bluuebunny/crossref_metadata_2025 huggingface dataset:
The Predictive Value of Urinary Kidney Injury Molecular 1 for the Diagnosis of Contrast-Induced Acute Kidney Injury after Cardiac Catheterization: A Meta-Analysis
Authors: Li Qing , Huang Yimin , Shang Weifeng , Zhang Ying , Liu Yanyan , Xu Gang
Published: August 2020

Background. Urinary kidney injury molecule 1 (uKIM-1) is a proximal tubular injury biomarker for predicting acute kidney injury (AKI); its prognostic value varies depending on the clinical and population characteristics. However, the predictive value of uKIM-1 for diagnosis of contrast-induced acute kidney injury (CI-AKI) remains unclear.Method. Medline, Embase, ClinicalTrials.gov, Cochrane Library database, and the China National Knowledge Infrastructure (CNKI) were used to identify relevant studies from their inception to November 31, 2019. Studies that met the inclusion criteria were included. Relevant data were extracted to obtain pooled sensitivity (SEN) and specificity (SPE), summary receiver operating characteristic curve (ROC), and area under the ROC (AUC or AUROC). A bivariate mixed-effects regression model was used for data analysis.Results. A total of 946 patients from 8 eligible studies were included. Across all the studies, the diagnostic odds ratio (DOR) for uKIM-1 level to predict CI-AKI was 19 (95% CI 10–39), with SEN and SPE of 0.84 and 0.78, respectively. The AUROC for uKIM-1 in predicting CI-AKI was 0.88 (95% CI 0.85–0.90). There was a substantial heterogeneity across the studies (I2was 37.73% for the summary sensitivity and 69.31% for the summary specificity).Conclusion. Urinary KIM-1 has a high predictive value for diagnosis of CI-AKI in patients who have undergone cardiac catheterization.
Circular RNA circ_0026359 Enhances Cisplatin Resistance in Gastric Cancer via Targeting miR‐1200/POLD4 Pathway
Authors: Zhang Zongyao , Yu Xin , Zhou Bo , Zhang Jiajia , Chang Jiacong
Published: August 2020

Human gastric cancer is one of the most common malignant tumors with a poor prognosis. Cisplatin (CDDP) is a well‐known first‐line chemotherapeutic drug. Acquired resistance retards the clinical application of CDDP in gastric cancer. In this study, circular RNA circ_0026359 was demonstrated to be overexpressed in gastric cancer tissues/cells compared with normal gastric tissues/cells and was overexpressed in CDDP‐resistant gastric cancer tissues/cells compared with CDDP‐sensitive gastric cancer tissues/cells. High levels of circ_0026359 were associated with low overall survival (OS) and relapse‐free survival (RFS) rates in gastric cancer patients. circ_0026359 was examined to promote CDDP resistance in gastric cancer cells. circ_0026359 directly interacted and negatively regulated miR‐1200. POLD4 was a direct target of miR‐1200. miR‐1200/POLD4 pathway mediated the promoting role of circ_0026359 in CDDP resistance of gastric cancer. circ_0026359 could be used as a potential target for CDDP‐resistant gastric cancer therapy.
Serum Actinin-4 Levels as a Potential Diagnostic and Prognostic Marker in Cervical Cancer
Authors: Ma Xigui , Xue Huiying , Zhong Jixiang , Feng Bo , Zuo Yanghua
Published: August 2020

Purpose. The present study was aimed at determining the serum levels of actinin-4 (ACTN4) in cervical cancer (CC) and investigating the diagnostic and prognostic value of serum ACTN4 in CC. Materials and Methods. We included 93 CC patients, 52 cervical intraepithelial neoplasia (CIN) patients, and 70 healthy women. Serum ACTN4 levels were assessed using an ELISA method. A receiver operating characteristic (ROC) curve was performed to evaluate the diagnostic value of serum ACTN4. The survival curves were used to display the overall survival distributions. Results. Serum ACTN4 levels in CC patients were 48.39±13.98 pg/mL which is significantly higher than those in CIN patients (32.72±9.44 pg/mL; P<0.001) and those in healthy controls (30.84±8.08 pg/mL; P<0.001). The ROC analysis demonstrated that the area under the curve (AUC) of ACTN4 was 0.852 (95%CI=0.796–0.908), with sensitivity of 76.3% and specificity of 87.7%. Serum ACTN4 levels were associated with the FIGO stage, lymph node metastasis, and lymphovascular space invasion of CC (all P<0.05). The survival curve suggested that high serum ACTN4 levels were related to poor prognosis. Conclusion. Our findings suggest that serum ACTN4 levels may be valuable diagnostic and prognostic biomarkers for CC.
A Two-Stage Method for Improving the Prediction Accuracy of Complex Traits by Incorporating Genotype by Environment Interactions inBrassica napus
Authors: Xiong Sican , Wang Meng , Zou Jun , Meng Jinling , Liu Yanyan
Published: August 2020

