tbuckley/cabot-search huggingface dataset:
Metabolic abnormalities in patients with non-alcoholic fatty liver disease with immune response to SARS-CoV-2
Authors: Yu.M. Stepanov, V.I. Didenko, I.A. Klenina, O.M. Tatarchuk, O.P. Petishko
Journal: GASTROENTEROLOGY (2024)

Background. It is known that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can directly infect hepatocytes. At the same time, overweight and obesity are surrogate markers of the adverse effects of coronavirus disease 2019 (COVID-19). The purpose of the study: to evaluate changes in lipid and carbohydrate metabolism and their indices in the serum of patients with non-alcoholic fatty liver disease (NAFLD) with an immune response to SARS-CoV-2. Materials and methods. We studied 37 patients with NAFLD who had IgG to SARS-CoV-2. All patients were divided into two groups: group I consisted of 19 participants who were PCR-negative for SARS-CoV-2, group II included 18 patients who had COVID-19, as confirmed by PCR testing. The content of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), glucose, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol (VLDL-C), atherogenicity coefficient, insulin resistance indices (HOMA-IR), TG to glucose (TG/Gly) and TG to HDL-C (TG/HDL-C) ratio were assessed in all patients. Results. Among patients with NAFLD with an immune response to SARS-CoV-2, dyslipidemia manifested by a probable increase in the median TG content in groups I and II by 2.5 and 3.4 times (р = 0.0001), respectively; TC — by 1.2 times (р = 0.0425) in both groups, with a tendency to increase; VLDL-C — by 1.8 (р = 0.010) and 2.5 times (р = 0.0022), respectively, and a decrease in the median content of HDL-C by 1.7 (р = 0.0016) and 1.9 times (р = 0.0008), respectively, in blood serum. The identified changes led to a statistically significant increase in the median atherogenicity coefficient in groups I and II — by 2.2 (р = 0.0036) and 2.5 times (р = 0.007). An increase in the HOMA-IR did not have a statistically significant difference between the groups: in group I, this index increased by 3.1 times (p &lt; 0.05) compared with the controls, in group II — by 3 times (p &lt; 0.05). In addition, patients in both groups had a statistically significant increase in TG/Gly and TG/HDL-C ratio compared to controls. However, the detected changes were more pronounced in group II, where TG/Gly and TG/HDL-C levels were 1.5 (р = 0.038) and 1.9 times (р = 0.035), respectively, higher than in group I. Conclusions. Patients with an immune response to SARS-CoV-2 with NAFLD have disorders of lipid and carbohydrate metabolism. At the same time, the signs of dyslipidemia were more pronounced in participants with a history of SARS-CoV-2. TG/Gly and TG/HDL-C ratio should be included in the diagnostic algorithm for assessing insulin resistance in patients with COVID-19 who are overweight or obese.
Decompensated liver cirrhosis: assessment of complications and mortality in hospitalised patients
Authors: L. Cuko, E. Sadiku, A. Hysenj, I. Tafaj, A. Idrizi
Journal: GASTROENTEROLOGY (2024)

Background. Liver cirrhosis is a severe, progressively fatal disease if untreated. Hospitalised patients face high mortality rates, and current methods for assessing prognosis vary widely. The research aims to investigate complications and predictors of mortality in patients admitted for decompensated cirrhosis to a tertiary care centre in Tirana, Albania. Materials and methods. The retrospective study included 212 patients aged (58.67 ± 10.09) years: 174 (82.1 %) men, 38 (17.9 %) women. The Child-Turcotte-Pugh, MELD, MELD-Na, MELD 3.0, iMELD, MESO, and UKELD scales were used to assess the severity of the condition and risk stratification of patients. The number of patients with a fatal outcome was 43 (20.3 %). Results. Among participants with different etiological factors of liver cirrhosis, the mortality rate did not differ significantly (p = 0.873). The presence of hepatic encepha­lopathy (0.43; p = 0.001), acute-on-chronic liver failure (r = 0.47; p = 0.001) and hepatorenal syndrome (r = 0.49; p = 0.001), and, to a lesser extent, ascites (r = 0.18; p = 0.006) and spontaneous bacterial peritonitis (r = 0.23; p = 0.041) was a marker of unfavourable prognosis of hospitalisation. Also, the risk of death increased in the presence of leukaemia (hazard ratio = 4.21 (1.65; 10.74); p = 0.003). Conclusions. The MELD 3.0 and MELD-Na scores, calculated based on laboratory values obtained within 48–72 hours of hospitalisation, were found to be the prognostically significant (p &lt; 0.05)
Pavlo Boichenko: a life given to people
Authors: M.P. Chaban, Z.I. Shevtsova, V.V. Gaponov
Journal: GASTROENTEROLOGY (2024)

