tbuckley/cabot-search huggingface dataset:
Pattern of Congenital Heart Diseases in Children with Congenital Malformations: An Echocardiographic study from a Tertiary Health facility in Sokoto, Nigeria
Authors: Isezuo KO, Sani UM, Waziri UM, Garba BI, Adamu A, Musa N, Falaye MA, Jiya FB
Journal: Clinical Cardiology and Cardiovascular Interventions (2021)

Background: Children with congenital malformations (CM) may have congenital heart diseases (CHDs) which may be initially asymptomatic. These need to be recognised and managed early in order to reduce unnecessary morbidity in affected patients. We report the pattern of CHDs in children with congenital malformations who had echocardiography over a one year period in UDUTH, Sokoto. Materials and Methods: A cross-sectional study carried out in the Paediatric Cardiology Unit from 1st January to 31st December 2019. Children presenting with CM were recruited and had echocardiagraphic screening for CHDs. Data were analysed with SPSS 23 version. Statistical significance was taken at p &lt; 0.05. Results: 81 children were seen with CM, comprising 42 females and 39 males (M:F=0.93:1); age range of 2 days to 13 years. Most frequent malformationswere anorectal malformations (ARM) in 28 (34.6%), Down syndrome in 17 (21.0%), multiple CM 10 (8.1%) and ocular abnormalities in 4 (4.9%). Thirty two (39.5%) of the patients with CM were diagnosed with CHD, out of which 24 (29.6%) had cardiac murmur. Most frequent CHD was atrioventricular septal defect in 9 (28.1%) followed by ventricular septal defect in 8 (25.0%) and patent arterial duct in 4 (12.5%). CHDs were found in all (100%) those with ocular abnormalities, in 76.5% of Down syndrome and in 14.3% of patients with ARM. Presence of murmur was significantly associated with CHD (χ2=18.0; p=0.001; OR=8.2; 95% C.1=2.8 – 24.1). Conclusion: Congenital malformations, particularly Down syndrome and ocular abnormalities, are significantly associated with CHDs. Cardiac murmurs were suggestive of CHD in children with congenital malformations.
Abstract 106: Utility of Ferritin as a Predictor of the Patients with Kawasaki Disease Refractory to Intravenous Immunoglobulin Therapy
Authors: Noboru Yamamoto, Kaoru Sato, Takayuki Hoshina, Masumi Kojiro, Koichi Kusuhara, Koichi Kusuhara
Journal: Circulation (2015)

Purpose: Several scoring systems for prediction of non-responsiveness to initial course of intravenous immunoglobulin (IVIG) therapy have been available in the patients diagnosed as Kawasaki disease (KD). However, all non-responders cannot be identified completely by these scoring systems. The aim of this study is to investigate whether ferritin can be a useful marker as a predictor of the patients with KD refractory to IVIG therapy. Materials and Methods: This retrospective study enrolled 63 patients with KD hospitalized at Kitakyushu General Hospital during 2010 to 2013. These patients were divided into IVIG responders (n= 41) and non-responders (n=22). Serum ferritin levels and the scoring systems for prediction of non-responsiveness to initial IVIG treatment were compared between these two groups. Results: Serum ferritin level was significantly elevated in non-responders (p=0.01). The area under the receiver-operating-characteristics curve was 0.698, and the sensitivity and specificity in more than 215 ng/ml of serum ferritin levels was 54.5% and 85.4%, respectively. Two of the three scoring systems for prediction of non-responsiveness to initial IVIG treatment in non-responders were also significantly higher scores than that in responders, but many non-responders had a low score of these scoring systems. Approximately half of the patients with low score of these scoring systems had high serum ferritin level (≧ 215 ng/ml). Conclusion: Serum ferritin level can be a useful marker for the prediction of non-responsiveness to initial IVIG treatment and may be an important complementary marker to the scoring systems for prediction of non-responsiveness to initial IVIG treatment.
Abstract PO-041: An immunologic niche of antigen presenting cells and stem-like CD8+ T-cells is present in non-small cell lung cancer brain metastases
Authors: Caroline S. Jansen, Luke del Balzo, Roshan Prabhu, Suzanna Logan, Prasanthi Chappa, Kirtesh Patel, Scott Wilkinson, Ross Lake, Hui-Kuo G. Shu, Jim Zhong, Vishal Dhere, Jeffrey Olson, Adam G. Sowalsky, Mohammad K. Khan, Haydn T. Kissick, Zachary S. Buchwald
Journal: Clinical Cancer Research (2021)

