bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and validation of a prediction model for invasive bacterial infections in febrile children at European Emergency Departments: MOFICHE, a prospective observational study
Authors: Hagedoorn Nienke N , Borensztajn Dorine , Nijman Ruud Gerard , Nieboer Daan , Herberg Jethro Adam , Balode Anda , von Both Ulrich , Carrol Enitan , Eleftheriou Irini , Emonts Marieke , van der Flier Michiel , de Groot Ronald , Kohlmaier Benno , Lim Emma , Maconochie Ian , Martinón-Torres Federico , Pokorn Marko , Strle Franc , Tsolia Maria , Zavadska Dace , Zenz Werner , Levin Michael , Vermont Clementien , Moll Henriette A
Published: November 2020

Objectives

To develop and cross-validate a multivariable clinical prediction model to identify invasive bacterial infections (IBI) and to identify patient groups who might benefit from new biomarkers.

Design

Prospective observational study.

Setting

12 emergency departments (EDs) in 8 European countries.

Patients

Febrile children aged 0–18 years.

Main outcome measures

IBI, defined as bacteraemia, meningitis and bone/joint infection. We derived and cross-validated a model for IBI using variables from the Feverkidstool (clinical symptoms, C reactive protein), neurological signs, non-blanching rash and comorbidity. We assessed discrimination (area under the receiver operating curve) and diagnostic performance at different risk thresholds for IBI: sensitivity, specificity, negative and positive likelihood ratios (LRs).

Results

Of 16 268 patients, 135 (0.8%) had an IBI. The discriminative ability of the model was 0.84 (95% CI 0.81 to 0.88) and 0.78 (95% CI 0.74 to 0.82) in pooled cross-validations. The model performed well for the rule-out threshold of 0.1% (sensitivity 0.97 (95% CI 0.93 to 0.99), negative LR 0.1 (95% CI 0.0 to 0.2) and for the rule-in threshold of 2.0% (specificity 0.94 (95% CI 0.94 to 0.95), positive LR 8.4 (95% CI 6.9 to 10.0)). The intermediate thresholds of 0.1%–2.0% performed poorly (ranges: sensitivity 0.59–0.93, negative LR 0.14–0.57, specificity 0.52–0.88, positive LR 1.9–4.8) and comprised 9784 patients (60%).

Conclusions

The rule-out threshold of this model has potential to reduce antibiotic treatment while the rule-in threshold could be used to target treatment in febrile children at the ED. In more than half of patients at intermediate risk, sensitive biomarkers could improve identification of IBI and potentially reduce unnecessary antibiotic prescriptions.
Young people’s advisory groups in health research: scoping review and mapping of practices
Authors: Sellars Elise , Pavarini Gabriela , Michelson Daniel , Creswell Cathy , Fazel Mina
Published: November 2020

Background

Young people’s advisory groups (YPAGs) for research are comprised of children or adolescents who work with researchers to shape different stages of the research process. Their involvement is expected to ensure studies better reflect the preferences and needs of targeted youth populations. However, despite their increasing use in health research, there is little systematic evidence on the methods and impacts associated with YPAGs.

Method

To address this gap, we conducted a scoping review of YPAGs in youth-focused health studies. We systematically searched MEDLINE for empirical studies in populations between 12 years and 18 years of age published in 2019. If a potential YPAG was identified, authors were contacted for additional information about the activities and level of involvement of the YPAG.

Findings

Of all studies that collected primary data from persons aged 12–18 years, only 21 studies reported using youth advice during their research. This represents less than 1% of all published empirical child and adolescent studies. There was variation in the type of research activity undertaken by YPAGs and their level of involvement. Most studies involved YPAGs in co-production of research design and/or in dissemination activities. The majority of authors that responded were positive about the impact of YPAGs.

Interpretation

Recommendations for consistent reporting of YPAG involvement in empirical studies include reporting on the match between YPAG and study populations, frequency/format of meetings, and the nature and level of involvement.
Influence of age on small incision lenticule extraction outcomes
Authors: Primavera Laura , Canto-Cerdan Mario , Alio Jorge L , Alio del Barrio Jorge L
Published: November 2020

Purpose

To evaluate the influence of patient’s age at the time of surgery on small incision lenticule extraction (SMILE) refractive outcomes.

Methods

This is a retrospective, consecutive, comparative study. We compared the refractive outcomes after myopic SMILE from two groups of patients divided by age (patients ≤35 and ≥40 years old). All eyes were evaluated preoperatively and at 1 and 6 months postoperatively. Main outcome measures were differences on efficacy, safety, predictability and astigmatic changes by vector analysis with ASSORT software between both study groups.

Results

102 matched eyes of 53 patients were included. Preoperatively, we evidenced no differences in the mean SE or astigmatism between groups. However, 6 months postoperatively we observed a significantly worse mean astigmatism (p=0.019), while not regarding SE, in the older population, with a trend towards undercorrection of the refractive cylinder in the ≥40 group. We also observed a statistically significant difference in the efficacy (0.86–1 month and 0.97–6 months in ≥40group vs 0.97–1 month and 1.07–6 months in the ≤35 group; p=0.003) and safety indexes (0.93–1 month and 1.04–6 months in ≥40 group vs 1.0–1 month and 1.11–6 months in the ≤35 group; p=0.008) at 6 months among groups.

