Remote Manipulation of TRPV1 Signaling by Near‐Infrared Light‐Triggered Nitric Oxide Nanogenerators for Specific Cancer Therapy
Authors: Shuangling Wang, Yalin Wang, Jie Lv, Chunzhe Xu, Yuxin Wei, Guiying Wang, Meng Li
Journal: Advanced Healthcare Materials (2023)

Specific activation of transient receptor potential vanilloid member 1 (TRPV1) channels provides a new avenue for cancer treatment by inducing excessive Ca
Exercise catheterization in adults <scp>post‐Fontan</scp> with normal and abnormal haemodynamic criteria: Insights into normal Fontan physiology
Authors: William R. Miranda, C. Charles Jain, Barry A. Borlaug, Heidi M. Connolly, Luke J. Burchill, Alexander Van De Bruaene, Alexander C. Egbe
Journal: European Journal of Heart Failure (2023)
Engineered extracellular vesicles: A new approach for targeted therapy of tumors and overcoming drug resistance
Authors: Chen Ming‐Kun, Chen Zi‐Xian, Cai Mao‐Ping, Chen Hong, Chen Zhuang‐Fei, Zhao Shan‐Chao
Journal: Cancer Communications (2023)

Abstract Targeted delivery of anti‐tumor drugs and overcoming drug resistance in malignant tumor cells remain significant clinical challenges. However, there are only few effective methods to address these issues. Extracellular vesicles (EVs), actively secreted by cells, play a crucial role in intercellular information transmission and cargo transportation. Recent studies have demonstrated that engineered EVs can serve as drug delivery carriers and showed promising application prospects. Nevertheless, there is an urgent need for further improvements in the isolation and purification of EVs, surface modification techniques, drug assembly processes, and precise recognition of tumor cells for targeted drug delivery purposes. In this review, we summarize the applications of engineered EVs in cancer treatment and overcoming drug resistance, and current challenges associated with engineered EVs are also discussed. This review aims to provide new insights and potential directions for utilizing engineered EVs as targeted delivery systems for anti‐tumor drugs and overcoming drug resistance in the near future.
EAACI/ENDA position paper on drug provocation testing
Authors: Annick Barbaud, Lene Heise Garvey, Maria Torres, Jose Julio Laguna, Alessandra Arcolaci, Patrizia Bonadonna, Kathrin Scherer Hofmeier, Anca Mirela Chiriac, Josefina Cernadas, Jean Christoph Caubet, Knut Brockow
Journal: Allergy (2023)

In drug hypersensitivity, drug provocation testing (DPT), also called drug challenge, is the gold standard for investigation. In recent years, risk stratification has become an important tool for adjusting the diagnostic strategy to the perceived risk, whilst still maintaining a high level of safety for the patient. Skin tests are recommended before DPT but may be omitted in low-risk patients. The task force suggests a strict definition of such low-risk patients in children and adults. Based on experience and evidence from studies of allergy to beta-lactam antibiotics, an algorithm on how to adjust DPT to the risk, and when to omit skin tests before DPT, is presented. For other antibiotics, non-steroidal anti-inflammatory drugs and other drugs, skin tests are poorly validated and DPT is frequently necessary. We recommend performing DPT with chemotherapeutics and biologicals to avoid unnecessary desensitization procedures and DPT with skin tests negative contrast media. We suggest DPT with anesthetics only in highly specialized centers. Specifics of DPT to proton pump inhibitors, anticonvulsants and corticosteroids are discussed. This position paper provides general recommendations and guidance on optimizing use of DPT, whilst balancing benefits with patient safety and optimizing the use of the limited available resources.
Enhancing Wound Healing and Bactericidal Efficacy: A Hydrogel Membrane of Bacterial Cellulose and Sanxan Gel for Accelerating the Healing of Infected Wounds
Authors: Xueqing Zhao, Yucheng Shi, Shaofang Niu, Xiaoya Wei, Tongtong Liu, Mingbo Yang, Mengmeng Wu, Ge Gao, Ting Ma, Guoqiang Li
Journal: Advanced Healthcare Materials (2023)