Abstract Background: Non-small cell lung cancer (NSCLC) patients with brain metastases have a very poor prognosis. The first line treatments for NSCLC brain metastases are typically surgery and pre- or post-operative stereotactic radiosurgery (SRS) or SRS alone. However, subsequent intra-cranial failure and death is common. Importantly, we have previously shown that a unique immune niche in genitourinary malignancies correlates with the risk for disease recurrence. Accordingly, here we investigated whether this immune niche was present in brain metastases, whether it correlated with patient outcomes, and whether it was modulated by SRS. Methods: Formalin fixed paraffin embedded brain metastases were stained by immunofluorescence for CD8, PD-1, TCF-1, MHC-II and DAPI. Following successful image acquisition using fluorescent whole slide scanning, we used a custom quantitative analysis pipeline to measure the cellularity, relative cellular locations, local cellular density, and marker staining intensity. Results: We identified immune niches consisting of both stem-like TCF-1+ CD8+ T-cells and antigen presenting cells (MHC-II+) in brain metastases. TCF-1+ CD8+ T-cells were found at in areas of higher MHC-II+ cell density than the TCF-1 CD8+negative T-cells. The amount of tumor issue occupied by immune niches correlated with TCF1+ CD8+ T-cell infiltration, as well as with total CD8+ T-cell and MHC-II+ cell infiltration. Importantly, we found that higher MHC-II+ cell density correlated with longer overall survival in this cohort of patients. Additionally, we found this immune niche is preserved following pre-operative SRS. Conclusions: Our study is the first to demonstrate stem-like CD8+ T-cells in brain metastases and that these cells form an immune niche similar to those described extra-cranial tumor sites. Additionally, we report that the immune niche is preserved following SRS, which is highly clinically relevant to the use of combinatorial strategies between SRS and checkpoint blockade. Citation Format: Caroline S. Jansen, Luke del Balzo, Roshan Prabhu, Suzanna Logan, Prasanthi Chappa, Kirtesh Patel, Scott Wilkinson, Ross Lake, Hui-Kuo G. Shu, Jim Zhong, Vishal Dhere, Jeffrey Olson, Adam G. Sowalsky, Mohammad K. Khan, Haydn T. Kissick, Zachary S. Buchwald. An immunologic niche of antigen presenting cells and stem-like CD8+ T-cells is present in non-small cell lung cancer brain metastases [abstract]. In: Proceedings of the AACR Virtual Special Conference on Radiation Science and Medicine; 2021 Mar 2-3. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(8_Suppl):Abstract nr PO-041.
Retrograde endosonography-guided hepaticojejunostomy after failed rendezvous in a patient with Child’s resection
Authors: Takeshi Okamoto, Kenji Nakamura, Minoru Yabuta, Katsuyuki Fukuda
Journal: Endoscopy (2021)

Corrected by: Correction: Retrograde endosonography-guided hepaticojejunostomy after failed rendezvous in a patient with Roux-en-Y anastomosisEndoscopy eFirstDOI: 10.1055/a-1634-1768
Abstract 15691: The Novel High Mobility Group Protein Hmgxb4 Promotes Neointimal Formation in Response to Arterial Injury
Authors: xiangqin he, Kunzhe Dong, Jian Shen, Islam Osman, Guoqing Hu, Jiliang Zhou
Journal: Circulation (2020)