Conclusions

Post-SMILE refractive outcomes in those patients over 40 years of age, although acceptable, are not as good as those obtained in younger patients, showing a significantly lower efficacy and safety indexes, and poorer astigmatic outcomes, with a tendency towards undercorrection. We hypothetise that the increased corneal stroma stiffness in the aged group modifies the post-SMILE corneal stroma remodelling capacity, thus affecting the SMILE refractive and visual response.
Sphingomyelin synthase 1 mediates hepatocyte pyroptosis to trigger non-alcoholic steatohepatitis
Authors: Koh Eun Hee , Yoon Ji Eun , Ko Myoung Seok , Leem Jaechan , Yun Ji-Young , Hong Chung Hwan , Cho Yun Kyung , Lee Seung Eun , Jang Jung Eun , Baek Ji Yeon , Yoo Hyun Ju , Kim Su Jung , Sung Chang Ohk , Lim Joon Seo , Jeong Won-Il , Back Sung Hoon , Baek In-Jeoung , Torres Sandra , Solsona-Vilarrasa Estel , Conde de la Rosa Laura , Garcia-Ruiz Carmen , Feldstein Ariel E , Fernandez-Checa Jose C , Lee Ki-Up
Published: November 2020

Objective

Lipotoxic hepatocyte injury is a primary event in non-alcoholic steatohepatitis (NASH), but the mechanisms of lipotoxicity are not fully defined. Sphingolipids and free cholesterol (FC) mediate hepatocyte injury, but their link in NASH has not been explored. We examined the role of free cholesterol and sphingomyelin synthases (SMSs) that generate sphingomyelin (SM) and diacylglycerol (DAG) in hepatocyte pyroptosis, a specific form of programmed cell death associated with inflammasome activation, and NASH.

Design

Wild-type C57BL/6J mice were fed a high fat and high cholesterol diet (HFHCD) to induce NASH. Hepatic SMS1 and SMS2 expressions were examined in various mouse models including HFHCD-fed mice and patients with NASH. Pyroptosis was estimated by the generation of the gasdermin-D N-terminal fragment. NASH susceptibility and pyroptosis were examined following knockdown of SMS1, protein kinase Cδ (PKCδ), or the NLR family CARD domain-containing protein 4 (NLRC4).

Results

HFHCD increased the hepatic levels of SM and DAG while decreasing the level of phosphatidylcholine. Hepatic expression of Sms1 but not Sms2 was higher in mouse models and patients with NASH. FC in hepatocytes induced Sms1 expression, and Sms1 knockdown prevented HFHCD-induced NASH. DAG produced by SMS1 activated PKCδ and NLRC4 inflammasome to induce hepatocyte pyroptosis. Depletion of Nlrc4 prevented hepatocyte pyroptosis and the development of NASH. Conditioned media from pyroptotic hepatocytes activated the NOD-like receptor family pyrin domain containing 3 inflammasome (NLRP3) in Kupffer cells, but Nlrp3 knockout mice were not protected against HFHCD-induced hepatocyte pyroptosis.

Conclusion

SMS1 mediates hepatocyte pyroptosis through a novel DAG-PKCδ-NLRC4 axis and holds promise as a therapeutic target for NASH.
Combining evidence for and against pathogenicity for variants in cancer susceptibility genes: CanVIG-UK consensus recommendations
Authors: Garrett Alice , Durkie Miranda , Callaway Alison , Burghel George J , Robinson Rachel , Drummond James , Torr Bethany , Cubuk Cankut , Berry Ian R , Wallace Andrew J , Ellard Sian , Eccles Diana M , Tischkowitz Marc , Hanson Helen , Turnbull Clare
Published: November 2020

Accurate classification of variants in cancer susceptibility genes (CSGs) is key for correct estimation of cancer risk and management of patients. Consistency in the weighting assigned to individual elements of evidence has been much improved by the American College of Medical Genetics (ACMG) 2015 framework for variant classification, UK Association for Clinical Genomic Science (UK-ACGS) Best Practice Guidelines and subsequent Cancer Variant Interpretation Group UK (CanVIG-UK) consensus specification for CSGs. However, considerable inconsistency persists regarding practice in the combination of evidence elements. CanVIG-UK is a national subspecialist multidisciplinary network for cancer susceptibility genomic variant interpretation, comprising clinical scientist and clinical geneticist representation from each of the 25 diagnostic laboratories/clinical genetic units across the UK and Republic of Ireland. Here, we summarise the aggregated evidence elements and combinations possible within different variant classification schemata currently employed for CSGs (ACMG, UK-ACGS, CanVIG-UK and ClinGen gene-specific guidance for PTEN, TP53 and CDH1). We present consensus recommendations from CanVIG-UK regarding (1) consistent scoring for combinations of evidence elements using a validated numerical ‘exponent score’ (2) new combinations of evidence elements constituting likely pathogenic’ and ‘pathogenic’ classification categories, (3) which evidence elements can and cannot be used in combination for specific variant types and (4) classification of variants for which there are evidence elements for both pathogenicity and benignity.
MELAS-associated m.5541C>T mutation caused instability of mitochondrial tRNATrp and remarkable mitochondrial dysfunction
Authors: Ji Kunqian , Lin Yan , Xu Xuebi , Wang Wei , Wang Dongdong , Zhang Chen , Li Wei , Zhao Yuying , Yan Chuanzhu
Published: November 2020

Background

Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episode (MELAS) is a group of genetic diseases caused by mutations in mitochondrial DNA and nuclear DNA. The causative mutations of MELAS have drawn much attention, among them, mutations in mitochondrial tRNA genes possessing prominent status. However, the detailed molecular pathogenesis of these tRNA gene mutations remains unclear and there are very few effective therapies available to date.

Methods

We performed muscle histochemistry, genetic analysis, molecular dynamic stimulation and measurement of oxygen consumption rate and respiratory chain complex activities to demonstrate the molecular pathomechanisms of m.5541C>T mutation. Moreover, we use cybrid cells to investigate the potential of taurine to rescue mitochondrial dysfunction caused by this mutation.