Improving the prediction accuracy of a complex trait of interest is key to performing genomic selection (GS) for crop breeding. For the complex trait measured in multiple environments, this paper proposes a two-stage method to solve a linear model that jointly models the genetic effects and the genotype × environment interaction (G × E) effects. In the first stage, the least absolute shrinkage and selection operator (LASSO) penalized method was utilized to identify quantitative trait loci (QTL). Then, the ordinary least squares (OLS) approach was used in the second stage to reestimate the QTL effects. As a case study, this approach was used to improve the prediction accuracies of flowering time (FT), oil content (OC), and seed yield per plant (SY) inBrassica napus(B. napus). The results showed that theG × Eeffects reduced the mean squared error (MSE) significantly. Numerous QTL were environment-specific and presented minor effects. On average, the two-stage method, named OLS post-LASSO, offers the highest prediction accuracies (correlations are 0.8789, 0.9045, and 0.5507 for FT, OC, and SY, respectively). It was followed by the marker × environment interaction (M × E) genomic best linear unbiased prediction (GBLUP) model (correlations are 0.8347, 0.8205, and 0.4005 for FT, OC, and SY, respectively), the LASSO method (correlations are 0.7583, 0.7755, and 0.2718 for FT, OC, and SY, respectively), and the stratified GBLUP model (correlations are 0.6789, 0.6361, and 0.2860 for FT, OC, and SY, respectively). The two-stage method showed an obvious improvement in the prediction accuracy, and this study will provide methods and reference to improve GS of breeding.
Deep Reinforcement Learning-Based Content Placement and Trajectory Design in Urban Cache-Enabled UAV Networks
Authors: Wu Chenyu , Shi Shuo , Gu Shushi , Zhang Lingyan , Gu Xuemai
Published: August 2020

Cache-enabled unmanned aerial vehicles (UAVs) have been envisioned as a promising technology for many applications in future urban wireless communication. However, to utilize UAVs properly is challenging due to limited endurance and storage capacity as well as the continuous roam of the mobile users. To meet the diversity of urban communication services, it is essential to exploit UAVs’ potential of mobility and storage resource. Toward this end, we consider an urban cache-enabled communication network where the UAVs serve mobile users with energy and cache capacity constraints. We formulate an optimization problem to maximize the sum achievable throughput in this system. To solve this problem, we propose a deep reinforcement learning-based joint content placement and trajectory design algorithm (DRL-JCT), whose progress can be divided into two stages: offline content placement stage and online user tracking stage. First, we present a link-based scheme to maximize the cache hit rate of all users’ file requirements under cache capacity constraint. The NP-hard problem is solved by approximation and convex optimization. Then, we leverage the Double Deep Q-Network (DDQN) to track mobile users online with their instantaneous two-dimensional coordinate under energy constraint. Numerical results show that our algorithm converges well after a small number of iterations. Compared with several benchmark schemes, our algorithm adapts to the dynamic conditions and provides significant performance in terms of sum achievable throughput.
Blueberry Extracts as a Novel Approach to Prevent Ozone-Induced Cutaneous Inflammasome Activation
Authors: Pambianchi Erika , Ferrara Francesca , Pecorelli Alessandra , Woodby Brittany , Grace Mary , Therrien Jean-Philippe , Lila Mary Ann , Valacchi Giuseppe
Published: August 2020

The World Health Organization estimates that 7 million people die every year due to pollution exposure. Among the different pollutants to which living organism are exposed, ozone (O3) represents one of the most toxic, because its location which is the skin is one of the direct tissues exposed to the outdoor environment. Chronic exposure to outdoor stressors can alter cutaneous redox state resulting in the activation of inflammatory pathways. Recently, a new player in the inflammation mechanism was discovered: the multiprotein complex NLRP1 inflammasome, which has been shown to be also expressed in the skin. The topical application of natural compounds has been studied for the last 40 years as a possible approach to prevent and eventually cure skin conditions. Recently, the possibility to use blueberry (BB) extract to prevent pollution-induced skin toxicity has been of great interest in the cosmeceutical industry. In the present study, we analyzed the cutaneous protective effect of BB extract in several skin models (2D, 3D, and human skin explants). Specifically, we observed that in the different skin models used, BB extracts were able to enhance keratinocyte wound closure and normalize proliferation and migration responses previously altered by O3. In addition, pretreatment with BB extracts was able to prevent ozone-induced ROS production and inflammasome activation measured as NRLP1-ASC scaffold formation and also prevent the transcripts of key inflammasome players such as CASP1 and IL-18, suggesting that this approach as a possible new technology to prevent cutaneous pollution damage. Our data support the hypothesis that BB extracts can effectively reduce skin inflammation and be a possible new technology against cutaneous pollution-induced damage.
COVID-19 y retiro del 10%
Authors: López Fernando
Published: August 2020

Luego de un intenso debate, el 30 de julio se publicó en el Diario Oficial la Ley No 21.248 que permite a los afiliados al sistema de AFP, de manera excepcional, voluntaria y por única vez, retirar hasta el 10 por ciento de los fondos acumulados en su cuenta de capitalización individual de cotizaciones obligatorias. El propósito fue mitigar los efectos sociales derivados de la crisis sanitaria. Este artículo presenta una descripción de los principales elementos de la Ley, el contexto económico y de legitimidad del sistema previsional en el que fue aprobado, así como algunas de las principales ventajas y desventajas del proyecto. Continuar leyendo...
Relationships between Breast Feeding and Breast Cancer Subtypes: Lessons Learned from Studies in Humans and in Mice
Authors: Ambrosone Christine B. , Higgins Michael J.
Published: August 2020

There are differential risk relationships between parity and breast cancer according to estrogen receptor (ER) status, with an increased risk of ER− disease reduced by breastfeeding. This may be particularly relevant for understanding the higher incidence of ER− tumors in Black women, who are more likely to be parous and less likely to breastfeed than other U.S. groups. Potential mechanisms for these relationships may include effects of disordered breast involution on inflammatory milieu in the breast as well as epigenetic reprogramming in the mammary gland, which can affect cell fate decisions in progenitor cell pools. In normal breast tissue, parity has been associated with hypermethylation of FOXA1, a pioneer transcription factor that promotes the luminal phenotype in luminal progenitors, while repressing the basal phenotype. In breast tumors, relationships between FOXA1 methylation and parity were strongest among women who did not breastfeed. Here, we summarize the epidemiologic literature regarding parity, breastfeeding, and breast cancer subtypes, and review potential mechanisms whereby these factors may influence breast carcinogenesis, with a focus on effects on progenitor cell pools in the mammary gland.
SUMOylation of E2F1 Regulates Expression of EZH2
Authors: Du Li , Fakih Marwan G. , Rosen Steven T. , Chen Yuan
Published: August 2020

