bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploration of anti-inflammatory mechanism of forsythiaside A and forsythiaside B in CuSO4-induced inflammation in zebrafish by metabolomic and proteomic analyses
Authors: Gong Lihong , Yu Linyuan , Gong Xiaohong , Wang Cheng , Hu Naihua , Dai Xuyang , Peng Cheng , Li Yunxia
Published: June 2020

Background

Inflammation is a general pathological phenomenon during severe disturbances to the homeostasis. Forsythiaside A (FA) and forsythiaside B (FB), isolated from the dried fruit ofForsythia suspensa(Thunb.) Vahl, are phenylethanoid compounds that show a significant anti-inflammatory effect. However, the properties and therapeutic mechanisms of this effect have not yet been systematically elucidated.

Methods

In this study, the anti-inflammatory effects of FA and FB were investigated in CuSO4-induced inflammation in zebrafish larvae. Intracellular generation of reactive oxygen species (ROS) and nitric oxide (NO) was investigated using fluorescence probes. Metabolomic and proteomic analyses using liquid chromatography-mass spectrometry were carried out to identify the expressions of metabolites and proteins associated with the anti-inflammatory mechanism of FA and FB. Quantitative polymerase chain reaction (PCR) was performed to detect the progressive changes in gene expression.

Results

FA and FB inhibited neutrophils migration to the damaged neuromasts and remarkably reduced CuSO4-induced ROS and NO generation in zebrafish larvae. Metabolomic analysis pointed to the involvement of nicotinate and nicotinamide metabolism, energy metabolism, pyrimidine metabolism, and purine metabolism. Proteomic analysis identified 146 differentially expressed proteins between the control and model groups. These included collagen [collagen type II alpha 1b precursor (col2a1b), collagen alpha-2(IX) chain precursor (col9a2), collagen type IX alpha I precursor (col9a1b)], nucleoside diphosphate kinase 3 isoform X1 (Nme3), WD repeat-containing protein 3 (Wdr3), and 28S ribosomal protein S7 mitochondrial precursor (Mrps7). FA and FB were shown to reverse the abnormal expressions of potential metabolite and protein biomarkers and alleviate CuSO4-induced damage to the neuromasts in the zebrafish lateral line.

Conclusions

Our results indicate that FA and FB possess remarkable anti-inflammatory properties, protecting against CuSO4-induced neuromasts damage in zebrafish larvae. The results also suggest a multi-component and multi-regulatory therapeutic mechanism for FA and FB.
Role of immune cells in the removal of deleterious senescent cells
Authors: Kale Abhijit , Sharma Amit , Stolzing Alexandra , Desprez Pierre-Yves , Campisi Judith
Published: June 2020

Cellular senescence is an essentially irreversible arrest of cell proliferation coupled to a complex senescence-associated secretory phenotype (SASP). The senescence arrest prevents the development of cancer, and the SASP can promote tissue repair. Recent data suggest that the prolonged presence of senescent cells, and especially the SASP, could be deleterious, and their beneficial effects early in life can become maladaptive such that they drive aging phenotypes and pathologies late in life. It is therefore important to develop strategies to eliminate senescent cells. There are currently under development or approved several immune cell-based therapies for cancer, which could be redesigned to target senescent cells. This review focuses on this possible use of immune cells and discusses how current cell-based therapies could be used for senescent cell removal.
Advances in blood–brain barrier modeling in microphysiological systems highlight critical differences in opioid transport due to cortisol exposure
Authors: Brown Jacquelyn A. , Faley Shannon L. , Shi Yajuan , Hillgren Kathleen M. , Sawada Geri A. , Baker Thomas K. , Wikswo John P. , Lippmann Ethan S.
Published: June 2020

Background

The United States faces a national crisis involving opioid medications, where currently more than 130 people die every day. To combat this epidemic, a better understanding is needed of how opioids penetrate into the central nervous system (CNS) to facilitate pain relief and, potentially, result in addiction and/or misuse. Animal models, however, are a poor predictor of blood–brain barrier (BBB) transport and CNS drug penetration in humans, and many traditional 2D cell culture models of the BBB and neurovascular unit have inadequate barrier function and weak or inappropriate efflux transporter expression. Here, we sought to better understand opioid transport mechanisms using a simplified microfluidic neurovascular unit (NVU) model consisting of human brain microvascular endothelial cells (BMECs) co-cultured with astrocytes.

Methods

Human primary and induced pluripotent stem cell (iPSC)-derived BMECs were incorporated into a microfluidic NVU model with several technical improvements over our previous design. Passive barrier function was assessed by permeability of fluorescent dextrans with varying sizes, and P-glycoprotein function was assessed by rhodamine permeability in the presence or absence of inhibitors; quantification was performed with a fluorescent plate reader. Loperamide, morphine, and oxycodone permeability was assessed in the presence or absence of P-glycoprotein inhibitors and cortisol; quantification was performed with mass spectrometry.

Results

We first report technical and methodological optimizations to our previously described microfluidic model using primary human BMECs, which results in accelerated barrier formation, decreased variability, and reduced passive permeability relative to Transwell models. We then demonstrate proper transport and efflux of loperamide, morphine, and oxycodone in the microfluidic NVU containing BMECs derived from human iPSCs. We further demonstrate that cortisol can alter permeability of loperamide and morphine in a divergent manner.