Results

We found a pathogenic m.5541C>T mutation in the tRNATrp gene in a large MELAS family. This mutation first affected the maturation and stability of tRNATrp and impaired mitochondrial respiratory chain complex activities, followed by remarkable mitochondrial dysfunction. Surprisingly, we identified that the supplementation of taurine almost completely restored mitochondrial tRNATrp levels and mitochondrial respiration deficiency at the in vitro cell level.

Conclusion

The m.5541C>T mutation disturbed the translation machinery of mitochondrial tRNATrp and taurine supplementation may be a potential treatment for patients with m.5541C>T mutation. Further studies are needed to explore the full potential of taurine supplementation as therapy for patients with this mutation.
Federated learning for privacy-preserving AI
Authors: Cheng Yong , Liu Yang , Chen Tianjian , Yang Qiang
Published: November 2020

Engineering and algorithmic framework to ensure data privacy and user confidentiality.
Technologies for the visually impaired
Authors: Kugler Logan
Published: November 2020

The last decade has seen major advancements in technology for the blind and visually impaired, but problems remain.
Operationalizing AI ethics principles
Authors: Canca Cansu
Published: November 2020

A better ethics analysis guide for developers.
Stability & Kinetics of the Bipolar Membrane Interface: Implications for Electrochemical Technologies
Authors: Grew Kyle N. , Chiu Wilson K. S.
Published: November 2020

Hybrids of acidic cation exchange membrane (CEM) and alkaline anion exchange membrane (AEM) electrolytes, known as bipolar membrane (BPM), are of interest to a host of electrochemical applications that range from galvanic and electrolytic to electrosynthetic systems. Hindering a more extensive establishment of BPMs into some of these devices are the characteristics of the interface, or junction, between the CEM and AEM materials. This junction must facilitate a low-loss ionic recombination or water dissociation process while also being able to withstand swelling, hydraulic, osmotic, and Maxwell stresses. We show that kinetics and stability of the BPM junction are coupled to the underlying material properties, membrane configuration, and operating conditions. We report material design guidelines as a roadmap for producing robust BPM interfaces.
The Concept of Effective Porosity in the Discharge Rate Performance of High-Density Positive Electrodes for Automotive Application
Authors: Tambio S. J. , Cadiou F. , Maire E. , Besnard N. , Deschamps M. , Lestriez B.
Published: November 2020

The discharge rate performance of NMC532-based electrodes designed for EV application were measured between 0 °C and 40 °C and were compared to the predictions of the electrolyte limited penetration depth model [Gallagher et al., J. Electrochem. Soc. 163, A138 (2016)], also called diffusion limited current density model [Heubner et al., J. Power Sources 419, 119 (2019)]. To support this analysis, we took into account the actual microstructure of the electrodes, previously characterized by FIB/SEM tomography, and their measured and/or simulated transport properties. We show that the performance of NMC532 electrodes, even with a low carbon content below the percolation threshold, are not limited by electrons transport through the electrode due to the high intrinsic conductivity of this active material. At 40 °C, the swelling of the PVdF by the electrolyte solvents penalizes performance, especially as the binder content is high. Above all, the current density at which a brutal decrease in capacity occurs is well predicted by the model, although by reducing the porosity to its percolated micrometer sized fraction. This is in good agreement with the numerical simulations of the ionic transport properties.
Influence of Humidity and Different Gases on a Resistive Room Temperature NO2 Gas Dosimeter Based on Al-Doped ZnO for ppb-Concentration Detection
Authors: Wagner Ricarda , Schönauer-Kamin Daniela , Moos Ralf
Published: November 2020

NO2 in the ppb-range can be detected at room temperature by aluminum-doped zinc oxide, whereby the sensor devices are operated as resistive gas dosimeters. In this operation mode, the dose of an analyte is measured directly and the actual analyte concentration can be determined by mathematical differentiation. It is crucial that already adsorbed analyte species do not desorb from the sensitive material and therefore their recovery time is infinite. As classically operated metal oxide sensors are known for their low selectivity, the selectivity of the sensor is investigated. The here-presented results show that the sensor can detect NO2 very selectively even at low concentrations in the low ppb range. Since it has already been reported that humidity can accelerate the desorption of gas molecules from metal oxides, furthermore, the influence of humidity on the dosimeter behavior is investigated. It is shown that the holding capability is negatively affected and the analyte desorbs faster in humid atmosphere.
Triphenyl Ether Amide as a Probe for Electrochemical and Optical Sensing of Copper, Cyanide and Arginine
Authors: Gupta Shivali , Mittal Susheel K , Chhibber Manmohan
Published: November 2020

A novel triphenyl ether amide (TPEAM) derivative has been synthesises and developed as a probe for electrochemical and optical sensing of copper, cyanide ions and arginine in the presence of other amino acids. The ionophore is selective for the copper and cyanide ions among various cations and anions, with detection limits as 40 nM and 0.4 μM, respectively. Sharp anodic and cathodic peaks in the differential pulse voltammograms of the TPEAM-Cu(II) complex indicated a good complexing tendency of the ligand molecule and it was confirmed by spectrofluorimetry and 1H NMR titrations. TPEAM-Cu2+ complex further detected arginine, a semi-essential amino acid, in aqueous medium with a lower detection limit of 4 μM. Host-guest interactions between TPEAM and Cu2+ ions and intramolecular charge transfer interactions (ICT) for CN− ions are proposed as possible mechanisms for the sensing of respective ions. Cyanide detection followed a non-sequential mechanism. The application of TPEAM as a probe for Cu2+ ions has also been validated on food samples and the results are compared with atomic absorption spectroscopy.
Improved Borohydride Oxidation Reaction Activity and Stability for Carbon-Supported Platinum Nanoparticles with Tantalum Oxyphosphate Interlayers
Authors: Swider-Lyons Karen , Hjelm Rachel M. E. , Garsany Yannick , Lafforgue Clemence , Chatenet Marian
Published: November 2020

