Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular Identification of Anisakis Larvae Extracted by Gastrointestinal Endoscopy from Health Check-up Patients in Korea

Anisakiasis is a zoonotic disease induced by anisakid nematodes, and endoscopic inspection is used for a diagnosis or remedy for it. Anisakis simplex, Anisakis physeteris, and Pseudoterranova decipiens had been reported to be the major species causing human infections, particularly, in Japan. However, in Korea, recent studies strongly suggested that Anisakis pegreffii is the major species of human infections. To support this suggestion, we collected anisakid larvae (n=20) from 20 human patients who were undergone gastrointestinal endoscopy at a health check-up center in Korea, and molecular identification was performed on the larvae using PCR-RFLP analysis and gene sequencing of rDNA ITS regions and mtDNA cox2. In addition, anisakid larvae (n=53) collected from the sea eel (Astroconger myriaster) were also examined for comparison with those extracted from humans. The results showed that all human samples (100%) were identified as A. pegreffii, whereas 90.7% of the samples from the sea eel were A. pegreffii with the remaining 9.3% being Hysterothylacium aduncum. Our study confirmed that A. pegreffii is the predominant species causing human anisakiasis in Korea, and this seems to be due to the predominance of this larval type in the fish (sea eels) popularly consumed by the Korean people. The possibility of human infection with H. aduncum in Korea is also suggested.
Allostery in BAX protein activation

BAX is a member of the proapoptotic BCL-2 family of proteins, which is involved in the regulation of the intrinsic pathway of apoptosis. In the process of apoptosis, BH3-only molecules activate cytosolic BAX. Activated BAX molecules insert into the mitochondrial outer membrane with their -helix and form oligomers that lead to membrane poration, resulting in the release of apoptogenic factors including cytochrome c. Recently, a novel interaction site for the binding of the BIM SAHB ligand to BAX was reported. BIM SAHB binding was shown to invoke the exposure of the 6A7 epitope (amino acids 13–19) and of the BH3 domain of BAX, followed by mobilization of the BAX -helix. However, the intramolecular pathway for signal transmission in BAX, from BIM SAHB binding to mobilization of the -helix largely remained elusive. For a molecular understanding of the activation of BAX, and thus the first steps in apoptosis, we performed microsecond atomistic molecular dynamics simulations both of the BAX protein and of the BAX:BIM SAHB complex in aqueous solution. In agreement with experiment, the 6A7 and BH3 domains adopt a more solvent-exposed conformation within the BAX:BIM SAHB complex. BIM SAHB binding was found to stabilize the secondary structure of the 9-helix. A force distribution analysis revealed a force network of residue–residue interactions responsible for signal transmission from the BIM SAHB binding site predominantly via the 4- and 6-helices to the 9-helix on the opposite site of the protein.
Reliability and Effectiveness of Smartphone Technology for the Diagnosis and Treatment Planning of Pediatric Elbow Trauma

Background: Mobile imaging, such as viewing radiographs as text messages, is increasingly prevalent in clinical settings. The purpose of this study was to determine whether remote diagnosis of pediatric elbow fractures using smartphone technology is reliable. In addition, this study aimed to determine whether the assessment regarding the decision for operative treatment is affected by evaluation of images on a mobile device as opposed to standard picture archiving and communication system (PACS). Methods: Standard anteroposterior and lateral radiographs of 50 pediatric elbow trauma cases were evaluated by 2 fellowship-trained pediatric orthopaedic surgeons and 2 senior orthopaedic residents. Raters were asked to classify the case as any of 6 diagnoses: supracondylar humerus, lateral condyle, medial epicondyle, radial neck fracture, positive posterior fat pad sign, or normal pediatric elbow. Raters were asked to choose operative or conservative treatment. After 1 week, photographs of the same images were taken from a standardized distance from a computer monitor with an iPhone 5 camera and transmitted by multimedia messaging to each rater. The same questions were again posed to raters. Interobserver and intraobserver reliabilities were calculated by Cohen &kgr;-statistics with bootstrapped 95% confidence intervals. Results: Intraobserver reliability of classification of injuries on PACS compared with smartphone images was excellent, with an overall &kgr; of 0.91. Treatment decision also demonstrated excellent intraobserver reliability (PACS vs. smartphones) with a &kgr; of 0.86 for all raters. Conclusions: Diagnosis of pediatric elbow injuries can be made equally reliably based on either PACS or transmitted multimedia messaging images taken with an iPhone camera from a computer screen and viewed on a smartphone. Treatment decisions can also be made reliably based on either image modality. Clinical Relevance: Using smartphones to transmit and display radiographs, which is common in current clinical practice, is effective and reliable for diagnosis and treatment planning of pediatric elbow injuries.
Objectively measured sedentary behaviour in overweight and obese prepubertal children: challenging the school