Conclusions

We reveal a novel role for the stress hormone cortisol in modulating the transport of opioids across the BBB, which could contribute to their abuse or overdose. Our updated BBB model represents a powerful tool available to researchers, clinicians, and drug manufacturers for understanding the mechanisms by which opioids access the CNS.
Should autism spectrum disorder be considered part of CHARGE syndrome? A cross-sectional study of 46 patients
Authors: Abadie Véronique , Hamiaux Priscilla , Ragot Stéphanie , Legendre Marine , Malecot Gaelle , Burtin Alexia , Attie-Bitach Tania , Lyonnet Stanislas , Bilan Frédéric , Gilbert-Dussardier Brigitte , Vaivre-Douret Laurence
Published: June 2020

Background

Behavioral problems are an important issue for people with CHARGE syndrome. The similarity of their behavioral traits with those of people with autism raises questions. In a large national cross-sectional study, we used specific standardized tools for diagnosing autism (Autism Diagnostic Interview-Revised and Diagnostic and Statistical Manual of Mental Disorders, 5th edition, DSM-5) and evaluating behavioral disorders (Developmental Behavior Checklist-Parents, DBC-P) to investigate a series of individuals with CHARGE syndrome, defined by Verloes’s criteria. We evaluated their adaptive functioning level and sensory particularities and extracted several data items from medical files to assess as potential risk factors for autism and/or behavioral disorders.

Results

We investigated 64 individuals with CHARGE syndrome (35 females; mean age 10.7 years, SD 7.1 years). Among 46 participants with complete results for the Autism Diagnostic Interview-Revised (ADI-R), 13 (28%) had a diagnosis of autism according to the ADI-R, and 25 (54%) had a diagnosis of autism spectrum disorder (ASD) according to the DSM-5 criteria. The frequency of autistic traits in the entire group was a continuum. We did not identify any risk factor for ASD but found a negative correlation between the ADI-R score and adaptive functioning level. Among 48 participants with data for the DBC-P, 26 (55%) had behavioral disorders, which were more frequent in patients with radiological brain anomalies, impaired adaptive functioning, later independent walking, and more sensory particularities.

Conclusions

ASD should be considered to be an independent risk requiring early screening and management in children born with CHARGE syndrome.
From basic research to the clinic: innovative therapies for ALS and FTD in the pipeline
Authors: Liscic Rajka Maria , Alberici Antonella , Cairns Nigel John , Romano Maurizio , Buratti Emanuele
Published: June 2020

Amyotrophic lateral sclerosis (ALS) and Frontotemporal Degeneration (FTD) are neurodegenerative disorders, related by deterioration of motor and cognitive functions and short survival. Aside from cases with an inherited pathogenic mutation, the causes of the disorders are still largely unknown and no effective treatment currently exists. It has been shown that FTD may coexist with ALS and this overlap occurs at clinical, genetic, and molecular levels. In this work, we review the main pathological aspects of these complex diseases and discuss how the integration of the novel pathogenic molecular insights and the analysis of molecular interaction networks among all the genetic players represents a critical step to shed light on discovering novel therapeutic strategies and possibly tailoring personalized medicine approaches to specific ALS and FTD patients.
Investigation of CTNNB1 gene mutations and expression in hepatocellular carcinoma and cirrhosis in association with hepatitis B virus infection
Authors: Javanmard Davod , Najafi Mohammad , Babaei Mohammad Reza , Karbalaie Niya Mohammad Hadi , Esghaei Maryam , Panahi Mahshid , Safarnezhad Tameshkel Fahimeh , Tavakoli Ahmad , Jazayeri Seyed Mohammad , Ghaffari Hadi , Ataei-Pirkooh Angila , Monavari Seyed Hamidreaz , Bokharaei-Salim Farah
Published: June 2020

Hepatitis B virus (HBV), along with Hepatitis C virus chronic infection, represents a major risk factor for hepatocellular carcinoma (HCC) development. However, molecular mechanisms involved in the development of HCC are not yet completely understood. Recent studies have indicated that mutations in CTNNB1 gene encoding for β-catenin protein lead to aberrant activation of the Wnt/ β-catenin pathway. The mutations in turn activate several downstream genes, including c-Myc, promoting the neoplastic process. The present study evaluated the mutational profile of the CTNNB1 gene and expression levels of CTNNB1 and c-Myc genes in HBV-related HCC, as well as in cirrhotic and control tissues. Mutational analysis of the β-catenin gene and HBV genotyping were conducted by direct sequencing. Expression of β-catenin and c-Myc genes was assessed using real-time PCR. Among the HCC cases, 18.1% showed missense point mutation in exon 3 of CTNNB1, more frequently in codons 32, 33, 38 and 45. The frequency of mutation in the hotspots of exon 3 was significantly higher in non-viral HCCs (29.4%) rather than HBV-related cases (12.7%, P = 0.021). The expression of β-catenin and c-Myc genes was found upregulated in cirrhotic tissues in association with HBV infection. Mutations at both phosphorylation and neighboring sites were associated with increased activity of the Wnt pathway. The results demonstrated that mutated β-catenin caused activation of the Wnt pathway, but the rate of CTNNB1 gene mutations was not related to HBV infection. HBV factors may deregulate the Wnt pathway by causing epigenetic alterations in the HBV-related HCC.
Urine cell cycle arrest biomarkers distinguish poorly between transient and persistent AKI in early septic shock: a prospective, multicenter study
Authors: Titeca-Beauport Dimitri , Daubin Delphine , Van Vong Ly , Belliard Guillaume , Bruel Cédric , Alaya Sami , Chaoui Karim , Andrieu Maud , Rouquette-Vincenti Isabelle , Godde Frederic , Pascal Michel , Diouf Momar , Vinsonneau Christophe , Klouche Kada , Maizel Julien
Published: June 2020

Background

The urine biomarkers tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) have been validated for predicting and stratifying AKI. In this study, we analyzed the utility of these biomarkers for distinguishing between transient and persistent AKI in the early phase of septic shock.