Platinum electrocatalysts are active for the borohydride oxidation reaction (BOR) in an alkaline environment. However, high surface area carbon-supported platinum (Pt/C) electrodes are not viable long term in alkaline solutions at 60 °C, because Pt nanoparticles are dislodged from the C surface over time due to carbonate formation and the Pt is poisoned by intermediates in the BOR, causing a significant loss in activity. We demonstrate that platinum has increased BOR activity and durability when supported on a tantalum oxyphosphate (TaOPO4) interlayer on Vulcan carbon (VC) (Pt/[TaOPO4/VC]). Pt/[TaOPO4/VC] is compared to Pt/VC electrocatalysts at the anode of a hydrogen peroxide direct borohydride fuel cell (H2O2-DBFC) and using rotating disk electrode (RDE) voltammetry in a half cell measurements. Accelerated stress testing with rotating disk electrode voltammetry is carried out in both 0.10 M NaOH at 25 °C and 0.05 M NaBH4 + 1 M NaOH at 60 °C. The TaOPO4 interlayer between the Pt and VC improves performance and durability in the range of 10 to 20%, suggesting that this is a promising approach for stabilizing Pt in aggressive alkaline environments.
Sensitive Electrochemical Analysis of Hydroxyproline in Achilles Tendon Collagen and Human Urine
Authors: Durairaj Sharmila , Sidhureddy Boopathi , Chen Aicheng
Published: November 2020

L-hydroxyproline (Hyp) is one of the significant amino acids present in connective tissue proteins such as collagen, elastin, and gelatin. The quantitative analysis of Hyp levels in bodily fluids is critical to assist with diagnosing diseases and early treatments. In the present study, for the first time, we report on a facile electrochemical method for the detection of Hyp using gold nanoparticles (AuNPs), which were electrochemically deposited on a glassy carbon electrode (GCE). The electrochemical behavior of the AuNPs/GCE for the oxidation of Hyp was examined using cyclic voltammetry, demonstrating higher electrocatalytic activity in contrast to GCE and bulk Au electrodes. Additionally, the mechanism for the electrochemical oxidation of Hyp was investigated using in situ Fourier transform infrared (FT-IR) spectroscopy. Moreover, the electrochemical sensing performance of the AuNPs was investigated using differential pulse voltammetry (DPV), exhibiting a low limit of detection (0.026 mM) and high sensitivity (8.5 μA (mM cm2)−1). The interference of other amino acids present in collagen and urine has been further tested, demonstrating high selectivity and good reproducibility. The novel electrochemical sensing approach described in the present study may lead to a facile non-enzymatic technique for the sensitive detection of Hyp, a significant biomarker.
The changing face of hunger: from fasting to the concept of atherogenesis
Authors: Magowska Anita Maria
Published: November 2020

The history of hunger is a story about natural disasters and wars, but, on the other hand, also about the investigation of evolutionary defense mechanisms concerning quantitative food shortages. The article presents how fasting and the experimental starving oriented the development of physiology, and it is based on a comparative analysis of monographs and articles on starvation in the medical context from library collections and the PubMed database. Over the centuries, doctors have believed that fasting has a beneficial effect on health, and they recommended a restrictive diet during an illness. In the 19th century, the growth of modern physiology was determined by experimental fasting of human subjects and animals. Furthermore, undernourishment and chronic hunger in large populations were recognized as a threat to public health for the first time. During both world wars, depriving civilians of food became a strategy of combat and a method of genocide. The mass nature of war hunger motivated doctors to research the pathophysiology of starvation and refeeding of emaciated people, even in the ghetto or concentration camps. After the Second World War, the invention of the scanning electron microscope enabled systematic studies on the effects of starvation on the human body. As a result, the pathogenesis of atherosclerosis and the cellular metabolism of cholesterol at the submolecular level were clarified. At the turn of the 21st century, the research on the metabolic response to starvation shed new light on atherogenesis and the link between lipid and carbohydrate metabolism.
Physical Training Is a Potential Modifier of Risk for Contrast‐Induced Acute Kidney Injury in Diabetes Mellitus
Authors: Couto Sheila M. F. , Machado Douglas I. , Conde Carolina , Silva Vinicius C. , Souza Adriana A. , Peres Karina B. , Brandi Beatriz A. , Vattimo Maria De Fátima F.
Published: November 2020