ABSTRACT Sedentary lifestyle is associated with unfavourable health outcomes; however, few studies have analysed the daily fluctuations of sedentary behaviour in children. The aim was to characterise sedentary behaviour in low active, overweight/obese prepubertal children and to examine whether there were daily, age- or gender-based differences. In this observational study free-living movement was measured by accelerometry for one week. Eighty-eight low active, overweight/obese children (8- to 12-year-olds) were included. Analysis was conducted for weekends, weekdays, school time and non-school time on weekdays. Participants spent half of their waking hours engaged in sedentary behaviour (48.1%). Short sedentary bouts (1–4 min) accounted for 86% of sedentary time. Sedentary time was similar on weekends and non-school time, while it was highest during school time. Interventions for the management of childhood obesity should include strategies for shifting sedentary time to physical activity on weekends and non-school time and implementing more activity-permissive classroom lessons.
The Functional Block of TNF but Not of IL‐6 Prevents Bone Loss in Ovariectomized Mice

Considerable evidence supports the hypothesis that estrogen prevents bone loss by blocking the bone marrow cell production of pro‐osteoclastogenic cytokines. However, controversy remains on the role of candidate factors, such as tumor necrosis factor (TNF) and interleukin‐6 (IL‐6). To investigate the contribution of these cytokines to the pathogenesis of ovariectomy (OVX)‐induced bone loss, OVX mice were treated with either TNF binding protein (TNFbp), an inhibitor of TNF, the anti–(IL‐6) antibody (Ab) 20F3, or estrogen for the first 2 weeks after surgery. OVX caused a rapid decrease in trabecular bone volume (TBV) and an increase in in vivo bone resorption, as assessed by bone histomorphometry. Treatment with TNFbp completely prevented bone loss and the increase in both osteoclast formation and bone resorption induced by OVX, but had no effects in sham‐operated controls. In contrast, treatment with anti–IL‐6 antibody failed to prevent bone loss, and the increase in bone resorption and osteoclastogenesis induced by OVX. These data demonstrate that in nongenetically manipulated mice, the estrogen‐regulated cytokine that plays a central role in the mechanism by which estrogen deficiency causes bone loss is not IL‐6, but rather TNF.
The dietary inflammatory index is associated with gastrointestinal infection symptoms in the national health and nutrition examination survey

Abstract Inflammation influences many aspects of health including gastrointestinal illnesses. Associations between the Dietary Inflammatory Index (DII®) and gastrointestinal symptoms were examined using cross-sectional data from the National Health and Nutrition Examination Survey (years 2005–2014, n = 25,553). Outcomes included self-reported presence of mucus or liquid in bowel leakage and stomach illness in the past month, diarrhoea in the past year and number of weekly bowel movements. Energy-adjusted DII (E-DII) scores were estimated from one 24-h dietary recall. Analyses included survey design-appropriate logistic and linear regression. Compared to E-DII quartile 1 (anti-inflammatory), E-DII quartile 4 (pro-inflammatory) had elevated odds of mucus in leakage: 71% (95% confidence interval [95%CI] = 1.01–1.20); liquid in leakage: 74% (95%CI = 1.30–2.33); stomach illness: 43% (95%CI = 1.18–1.72); and diarrhoea: 65% (95%CI = 1.21–2.26). Those with more anti-inflammatory diets had more bowel movements. Future questions should address whether anti-inflammatory diets provide protective effects against gastrointestinal infections and if these relationships are modified by other health behaviours.
Utilization of Galleria mellonella larvae to characterize the development of Staphylococcus aureus infection.