Elevated expression of EZH2, the enzymatic subunit of polycomb repressive complex 2 (PRC2), often occurs in cancer. EZH2 expression results in the silencing of genes that suppress tumor formation and metastasis through trimethylation of histone H3 at lysine 27 (H3K27me3) at their promoters. However, inhibitors of EZH2 enzymatic activity have not shown the expected efficacy against cancer in clinical trials, suggesting a need for other strategies to address EZH2 overexpression. Here, we show that SUMOylation, a posttranslational modification characterized by covalent attachment of small ubiquitin-like modifier (SUMO) proteins to a lysine (Lys) residue on target proteins, enhances EZH2 transcription. Either knockdown of the SUMO-activating enzyme SAE2 or pharmacologic inhibition of SUMOylation resulted in decreased levels of EZH2 mRNA and protein as well as reduced H3K27me3 levels. SUMOylation regulated EZH2 expression by enhancing binding of the E2F1 transcriptional activator to the EZH2 promoter. Inhibition of SUMOylation not only resulted in reduced EZH2 mRNA and protein levels but also increased expression of genes silenced by EZH2, such as E-cadherin, which suppresses epithelial–mesenchymal transition and metastasis. In more than 6,500 patient tumor samples across different cancer types, expression of UBA2 and EZH2 was positively correlated. Taken together, our findings suggest that inhibition of SUMOylation may serve as a potential strategy to address EZH2 overexpression and improve current cancer therapeutic approaches.

Significance:

These findings provide important biological insights into the mechanism of EZH2 overexpression in cancers and suggest that inhibiting SUMOylation may improve current cancer therapeutic approaches.
Coffee Consumption and Invasive Breast Cancer Incidence among Postmenopausal Women in the Cancer Prevention Study-II Nutrition Cohort
Authors: Gapstur Susan M. , Gaudet Mia M. , Wang Ying , Hodge Rebecca A. , Um Caroline Y. , Hartman Terryl J. , McCullough Marjorie L.
Published: August 2020

Background:

There is limited evidence of a potential inverse association between coffee, particularly caffeinated coffee, consumption and postmenopausal breast cancer risk, and few studies have examined this association by tumor hormone receptor status. To provide further evidence, we examined total, caffeinated, and decaffeinated coffee consumption in relation to postmenopausal invasive breast cancer incidence overall, and by tumor estrogen receptor (ER) and/or progesterone receptor (PR) subtype.

Methods:

Among 57,075 postmenopausal women in the Cancer Prevention Study-II Nutrition Cohort who were cancer free and reported coffee intake in 1999, we identified 2,980 women diagnosed with invasive breast cancer during follow-up through June 2015. Multivariable-adjusted Cox proportional hazards regression was used to compute hazard ratios (HR) and 95% confidence intervals (CI).

Results:

Neither total, caffeinated, nor decaffeinated coffee consumption was associated with invasive breast cancer risk; HRs (95% CIs) comparing consumption of ≥2 cups per day with <1 cup per month were 0.99 (0.89–1.11), 0.96 (0.87–1.06), and 1.06 (0.95–1.19), respectively. Similarly, coffee consumption was not associated with risk of hormone receptor–positive (ER+ or PR+) or hormone receptor–negative (ER− and PR−) breast tumors.

Conclusions:

These findings do not support an association between coffee consumption and invasive breast cancer risk among postmenopausal women.

Impact:

This large prospective study contributes to the limited evidence on coffee consumption and breast cancer risk, finding no association overall or by tumor receptor subtype.
Phase I and Pharmacokinetic Study of Romidepsin in Patients with Cancer and Hepatic Dysfunction: A National Cancer Institute Organ Dysfunction Working Group Study
Authors: Connolly Roisin M. , Laille Eric , Vaishampayan Ulka , Chung Vincent , Kelly Karen , Dowlati Afshin , Alese Olatunji B. , Harvey R. Donald , Haluska Paul , Siu Lillian L. , Kummar Shivaani , Piekarz Richard , Ivy S. Percy , Anders Nicole M. , Downs Melinda , O'Connor Ashley , Scardina Angela , Saunders Jacqueline , Rosner Gary L. , Carducci Michael A. , Rudek Michelle A.
Published: August 2020

Purpose:

Romidepsin dosing recommendations for patients with malignancy and varying degrees of hepatic dysfunction was lacking at the time of regulatory approval for T-cell lymphoma. We conducted a multicenter phase I clinical trial (ETCTN-9008) via the NCI Organ Dysfunction Working Group to investigate safety, first cycle MTD, and pharmacokinetic profile of romidepsin in this setting.

Patients and Methods:

Patients with select advanced solid tumors or hematologic malignancies were stratified according to hepatic function. Romidepsin was administered intravenously on days 1, 8, and 15 of a 28-day cycle and escalation followed a 3 + 3 design in moderate and severe impairment cohorts. Blood samples for detailed pharmacokinetic analyses were collected after the first dose.

Results:

Thirty-one patients received one dose of romidepsin and were evaluable for pharmacokinetic analyses in normal (n = 12), mild (n = 8), moderate (n = 5), and severe (n = 6) cohorts. Adverse events across cohorts were similar, and dose-limiting toxicity occurred in two patients (mild and severe impairment cohorts). The MTD was not determined because the geometric mean AUC values of romidepsin in moderate (7 mg/m2) and severe (5 mg/m2) impairment cohort were 114% and 116% of the normal cohort (14 mg/m2).