Background. Iodinated contrast (IC) is a leading cause of hospital‐based acute kidney injury (AKI). Contrast‐induced acute kidney injury (CI‐AKI) is a decline in renal function due to iodinated contrast administration and occurs more frequently in individuals with increasingly common risk factors, such as diabetes mellitus (DM). Physical training (PT) can have renoprotective effects on CI‐AKI in diabetic nephropathy. The aim of this study was to evaluate the injury in kidneys of diabetic rats submitted to treatment with IC, evaluating the impact of PT on hemodynamics and renal function in addition to oxidative profile in diabetic rats submitted to IC‐AKI. Materials and Methods. Adult male Wistar rats are randomized into four groups: citrate (n = 7): control group, citrate buffer (streptozotocin‐STZ vehicle), intravenous tail (iv), single dose; DM (n = 7): STZ, 60 mg/kg, iv, single dose; DM+IC (n = 7): DM rats treated with IC (sodium meglumine ioxithalamate, 6 mL/kg, intraperitoneal (ip), single dose); DM+IC+PT (n = 7): DM rats treated with IC as mentioned and submitted to physical training. Renal function parameters (inulin clearance, neutrophil gelatinase‐associated lipocalin (NGAL), serum creatinine, and urinary albumin), hemodynamics (renal blood flow and renal vascular resistance), and oxidative profile (urinary peroxides, urinary TBARS, urinary nitric oxide, and renal tissue thiols) were evaluated. Results. It was possible to observe a decrease in inulin clearance, renal blood flow, and thiols in renal tissue accompanied by an increase in urinary flow, serum creatinine, urinary albumin, renal vascular resistance, urinary peroxides, urinary nitrate, and TBARS in the DM group compared to the citrate group. The DM+IC group showed a reduction in inulin clearance, and the renal dysfunction was also seen by the increased NGAL. Renal hemodynamics and oxidative profile compared were also worsened in the DM group. PT improved renal function by increasing renal blood flow and thiol levels in renal tissue and reduced renal vascular resistance, metabolites of reactive oxygen, nitrogen species, and lipid peroxidation in the DM+IC+PT group compared to DM+IC. Conclusions. Our results confirmed that DM induction increases renal vulnerability to the toxicity of IC and an association between DM with IC predisposes to severe AKI with reduced renal function alongside with renal hemodynamic alterations and oxidative mechanism of injury. The PT showed a renoprotective effect in DM animals subjected to damage with IC by modulating renal hemodynamics and oxidative profile, confirming a potential to modify the risk of CI‐AKI when diabetes mellitus is present.
Differentially Expressed mRNAs and Their Long Noncoding RNA Regulatory Network with Helicobacter pylori‐Associated Diseases including Atrophic Gastritis and Gastric Cancer
Authors: Liu Songyi , Yin Honghao , Zheng Shuwen , Chu Aining , Li Yizhi , Xing Chengzhong , Yuan Yuan , Gong Yuehua
Published: November 2020

Background. Helicobacter pylori (Hp) infection is the strongest risk factor for gastric cancer (GC). However, the mechanisms of Hp‐associated GC remain to be explored. Methods. The gene expression profiling (GSE111762) data were downloaded from the GEO database. Differentially expressed genes (DEGs) between normal samples (NO) and Hp‐atrophic gastritis (GA) or Hp‐GA and Hp‐GC were identified by GEO2R. Gene Ontology and pathway enrichment analysis were performed using the DAVID database. lncRNA‐TF‐mRNA and ceRNA regulation networks were constructed using Cytoscape. The cross‐networks were obtained by overlapping molecules of the above two networks. GSE27411 and GSE116312 datasets were employed for validation. Results. DEGs between NO and Hp‐GA are linked to the activity of inward rectifying potassium channels, digestion, etc. DEGs between Hp‐GA and Hp‐GC were associated with digestion, positive regulation of cell proliferation, etc. According to the lncRNA‐TF‐mRNA network, 63 lncRNAs, 12 TFs, and 209 mRNAs were involved in Hp‐GA while 16 lncRNAs, 11 TFs, and 92 mRNAs were contained in the Hp‐GC network. In terms of the ceRNA network, 120 mRNAs, 18 miRNAs, and 27 lncRNAs were shown in Hp‐GA while 72 mRNAs, 8 miRNAs, and 1 lncRNA were included in the Hp‐GC network. In the cross‐network, we found that immune regulation and differentiation regulation were important in the process of NO‐GA. Neuroendocrine regulation was mainly related to the process of GA‐GC. In the end, we verified that CDX2 plays an important role in the pathological process of NO to Hp‐GA. Comparing Hp‐GA with Hp‐GC, DEGs (FPR1, TFF2, GAST, SST, FUT9, and SHH), TF, and GATA5 were of great significance. Conclusions. We identified the DEGs, and their lncRNA regulatory network of Hp‐associated diseases might provide insights into the mechanism between Hp infection and GC. Furthermore, in‐depth studies of the molecules might be useful to explore the multistep process of gastric diseases.
Downregulated miR‐204 Promotes Skeletal Muscle Regeneration
Authors: Tan Ya , Shen Linyuan , Gan Mailin , Fan Yuan , Cheng Xiao , Zheng Ting , Niu Lili , Chen Lei , Jiang Dongmei , Li Xuewei , Zhang Shunhua , Zhu Li
Published: November 2020

Skeletal muscle is the most abundant and a highly plastic tissue of the mammals, especially when it comes to regenerate after trauma, but there is limited information about the mechanism of muscle repair and its regeneration. In the present study, we found that miR‐204 is downregulated after skeletal muscle injury. In vitro experiments showed that over‐expression of miR‐204 by transfecting with miR‐204 mimics suppressed C2C12 cell proliferation, migration, and blocked subsequent differentiation, whereas inhibition of miR‐204 by transfecting with miR‐204 inhibitor showed the converse effects. Furthermore, through the dual luciferase reporter system, we demonstrated that miR‐204 can target the 3’UTR regions of Pax7, IGF1, and Mef2c and inhibit their expression. Taken together, our results suggest that Pax7, IGF1, and Mef2c are the target genes of miR‐204 in the process of myoblasts proliferation, cell migration, and differentiation, respectively, and may contribute to mouse skeletal muscle regeneration. Our results may provide new ideas and references for the skeletal muscle study and may also provide therapeutic strategies of skeletal muscle injury.
Effect of EGLN1 Genetic Polymorphisms on Hemoglobin Concentration in Andean Highlanders
Authors: Yasukochi Yoshiki , Nishimura Takayuki , Ugarte Juan , Ohnishi Mayumi , Nishihara Mika , Alvarez Guillermo , Fukuda Hideki , Mendoza Victor , Aoyagi Kiyoshi
Published: November 2020