Staphylococcus aureus is a human opportunistic pathogen that causes a wide range of superficial and systemic infections in susceptible patients. Here we describe how an inoculum of S. aureus activates the cellular and humoral response of Galleria mellonella larvae while growing and disseminating throughout the host, forming nodules and ultimately killing the host. An inoculum of S. aureus (2×106 larva- 1 ) decreased larval viability at 24 (80±5.77 %), 48 (55.93±5.55 %) and 72 h (10.23±2.97 %) and was accompanied by significant proliferation and dissemination of S. aureus between 6 and 48 h and the formation of nodules in the host. The hemocyte (immune cell) densities increased between 4 and 24 h and hemocytes isolated from larvae after 24 h exposure to heat-killed S. aureus (2×106 larva- 1 ) showed altered killing kinetics as compared to those from control larvae. Alterations in the humoral immune response of larvae 6 and 24 h post-infection were also determined by quantitative shotgun proteomics. The proteome of 6 h-infected larvae was enriched for antimicrobial proteins, proteins of the prophenoloxidase cascade and a range of peptidoglycan recognition proteins. By 24 h there was a significant increase in the abundance of a range of antimicrobial peptides with anti-staphylococcal activity and proteins associated with nodule formation. The results presented here indicate how S. aureus interacts with the larval immune response, induces the expression of a variety of immune-related peptides and also forms nodules which are a hallmark of soft tissue infections during human infection.
Primary structure and functional expression of the Na/Ca,K‐exchanger from bovine rod photoreceptors.

Complementary DNA encoding the Na/Ca,K‐exchanger was isolated from bovine retina cDNA libraries. The complete full‐length cDNA is approximately 4 kb long and contains an open reading frame of 3597 bp. The deduced amino acid sequence corresponds to a protein of 1199 amino acids with a calculated molecular weight of approximately 130 kDa. Hydrophobicity analysis revealed the presence of two alternating sets of hydrophobic and hydrophilic domains. There also exists a hydrophobic region at the N‐terminus which may be part of a cleavable signal peptide. The protein shares limited sequence homology with the Na/Ca‐exchanger from cardiac sarcolemma. Northern blot analysis indicates that the approximately 6 kb transcript is highly specific for retinal tissue. Insect cells infected with recombinant baculovirus bearing the full‐length cDNA express a functional Na/Ca,K‐exchanger with an apparent relative molecular weight of approximately 210 kDa, as determined by Western blotting.
Breast cancer treatment and sulfotransferase

Introduction: Sustained exposure to excessive estrogen is an established risk factor for breast cancer. Sulfotransferase (SULT)-mediated sulfonation represents an effective approach for estrogen deprivation as estrogen sulfates do not bind and activate estrogen receptors (ERs). The nuclear receptor (NR) superfamily functions as a sensor for xenobiotics as well as endogenous molecules, which can regulate the expression of SULT. Areas covered: In this review, we summarize the mechanisms of SULT regulation by NRs and inactivation of estrogen by SULT. Furthermore, we discuss the potential of clinical therapy targeting SULT in breast cancer treatment. Gaps in current knowledge that require further study are also highlighted. Expert opinion: The prevention of estrogen binding to ER by antiestrogen and inhibition of estrogen synthesis by aromatase or sulfatase inhibitor have been used in clinical therapy for breast cancer. Although the induction of SULT has been proven effective to estrogen inactivation, reports on this method applied to breast cancer treatment are rare. Targeted activation of SULT may open up a new means of treating hormone-dependent breast cancer.
Prognostic factors in patients treated with transarterial radioembolization for unresectable and chemorefractory colorectal cancer with liver metastases

ABSTRACT Background: Transarterial radioembolization (TARE) is used to treat unresectable colorectal cancer with liver metastases (CRCLM). This study aimed to assess survival after TARE and to identify potential prognostic factors in this patient population. Methods: Patients with unresectable and chemorefractory CRCLM treated with TARE at our institution between February 2006 and September 2015 were included in the study. Survival rate, hepatic tumor response, and potential prognostic factors were analyzed. Results: In the 43 study patients, the mean follow-up was 15.0 ± 14.2 months, with a median survival of 13.0 months and 1-, 2-, 3-, 4-, and 5-year survival rates of 52.1%, 24.9%, 21.4%, 21.4%, and 7.1%, respectively. The mean activity of yttrium-90 administered was 1.55 ± 0.28 GBq for the disease-controlled group and 1.19 ± 0.27 GBq for the progressive disease group (p= 0.031). Survival was correlated with Child-Pugh class (p< 0.001), hepatic tumor response (p= 0.001), and baseline carcinoembryonic antigen (CEA) level (p= 0.013). Conclusion: Child-Pugh class B, low degree of hepatic tumor response, and normal baseline CEA levels are prognostic factors for poorer survival after TARE in patients with unresectable and chemorefractory CRCLM. Hepatic tumor response is related to radiation activity delivered to the liver.
The influence of model parameters on model validation