Conclusions:

Data from the ETCTN-9008 trial led to changes in the romidepsin labeling to reflect starting dose adjustment for patients with cancer and moderate and severe hepatic impairment, with no adjustment for mild hepatic impairment.
Analysis of Differentially Expressed Long Noncoding RNA in Renal Ischemia-Reperfusion Injury
Authors: Liu Fen , Yang Yang , Liu Tong , Deng Jun , Zhang Heng , Luo Dan , Lou Yuan-Lei
Published: August 2020

Background: Renal ischemia-reperfusion (IR) injury is one of the major causes of acute renal failure which seriously endangers the health and life of patients. Currently, there is still lack of comprehensive knowledge of the molecular mechanism of renal IR injury, and the regulatory role of long noncoding RNA (lncRNA) in renal IR damage remains poorly understood. Aim: The aim of this study was to analyze the expression spectrum of lncRNA in renal IR damage in mice and to explore specific lncRNA that may be involved in regulating the development of human renal IR injury. Methods: RNA-Seq was used to investigate the lncRNA profile of renal IR injury in a mouse model, and conservation analysis was performed on mouse lncRNAs with differential expression (fragments per kilobase of transcript per million mapped reads ≥2) by BLASTN. The potential functions and associated pathways of the differentially expressed lncRNA were explored by bioinformatics analysis. The cell hypoxia model was used to detect the expression of the candidate lncRNA. Results: Of the 45,923 lncRNA transcripts detected in the samples, and 5,868 lncRNAs were found to be significantly differentially expressed (p < 0.05 and fold change ≥ 2) in 24-h IR kidney tissue compared to the expression in the control group. It was found that 56 differently expressed mouse lncRNA transcripts have human homology by analyzing the conserved sequences. We also found that lncRNA-NONHSAT183385.1 expression significantly increased in HK2 cells after 24 h of hypoxia and increased further 6 h after reoxygenation, and after 24 h of reoxygenation it was dramatically downregulated, indicating that NONHSAT183385.1 may be involved in the pathophysiological process of renal tubular epithelial cells in response to ischemia in human renal IR. Conclusion: Our study revealed differentially expressed lncRNAs in renal IR damage in mice and identified a set of conserved lncRNAs, which would help to explore lncRNAs that may play important regulatory roles in human renal IR injury.
Prevalence of Dementia among Well-Educated Old-Age Pensioners in Parakou (Benin) in 2014
Authors: Adoukonou Thierry , Yoro-Zohoun Inès , Gnonlonfoun Dieu Donné , Amoussou Paulin , Takpara Claire , Agbetou Mendinatou , Guerchet Maëlenn , Preux Pierre-Marie , Houinato Dismand , Ouendo Edgard-Marius
Published: August 2020

Introduction: The number of people living with dementia is growing worldwide and most rapidly in low- and middle-income countries. Little is known about dementia in Benin. We estimated the prevalence of dementia among retired people in Parakou, a northern city in Benin, and then assessed associated factors. Methods: A cross-sectional study was performed in Parakou from July to August 2014. Participants were recruited at 2 centers, the National Center of Social Security and the Public Treasury of Benin. Participants with cognitive impairment were defined as having a low cognitive score (<7) for the brief version of the Community Screening Interview for Dementia and were invited to neurological examination. DSM-IV-TR criteria were used to diagnose dementia and the HACHINSKI score was used to differentiate dementia subtypes. A logistic regression model was performed to identify factors associated with dementia. Results: Overall, 440 retired people were included in the study. They were mainly male (92.3%) and their mean age was 64.9 ± 6.0 years. The prevalence of cognitive impairment was 7.7% (95% CI 5.2–10.2). Fourteen participants were diagnosed with dementia, representing a prevalence of 3.2% (95% CI 1.5–4.8). Alzheimer disease was the most frequent subtype (64.3%), followed by vascular dementia (21.4%). Retired people diagnosed with dementia were all men and were aged between 61 and 71 years. Most of them were living alone. The main factors associated with dementia were older age, low fruit and vegetables consumption, and living alone. Discussion: This study showed a low prevalence of dementia among retired older people in Benin. Despite this, greater attention must be given to the potential burden dementia places on families for better care, before the expected aging of the population becomes more significant.
Tumor-Infiltrating Lymphocytes in Biopsy Specimens Obtained 7 Days after Starting Chemoradiotherapy for Rectal Cancer Are Predictors of the Response to Chemoradiotherapy
Authors: Miyakita Hiroshi , Sadahiro Sotaro , Suzuki Toshiyuki , Chan Lin Fung , Ogimi Takashi , Okada Kazutake , Yamamoto Seiichiro , Kajiwara Hiroshi
Published: August 2020

Background: Neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision surgery is a standard treatment for locally advanced rectal cancer (LARC). Tumor-infiltrating lymphocytes (TILs) have been reported to be associated with tumor response; however, this remains to be established. We previously reported that histological changes on biopsy specimens obtained 7 days after starting nCRT are strong predictors of response to nCRT. Methods: The subjects were 208 patients with LARC who received nCRT. TILs on hematoxylin-eosin staining together with immunohistochemical staining of lymphocyte surface markers including CD3, CD4, CD8, and FoxP3 were performed both on the biopsy specimens before and 7 days after starting nCRT. Results: The proportions of patients with high densities of CD3+, CD4+, CD8+, and FoxP3+ cells 7 days after starting CRT were significantly lower than the respective values before starting nCRT (p < 0.0001, p < 0.0001, p = 0.0023, and p = 0.0046). In biopsy specimens obtained before treatment, high-density CD4+ cells and FOXP3+ cells were significantly associated with tumor shrinkage rate. High-density FOXP3+ cells were significantly associated with marked tumor regression. In biopsy specimens obtained 7 days after starting treatment, high-density CD4+ cells were significantly associated with marked tumor regression, tumor regression grade 1, and tumor shrinkage rate. High-density FoxP3+ cells were significantly associated with marked tumor regression and tumor shrinkage rate. Conclusions: In patients who received nCRT for LARC, the evaluations of immunohistochemical staining for CD4+ and FOXP3+ TILs were more intimately related to histological response to CRT and tumor shrinkage rates in biopsy specimens obtained 7 days after starting treatment than in biopsy specimens obtained before CRT.
When the Tumor Lyses: A Case Report on Spontaneous Tumor Lysis Syndrome
Authors: Dong Jiaxi , Cao Thanh , Tanner Natalee , Kundranda Madappa
Published: August 2020