The physiological characteristics of Andean natives living at high altitudes have been investigated extensively, with many studies reporting that Andean highlanders have a higher hemoglobin (Hb) concentration than other highlander populations. It has previously been reported that positive natural selection has acted independently on the egl‐9 family hypoxia inducible factor 1 (EGLN1) gene in Tibetan and Andean highlanders and is related to Hb concentration in Tibetans. However, no study has yet revealed the genetic determinants of Hb concentration in Andeans even though several single‐nucleotide polymorphisms (SNPs) in EGLN1 have previously been examined. Therefore, we explored the relationship between hematological measurements and tag SNPs designed to cover the whole EGLN1 genomic region in Andean highlanders living in Bolivia. Our findings indicated that haplotype frequencies estimated from the EGLN1 SNPs were significantly correlated with Hb concentration in the Bolivian highlanders. Moreover, we found that an Andean‐dominant haplotype related to high Hb level may have expanded rapidly in ancestral Andean highlander populations. Analysis of genotype data in an ~436.3 kb genomic region containing EGLN1 using public databases indicated that the population structure based on EGLN1 genetic markers in Andean highlanders was largely different from that in other human populations. This finding may be related to an intrinsic or adaptive physiological characteristic of Andean highlanders. In conclusion, the high Hb concentrations in Andean highlanders can be partly characterized by EGLN1 genetic variants.
Alpha‐Defensin versus Leukocyte Esterase in Periprosthetic Joint Infection: An Updated Meta‐Analysis
Authors: Li Zhizhuo , Zhang Qingyu , Shi Lijun , Gao Fuqiang , Sun Wei , Li Zirong
Published: November 2020

Periprosthetic joint infection (PJI) is a devastating complication after arthroplasty. Prompt establishment of an infection diagnosis is critical but can be very challenging at present. In order to evaluate the diagnostic accuracy of alpha‐defensin or leukocyte esterase for PJI, we performed systematic research in PubMed, Embase, and Cochrane Library to retrieve relevant studies. Data extraction and quality assessment were performed by two reviewers independently. A total of thirty‐one eligible studies were finally included in the quantitative analysis. The pooled sensitivity and specificity of alpha‐defensin (21 studies) for the diagnosis of PJI were 0.89 (95% confidence interval (CI), 0.83 to 0.93) and 0.96 (95% CI, 0.95 to 0.97), respectively. The value of the pooled diagnostic odds ratios (DOR) of alpha‐defensin for PJI was 209.14 (95% CI, 97.31 to 449.50), and the area under the curve (AUC) was 0.98 (95% CI, 0.96 to 0.99). The pooled sensitivity and specificity of leukocyte esterase (17 studies) for the diagnosis of PJI were 0.90 (95% CI, 0.84 to 0.95) and 0.96 (95% CI, 0.93 to 0.97), respectively. The value of the DOR of leukocyte esterase for PJI was 203.23 (95% CI, 96.14 to 429.61), and the AUC was 0.98 (95% CI, 0.96 to 0.99). Based on the results of our meta‐analysis, we can conclude that alpha‐defensin and leukocyte esterase are valuable synovial fluid markers for identifying PJI with comparable high diagnostic accuracy.
Changes in Tumor Stem Cell Markers and Epithelial‐Mesenchymal Transition Markers in Nonluminal Breast Cancer after Neoadjuvant Chemotherapy and Their Correlation with Contrast‐Enhanced Ultrasound
Authors: Leng Xiaoling , Huang Guofu , Zhang Lianhua , Ding Jianbing , Ma Fucheng
Published: November 2020

Nonluminal breast cancer has high early metastasis and treatment resistance, and neoadjuvant chemotherapy (NAC) is needed. The presence of cancer stem cells (CSC) and epithelial‐mesenchymal transition (EMT) leads to poor prognosis. This study investigated the changes in CSC markers and EMT markers after NAC in nonluminal breast cancer and their correlation with contrast‐enhanced ultrasound (CEUS) features and chemotherapy efficacy. Before NAC, the range of nonluminal breast cancer on CEUS was larger than that of two‐dimensional ultrasound, but after NAC, it was significantly smaller than that of two‐dimensional ultrasound and closer to the postoperative pathological size. After NAC, the enlarged lesions and perfusion defects were significantly less than those before NAC. The time‐intensity curve showed the characteristics of slow‐in, low enhancement, and low perfusion. Nonluminal breast cancer downregulated the expression of CSC markers and EMT markers after NAC, but the epithelial phenotype of nonluminal breast cancer with good response to chemotherapy was upregulated. In nonluminal breast cancer with poor response to chemotherapy, markers of CSC and EMT were highly expressed before chemotherapy. In conclusion, CEUS is better than conventional ultrasound in estimating NAC efficacy in this mode. CEUS can also predict the prognosis of nonluminal breast cancer before NAC with the characteristics of enhanced enlargement and perfusion defects. The contrast‐enhanced time‐intensity curve of lesions with relatively poor blood supply may have more CSC and EMT characteristics.
Mesenchymal Stem Cells Activate the MEK/ERK Signaling Pathway and Enhance DNA Methylation via DNMT1 in PBMC from Systemic Lupus Erythematosus
Authors: Xiong Hui , Guo Zhixuan , Tang Zengqi , Ai Xuechen , Qi Qing , Liu Xiuting , Huang Danqi , Li Zhaofeng , Ji Suyun , Guo Qing
Published: November 2020