Abstract The study examined the sensitivity of two musculoskeletal models to the parameters describing each model. Two different models were examined: a phenomenological model of human jumping with parameters based on live subject data, and the second a model of the First Dorsal Interosseous with parameters based on cadaveric measurements. Both models were sensitive to the model parameters, with the use of mean group data not producing model outputs reflective of either the performance of any group member or the mean group performance. These results highlight the value of subject specific model parameters, and the problems associated with model validation.
Use of Genome-Scale Integrated Analysis to Identify Key Genes and Potential Molecular Mechanisms in Recurrence of Lower-Grade Brain Glioma

Background The aim of this study was to identify gene signals for lower-grade glioma (LGG) and to assess their potential as recurrence biomarkers. Material/Methods An LGG-related mRNA sequencing dataset was downloaded from The Cancer Genome Atlas (TCGA) Informix. Multiple bioinformatics analysis methods were used to identify key genes and potential molecular mechanisms in recurrence of LGG. Results A total of 326 differentially-expressed genes (DEGs), were identified from 511 primary LGG tumor and 18 recurrent samples. Gene ontology (GO) analysis revealed that the DEGs were implicated in cell differentiation, neuron differentiation, negative regulation of neuron differentiation, and cell proliferation in the forebrain. The Kyoto Encyclopedia of Genes and Genomes (KEGG) database suggests that DEGs are associated with proteoglycans in cancer, the Wnt signaling pathway, ECM-receptor interaction, the PI3K-Akt signaling pathway, transcriptional deregulation in cancer, and the Hippo signaling pathway. The hub DEGs in the protein–protein interaction network are apolipoprotein A2 (APOA2), collagen type III alpha 1 chain (COL3A1), collagen type I alpha 1 chain (COL1A1), tyrosinase (TYR), collagen type I alpha 2 chain (COL1A2), neurotensin (NTS), collagen type V alpha 1 chain (COL5A1), poly(A) polymerase beta (PAPOLB), insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), and anomalous homeobox (ANHX). GSEA revealed that the following biological processes may associated with LGG recurrence: cell cycle, DNA replication and repair, regulation of apoptosis, neuronal differentiation, and Wnt signaling pathway. Conclusions Our study demonstrated that hub DEGs may assist in the molecular understanding of LGG recurrence. These findings still need further molecular studies to identify the assignment of DEGs in LGG.
Use of RNA Interference-mediated Gene Silencing and Adenoviral Overexpression to Elucidate the Roles of AKT/Protein Kinase B Isoforms in Insulin Actions*

Insulin plays a central role in the regulation of glucose homeostasis in part by stimulating glucose uptake and glycogen synthesis. The serine/threonine protein kinase Akt has been proposed to mediate insulin signaling in several processes. However, it is unclear whether Akt is involved in insulin-stimulated glucose uptake and which isoforms of Akt are responsible for each insulin action. We confirmed that expression of a constitutively active Akt, using an adenoviral expression vector, promoted translocation of glucose transporter 4 (GLUT4) to plasma membrane, 2-deoxyglucose (2-DG) uptake, and glycogen synthesis in both Chinese hamster ovary cells and 3T3-L1 adipocytes. Inhibition of Akt either by adenoviral expression of a dominant negative Akt or by the introduction of synthetic 21-mer short interference RNA against Akt markedly reduced insulin-stimulated GLUT4 translocation, 2-DG uptake, and glycogen synthesis. Experiments with isoform-specific short interference RNA revealed that Akt2, and Akt1 to a lesser extent, has an essential role in insulin-stimulated GLUT4 translocation and 2-DG uptake in both cell lines, whereas Akt1 and Akt2 contribute equally to insulin-stimulated glycogen synthesis. These data suggest a prerequisite role of Akt in insulin-stimulated glucose uptake and distinct functions among Akt isoforms.
c‐Met activation in lung adenocarcinoma tissues: An immunohistochemical analysis