Methods

We performed a prospective, multicenter study in 11 French ICUs. Patients presenting septic shock, with the development of AKI within the first 6 h, were included. Urine [TIMP-2]*[IGFBP7] was determined at inclusion (0 h), 6 h, 12 h, and 24 h. AKI was considered transient if it resolved within 3 days. Discriminative power was evaluated by receiver operating characteristic (ROC) curve analysis.

Results

We included 184 patients, within a median [IQR] time of 1.0 [0.0–3.0] h after norepinephrine (NE) initiation; 100 (54%) patients presented transient and 84 (46%) presented persistent AKI. Median [IQR] baseline urine [TIMP-2]*[IGFBP7] was higher in the persistent AKI group (2.21 [0.81–4.90] (ng/ml)2/1000) than in the transient AKI group (0.75 [0.20–2.12] (ng/ml)2/1000; p < 0.001). Baseline urine [TIMP-2]*[IGFBP7] was poorly discriminant, with an AUROC [95% CI] of 0.67 [0.59–0.73]. The clinical prediction model combining baseline serum creatinine concentration, baseline urine output, baseline NE dose, and baseline extrarenal SOFA performed well for the prediction of persistent AKI, with an AUROC [95% CI] of 0.81 [0.74–0.86]. The addition of urine [TIMP-2]*[IGFBP7] to this model did not improve the predictive performance.

Conclusions

Urine [TIMP-2]*[IGFBP7] measurements in the early phase of septic shock discriminate poorly between transient and persistent AKI and do not improve clinical prediction over that achieved with the usual variables.

Trial registration

NCT02812784
FAK activates AKT-mTOR signaling to promote the growth and progression of MMTV-Wnt1-driven basal-like mammary tumors
Authors: Paul Ritama , Luo Ming , Mo Xueying , Lu Jason , Yeo Syn Kok , Guan Jun-Lin
Published: June 2020

Background

Breast cancer is a heterogeneous disease. Hence, stratification of patients based on the subtype of breast cancer is key to its successful treatment. Among all the breast cancer subtypes, basal-like breast cancer is the most aggressive subtype with limited treatment options. Interestingly, we found focal adhesion kinase (FAK), a cytoplasmic tyrosine kinase, is highly overexpressed and activated in basal-like breast cancer.

Methods

To understand the role of FAK in this subtype, we generated mice with conditional deletion of FAK and a knock-in mutation in its kinase domain in MMTV-Wnt1-driven basal-like mammary tumors. Tumor initiation, growth, and metastasis were characterized for these mice cohorts. Immunohistochemical and transcriptomic analysis of Wnt1-driven tumors were also performed to elucidate the mechanisms underlying FAK-dependent phenotypes. Pharmacological inhibition of FAK and mTOR in human basal-like breast cancer cell lines was also tested.

Results

We found that in the absence of FAK or its kinase function, growth and metastasis of the tumors were significantly suppressed. Furthermore, immunohistochemical analyses of cleaved caspase 3 revealed that loss of FAK results in increased tumor cell apoptosis. To further investigate the mechanism by which FAK regulates survival of the Wnt1-driven tumor cells, we prepared an isogenic pair of mammary tumor cells with and without FAK and found that FAK ablation increased their sensitivity to ER stress-induced cell death, as well as reduced tumor cell migration and tumor sphere formation. Comparative transcriptomic profiling of the pair of tumor cells and gene set enrichment analysis suggested mTOR pathway to be downregulated upon loss of FAK. Immunoblot analyses further confirmed that absence of FAK results in reduction of AKT and downstream mTOR pathways. We also found that inhibition of FAK and mTOR pathways both induces apoptosis, indicating the importance of these pathways in regulating cell survival.

Conclusions

In summary, our studies show that in a basal-like tumor model, FAK is required for survival of the tumor cells and can serve as a potential therapeutic target.
Genetic basis for prediction of non-responders to dietary plant sterol intervention (GenePredict-PS): a study protocol for a double-blind, placebo-controlled, randomized two-period crossover study
Authors: Shamloo Maryam , Granger Matthew J. , Trautwein Elke A. , House James D. , MacKay Dylan
Published: June 2020

Background

Functional food ingredients and natural health products have been demonstrated to reduce disease risk and thereby help to lower health care costs across populations at risk for chronic or degenerative diseases. However, typically a wide range of interindividual variability exists in response across individuals to nutritional and natural health product bioactives, such as plant sterols (PS). This study aims to determine and utilize information on the associations between genosets and the degree of responsiveness to dietary PS intervention, with a long-term objective of developing genetic tests to predict responses to PS.

Methods

This clinical trial is designed as a double-blind, placebo controlled, randomized two-period crossover study. Sixty-four eligible participants with the specific a priori-determined single nucleotide polymorphisms (SNPs) associated with a responsiveness to PS will consume PS or a placebo treatment for two 4-week periods. The PS treatment consists of two daily single portions of margarine, each providing 1 g PS during the PS period (2.0 g/day of PS in total). The placebo will be an identical margarine containing no added PS. Low-density lipoprotein cholesterol (LDL-C) responsiveness to the controlled administration of PS will be investigated as the primary outcome, and the associations between interindividual genoset variabilities and response to PS consumption will be determined.

Discussion

This research will provide further insight into whether the associations between previously identified SNPs and the response of LDL-C to PS consumption can be used in a predictive manner. It will also provide insight into the complexities of undertaking a nutrigenetic trial with prospective recruitment based on genotype.