Tumor lysis syndrome (TLS) is an oncological emergency characterized by severe electrolyte disturbance that typically occurs when hematologic cancer patients have been started on systemic chemotherapy. We present an uncommon case of spontaneous TLS (STLS) occurring in a patient with cholangiocarcinoma. The patient was a 59-year-old male with newly diagnosed differentiated carcinoma of unknown origin who presented with weakness, fatigue, and lightheadedness. Initial imaging revealed cholangiocarcinoma with innumerable pulmonary and hepatic metastases. The laboratory values showed leukocytosis, hypercalcemia, and lactic acidosis. He was diagnosed and treated for sepsis of pulmonary origin. Over the next 3 days, the patient’s clinical condition steadily worsened despite aggressive treatment, with new-onset hypoxic respiratory failure, acute kidney injury, and septic shock. Chemotherapy was administered, with new laboratory values showing hyperuricemia and hyperkalemia, consistent with STLS. The patient was transferred to the ICU and emergently started on dialysis but expired a day later from multi-organ failure. To our knowledge, this is the second case of STLS in cholangiocarcinoma. Our patient was unique in that he presented with hypercalcemia and normal phosphorus levels, instead of the typical hyperphosphatemia and secondary consumptive hypocalcemia. While the exact pathophysiology of STLS is still elusive, we believe that the patient’s initial sepsis-induced hypotension, aggressively enlarging tumor, and extent of metastasis all contributed to his rapid decline. Given the high mortality rate with TLS and its vague presentation, particularly in a chemotherapy-naïve solid tumor, a high level of clinical suspicion is needed to improve patients’ outcome.
The Relationship between Oxidative Stress, Intermittent Hypoxemia, and Hospital Duration in Moderate Preterm Infants
Authors: Shah Vidhi P. , Raffay Thomas M. , Martin Richard J. , Vento Máximo , Sánchez-Illana Ángel , Piñeiro-Ramos José David , Kuligowski Julia , Di Fiore Juliann M.
Published: August 2020

Introduction: Lipid peroxidation products are present following oxidation of polyunsaturated fatty acids in the eye, brain, and various cell membranes. Elevated levels of lipid peroxidation products and increased intermittent hypoxemia (IH) events have been associated with adverse outcomes in extremely preterm infants. The moderate preterm newborn has a still-developing oxidant defense system and immature respiratory control, but little is known about lipid peroxidation levels and IH in this larger and more common preterm population. Objective: To determine the association between oxidative stress and IH in moderate preterm infants. Method: Oxygen saturation was continuously monitored in 51 moderate preterm infants (i.e., 31 + 0/7 to 33 + 6/7 weeks’ gestation). Urine samples were collected at the end of the first and second weeks of life. Samples were analyzed for total lipid peroxidation products (neurofurans, isofurans, neuroprostanes, isoprostanes, and di-homo-isofurans). Result: At week 1, there was a correlation between increased IH frequency and neurofurans (p < 0.04) and di-homo-isofurans (p < 0.003). At week 2, there was no correlation between IH and lipid peroxidation markers. Ele­vations in neurofurans, isofurans, neuroprostanes, and di-homo-isofurans in the first and/or second week of life were associated with a longer stay in hospital. Conclusion: Elevations in lipid peroxidation biomarkers in moderate preterm infants during their first weeks of life are associated with a higher frequency of IH and prolonged hospitalization.
The Thioredoxin-Interacting Protein TXNIP Is a Putative Tumour Suppressor in Cutaneous T-Cell Lymphoma
Authors: Stolearenco Veronica , Levring Trine B. , Nielsen Helene Myrtue , Lindahl Lise , Fredholm Simon , Kongsbak-Wismann Martin , Willerslev-Olsen Andreas , Buus Terkild B. , Nastasi Claudia , Hu Tengpeng , Gluud Maria , Côme Christophe R.M. , Krejsgaard Thorbjørn , Iversen Lars , Bonefeld Charlotte Menné , Grønbæk Kirsten , Met Özcan , Woetmann Anders , Ødum Niels , Geisler Carsten
Published: August 2020