Introduction: Restenosis after percutaneous intervention is predominantly attributed to proliferation and migration of vascular smooth muscle cells (VSMCs). However, the key regulators responsible for VSMC proliferation and migration remain to be identified. Hypothesis: We previously reported that the novel high mobility group (HMG) nuclear protein HMGXB4 (HMG-Box containing 4) plays a critical role in the de-differentiation of vascular smooth muscle cells in vitro and in acute inflammatory response to septic shock. We hypothesize that HMGXB4 is critical for neointimal hyperplasia in response to inflammatory stimuli. Methods and Results: We found that the expression of HMGXB4 is dramatically induced in ligation or wire injury-induced neointimal hyperplasia and correlated with the activation of inflammatory signaling in mice. Using an inducible smooth muscle-specific Hmgxb4 KO (knockout) mice model, we found specific KO of Hmgxb4 in VSMCs ameliorates ligation- or wire- injury induced neointimal formation. Among an array of growth factors and inflammation cytokines, we found that TNFα and INFγ effectively induces the expression of HMGXB4 in VSMCs and correlates with the VSMC proliferation in vitro. Furthermore, we found deletion of HMGXB4 attenuates while over-expression of HMGXB4 promotes inflammation cytokines-induced VSMC proliferation in vitro. These results suggest injury-induced inflammatory signal triggers HMGXB4 induction, which, in turn, promotes the VSMC proliferation and neointimal formation. Conclusions: Our study not only demonstrates a critical role of HMGXB4 in promoting neointimal hyperplasia in response the arterial injury, but also suggests HMGXB4 is a potential novel target for the management of restenosis in human.
Irx3 and Irx5 in Ins2-Cre+ cells regulate hypothalamic postnatal neurogenesis and leptin response
Authors: Joe Eun Son, Zhengchao Dou, Kyoung-Han Kim, Siyi Wanggou, Vincent Su Bin Cha, Rong Mo, Xiaoyun Zhang, Xinyu Chen, Troy Ketela, Xuejun Li, Xi Huang, Chi-chung Hui
Journal: Nature Metabolism (2021)
Commentary on “Limitations in the literature regarding Mohs surgery and staged excision for melanoma: A critical review of quality and data reporting”
Authors: Christopher J. Miller, Jeremy R. Etzkorn, Justin J. Leitenberger, Anna Bar, Christian L. Baum, Jerry D. Brewer, Divya Srivastava, Rajiv I. Nijhawan
Journal: Journal of the American Academy of Dermatology (2021)
Evaluation of myCOPD, a digital selfmanagement technology for people with COPD, in a remote and rural population
Authors: R. J. Cooper, J. Colligan, S. Hamilton, E. Finlayson, M. Duffy, J. Gilliatt, M. Swanson, A. Giangreco, E. K. Sage
Journal: Gut (2021)

Aim The prevalence of chronic obstructive pulmonary disease (COPD) in poor, remote, and rural populations is twice that of cities (15 4% versus 8 4%) 1 COPD costs the NHS an estimated ≤1 9bn/year2 and is characterised by exacerbation frequency and severity  Disease education and self-management are critical to reducing the healthcare burden for patients with COPD  We evaluated myCOPD, a digital self-management technology in a predominantly remote and rural population  Weassessed whether myCOPD was effective in reducing hospital admissions, inpatient bed days and other NHS service usage  Method 120 people were recruited over 6 months  We compared data regarding hospital admissions, inpatient bed days, clinic attendances, out of hours contacts and home visits 12 months before and up to 12 months after myCOPD activation  To account for differences in activation rates and the early termination of the study due to COVID-19 data was reported as daily outcome measures  Results The average participant age was 67, with a GOLD score 1-4 (average 2 7)  The average 6-fold urban-rural score was 4 23 indicating a predominantly remote and/or rural population  78% of patients activated myCOPD, 70% recorded their symptom score at least once, and 45% used >1 myCOPD module  There was no association between myCOPD use and participant demographics  There were no statistically significant differences in hospital admissions, inpatient bed days, or other health service utilisation before and after myCOPD activation  However, a subgroup analysis found that those individuals with the greatest degree of myCOPD engagement either by frequency of symptom scoring (figure 1A) or by numbers of modules used (figure 1B) did show a reduction in bed days  Conclusion These data indicate no association between myCOPD use and either reduced bed days or other NHS service use on a whole group level however it may be of benefit to individuals with higher levels of engagement  Overall these results have significant implications regarding the design and evaluation of novel service innovations in COPD and other chronic disorders
Connecting the dots: Targeting the microbiome in drug toxicity
Authors: Yusha Luo, Tingting Zhou
Journal: Medicinal Research Reviews (2021)