Trial registration

ClinicalTrials.gov: Identifier: NCT02765516. Registered on 6 May 2016.
The efficacy of the novel zinc-containing desensitizer CAREDYNE Shield on dentin hypersensitivity: a study protocol for a pilot randomized controlled trial
Authors: Matsuura Takashi , Mae Megumi , Ohira Masayuki , Yamashita Yasunori , Nakazono Ayako , Sugimoto Kouji , Yanagiguchi Kajiro , Yamada Shizuka
Published: June 2020

Background

Dentin hypersensitivity (DH) is a condition characterized by short and sharp episodes of pain which will arise in response to tactile, chemical, thermal, evaporative or osmotic stimuli. The painful symptoms cause discomfort in patients and reduce their quality of life. Recently, the novel zinc-containing desensitizer CAREDYNE Shield has been developed as a new type of desensitizer that acts by inducing chemical occlusion of dentinal tubules, and releasing zinc ion for root caries prevention. However, the clinical effectiveness of CAREDYNE Shield on DH remains unclear. Therefore, the aim of this study is to evaluate the effectiveness of CAREDYNE Shield on DH by comparing with that of another desensitizer, Nanoseal, commonly used in Japan.

Methods/design

This study protocol is a two-arm, parallel, pilot randomized controlled trial. Forty DH patients will be randomly allocated to two groups. Participants in the intervention group will be treated with CAREDYNE Shield, while those in the control group will be treated with Nanoseal. The primary outcome is the reduction of pain intensity in response to air stimuli measured with a 5-point verbal response scale from baseline to 4 weeks after the intervention, and Fisher’s exact test will be used for analyses.

Discussion

CAREDYNE Shield can be casually applied to subgingival areas and proximal surfaces because it reacts with only tooth substance. Furthermore, zinc has been reported to reduce the demineralization of enamel and dentin and inhibit biofilm formation, plaque growth and dentin-collagen degradation. Therefore, CAREDYNE Shield may be expected to be a useful novel desensitizer that acts not only as a desensitizer but also as a root caries inhibitor.

Trial registration

UMIN Clinical Trials Registry (UMIN-CTR), ID: UMIN000038072. Registered on 21 September 2019.

Trial status

This study (protocol version number: version 1.4.0; approved on 22 October 2019) is ongoing. The recruitment of participants began in December 2019 and will be continued until November 2020 (Hanke, Am Dent Assoc 27:1379–1393, 1940).
Correction to: Rectal indomethacin alone versus indomethacin and prophylactic pancreatic stent placement for preventing pancreatitis after ERCP: study protocol for a randomized controlled trial
Authors: Elmunzer B. Joseph , Serrano Jose , Chak Amitabh , Edmundowicz Steven A. , Papachristou Georgios I. , Scheiman James M. , Singh Vikesh K. , Varadarajulu Shyam , Vargo John J. , Willingham Field F. , Baron Todd H. , Coté Gregory A. , Romagnuolo Joseph , Wood-Williams April , Depue Emily K. , Spitzer Rebecca L. , Spino Cathie , Foster Lydia D. , Durkalski Valerie ,   on behalf of the SVI study group and the United States Cooperative for Outcomes Research in Endoscopy (USCORE)
Published: June 2020

An amendment to this paper has been published and can be accessed via the original article.
An integrated dataset of malaria notifications in the Legal Amazon
Authors: Baroni Lais , Pedroso Marcel , Barcellos Christovam , Salles Rebecca , Salles Samella , Paixão Balthazar , Chrispino Alvaro , Guedes Gustavo , Ogasawara Eduardo
Published: June 2020

Objectives

Malaria is an infectious disease that annually presents around 200,000 cases in Brazil. The availability of data on malaria is crucial for enabling and supporting studies that can promote actions to prevent it. Therefore, the goal of this paper is to contribute to such studies by offering an integrated dataset containing data on reported and suspected cases of malaria in the Brazilian Legal Amazon comprising the period from the years 2009 to 2019.

Data description

This paper presents a dataset with all medical records of patients who were tested for malaria in the Brazilian Legal Amazon from 2009 to 2019. The dataset has 40 attributes and 22,923,977 records of suspected cases of malaria. Around 12% of the data correspond to confirmed cases of malaria. The attributes include data regarding the notifications, examinations, as well as personal patient information, which are organized into health regions.
Quantification and reliability of [11C]VC - 002 binding to muscarinic acetylcholine receptors in the human lung — a test-retest PET study in control subjects
Authors: Cselényi Zsolt , Jucaite Aurelija , Kristensson Cecilia , Stenkrona Per , Ewing Pär , Varrone Andrea , Johnström Peter , Schou Magnus , Vazquez-Romero Ana , Moein Mohammad Mahdi , Bolin Martin , Siikanen Jonathan , Grybäck Pär , Larsson Bengt , Halldin Christer , Grime Ken , Eriksson Ulf G. , Farde Lars
Published: June 2020

Background

The radioligand [11C]VC-002 was introduced in a small initial study long ago for imaging of muscarinic acetylcholine receptors (mAChRs) in human lungs using positron emission tomography (PET). The objectives of the present study in control subjects were to advance the methodology for quantification of [11C]VC-002 binding in lung and to examine the reliability using a test-retest paradigm. This work constituted a self-standing preparatory step in a larger clinical trial aiming at estimating mAChR occupancy in the human lungs following inhalation of mAChR antagonists.

Methods

PET measurements using [11C]VC-002 and the GE Discovery 710 PET/CT system were performed in seven control subjects at two separate occasions, 2–19 days apart. One subject discontinued the study after the first measurement.

Radioligand binding to mAChRs in lung was quantified using an image-derived arterial input function. The total distribution volume (VT) values were obtained on a regional and voxel-by-voxel basis. Kinetic one-tissue and two-tissue compartment models (1TCM, 2TCM), analysis based on linearization of the compartment models (multilinear Logan) and image analysis by data-driven estimation of parametric images based on compartmental theory (DEPICT) were applied.