Background: The thioredoxin-interacting protein (TXNIP) is involved in cellular metabolism and cell proliferation, and recently, deficient expression of TXNIP has been associated with progression and poor outcome for cancer patients. Objectives: To assess TXNIP expression and function in malignant T cells from cutaneous T-cell lymphoma (CTCL). Methods: CTCL-derived malignant (MyLa2059, PB2B) and non-malignant (MyLa1850) cell lines were analysed by Western blotting and qPCR for TXNIP expression. Subsequently, the malignant CTCL cell lines were treated with GSK126 – an inhibitor of enhancer of zeste homolog 2 (EZH2) methyltransferase activity or assessed by bisulphite sequencing for TXNIP promoter methylation. Methylation was also assessed with the demethylating agent 5-azacytidine (5AZA). Finally, TXNIP was overexpressed in the malignant PB2B cell line via plasmid transduction, and the effect of TXNIP was further analysed by flow cytometry. Results: We report on low expression of TXNIP protein in all cell lines representing different subtypes and stages of CTCL when compared to non-malignant T cells. Epigenetic silencing and other mechanisms were involved in the repression of TXNIP whereas forced expression of TXNIP strongly inhibited proliferation of malignant T cells. Conclusions: Epigenetic silencing and other as yet unknown mechanisms repress TXNIP expression in malignant T cells. As forced expression of TXNIP inhibits malignant proliferation, we propose that TXNIP is a putative tumour suppressor in CTCL.
Inter-α-Trypsin Inhibitor Heavy Chain 5 (ITIH5) Is a Natural Stabilizer of Hyaluronan That Modulates Biological Processes in the Skin
Authors: Huth Sebastian , Huth Laura , Marquardt Yvonne , Fietkau Katharina , Dahl Edgar , Esser Philipp R. , Martin Stefan F. , Heise Ruth , Merk Hans F. , Baron Jens Malte
Published: August 2020

Introduction: Hyaluronan (HA) is a major component of the skin that exerts a variety of biological functions. Inter-α-trypsin inhibitor heavy chain (ITIH) proteins comprise a family of hyaladherins of which ITIH5 has recently been described in skin, where it plays a functional role in skin morphology and inflammatory skin diseases including allergic contact dermatitis (ACD). Objective: The current study focused on the ITIH5-HA interaction and its potential clinical and functional impact in extracellular matrix (ECM) stabilization. Methods: Studying the molecular effects of ITIH5 in skin, we established skin models comprising murine skin cells of Itih5 knockout mice and corresponding wild-type controls. In addition, human dermal fibroblasts with an ITIH5 knockdown as well as a murine recombinant Itih5 protein were established to examine the interaction between ITIH5 and HA using in vitro adhesion and HA degradation assays. To understand more precisely the role of ITIH5 in inflammatory skin diseases such as ACD, we generated ITIH5 knockout cells of the KeratinoSens® cell line. Results: Using murine skin models, ITIH5 knockdown fibroblasts, and a reactive oxygen species (ROS)-mediated HA degradation assay, we proved that ITIH5 binds to HA, thereby acting as a stabilizer of HA. Moreover, microarray profiling revealed the impact of ITIH5 on biological processes such as skin development and ECM homeostasis. Performing the in vitro KeratinoSens skin sensitization assay, we detected that ITIH5 decreases the sensitizing potential of moderate and strong contact sensitizers. Conclusion: Taken together, our experiments revealed that ITIH5 forms complexes with HA, thereby on the one hand stabilizing HA and facilitating the formation of ECM structures and on the other hand modulating inflammatory responses.
Reconstrução de fratura panfacial cominuta
Authors: Santiago Larissa Rodrigues , Rodrigues Cristóvão Marcondes de Castro , Santos Daniela Meneses , Batista Jonas Dantas , Furtado Lair Mambrini , Rocha Flaviana Soares
Published: August 2020

Modelo de estudo: Relato de Caso. Importância do problema: As fraturas panfaciais recebem essa denominação quando os terços faciais apresentam fraturas concomitantes. Com frequência, essas lesões estão relacionadas a danos importantes aos tecidos moles, cominuição e perda de segmentos ósseos e/ou dentários, que podem gerar má oclusão e graves deformidades faciais, visto que etiologia de tal condição se deve à acidentes de alta dissipação de energia. O tratamento das fraturas panfaciais com o uso de fixação interna rígida permite restaurar as funções mastigatórias, bem como os contornos faciais. Comentários: O objetivo desse trabalho é relatar a reconstrução de uma fratura panfacial, envolvendo a mandíbula e com elevado grau de cominuição do complexo zigomático orbitário e do arco zigomático, em uma paciente do sexo feminino, em que acesso hemicoronal e retromandibular foram escolhidos para reconstrução e reestruturação do complexo facial. Conclusão: O correto manejo das fraturas panfaciais, é um dos grandes desafios do cirurgião buco maxilo facial, visto o nível de dificuldade para reestabelecer de maneira satisfatória as condições estéticas e funcionais existentes previamente ao trauma. Diferentes sequências de tratamento vêm sendo propostas, podendo ser utilizadas com sucesso após análise adequada do caso clínico e correta indicação.
Investigações sobre o trabalho do classicista digital: aportes iniciais
Authors: Reis Michel Ferreira dos
Published: August 2020

O presente artigo tem a finalidade de trazer uma contribuição em relação ao trabalho do professor e pesquisador de línguas clássicas, mais especificamente, o de língua/literatura grega, que vem se apoiando em métodos e tecnologias digitais para o estudo, pesquisa e ensino da antiguidade. Em tal empreitada, usaremos as fundamentações teórica e metodológica do Interacionismo Sociodiscursivo (BRONCKART, 2006, 2008, 2012) e nos valemos do conceito de gênero professional (CLOT; FAÏTA, 2000) advindo da Clínica da Atividade. Dessa forma, para a análise da pesquisa que ainda está em desenvolvimento, teremos como o foco neste artigo os dados coletados de duas entrevistas com um professor/pesquisador do curso de Humanidades Digitais, mas que é um classicista digital. A partir disso, serão apontados aspectos relativos à percepção do seu trabalho numa perspectiva interdisciplinar entre Humanidades e Informática.
Resenhas dos livros didáticos aprovados pelo Guia PNLD 2020 de língua portuguesa: uma ferramenta para o trabalho docente
Authors: Tognato Maria Izabel Rodrigues , Buttler Daniella Barbosa
Published: August 2020