The article represents a life and a professional path of zemstvo doctor Pavlo Nikiforovich Boichenko. His contribution to the development of medical services in the Dnipro region has been presented. The doctor participated in the provision of medical aid to the wounded people during the Crimean War (1853–1856), and assisted in the elimination of the cholera epidemic. The ascetic created the description of Church institutions in Katerynoslav, took care of orphanages. Pavlo Boichenko received awards and gratitude from the authorities, zemstvo, and fellow citizens. The provided material will contribute to the popularization of the figure of the Ukrainian zemstvo doctor.
Hypoperfusion in Alzheimer’s Disease–Prone Regions and Dementia Conversion in Parkinson’s Disease
Authors: Min Young Chun, Taein Lee, Su Hong Kim, Hye Sun Lee, Yun Joong Kim, Phil Hyu Lee, Young H. Sohn, Yong Jeong, Seok Jong Chung
Journal: Clinical Nuclear Medicine (2024)

Although early detection of individuals at risk of dementia conversion is important in patients with Parkinson's disease (PD), there is still no consensus on neuroimaging biomarkers for predicting future cognitive decline. We aimed to investigate whether cerebral perfusion patterns on early-phase 18 F-N-(3-fluoropropyl)-2β-carboxymethoxy-3β-(4-iodophenyl) nortropane ( 18 F-FP-CIT) PET have the potential to serve as a neuroimaging predictor for early dementia conversion in patients with PD.
18F-MFBG PET/CT and MRI in Identifying Brain Metastases in a Posttreatment Neuroblastoma Patient
Authors: Peipei Wang, Tuo Li, Hongming Zhuang, Fang Li, Hongli Jing
Journal: Clinical Nuclear Medicine (2024)

Abstract A 7-year-old girl with known brain metastasis from neuroblastoma developed new onset of severe headache. A brain MRI confirmed known metastasis in the right frontal lobe of the brain without new abnormalities. The patient was enrolled in a clinical trial using 18 F-MFBG PET/CT to evaluate patients with neuroblastoma. The images confirmed abnormal activity in the known lesion in the right frontal lobe. In addition, the PET showed additional foci of abnormal activity in the left cerebellopontine region. A follow-up brain MRI study acquired 4 months later revealed abnormal signals in the same region.
The evolution of robotics: research and application progress of dental implant robotic systems
Authors: Chen Liu, Yuchen Liu, Rui Xie, Zhiwen Li, Shizhu Bai, Yimin Zhao
Journal: International Journal of Oral Science (2024)

Abstract The use of robots to augment human capabilities and assist in work has long been an aspiration. Robotics has been developing since the 1960s when the first industrial robot was introduced. As technology has advanced, robotic-assisted surgery has shown numerous advantages, including more precision, efficiency, minimal invasiveness, and safety than is possible with conventional techniques, which are research hotspots and cutting-edge trends. This article reviewed the history of medical robot development and seminal research papers about current research progress. Taking the autonomous dental implant robotic system as an example, the advantages and prospects of medical robotic systems would be discussed which would provide a reference for future research.
A cross-sectional study of erythromelalgia in patients with pachyonychia congenita
Authors: Rebecca L McCarthy, Janice Schwartz, Jaimie Oldham, Christine Bodemer, Celine Greco, Alain Hovnanian, C  David Hansen, Edel A O’Toole
Journal: British Journal of Dermatology (2024)

Pachyonychia congenita (PC) is a rare genodermatosis characterized by focal palmoplantar keratoderma, severe plantar pain and dystrophic nails. Anecdotally, some patients with PC have erythematous soles and episodic burning plantar pain, indicative of secondary erythromelalgia. This study aimed to identify the prevalence and genetic predictors of erythromelalgia in PC.
Debunking the myth that all emollients are equal opens the door for future atopic dermatitis prevention studies
Authors: Simon G Danby
Journal: British Journal of Dermatology (2024)