The test-retest repeatability of VT estimates was evaluated by absolute variability (VAR) and intraclass correlation coefficients (ICCs).

Results

The 1TCM was the statistically preferred model for description of [11C]VC-002 binding in the lungs. Low VAR (< 10%) across analysis methods indicated good reliability of the PET measurements. The VT estimates were stable after 60 min.

Conclusions

The kinetic behaviour and good repeatability of [11C]VC-002 as well as the novel lung image analysis methodology support its application in applied studies on drug-induced mAChR receptor occupancy and the pathophysiology of pulmonary disorders.

Trial registration

ClinicalTrials.gov identifier: NCT03097380, registered: 31 March 2017.
Synthesis of a novel 89Zr-labeled HER2 affibody and its application study in tumor PET imaging
Authors: Xu Yuping , Wang Lizhen , Pan Donghui , Yan Junjie , Wang Xinyu , Yang Runlin , Li Mingzhu , Liu Yu , Yang Min
Published: June 2020

Background

Human epidermal growth factor receptor-2 (HER2) is an essential biomarker for tumor treatment. Affibody is an ideal vector for preparing HER2 specific probes because of high affinity and rapid clearance from normal tissues, etc. Zirconium-89 is a PET imaging isotope with a long half-life and suitable for monitoring biological processes for more extended periods. In this study, a novel 89Zr-labeled HER2 affibody, [89Zr]Zr-DFO-MAL-Cys-MZHER2, was synthesized, and its imaging characters were also assessed.

Results

The precursor, DFO-MAL-Cys-MZHER2, was obtained with a yield of nearly 50%. The radiochemical yield of [89Zr]Zr -DFO-MAL-Cys-MZHER2 was 90.2 ± 1.9%, and the radiochemical purity was higher than 95%. The total synthesis time was only 30 min. The probe was stable in PBS and serum. The tracer accumulated in HER2 overexpressing human ovarian cancer SKOV-3 cells. In vivo studies in mice bearing tumors showed that the probe was highly retained in SKOV-3 xenografts even for 48 h. The tumors were visualized with good contrast to normal tissues. ROI analysis revealed that the average uptake values in the tumor were greater than 5% IA/g during 48 h postinjection. On the contrary, the counterparts of MCF-7 tumors kept low levels ( ~ 1% IA/g). The outcome was consistent with the immunohistochemical analysis and ex vivo autoradiography. The probe quickly cleared from the normal organs except kidneys and mainly excreted through the urinary system.

Conclusion

The novel HER2 affibody for PET imaging was easily prepared with satisfactory labeling yield and radiochemical purity. [89Zr]Zr-DFO-MAL-Cys-MZHER2 is a potential candidate for detecting HER2 expression. It may play specific roles in clinical cancer theranostics.
Latinx bullying and depression in children and youth: a systematic review
Authors: Lutrick Karen , Clark Robert , Nuño Velia Leybas , Bauman Sheri , Carvajal Scott
Published: June 2020

Background

Bullying is associated with negative health outcomes such as depression. Most studies target non-Latinxs, though they often experience higher rates of bullying and depression. This review examines the inclusion of Latinxs in studies of bullying and depression and factors unique to them.

Methods

Databases were searched for articles related to bullying and depression. Two reviewers found 957 publications and identified 17 for inclusion.

Results

All 17 studies demonstrated a relationship between bullying and depression. Nine examined variables unique to Latinxs.

Conclusions

Studies that included variables unique to Latinxs found a stronger relationship between bullying and depression. Inclusive measures and design are key to understanding and reducing the consequences of bullying in this population.
A mechanistic approach to prove the efficacy of combination therapy against New Delhi metallo-β-lactamases producing bacterial strain: a molecular and biochemical approach
Authors: Maryam Lubna , Ali Abid , Khalid Shamsi , Khan Asad U.
Published: June 2020

Background

NDM-1 is a novel broad-spectrum metallo-β-lactamase with the capability to grant resistance to almost all β-lactam antibiotics. Its widespread dissemination made treatment options a major challenge to combat, causing threat to public health worldwide. Due to antibiotic resistance problems, development of effective therapeutics for infections caused by NDM-1 producing strains is urgently required. Since combination therapies are proved to be effective in many cases, this study was initiated to put forward novel effective antibiotics combinations for fighting infections caused by NDM-1 producing strains.

Methods

Streptomycin and amikacin combination and streptomycin and ciprofloxacin combination were tested by checkerboard assay. NDM-1 protein/enzyme was then expressed and purified to carry out enzyme kinetics study, CD and fluorescence spectroscopic studies.

Results

Streptomycin and amikacin combination and streptomycin and ciprofloxacin combination showed synergistic effect towards NDM-1 producing bacterial strains as shown by FICI results. NDM-1 producing bacterial cells were expressed and purified to obtain protein as the source of enzyme. When NDM-1 enzyme was treated with streptomycin along with amikacin, the efficiency of enzyme was decreased by 49.37% and when the enzyme was treated with streptomycin along with ciprofloxacin, the efficiency of enzyme was decreased by 29.66% as revealed by enzyme kinetic studies. Due to binding of streptomycin and amikacin in combination and streptomycin and ciprofloxacin in combination, conformational changes in the secondary structure of NDM-1 enzyme were observed by CD spectroscopic studies. Antibiotics streptomycin and ciprofloxacin bind with NDM-1 through exothermic processes, whereas amikacin binds through an endothermic process. All three antibiotics bind spontaneously with an association constant of the order of 104 M−1as revealed by fluorescence spectroscopic studies.