Abstract The gut microbiota has a vast influence on human health and its role in initiating, aggravating, or ameliorating diseases is beginning to emerge. Recently, its contribution to heterogeneous toxicological responses is also gaining attention, especially in drug‐induced toxicity. Whether they are orally administered or not, drugs may interact with the gut microbiota directly or indirectly, which leads to altered toxicity. Present studies focus more on the unidirectional influence of how xenobiotics disturb intestinal microbial composition and functions, and thus induce altered homeostasis. However, interactions between the gut microbiota and xenobiotics are bidirectional and the impact of the gut microbiota on xenobiotics, especially on drugs, should not be neglected. Thus, in this review, we focus on how the gut microbiota modulates drug toxicity by highlighting the microbiome, microbial enzyme, and microbial metabolites. We connect the dots between drugs, the microbiome, microbial enzymes or metabolites, drug metabolites, and host toxicological responses to facilitate the discovery of microbial targets and mechanisms associated with drug toxicity. Besides this, current mainstream strategies to manipulate drug toxicity by targeting the microbiome are summarized and discussed. The review provides technical reference for the evaluation of medicinal properties in the research and development of innovative drugs, and for the future exploitation of strategies to reduce drug toxicity by targeting the microbiome.
A population-based study on associations of stool microbiota with atopic diseases in school-age children
Authors: Chen Hu, Evelien R. van Meel, Carolina Medina-Gomez, Robert Kraaij, Monica Barroso, Jessica Kiefte-de Jong, Djawad Radjabzadeh, Suzanne G.M.A. Pasmans, Nicolette W. de Jong, Johan C. de Jongste, Henriette A. Moll, Tamar Nijsten, Fernando Rivadeneira, Luba M. Pardo, Liesbeth Duijts
Journal: Journal of Allergy and Clinical Immunology (2021)

Infants with less diverse gut microbiota seem to have higher risks of atopic diseases in early life, but any associations at school age are unclear.This study sought to examine the associations of diversity, relative abundance, and functional pathways of stool microbiota with atopic diseases in school-age children.We performed a cross-sectional study within an existing population-based prospective cohort among 1440 children 10 years of age. On stool samples, 16S ribosomal RNA gene sequencing was performed, and taxonomic and functional tables were produced. Physician-diagnosed eczema, allergy, and asthma were measured by questionnaires, allergic sensitization by skin prick tests, and lung function by spirometry.The α-diversity of stool microbiota was associated with a decreased risk of eczema (odds ratio [OR], 0.98; 95% CI, 0.97, 1.00), and β-diversity was associated with physician-diagnosed inhalant allergy (R2 = 0.001; P = .047). Lachnospiraceae, Ruminococcaceae_UCG-005, and Christensenellaceae_R-7_group species were associated with decreased risks of eczema, inhalant allergic sensitization, and physician-diagnosed inhalant allergy (OR range, 0.88-0.94; 95% CI range, 0.79-0.96 to 0.88-0.98), while Agathobacter species were associated with an increased risk of physician-diagnosed inhalant allergy (OR, 1.23; 95% CI, 1.08-1.42). Functional pathways related to heme and terpenoid biosynthesis were associated with decreased risks of physician-diagnosed inhalant allergy and asthma (OR range, 0.89-0.86; 95% CI range, 0.80-0.99 to 0.73-1.02). No associations of stool microbiota with lung function were observed.The diversity, relative abundance and functional pathways of stool microbiota were most consistently associated with physician-diagnosed inhalant allergy in school-age children and less consistently with other atopic diseases.
Patient-derived glial enriched progenitors repair functional deficits due to white matter stroke and vascular dementia in rodents
Authors: Irene L. Llorente, Yuan Xie, Jose A. Mazzitelli, Emily A. Hatanaka, Jessica Cinkornpumin, David R. Miller, Ying Lin, William E. Lowry, S. Thomas Carmichael
Journal: Science Translational Medicine (2021)