Considerando o contexto sócio-histórico mais amplo em que temos vivido em relação ao uso do livro didático na Educação Básica da rede pública de ensino, buscamos contribuir para um debate social acerca do processo de escolha dos livros didáticos nas escolas e o Guia PNLD 2020, uma vez que o documento oferece resenhas a respeito dos livros didáticos de Língua Portuguesa aprovados, bem como sobre as possíveis relações que o Guia PNLD 2020 estabelece com os saberes e as Capacidades Cocentes (HOFSTETTER; SCHNEUWLY, 2009; STUTZ, 2012), além das capacidades de linguagem (DOLZ; PASQUIER; BRONCKART, 1993; SCHNEUWLY; DOLZ, 2004; STUTZ; CRISTOVÃO, 2011; CRISTOVÃO, 2013), necessários ao ensino de línguas. Para tanto, pautamos nosso estudo na perspectiva teóricometodológica do Interacionismo Sociodiscursivo (ISD) (BRONCKART, [1997]2009). Quanto aos procedimentos metodológicos, utilizamos o Guia PNLD 2020 como objeto de análise no que tange às Resenhas dos livros aprovados pelo PNLD 2020, tomando as capacidades de linguagem, os saberes e as Capacidades Docentes como categorias de análise destas Resenhas. Os resultados apontam para possíveis contribuições e/ou limitações do Guia PNLD 2020 para o ensino de Língua Portuguesa. Com isso, esperamos contribuir para a discussão acerca do processo de avaliação e escolha do livro didático pelo professor de línguas.
Ensinar o debate regrado sobre as (des)igualdades entre os sexos no primário: evolução da distribuição da fala entre os(as) participantes
Authors: Coppola Anthony , Dolz Joaquim
Published: August 2020

Neste artigo, buscamos apresentar os resultados da pesquisa realizada pelo grupo GRAFE (Grupo de Pesquisa para a Análise do Francês Ensinado), por meio do dispositivo Atelier Filé, implementado em três turmas de uma escola primária do Cantão de Vaud, na Suíça, com alunos com idade entre 8 e 10 anos. O objetivo da pesquisa era o de compreender como intervenções didáticas específicas e reiteradas para o ensino do gênero debate regrado permitem, ao mesmo tempo, promover o desenvolvimento das capacidades argumentativas dos alunos em francês e influenciar a adesão dos alunos ao sistema de gênero, temática central escolhida para discussão nos diferentes debates regrados propostos pelo dispositivo. Dessa forma, os pesquisadores visavam investigar se o dispositivo era eficaz como procedimento para uma educação cidadã, de modo a formar cidadãos conscientes dos efeitos sociais da desigualdade de gêneros e linguisticamente atuantes na busca de maior igualdade no sistema de gêneros.
Association of Operator and Hospital Experience With Procedural Success Rates and Outcomes in Patients Undergoing Percutaneous Coronary Interventions for Chronic Total Occlusions
Authors: Zein Rami , Seth Milan , Othman Hussein , Rosman Howard S. , Lalonde Thomas , Alaswad Khaldoon , Menees Daniel , Daher Edouard , Mehta Rajendra H. , Gurm Hitinder S.
Published: August 2020

Background:

An inverse relationship has been described between procedural success and outcomes of all major cardiovascular procedures. However, this relationship has not been studied for percutaneous coronary intervention (PCI) of chronic total occlusion (CTO).

Methods:

We analyzed the data on patients enrolled in Blue Cross Blue Shield of Michigan Cardiovascular Consortium registry in Michigan (January 1, 2010 to March 31, 2018) to evaluate the association of operator and hospital experience with procedural success and outcomes of patients undergoing CTO-PCI. CTO-PCI was defined as intervention of a 100% occluded coronary artery presumed to be ≥3 months old.

Results:

Among 210 172 patients enrolled in the registry, 7389 (3.5%) CTO-PCIs were attempted with a success rate of 53%. CTO-PCI success increased with operator experience (45% and 65% in the lowest and highest experience tertiles) and was the highest for highly experienced operators at higher experience centers and the lowest for inexperienced operators at low experience hospitals. Multivariable logistic regression models (with spline transformed prior operator and institutional experience) demonstrated a positive relationship between prior operator and site experience and procedural success rates (likelihood ratio test=141.12, df=15,
P
<0.001) but no relationship between operator and site experience and major adverse cardiac event (likelihood ratio test=19.12, df=15,
P
=0.208).

Conclusions:

Operator and hospital CTO-PCI experiences were directly related to procedural success but were not related to major adverse cardiac event among patients undergoing CTO-PCIs. Inexperienced operators at high experience centers had significantly higher success but not major adverse cardiac event rates compared with inexperienced operators at low experience centers. These data suggested that CTO-PCI safety and success could potentially be improved by selective referral of these procedures to experienced operators working at highly experienced centers.
A Notch3-Marked Subpopulation of Vascular Smooth Muscle Cells Is the Cell of Origin for Occlusive Pulmonary Vascular Lesions
Authors: Steffes Lea C. , Froistad Alexis A. , Andruska Adam , Boehm Mario , McGlynn Madeleine , Zhang Fan , Zhang Wenming , Hou David , Tian Xuefei , Miquerol Lucile , Nadeau Kari , Metzger Ross J. , Spiekerkoetter Edda , Kumar Maya E.
Published: August 2020

Background:

Pulmonary arterial hypertension (PAH) is a fatal disease characterized by profound vascular remodeling in which pulmonary arteries narrow because of medial thickening and occlusion by neointimal lesions, resulting in elevated pulmonary vascular resistance and right heart failure. Therapies targeting the neointima would represent a significant advance in PAH treatment; however, our understanding of the cellular events driving neointima formation, and the molecular pathways that control them, remains limited.