c‐Met is often overexpressed in non‐small cell lung cancer, but it remains unsolved whether its overexpression leads to its activation. We used an antibody specific to phospho‐c‐Met (Tyr1235) to investigate c‐Met activation immunohistochemically in 130 surgically resected lung adenocarcinomas. The expression of c‐Met and hepatocyte growth factor (HGF) was also investigated. Phospho‐c‐Met was positive in 21.5% (28/130) of cases. c‐Met was positive in 74.6% of cases (97/130) and was expressed at high levels in 36.1% of cases (47/130). HGF was expressed at high levels in 31.5% of cases (41/130). Phospho‐c‐Met was correlated with high levels of HGF (P =0.0010) and high levels c‐Met expression (P = 0.0303), but it was also found to be positive in 12 cases with little to no HGF expression. Phospho‐c‐Met expression was significantly associated with tumor differentiation (P = 0.0023) and papillary histology (P = 0.0011), but not with pathological stage, lymph node metastasis or survival. High levels of c‐Met and HGF were also associated with papillary histology (P = 0.0056 and P = 0.0396, respectively), but not with tumor differentiation. Phospho‐c‐Met was correlated with phospho‐Akt (P = 0.0381), but not with phospho‐Erk or phospho‐Stat3. Phospho‐Akt expression was marginally correlated with the expression of phospho‐epidermal growth factor receptor (EGFR) (P = 0.0533) and, importantly, it was strongly correlated with the expression of either phospho‐c‐Met or phospho‐EGFR (P = 0.0013). The data suggest that in lung adenocarcinoma tissue, c‐Met activation may take place either ligand‐dependently or ligand‐independently via c‐Met overexpression. c‐Met activation may play special roles in the papillary subtype and in well differentiated lung adenocarcinomas. (Cancer Sci 2007; 98: 1006–1013)
Dermoscopy Use in Primary Care: A Scoping Review.

Background Patients in many countries with new or changing skin lesions will first consult a primary care physician, often called a general practitioner (GP). With the dramatic rise in melanoma incidence over recent decades, dermoscopy offers a tool with an evidence base supporting its use in skin lesion assessment. How GPs use dermoscopy is unclear. Objectives A scoping literature review was carried out to examine the current state of published evidence about dermoscopy use in primary care. Methods The methodological steps taken in this review followed those developed by Arksey and O'Malley, as revised by Levac and colleagues. Four electronic databases were searched for evidence published up to January 2018 describing the use of dermoscopy in a generalist primary care setting. Seven articles were identified for analysis. Results All included articles have been published since 2007. Most were questionnaire studies and revealed that generally a small minority of GPs use dermoscopy, although some jurisdictions such as Australia report greater use. Dermoscopy is generally used only for the assessment of pigmented skin lesions, but is not used consistently. Several perceived barriers to dermoscopy use, including the need for training, have been reported. Conclusions There is a paucity of data on dermoscopy use among GPs, and diversity in questionnaire items prevents comparison between jurisdictions. Perceived barriers to dermoscopy use require more in-depth exploration, potentially including qualitative data, to evaluate them more fully. Understanding these factors, including how GPs train in dermoscopy, will be crucial in widening dermoscopy use in primary care.
A Model-Based Method for Retrospective Correction of Geometric Distortions in Diffusion-Weighted EPI

The self-diffusion tensor may be calculated from several echo-planar image acquisitions preceded by different diffusion gradients. Unfortunately, these diffusion gradients cause geometric distortion that must be corrected before estimation of the tensor. In the present paper we suggest and implement a method for retrospective correction of these distortions firmly based on a physical model for the diffusion-weighted images. This method simultaneously estimates subject movement and distortion parameters by finding the set of parameters that minimizes residual error when fitting data to the diffusion tensor model. We show how this notion can be formalized as a quadratic form thereby facilitating the implementation of a rapid algorithm. In addition, we suggest models for how distortions vary with slice position and gradient direction that allow us to substantially reduce the dimensionality of the parameter space. Our results indicate that we are able to estimate both eddy current-induced distortion and subject movement directly from the data without need of any additional measurements.