A specific prorepair glial stem cell therapy promotes brain repair in vascular dementia in rodent models.
Abstract 16277: PCSK9 Inhibitors, an Ineffectual Treatment for Apolipoprotein B-100 Defective Familial Hypercholesterolemia
Authors: Michael D Holyoak, Lauryn K Gorby, Patrick M Moriarty
Journal: Circulation (2019)

Introduction: Pro-protein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) are a lipid modifying therapy (LMT) approved for patients with cardiovascular disease (CVD) and primary hyperlipidem...
Bcl-2は,BRCA1を内膜に局在化することによって,核相同組み換えを阻害する
Authors: Laulier Corentin, Barascu Aurelia, Guirouilh-Barbat Josee, Pennarun Gaelle, LE Chalony Catherine, Chevalier Francois, Palierne Gaelle, Bertrand Pascale, Verbavatz Jean Marc, S Lopez Bernard
Journal: Cancer Research (2011)
Multi-omics study reveals that statin therapy is associated with restoration of gut microbiota homeostasis and improvement in outcomes in patients with acute coronary syndrome
Authors: Xiaomin Hu, Hanyu Li, Xinyue Zhao, Ruilin Zhou, Honghong Liu, Yueshen Sun, Yue Fan, Yanan Shi, Shanshan Qiao, Shuangjiang Liu, Hongwei Liu, Shuyang Zhang
Journal: Theranostics (2021)

Prior chronic treatment with statins has been shown to be associated with more favorable outcomes in patients with acute coronary syndrome (ACS). Specific changes in the gut microbiota and microbial metabolites have been shown to influence the progression of coronary artery disease. However, the critical microbial and metabolomic changes associated with the cardiovascular protective effects of statins in ACS remain elusive.
Notch‐1 and Notch‐3 Mediate Hypoxia‐Induced Activation of Synovial Fibroblasts in Rheumatoid Arthritis
Authors: Jianhai Chen, Wenxiang Cheng, Jian Li, Yan Wang, Jingqin Chen, Xin Shen, Ailing Su, Donghao Gan, Liqing Ke, Gang Liu, Jietao Lin, Liang Li, Xueling Bai, Peng Zhang
Journal: Arthritis & Rheumatology (2021)

Objective To investigate the molecular mechanism of hypoxia‐induced rheumatoid arthritis synovial fibroblast (RASF) activation via Notch‐1 and Notch‐3 signaling, and to evaluate its potential as a therapeutic target. Methods Expression of Notch‐1 intracellular domain (N1ICD), N3ICD, and hypoxia‐inducible factor 1α (HIF‐1α) was assessed by immunhistology in synovial tissue from patients with RA. RASFs were cultured under hypoxic conditions and normoxic conditions with or without small interfering RNAs (siRNAs), and N1ICD and N3ICD were overexpressed under normoxic conditions. Rats with collagen‐induced arthritis (CIA) were administered LY411575 (inhibitor of N1ICD and N3ICD) for 15 days and 28 days, and its therapeutic efficacy was assessed by histologic and radiologic evaluation of the rat synovial tissue, and by analysis of inflammatory cytokine production in the serum of rats. Results N1ICD, N3ICD, and HIF‐1α were expressed abundantly in the synovial tissue of RA patients. HIF‐1α was shown to directly regulate the expression of Notch‐1 and Notch‐3 genes under hypoxic conditions. Moreover, hypoxia‐induced N1ICD and N3ICD expression in RASFs was blocked by HIF‐1α siRNA. Notch‐1 siRNA and Notch‐3 siRNA inhibited hypoxia‐induced RASF invasion and angiogenesis in vitro, whereas overexpression of N1ICD and N3ICD promoted these processes. In addition, Notch‐1 was shown to regulate RASF migration and epithelial–mesenchymal transition under hypoxic conditions, whereas Notch‐3 was shown to regulate the processes of anti‐apoptosis and autophagy. Furthermore, in vivo studies in rats with CIA showed that the N1ICD and N3ICD inhibitor LY411575 had a therapeutic effect in terms of ameliorating the symptoms and severity of the disease. Conclusion This study identified a functional link between HIF‐1α, Notch‐1, and Notch‐3 signaling in regulating activation of RASFs and the processes involved in the pathogenesis of RA.
scMET: Bayesian modeling of DNA methylation heterogeneity at single-cell resolution
Authors: Chantriolnt-Andreas Kapourani, Ricard Argelaguet, Guido Sanguinetti, Catalina A. Vallejos
Journal: Genome biology (2021)