Journal Article Accepted manuscript Debunking the myth that all emollients are equal opens the door for future AD prevention studies Get access Simon G Danby Simon G Danby Sheffield Dermatology Research, Division of Clinical Medicine, School of Medicine and Population Health, The University of Sheffield, Sheffield, UK Corresponding author: Email:s.danby@sheffield.ac.uk https://orcid.org/0000-0001-7363-140X Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljae146, https://doi.org/10.1093/bjd/ljae146 Published: 08 April 2024 Article history Received: 25 March 2024 Revision received: 02 April 2024 Accepted: 04 April 2024 Published: 08 April 2024
Frizzleds act as dynamic pharmacological entities
Authors: Gunnar Schulte, Magdalena M. Scharf, Julien Bous, Jan Hendrik Voss, Lukas Grätz, Pawel Kozielewicz
Journal: Trends in Pharmacological Sciences (2024)

The Frizzled family of transmembrane receptors (FZD1–10) belongs to the class F of G protein-coupled receptors (GPCRs). FZDs bind to and are activated by Wingless/Int1 (WNT) proteins. The WNT/FZD signaling system regulates crucial aspects of developmental biology and stem-cell regulation. Dysregulation of WNT/FZD communication can lead to developmental defects and diseases such as cancer and fibrosis. Recent insight into the activation mechanisms of FZDs has underlined that protein dynamics and conserved microswitches are essential for FZD-mediated information flow and build the basis for targeting these receptors pharmacologically. In this review, we summarize recent advances in our understanding of FZD activation, and how novel concepts merge and collide with existing dogmas in the field.
EMC10 modulates hepatic ER stress and steatosis in an isoform-specific manner
Authors: Kuangyang Chen, Yahao Wang, Jia Yang, Nora Klöting, Chuanfeng Liu, Jiarong Dai, Shuoshuo Jin, Lijiao Chen, Shan Liu, Yuzhao Liu, Yongzhuo Yu, Xiaoxia Liu, Qing Miao, Chong Wee Liew, Yangang Wang, Arne Dietrich, Matthias Blüher, Xuanchun Wang
Journal: Journal of Hepatology (2024)

Background & aimsEndoplasmic reticulum (ER) membrane protein complex subunit 10 (EMC10) has been implicated in obesity. Here we investigated the roles of the two isoforms of EMC10, including a secreted isoform (scEMC10) and an ER membrane-bound isoform (mEMC10), in MASLD.MethodsManifold steatotic mouse models and HepG2 cells were employed to investigate the role of EMC10 in the regulation of hepatic PERK-eIF2α-ATF4 signaling and hepatosteatosis. The therapeutic effect of scEMC10-neutralizing antibody on mouse hepatosteatosis was explored. Associations of MASLD with serum scEMC10 and hepatic mEMC10 were determined in two cohorts of participants with MASLD.ResultsscEMC10 promoted, while mEMC10 suppressed the activation of hepatocytic PERK-eIF2α-ATF4 signaling. Emc10 gene knockout exacerbated, while hepatic overexpression of mEMC10 ameliorated hepatic ER stress and steatosis in mice challenged with either a MCD diet or tunicamycin, highlighting a direct, suppressive role of mEMC10 in MASLD via modulation of hepatic ER stress. Overexpression of scEMC10 promoted, whereas neutralization of circulating scEMC10 prevented hepatosteatosis in mice with fatty liver, suggesting a progressive role of scEMC10 in MASLD. Clinically, serum scEMC10 increased, while hepatic mEMC10 decreased in participants with MASLD. Correlative analysis indicated serum scEMC10 positively, whereas hepatic mEMC10 negatively correlated with liver fat content and serum ALT, AST, and GGT.ConclusionsThese findings demonstrate a novel, isoform specific role for EMC10 in the pathogenesis of MASLD and identify the secreted isoform as a tractable therapeutic target for MASLD via antibody-based neutralization.Impact and ImplicationsWe have shown the role of EMC10 in the regulation of energy homeostasis and obesity. In this study, we determine the distinct roles of the two isoforms of EMC10 in the regulation of hepatic ER stress and steatosis in mice, and associations of MASLD with different EMC10 isoforms in humans. Our findings delineate a novel regulatory axis for hepatosteatosis and identify EMC10 as a modulator of the PERK-eIF2α-ATF4 signaling cascade that may be of broad physiological significance. Moreover, our pre-clinical and clinical studies clearly provide the foundations for translation of scEMC10 modulation for the treatment of MASLD.
<i>GLMN</i> variants cause skin hyperpigmentation: a promising potential therapeutic target
Authors: Qiaoyu Cao, Ming Li
Journal: British Journal of Dermatology (2024)