Methods:

We comprehensively map the stepwise remodeling of pulmonary arteries in a robust, chronic inflammatory mouse model of pulmonary hypertension. This model demonstrates pathological features of the human disease, including increased right ventricular pressures, medial thickening, neointimal lesion formation, elastin breakdown, increased anastomosis within the bronchial circulation, and perivascular inflammation. Using genetic lineage tracing, clonal analysis, multiplexed in situ hybridization, immunostaining, deep confocal imaging, and staged pharmacological inhibition, we define the cell behaviors underlying each stage of vascular remodeling and identify a pathway required for neointima formation.

Results:

Neointima arises from smooth muscle cells (SMCs) and not endothelium. Medial SMCs proliferate broadly to thicken the media, after which a small number of SMCs are selected to establish the neointima. These neointimal founder cells subsequently undergoing massive clonal expansion to form occlusive neointimal lesions. The normal pulmonary artery SMC population is heterogeneous, and we identify a Notch3-marked minority subset of SMCs as the major neointimal cell of origin. Notch signaling is specifically required for the selection of neointimal founder cells, and Notch inhibition significantly improves pulmonary artery pressure in animals with pulmonary hypertension.

Conclusions:

This work describes the first nongenetically driven murine model of pulmonary hypertension (PH) that generates robust and diffuse occlusive neointimal lesions across the pulmonary vascular bed and does so in a stereotyped timeframe. We uncover distinct cellular and molecular mechanisms underlying medial thickening and neointima formation and highlight novel transcriptional, behavioral, and pathogenic heterogeneity within pulmonary artery SMCs. In this model, inflammation is sufficient to generate characteristic vascular pathologies and physiological measures of human PAH. We hope that identifying the molecular cues regulating each stage of vascular remodeling will open new avenues for therapeutic advancements in the treatment of PAH.
Diagnostic Yield of Electroanatomic Voltage Mapping in Guiding Endomyocardial Biopsies
Authors: Casella Michela , Dello Russo Antonio , Bergonti Marco , Catto Valentina , Conte Edoardo , Sommariva Elena , Gasperetti Alessio , Vettor Giulia , Tundo Fabrizio , Sicuso Rita , Rizzo Stefania , Mushtaq Saima , Della Rocca Domenico , Pompilio Giulio , Di Biase Luigi , Andreini Daniele , Natale Andrea , Basso Cristina , Tondo Claudio
Published: August 2020

Background:

Electroanatomic voltage mapping (EVM) is a promising modality for guiding endomyocardial biopsies (EMBs). However, few data support its feasibility and safety. We now report the largest cohort of patients undergoing EVM-guided EMBs to show its diagnostic yield and to compare it with a cardiac magnetic resonance (CMR)–guided approach.

Methods:

We included 162 consecutive patients undergoing EMB at our institution from 2010 to 2019. EMB was performed in pathological areas identified at EVM and CMR. CMR and EVM sensitivity and specificity regarding the identification of pathological substrates of myocardium were evaluated according to EMB results.

Results:

Preoperative CMR showed late gadolinium enhancement in 70% of the patients, whereas EVM identified areas of low voltage in 61%. Right (73%), left (19%), or both ventricles (8%) underwent sampling. EVM proved to have sensitivity similar to CMR (74% versus 77%), with specificity being 70% and 47%, respectively. In 12 patients with EMB-proven cardiomyopathy, EVM identified pathological areas that had been undetected at CMR evaluation. Sensitivity of pooled EVM and CMR was as high as 95%. EMB analysis allowed us to reach a new diagnosis, different from the suspected clinical diagnosis, in 39% of patients. The complications rate was low, mostly related to vascular access, with no patients requiring urgent management.

Conclusions:

EVM proved to be a promising tool for targeted EMB because of its sensitivity and specificity for identification of myocardial pathological substrates. EVM was demonstrated to have accuracy similar to CMR. EVM and CMR together conferred a positive predictive value of 89% on EMB.
Blood Pressure and Chronic Kidney Disease Stratified by Gender and the Use of Antihypertensive Drugs
Authors: Satoh Michihiro , Hirose Takuo , Nakayama Shingo , Murakami Takahisa , Takabatake Kyosuke , Asayama Kei , Imai Yutaka , Ohkubo Takayoshi , Mori Takefumi , Metoki Hirohito
Published: August 2020

Background

The present study assessed the association between blood pressure (BP) and the risk of chronic kidney disease (CKD) according to gender and the use of antihypertensive drugs using data from a large‐scale health checkup.

Methods and Results

We conducted a retrospective cohort study using the JMDC database, which contains annual health checkup data of Japanese employees and their dependents aged <75 years. We included 154 692 participants (men, 69.68%; mean age, 44.74 years) without CKD. CKD was indicated by an estimated glomerular filtration rate <60 mL/min per 1.73 m
2
or the presence of proteinuria. During the mean follow‐up period of 4.78 years, new‐onset CKD occurred in 14 888 participants. When the normal BP group (systolic/diastolic BP <120/<80 mm Hg) without treatment was used as a reference, the hazard ratios of the high BP (130–139/80–89 mm Hg) and grade 1 (140–159/90–99 mm Hg) and grade 2 or 3 hypertension (≥160/≥100 mm Hg) groups were 1.11 (95% CI, 1.06–1.17), 1.36 (95% CI, 1.28–1.45), and 1.76 (95% CI, 1.56–1.99) for untreated men, respectively. However, in treated men, even normal BP was associated with a 1.5‐fold higher risk of CKD. The association between BP and the risk of CKD was weaker in untreated women than in untreated men. The risk of CKD in treated women with normal BP was similar to that of untreated women with normal BP.

Conclusions

Gender differences were found in the association between BP and CKD risk. Kidney function in treated individuals should be followed carefully, especially in men.