High-throughput single-cell measurements of DNA methylomes can quantify methylation heterogeneity and uncover its role in gene regulation. However, technical limitations and sparse coverage can preclude this task. scMET is a hierarchical Bayesian model which overcomes sparsity, sharing information across cells and genomic features to robustly quantify genuine biological heterogeneity. scMET can identify highly variable features that drive epigenetic heterogeneity, and perform differential methylation and variability analyses. We illustrate how scMET facilitates the characterization of epigenetically distinct cell populations and how it enables the formulation of novel hypotheses on the epigenetic regulation of gene expression. scMET is available at https://github.com/andreaskapou/scMET .
Clinico-radiological recovery following severe COVID-19 pneumonia
Authors: A. W. Creamer, S. Alaee, H. Iftikhar, F. Ahmed, H. Steer, C. Sharp
Journal: Gut (2021)

Background The recovery course following COVID-19 pneumonia remains poorly understood  Analysis of routine clinical and imaging follow up of patients admitted with COVID-19 pneumonia undertaken in accordance with British Thoracic Society (BTS) guidance offers an opportunity to improve our understanding of the recovery course following acute infection  Methods All patients requiring Intensive or Respiratory High Dependency Unit care with COVID-19 pneumonia who survived to discharge were offered telephone review and interval chest radiograph (CXR) at 6 and 12 weeks respectively in accordance with BTS guidance  Patients were contacted in chronological order by discharge date  The data presented here covers discharges between 25/03-03/05/20 inclusive  All chest radiographs were reported by a consultant radiologist  Results A total of N=73 patients were identified (74% male, mean age 57 6 years, range 22-84)  N=41 (56 1%) had been admitted to ITU, with the remainder admitted to HDU  Following discharge, N=6 (8 2%) were re-admitted within 30 days (median time to first re-admission 19 1 days)  N=2 (3 5%) patients were diagnosed with pulmonary emboli following the index admission  1 patient died within 30 days of discharge (unrelated to COVID infection)  Follow up calls occurred with N=57 patients, at median 9 6 weeks post discharge (range 6-12 weeks)  Patient reported persistence of symptoms at time of review is summarised in table 1  Interval CXR was available in N=49 patients  Of these, N=34 (71 7%) were clear, N=10 (19 5%) showed linear atelectasis, and N=5 (8 7%) showed persistent consolidation (all improved compared to admission CXR)  Discussion These data describe the clinico-radiological course following admission with severe COVID-19 pneumonia  Limitations of this analysis include limitation to patients receiving HDU/ITU level care and the retrospective categorisation of symptom persistence  Prospective studies serially assessing full symptomatology are required  Nevertheless, these data highlight persistent symptoms at 6-12 weeks;particularly exertional dyspnoea and fatigue  91% of patients were free from cough at this time;investigating for possible alternative causes should therefore be considered in patients experiencing chronic cough  These data are valuable in planning long-term support for patients following COVID-19 pneumonia, and support the BTS recommendations for early proactive follow up of this cohort