Abstract Bacterial cellulose is an extracellular polysaccharide produced by microorganisms, offering advantages such as high water‐holding capacity, flexibility, and biocompatibility. However, its lack of bactericidal activity hampers its wide application. Usnic acid, a secondary metabolite derived from lichens of the Usnea genus, is recognized for its antibacterial and anti‐biofilm efficiency, coupled with anti‐inflammatory properties. Its water insolubility presents challenges for wide utilization and stable release. Sanxan gel, a novel polysaccharide, exhibits exceptional freeze‐thaw stability, suspension properties, and high elasticity, rendering it effective as a suspending agent to improve the bioavailability of water‐insoluble drugs. In this study, a hydrogel membrane is designed by combining bacterial cellulose and usnic acid suspended in sanxan gel through a simple in situ microorganism fermentation. The obtained membranes demonstrate excellent ability for sustained drug release, strong eradication capability against tested bacteria in both in vitro and in vivo experiments, effective inhibition of biofilm formation, and excellent hemocompatibility and cytocompatibility. Additionally, the composite membranes promote wound healing with reduced inflammation and bacterial infection in a full‐thickness wound infection model in mice. This study provides innovative insights and strategies for the development of functional dressings for infected wounds in future clinical applications.
Genetic and transcriptomic analyses of diffuse large B-cell lymphoma patients with poor outcomes within two years of diagnosis
Authors: Weicheng Ren, Hui Wan, Sulaf Abd Own, Mattias Berglund, Xianhuo Wang, Mingyu Yang, Xiaobo Li, Dongbing Liu, Xiaofei Ye, Kristina Sonnevi, Gunilla Enblad, Rose-Marie Amini, Birgitta Sander, Kui Wu, Huilai Zhang, Björn Engelbrekt Wahlin, Karin E Smedby, Qiang Pan-Hammarström
Journal: Leukemia (2023)

Despite the improvements in clinical outcomes for DLBCL, a significant proportion of patients still face challenges with refractory/relapsed (R/R) disease after receiving first-line R-CHOP treatment. To further elucidate the underlying mechanism of R/R disease and to develop methods for identifying patients at risk of early disease progression, we integrated clinical, genetic and transcriptomic data derived from 2805 R-CHOP-treated patients from seven independent cohorts. Among these, 887 patients exhibited R/R disease within two years (poor outcome), and 1918 patients remained in remission at two years (good outcome). Our analysis identified four preferentially mutated genes (TP53, MYD88, SPEN, MYC) in the untreated (diagnostic) tumor samples from patients with poor outcomes. Furthermore, transcriptomic analysis revealed a distinct gene expression pattern linked to poor outcomes, affecting pathways involved in cell adhesion/migration, T-cell activation/regulation, PI3K, and NF-κB signaling. Moreover, we developed and validated a 24-gene expression score as an independent prognostic predictor for treatment outcomes. This score also demonstrated efficacy in further stratifying high-risk patients when integrated with existing genetic or cell-of-origin subtypes, including the unclassified cases in these models. Finally, based on these findings, we developed an online analysis tool ( https://lymphprog.serve.scilifelab.se/app/lymphprog ) that can be used for prognostic prediction for DLBCL patients.
Deep Anterior Lamellar Keratoplasty Using Dehydrated versus Standard Organ Culture-Stored Donor Corneas
Authors: Cristina Bovone, Luigi De Rosa, Marco Pellegrini, Alessandro Ruzza, Stefano Ferrari, Davide Camposampiero, Diego Ponzin, Giorgio Zauli, Angeli Christy Yu, Massimo Busin
Journal: Ophthalmology (2023)