The defective MEK/ERK signaling pathway and downstream hypomethylation pattern of lymphocytes are crucial for the pathogenesis of systemic lupus erythematosus (SLE). However, the role that the mesenchymal stem cells play in the MEK/ERK signaling pathway and DNA methylation of peripheral blood mononuclear cells (PBMC) from SLE patients remains unknown. In this study, we found that the MEK/ERK signaling pathway of PBMC from SLE patients was activated after the coculture with bone marrow‐derived mesenchymal stem cells (BM‐MSC) compared with that from the control group. In addition, the expression level of DNA methyltransferase 1 (DNMT1) increased while the levels of CD70, integrin, alpha L (ITGAL), selectin‐l, and IL‐13 were reduced in PBMC from SLE patients. However, no obvious effect of BM‐MSC on PBMC from healthy controls was observed. These findings revealed that BM‐MSC might downregulate the expression of methylation‐sensitive genes and then suppress the autoactivated PBMC via the MEK/ERK signaling pathway. And it may be one of the mechanisms that BM‐MSC ameliorated SLE.
Circulating Soluble ST2 Predicts All-Cause Mortality in Severe Heart Failure Patients with an Implantable Cardioverter Defibrillator
Authors: Hou Zhi-wei , Yu Hai-bo , Liang Yan-chun , Gao Yang , Xu Guo-qing , Wu Min , Mei Zhu , Wang Zu-lu , Li Zhi-guo , Li Yu-ying , Song Hai-xu , Li Jia-yin , Han Ya-ling
Published: November 2020

Background. Heart failure (HF) is the terminal stage of all cardiovascular events. Although implantable cardioverter defibrillator (ICD) therapies have reduced mortality among the high-risk HF population, it is necessary to determine whether certain factors can predict mortality even after cardiac device implantation. Growth stimulation expressed gene 2 (ST2) is an emerging biomarker for HF patient stratification in different clinical settings. Aims. This study aimed to investigate the relationship between baseline soluble ST2 (sST2) levels in serum and the clinical outcomes of high-risk HF patients with device implantation. Methods. Between January 2017 and August 2018, we prospectively recruited consecutive patients implanted with an ICD for heart failure, with LVEF ≤35% as recommended, and analyzed the basic characteristics, baseline serum sST2, and NT-proBNP levels, with at least 1-year follow-up. All-cause mortality was the primary endpoint. Results. During a 643-day follow-up, all-cause mortality occurred in 16 of 150 patients (10.67%). Incidence of all-cause mortality increased significantly in patients with sST2 levels above 34.98846 ng/ml (16.00% vs. 5.33%,

P
=
0.034

). After adjusting the model (age, gender, device implantation, prevention of sudden death, LVEDD, LVEF, WBC and CLBBB, hsTNT, etiology, and eGFR) and the model combined with NT-proBNP, the risk of all-cause death was increased by 2.5% and 1.9%, respectively, per ng/ml of sST2. The best sST2 cutoff for predicting all-cause death was 43.42671 ng/ml (area under the curve: 0.72, sensitive: 0.69, and specificity: 0.69). Compared to patients with sST2 levels below 43.42671 ng/ml, the risk of all-cause mortality was higher in those with values above the threshold (5.1% vs. 21.2%,

P
=
0.002

). ST2 level ≥43.42671 ng/ml was an independent predictor of all-cause mortality (HR: 3.30 [95% CI 1.02–10.67]). Age (HR: 1.06 [95% CI: 1.01–1.12]) and increased NT-proBNP per 100 (HR: 1.02 [95% CI: 1.01–1.03]) were also associated with all-cause mortality in ICD patients. Conclusions. sST2 level was associated with risk of all-cause mortality, and a threshold of 43.43 ng/ml showed good distinguishing performance to predict all-cause mortality in patients with severe heart failure, recommended for ICD implantation. Patients with sST2 levels more than 43.42671 ng/ml even after ICD implantation should therefore be monitored carefully.
TTK, CDC25A, and ESPL1 as Prognostic Biomarkers for Endometrial Cancer
Authors: Yang Qiannan , Yu Bojun , Sun Jing
Published: November 2020

Objective. Endometrial cancer (EC) is one of the most common malignant gynaecological tumours worldwide. This study was aimed at identifying EC prognostic genes and investigating the molecular mechanisms of these genes in EC. Methods. Two mRNA datasets of EC were downloaded from the Gene Expression Omnibus (GEO). The GEO2R tool and Draw Venn Diagram were used to identify differentially expressed genes (DEGs) between normal endometrial tissues and EC tissues. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID). Next, the protein‐protein interactions (PPIs) of these DEGs were determined by the Search Tool for the Retrieval of Interacting Genes (STRING) tool and Cytoscape with Molecular Complex Detection (MCODE). Furthermore, Kaplan‐Meier survival analysis was performed by UALCAN to verify genes associated with significantly poor prognosis. Next, Gene Expression Profiling Interactive Analysis (GEPIA) was used to verify the expression levels of these selected genes. Additionally, a reanalysis of the KEGG pathways was performed to understand the potential biological functions of selected genes. Finally, the associations between these genes and clinical features were analysed based on TCGA cancer genomic datasets for EC. Results. In EC tissues, compared with normal endometrial tissues, 147 of 249 DEGs were upregulated and 102 were downregulated. A total of 64 upregulated genes were assembled into a PPI network. Next, 14 genes were found to be both associated with significantly poor prognosis and highly expressed in EC tissues. Reanalysis of the KEGG pathways found that three of these genes were enriched in the cell cycle pathway. TTK, CDC25A, and ESPL1 showed higher expression in cancers with late stage and higher tumour grade. Conclusion. In summary, through integrated bioinformatics approaches, we found three significant prognostic genes of EC, which might be potential therapeutic targets for EC patients.
A Novel Seventeen‐Gene Metabolic Signature for Predicting Prognosis in Colon Cancer
Authors: Luo Dakui , Shan Zezhi , Liu Qi , Cai Sanjun , Li Qingguo , Li Xinxiang
Published: November 2020