Conclusions

The therapeutic combination of streptomycin with amikacin and ciprofloxacin plays an important role in inhibiting NDM-1 producing bacterial strains. Therefore, these combinations can be used as effective future therapeutic candidates against NDM-1 producing bacterial cells.
Analysis of Interface Properties Between TRC and Concrete Under Chloride Attack Based on Fracture Energy
Authors: Li Shichang , Yin Shiping , Gao Yu
Published: June 2020

As a type of cement-based composite reinforcement material, textile reinforced concrete (TRC) has the advantages of corrosion resistance, high bearing capacity and good crack limit performance. Its bonding performance with the existing concrete interface is the key factor affecting the reinforcement effect. To study the interfacial adhesion between TRC and existing concrete, the sodium chloride concentration, the frequency and number of dry and wet cycles, the bonding length of the TRC reinforcement layer and the type of reinforcement were analysed by a double-sided shear test, XRD (X-ray diffraction) and SEM (scanning electron microscope) micro-test techniques. The influence of other factors on the interfacial bonding properties was further elaborated based on the theory of fracture energy. The results show that interface damage under chloride attack was mainly divided into three typical interface failure modes. By increasing the concentration of sodium chloride, reducing the frequency of dry and wet cycles and increasing the number of dry and wet cycles, the interface microstructure damage could be aggravated. Using cast-in-place reinforcement and increasing the bonding length could enhance the bonding performance of the interface.
Diversity of isoprene-degrading bacteria in phyllosphere and soil communities from a high isoprene-emitting environment: a Malaysian oil palm plantation
Authors: Carrión Ornella , Gibson Lisa , Elias Dafydd M. O. , McNamara Niall P. , van Alen Theo A. , Op den Camp Huub J. M. , Supramaniam Christina Vimala , McGenity Terry J. , Murrell J. Colin
Published: June 2020

Background

Isoprene is the most abundantly produced biogenic volatile organic compound (BVOC) on Earth, with annual global emissions almost equal to those of methane. Despite its importance in atmospheric chemistry and climate, little is known about the biological degradation of isoprene in the environment. The largest source of isoprene is terrestrial plants, and oil palms, the cultivation of which is expanding rapidly, are among the highest isoprene-producing trees.

Results

DNA stable isotope probing (DNA-SIP) to study the microbial isoprene-degrading community associated with oil palm trees revealed novel genera of isoprene-utilising bacteria including Novosphingobium, Pelomonas, Rhodoblastus, Sphingomonas and Zoogloea in both oil palm soils and on leaves. Amplicon sequencing of isoA genes, which encode the α-subunit of the isoprene monooxygenase (IsoMO), a key enzyme in isoprene metabolism, confirmed that oil palm trees harbour a novel diversity of isoA sequences. In addition, metagenome-assembled genomes (MAGs) were reconstructed from oil palm soil and leaf metagenomes and putative isoprene degradation genes were identified. Analysis of unenriched metagenomes showed that isoA-containing bacteria are more abundant in soils than in the oil palm phyllosphere.

Conclusion

This study greatly expands the known diversity of bacteria that can metabolise isoprene and contributes to a better understanding of the biological degradation of this important but neglected climate-active gas.
Local adaptive evolution of two distinct clades of Beijing and T families of Mycobacterium tuberculosis in Chongqing: a Bayesian population structure and phylogenetic study
Authors: Liang Peng-Kuan , Zheng Chao , Xu Xiao-Fang , Zhao Zhe-Ze , Zhao Chang-Song , Li Chang-He , Couvin David , Reynaud Yann , Zozio Thierry , Rastogi Nalin , Sun Qun
Published: June 2020

Background

Beijing sub-pedigree 2 (BSP2) and T sub-lineage 6 (TSL6) are two clades belonging to Beijing and T family of Mycobacterium tuberculosis (MTB), respectively, defined by Bayesian population structure analysis based on 24-loci mycobacterial interspersed repetitive unit-variable number of tandem repeats (MIRU-VNTR). Globally, over 99% of BSP2 and 89% of TSL6 isolates were distributed in Chongqing, suggesting their possible local adaptive evolution. The objective of this paper is to explore whether BSP2 and TSL6 originated by their local adaptive evolution from the specific isolates of Beijing and T families in Chongqing.

Methods

The genotyping data of 16 090 MTB isolates were collected from laboratory collection, published literatures and SITVIT database before subjected to Bayesian population structure analysis based on 24-loci MIRU-VNTR. Spacer Oligonucleotide Forest (Spoligoforest) and 24-loci MIRU-VNTR-based minimum spanning tree (MST) were used to explore their phylogenetic pathways, with Bayesian demographic analysis for exploring the recent demographic change of TSL6.

Results

Phylogenetic analysis suggested that BSP2 and TSL6 in Chongqing may evolve from BSP4 and TSL5, respectively, which were locally predominant in Tibet and Jiangsu, respectively. Spoligoforest showed that Beijing and T families were genetically distant, while the convergence of the MIRU-VNTR pattern of BSP2 and TSL6 was revealed by WebLogo. The demographic analysis concluded that the recent demographic change of TSL6 might take 111.25 years.