PurposeTo compare the outcomes of deep anterior lamellar keratoplasty (DALK) using dehydrated versus standard organ culture stored donor corneas for eyes with keratoconus.DesignProspective, randomized, single-center trial conducted in ItalyParticipantsAdult patients with keratoconus (≥ 18 years old) with keratoconus scheduled for an elective DALKMethodsCases with successful type 1 bubble pneumatic dissection using standard DALK technique were intraoperatively randomized to receive either dehydrated (n=30) or standard organ culture stored donor corneas (n=30).Main Outcome MeasuresThe primary study outcome was best spectacle-corrected visual acuity (BSCVA) 12 months after surgery. Secondary outcomes were refractive astigmatism (RA), endothelial cell density (ECD) and complication rates.ResultsPostoperative logMAR BSCVA did not significantly differ between groups at both time points (mean difference at 6 months = 0.030 [95%CI: -0.53-0.10] p = 0.471) and at 12 months = -0.013 [95%CI: -0.10-0.08] p = 0.764). No significant differences between groups were observed in terms of postoperative RA and ECD at all time points. In the first 3 days after DALK, an epithelial defect was present in 10 cases (33%) of the organ culture cornea group and in 29 cases (97%) of the dehydrated cornea group. Complete re-epithelialization was achieved by day 7 in all cases (100%) of both groups.ConclusionsThe study provides evidence that the use of dehydrated corneas is non-inferior to the use of standard organ culture donor corneas for DALK. Corneal tissue dehydration represents a viable solution that can allow long-term cornea preservation and avoid wastage of unused corneas.
RNAkines are secreted messengers shaping health and disease
Authors: Jing Li, Jingwen Fang, Xiaohong Jiang, Yujing Zhang, Antonio Vidal-Puig, Chen-Yu Zhang
Journal: Trends in Endocrinology and Metabolism (2023)

Extracellular noncoding RNAs (ncRNAs) have crucial roles in intercellular communications. The process of ncRNA secretion is highly regulated, with specific ncRNA profiles produced under different physiological and pathological circumstances. These ncRNAs are transported primarily via extracellular vesicles (EVs) from their origin cells to target cells, utilising both endocrine and paracrine pathways. The intercellular impacts of extracellular ncRNAs are essential for maintaining homeostasis and the pathogenesis of various diseases. Given the unique aspects of extracellular ncRNAs, here we propose the term 'RNAkine' to describe these recently identified secreted factors. We explore their roles as intercellular modulators, particularly in their ability to regulate metabolism and influence tumorigenesis, highlighting their definition and importance as a distinct class of secreted factors.
Trem2 expression in microglia is required to maintain normal neuronal bioenergetics during development
Authors: Erica Tagliatti, Genni Desiato, Sara Mancinelli, Matteo Bizzotto, Maria C. Gagliani, Elisa Faggiani, Rebeca Hernández-Soto, Andrea Cugurra, Paola Poliseno, Matteo Miotto, Rafael J. Argüello, Fabia Filipello, Katia Cortese, Raffaella Morini, Simona Lodato, Michela Matteoli
Journal: Immunity (2023)

Triggering receptor expressed on myeloid cells 2 (Trem2) is a myeloid cell-specific gene expressed in brain microglia, with variants that are associated with neurodegenerative diseases, including Alzheimer's disease. Trem2 is essential for microglia-mediated synaptic refinement, but whether Trem2 contributes to shaping neuronal development remains unclear. Here, we demonstrate that Trem2 plays a key role in controlling the bioenergetic profile of pyramidal neurons during development. In the absence of Trem2, developing neurons in the hippocampal cornus ammonis (CA)1 but not in CA3 subfield displayed compromised energetic metabolism, accompanied by reduced mitochondrial mass and abnormal organelle ultrastructure. This was paralleled by the transcriptional rearrangement of hippocampal pyramidal neurons at birth, with a pervasive alteration of metabolic, oxidative phosphorylation, and mitochondrial gene signatures, accompanied by a delay in the maturation of CA1 neurons. Our results unveil a role of Trem2 in controlling neuronal development by regulating the metabolic fitness of neurons in a region-specific manner.