A metabolic disorder is considered one of the hallmarks of cancer. Multiple differentially expressed metabolic genes have been identified in colon cancer (CC), and their biological functions and prognostic values have been well explored. The purpose of the present study was to establish a metabolic signature to optimize the prognostic prediction in CC. The related data were downloaded from The Cancer Genome Atlas (TCGA), Genotype‐Tissue Expression (GTEx) database, and Gene Expression Omnibus (GEO) combined with GSE39582 set, GSE17538 set, GSE33113 set, and GSE37892 set. The differentially expressed metabolic genes were selected for univariate Cox regression and lasso Cox regression analysis using TCGA and GTEx datasets. Finally, a seventeen‐gene metabolic signature was developed to divide patients into a high‐risk group and a low‐risk group. Patients in the high‐risk group presented poorer prognosis compared to the low‐risk group in both TCGA and GEO datasets. Moreover, gene set enrichment analyses demonstrated multiple significantly enriched metabolism‐related pathways. To sum up, our study described a novel seventeen‐gene metabolic signature for prognostic prediction of colon cancer.
The Efficacy and Safety of Compound Danshen Dripping Pill Combined with Percutaneous Coronary Intervention for Coronary Heart Disease
Authors: Li Cailan , Li Qian , Xu Jiamin , Wu Wenzhen , Wu Yuling , Xie Jianhui , Yang Xiaobo
Published: November 2020

Objective. Compound Danshen dripping pill (CDDP) is a well‐known Chinese patent medicine, which is commonly used for the treatment of coronary heart disease (CHD) in China. This study is aimed at systematically assessing the clinical efficacy of CDDP for CHD patients. Methods. Eight databases were retrieved for eligible research studies from the founding date to April 20, 2020. Risk ratio (RR) was used to assess major adverse cardiac events (MACE) and adverse reactions, and mean difference (MD) was adopted to evaluate the hemorheology and blood lipid indexes, vascular endothelial function, cardiac function, and inflammation. Result. Twenty randomized controlled trials involving 2574 participants with CHD were included. The results indicated that, compared with percutaneous coronary intervention (PCI) alone, the combination of CDDP with PCI treatment remarkably reduced MACE (RR = 0.53, 95% confidence interval (CI) (0.44, 0.65), P < 0.00001). Moreover, hemorheology and blood lipid parameters and inflammatory mediators of CHD patients were also dramatically mitigated after the combined therapy (P < 0.01). In addition, vascular endothelial function and cardiac function were prominently improved by this combination (P < 0.001). However, there was no significant difference in adverse reactions between the two groups (P > 0.05). Conclusion. Evidence from the meta‐analysis demonstrated that CDDP combined with PCI treatment prominently reduced the incidence of MACE, improved cardiovascular functions, and inhibited inflammation in CHD patients. Therefore, CDDP combined with PCI treatment could be an effective and safe therapeutic method for CHD patients.
Diagnosis of Temporomandibular Disorders Using Thermovision Imaging
Authors: Machoy Monika , Szyszka-Sommerfeld Liliana , Rahnama Mansur , Koprowski Robert , Wilczyński Sławomir , Woźniak Krzysztof
Published: November 2020

Temporomandibular joint dysfunction (TMD) is a chronic disease of various etiologies. Correct TMD diagnosis enables to apply effective treatment and significantly improves the quality of patients’ lives. One of the diagnostic methods subjected to evaluation in recent years is thermography, which enables safe, noninvasive, and quick imaging of the temperature distribution of temporomandibular joint-associated tissues. This paper, based on Medline, Dentistry & Oral Sciences Source, Academic Search Ultimate, Medline Complete databases, presents basic information related to thermovision imaging and outlines the direction of research conducted in recent years which fight with difficulties in the interpretation of thermograms that require specialized, dedicated analysis and processing of the obtained images. The problem concerns also no standardized protocol for measuring masticatory muscle temperature.
The Prognostic Values of the Insulin‐Like Growth Factor Binding Protein Family in Ovarian Cancer
Authors: Zheng Ruoyi , Chen Wenming , Xia Weiting , Zheng Jingyu , Zhou Qing
Published: November 2020

Purpose. To assess the expression of insulin‐like growth factor binding protein (IGFBP) family and its prognostic impact in ovarian cancer (OC) patients. Materials and Methods. The mRNA expression and protein expression of individual IGFBPs in healthy ovarian samples and OC tissues were explored through Oncomine, Gene Expression Profiling Interactive Analysis, and Human Protein Atlas database. Additionally, the prognostic values of the six IGFBP members in patients with OC were evaluated by Kaplan‐Meier plotter. Results. IGFBP2 and IGFBP4 mRNA expression were remarkably upregulated in patients with OC. To be specific, the mRNA expression of IGFBP2 was upregulated in patients with serous ovarian cancer (SOC), while IGFBP1/3/4/5/6 mRNA levels were downregulated. In addition, the IGFBP4 protein expression was upregulated in SOC, and the IGFBP6 protein expression was upregulated in both of SOC and endometrioid ovarian cancer (EOC) tissues. High IGFBP1 mRNA levels showed favorable overall survival (OS) and progression‐free survival (PFS) in all OC. Meanwhile, increased IGFBP5/6 mRNA levels revealed worsen OS and PFS in all OC patients. IGFBP4/6 mRNA levels predicted unfavorable OS and PFS only in SOC patients. Moreover, the aberrant mRNA expression of IGFBP1/2/4/5/6 was correlated with significantly prognosis in patients receiving different chemotherapeutic regimens. Conclusion. This study indicates that the IGFBP family reveals distinct prognosis in patients with OC. IGFBP1/2/4/5/6 are useful prognostic predictors for chemotherapeutic effect in OC patients, and IGFBP2/4 are potential tumor markers for the diagnosis of OC.