Conclusions

BSP2 and TSL6 clades might originate from BSP4 and TSL5, respectively, by their local adaptive evolution in Chongqing. Our study suggests MIRU-VNTR be combined with other robust markers for a more comprehensive genotyping approach, especially for families of clades with the same MIRU-VNTR pattern.
No symphony without bassoon and piccolo: changes in synaptic active zone proteins in Huntington’s disease
Authors: Huang Ting-Ting , Smith Ruben , Bacos Karl , Song Dong-Yan , Faull Richard M. , Waldvogel Henry J. , Li Jia-Yi
Published: June 2020

Prominent features of HD neuropathology are the intranuclear and cytoplasmic inclusions of huntingtin and striatal and cortical neuronal cell death. Recently, synaptic defects have been reported on HD-related studies, including impairment of neurotransmitter release and alterations of synaptic components. However, the definite characteristics of synapse dysfunction and the underlying mechanisms remain largely unknown. We studied the gene expression levels and patterns of a number of proteins forming the cytoskeletal matrix of the presynaptic active zones in HD transgenic mice (R6/1), in hippocampal neuronal cultures overexpressing mutant huntingtin and in postmortem brain tissues of HD patients. To investigate the interactions between huntingtin and active proteins, we performed confocal microscopic imaging and immunoprecipitation in mouse and HEK 293 cell line models. The mRNA and protein levels of Bassoon were reduced in mouse and cell culture models of HD and in brain tissues of patients with HD. Moreover, a striking re-distribution of a complex of proteins including Bassoon, Piccolo and Munc 13–1 from the cytoplasm and synapses into intranuclear huntingtin aggregates with loss of active zone proteins and dendritic spines. This re-localization was age-dependent and coincided with the formation of huntingtin aggregates. Using co-immunoprecipitation, we demonstrated that huntingtin interacts with Bassoon, and that this interaction is likely mediated by a third linking protein. Three structural proteins involved in neurotransmitter release in the presynaptic active zones of neurons are altered in expression and that the proteins are redistributed from their normal functional site into mutant huntingtin aggregates.
Fusions involving BCOR and CREBBP are rare events in infiltrating glioma
Authors: Pisapia David J. , Ohara Kentaro , Bareja Rohan , Wilkes David C. , Hissong Erika , Croyle Jaclyn A. , Kim Joon-Hyung , Saab Jad , MacDonald Theresa Y. , Beg Shaham , O’Reilly Catherine , Kudman Sarah , Rubin Mark A. , Elemento Olivier , Sboner Andrea , Greenfield Jeffrey , Mosquera Juan Miguel
Published: June 2020

BCOR has been recognized as a recurrently altered gene in a subset of pediatric tumors of the central nervous system (CNS). Here, we describe a novel BCOR-CREBBP fusion event in a case of pediatric infiltrating astrocytoma and further probe the frequency of related fusion events in CNS tumors. We analyzed biopsy samples taken from a 15-year-old male with an aggressive, unresectable and multifocal infiltrating astrocytoma. We performed RNA sequencing (RNA-seq) and targeted DNA sequencing. In the index case, the fused BCOR-CREBBP transcript comprises exons 1–4 of BCOR and exon 31 of CREBBP. The fused gene thus retains the Bcl6 interaction domain of BCOR while eliminating the domain that has been shown to interact with the polycomb group protein PCGF1. The fusion event was validated by FISH and reverse transcriptase PCR. An additional set of 177 pediatric and adult primary CNS tumors were assessed via FISH for BCOR break apart events, all of which were negative. An additional 509 adult lower grade infiltrating gliomas from the publicly available TCGA dataset were screened for BCOR or CREBBP fusions. In this set, one case was found to harbor a CREBBP-GOLGA6L2 fusion and one case a CREBBP-SRRM2 fusion. In a third patient, both BCOR-L3MBTL2 and EP300-BCOR fusions were seen. Of particular interest to this study, EP300 is a paralog of CREBBP and the breakpoint seen involves a similar region of the gene to that of the index case; however, the resultant transcript is predicted to be completely distinct. While this gene fusion may play an oncogenic role through the loss of tumor suppressor functions of BCOR and CREBBP, further screening over larger cohorts and functional validation is needed to determine the degree to which this or similar fusions are recurrent and to elucidate their oncogenic potential.
Stress loading and the occurrence of normal-type earthquakes under Boso Peninsula, Japan
Authors: Hashima Akinori , Sato Hiroshi , Sato Toshinori
Published: June 2020

Boso Peninsula, Japan, was formed by the interaction of the Philippine Sea, Eurasian and Pacific plates around the trench–trench–trench Boso triple junction. Normal-type earthquakes are persistently observed in the subducting Philippine Sea slab under the peninsula at a depth of ~ 30 km, including a recent (2019) Mw 4.9 earthquake which caused shaking throughout the Kanto region (greater Tokyo). Such shallow intraplate earthquakes are potentially hazardous to this heavily populated region, yet their mechanism is poorly understood, especially in the context of a three-plate system. Here, we calculate stress rates in the Philippine Sea slab and the surrounding area, using a subduction model constructed in a previous study, to explain the generation of the regional stress field and its effect on earthquake occurrence. In general, the calculated stress rates under Boso Peninsula are horizontally extensional both above and below the Eurasian–Philippine Sea plate interface. We apply our calculated stress rates to the nodal planes of the observed earthquakes to calculate the Coulomb failure function (ΔCFF). These calculated ΔCFFs are generally positive on normal-type earthquakes under Boso. The ΔCFFs are also consistent with earthquakes in adjacent areas that are seismically active, for example, in the Philippine Sea plate to the south, in the collision zone around Izu Peninsula, and in the cluster in the Eurasian plate northeast of Boso Peninsula, which further supports our stress loading model. Calculation of the individual contributions of Philippine Sea plate and Pacific plate subduction shows that the development of the stress field around Boso is dependent upon contributions from both subducting plates. In contrast, the arc–arc collision at Izu Peninsula has little influence.
Toward comparable relative locations between the mainshock slip and aftershocks via empirical approaches
Authors: Chang Ta-Wei , Ide Satoshi
Published: June 2020