Journal Article Accepted manuscript GLMN variants cause skin hyperpigmentation: a promising potential therapeutic target Get access Qiaoyu Cao, Qiaoyu Cao Department of Dermatology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China Search for other works by this author on: Oxford Academic Google Scholar Ming Li Ming Li Department of Dermatology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China Corresponding author: Ming Li, M.D., Ph.D., Email:mingli@fudan.edu.cn https://orcid.org/0000-0003-3053-2756 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljae149, https://doi.org/10.1093/bjd/ljae149 Published: 08 April 2024 Article history Received: 01 April 2024 Accepted: 04 April 2024 Published: 08 April 2024
Effects of sacubitril/valsartan according to polypharmacy status in <scp>PARAGON‐HF</scp>
Authors: Shingo Matsumoto, Mingming Yang, Li Shen, Alasdair Henderson, Brian L. Claggett, Akshay S. Desai, Martin Lefkowitz, Jean L. Rouleau, Orly Vardeny, Michael R. Zile, Pardeep S. Jhund, Muthiah Vaduganathan, Scott D. Solomon, John J.V. McMurray
Journal: European Journal of Heart Failure (2024)
Neuronal activity rapidly reprograms dendritic translation via eIF4G2:uORF binding
Authors: Ezgi Hacisuleyman, Caryn R. Hale, Natalie Noble, Ji-dung Luo, John J. Fak, Misa Saito, Jin Chen, Jonathan S. Weissman, Robert B. Darnell
Journal: Nature Neuroscience (2024)

Abstract Learning and memory require activity-induced changes in dendritic translation, but which mRNAs are involved and how they are regulated are unclear. In this study, to monitor how depolarization impacts local dendritic biology, we employed a dendritically targeted proximity labeling approach followed by crosslinking immunoprecipitation, ribosome profiling and mass spectrometry. Depolarization of primary cortical neurons with KCl or the glutamate agonist DHPG caused rapid reprogramming of dendritic protein expression, where changes in dendritic mRNAs and proteins are weakly correlated. For a subset of pre-localized messages, depolarization increased the translation of upstream open reading frames (uORFs) and their downstream coding sequences, enabling localized production of proteins involved in long-term potentiation, cell signaling and energy metabolism. This activity-dependent translation was accompanied by the phosphorylation and recruitment of the non-canonical translation initiation factor eIF4G2, and the translated uORFs were sufficient to confer depolarization-induced, eIF4G2-dependent translational control. These studies uncovered an unanticipated mechanism by which activity-dependent uORF translational control by eIF4G2 couples activity to local dendritic remodeling.
Maternal diabetes and risk of attention-deficit/hyperactivity disorder in offspring in a multinational cohort of 3.6 million mother–child pairs
Authors: Adrienne Y. L. Chan, Le Gao, Miyuki Hsing-Chun Hsieh, Lars J. Kjerpeseth, Raquel Avelar, Tobias Banaschewski, Amy Hai Yan Chan, David Coghill, Jacqueline M. Cohen, Mika Gissler, Jeff Harrison, Patrick Ip, Øystein Karlstad, Wallis C. Y. Lau, Maarit K. Leinonen, Wing Cheong Leung, Tzu-Chi Liao, Johan Reutfors, Shih-Chieh Shao, Emily Simonoff, Kathryn Choon Beng Tan, Katja Taxis, Andrew Tomlin, Carolyn E. Cesta, Edward Chia-Cheng Lai, Helga Zoega, Kenneth K. C. Man, Ian C. K. Wong
Journal: Nature Medicine (2024)

Abstract Previous studies report an association between maternal diabetes mellitus (MDM) and attention-deficit/hyperactivity disorder (ADHD), often overlooking unmeasured confounders such as shared genetics and environmental factors. We therefore conducted a multinational cohort study with linked mother–child pairs data in Hong Kong, New Zealand, Taiwan, Finland, Iceland, Norway and Sweden to evaluate associations between different MDM (any MDM, gestational diabetes mellitus (GDM) and pregestational diabetes mellitus (PGDM)) and ADHD using Cox proportional hazards regression. We included over 3.6 million mother–child pairs between 2001 and 2014 with follow-up until 2020. Children who were born to mothers with any type of diabetes during pregnancy had a higher risk of ADHD than unexposed children (pooled hazard ratio (HR) = 1.16, 95% confidence interval (CI) = 1.08-1.24). Higher risks of ADHD were also observed for both GDM (pooled HR = 1.10, 95% CI = 1.04-1.17) and PGDM (pooled HR = 1.39, 95% CI = 1.25-1.55). However, siblings with discordant exposure to GDM in pregnancy had similar risks of ADHD (pooled HR = 1.05, 95% CI = 0.94-1.17), suggesting potential confounding by unmeasured, shared familial factors. Our findings indicate that there is a small-to-moderate association between MDM and ADHD, whereas the association between GDM and ADHD is unlikely to be causal. This finding contrast with previous studies, which reported substantially higher risk estimates, and underscores the need to reevaluate the precise roles of hyperglycemia and genetic factors in the relationship between MDM and ADHD.
Histopathological biomarkers for predicting the tumour accumulation of nanomedicines
Authors: Jan-Niklas May, Jennifer I. Moss, Florian Mueller, Susanne K. Golombek, Ilaria Biancacci, Larissa Rizzo, Asmaa Said Elshafei, Felix Gremse, Robert Pola, Michal Pechar, Tomáš Etrych, Svea Becker, Christian Trautwein, Roman D. Bülow, Peter Boor, Ruth Knuechel, Saskia von Stillfried, Gert Storm, Sanyogitta Puri, Simon T. Barry, Volkmar Schulz, Fabian Kiessling, Marianne B. Ashford, Twan Lammers
Journal: Nature Biomedical Engineering (2024)

The clinical prospects of cancer nanomedicines depend on effective patient stratification. Here we report the identification of predictive biomarkers of the accumulation of nanomedicines in tumour tissue. By using supervised machine learning on data of the accumulation of nanomedicines in tumour models in mice, we identified the densities of blood vessels and of tumour-associated macrophages as key predictive features. On the basis of these two features, we derived a biomarker score correlating with the concentration of liposomal doxorubicin in tumours and validated it in three syngeneic tumour models in immunocompetent mice and in four cell-line-derived and six patient-derived tumour xenografts in mice. The score effectively discriminated tumours according to the accumulation of nanomedicines (high versus low), with an area under the receiver operating characteristic curve of 0.91. Histopathological assessment of 30 tumour specimens from patients and of 28 corresponding primary tumour biopsies confirmed the score's effectiveness in predicting the tumour accumulation of liposomal doxorubicin. Biomarkers of the tumour accumulation of nanomedicines may aid the stratification of patients in clinical trials of cancer nanomedicines.
Medical algorithm: Diagnosis and treatment of drug reaction with eosinophilia and systemic symptoms in adult patients
Authors: Marie‐Charlotte Brüggen, Stephan Traidl, Yasutaka Mitamura, Sarah Walsh, Lars E. French, Nicholas Gulati, Elizabeth Phillips, Emanual Maverakis, Saskia Ingen‐Housz‐Oro
Journal: Allergy (2024)

The authors have no conflicts of interest to declare. Not applicable: there are no original data shown provided in this paper and all references are provided. Table S1. Table S2. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Smoking-associated gene expression alterations in nasal epithelium reveal immune impairment linked to lung cancer risk
Authors: Maria Stella de Biase, Florian Massip, Tzu-Ting Wei, Federico M. Giorgi, Rory Stark, Amanda Stone, Amy Gladwell, Martin O’Reilly, Daniel Schütte, Ines de Santiago, Kerstin B. Meyer, Florian Markowetz, Bruce A. J. Ponder, Robert C. Rintoul, Roland F. Schwarz
Journal: Genome Medicine (2024)

Abstract Background Lung cancer is the leading cause of cancer-related death in the world. In contrast to many other cancers, a direct connection to modifiable lifestyle risk in the form of tobacco smoke has long been established. More than 50% of all smoking-related lung cancers occur in former smokers, 40% of which occur more than 15 years after smoking cessation. Despite extensive research, the molecular processes for persistent lung cancer risk remain unclear. We thus set out to examine whether risk stratification in the clinic and in the general population can be improved upon by the addition of genetic data and to explore the mechanisms of the persisting risk in former smokers. Methods We analysed transcriptomic data from accessible airway tissues of 487 subjects, including healthy volunteers and clinic patients of different smoking statuses. We developed a computational model to assess smoking-associated gene expression changes and their reversibility after smoking is stopped, comparing healthy subjects to clinic patients with and without lung cancer. Results We find persistent smoking-associated immune alterations to be a hallmark of the clinic patients. Integrating previous GWAS data using a transcriptional network approach, we demonstrate that the same immune- and interferon-related pathways are strongly enriched for genes linked to known genetic risk factors, demonstrating a causal relationship between immune alteration and lung cancer risk. Finally, we used accessible airway transcriptomic data to derive a non-invasive lung cancer risk classifier. Conclusions Our results provide initial evidence for germline-mediated personalized smoke injury response and risk in the general population, with potential implications for managing long-term lung cancer incidence and mortality.