The relative locations between mainshocks and their aftershocks have long been studied to characterize the mainshock–aftershock relationships, yet these comparisons may be subjected to biases inherited from various sources, such as the analysis method, data, and model parameters. Here, we perform both a relocation analysis of interplate events to obtain accurate relative centroid locations and a slip inversion analysis of the mainshock slip relative to the relocated events, with some of the relocated events used as empirical Green’s functions, to retrieve the spatiotemporal slip features of the mainshock relative to all of the relocated events. We perform these analyses on the large ($$6.0 \le M_{W} \le 7.3$$6.0≤MW≤7.3) interplate earthquakes that occurred near four giant ($$M_{W} \ge 8.5$$MW≥8.5) megathrust earthquakes: the 2007$$M_{W} \;8.5$$MW8.5Bengkulu (Indonesia), 2005$$M_{W} \;8.6$$MW8.6Nias (Indonesia), 2010$$M_{W} \;8.8$$MW8.8Maule (Chile), and 2011$$M_{W} \;9.1$$MW9.1Tohoku-Oki (Japan) earthquakes. Most of the spatiotemporal slip features of the mainshocks are consistently recovered using different empirical Green’s functions. We qualitatively and quantitatively demonstrate that the large interplate aftershocks within 5 years of the four analyzed mainshocks are largely located on the periphery or outside of the large-slip regions of these four giant megathrust earthquakes.
Colonic varices treated with embolization after pancreatoduodenectomy with portal vein resection: a case report
Authors: Kuwabara Shota , Matsumoto Joe , Tojima Hiroyasu , Wada Hideyuki , Kato Kohei , Tabata Yukiko , Ichinokawa Masaomi , Yoshioka Tatsuya , Murakawa Katsuhiko , Ikeda Atsushi , Ohtake Setsuyuki , Ono Koichi
Published: June 2020

Background

Pancreatoduodenectomy with resection of the portal vein or superior mesenteric vein confluence has been safely performed in patients with pancreatic head cancer associated with infiltration of the portal vein or superior mesenteric vein. In recent years, left-sided portal hypertension, a late postoperative complication, has received focus owing to increased long-term survival with advances in chemotherapy. Left-sided hypertension may sometimes cause fatal gastrointestinal bleeding because of the rupture of gastrointestinal varices. Here, we present a case of colonic varices caused by left-sided portal hypertension after pancreatoduodenectomy with portal vein resection.

Case presentation

A 69-year-old man diagnosed with pancreatic head cancer was referred to our department for surgery after undergoing chemotherapy with nine courses of gemcitabine and nab-paclitaxel. Computed tomography showed a mass 25 mm in diameter and in contact with the portal vein. He had undergone subtotal stomach-preserving pancreatoduodenectomy with portal vein resection. Four centimeters of the portal vein had been resected, and end-to-end anastomosis was performed without splenic vein reconstruction. We had to completely resect the right colic vein, accessary right colic vein, and middle colic vein due to tumor invasion. The pathological diagnosis was ypT3, ypN1a, ypM0, and ypStageIIB, and he was administered TS-1 as postoperative adjuvant chemotherapy. Seven months after therapeutic radical surgery, he presented with melena with progressive anemia. Computed tomography revealed transverse colonic varices. He was offered interventional radiology. Trans-splenic arterial splenic venography showed that transverse colonic varices had developed as collateral circulation of the splenic vein and inferior mesenteric vein system. An embolic substance was injected into the transverse colonic varices, which halted the progression of the anemia caused by melena. Fifteen months after therapeutic radical surgery, local recurrence of the tumor occurred; he died 28 months after the surgery.

Conclusions

When subtotal stomach-preserving pancreatoduodenectomy with portal vein resection is performed without splenic vein reconstruction, colonic varices may result from left-sided portal hypertension. Interventional radiology is an effective treatment for gastrointestinal bleeding due to colonic varices, but it is important to be observant for colonic necrosis and new varices.
Efficacy of nanosecond laser treatment in central serous chorioretinopathy with and without atrophy of retinal pigment epithelium
Authors: Kaymak Hakan , Funk Saskia , Fricke Andreas , Fulga Roxana , Klabe Karsten , Seitz Berthold , Langenbucher Achim , Schwahn Hartmut
Published: June 2020

Background

To evaluate the outcomes of subthreshold nanosecond laser treatment of chronic central serous chorioretinopathy (CSC) as a function of the severity of concomitant of retinal pigment epithelium (RPE) defects.

Methods

This retrospective study compares data from 23 CSC diagnosed eyes with only mild RPE defects (group 1), 16 CSC eyes with moderate RPE defects (group 2), and 17 CSC eyes having severe RPE defects (group 3). After subthreshold treatment with the standard Ellex 2RT™ nanosecond laser (Ellex Medical Lasers Ltd, Australia), changes in macular structure and levels of subretinal fluid (SRF) were assessed by OCT-SD, OCT-A, functional integrity of the retina was assessed by corrected distance visual acuity (CDVA) and microperimetry, each at baseline and 1, 3, 6, and 12 months after initial treatment; re-treatment took place in cases of persistent SRF pro re nata.

Results

During the 12 months observation period, group 1 and 2 mostly required on initial and one re-treatment (1.9 ± 1.0 treatments; 1.9 ± 1.3 treatments). In contrast, group 3 was subject to three to four treatments (3.7 ± 1.5 treatments). 6 to 12 months after treatment, subretinal fluid (SRF) disappeared in 100% of the eyes of group 1 and in 76.9%, and 42.9% of the eyes of group 2 and group 3, respectively. Retinal sensitivity and CDVA improved in group 1 and 2, but did not change significantly in group 3 during the 12 months period.

Conclusions

Subthreshold nanosecond laser treatment is an effective and safe method for the restoration of macular anatomy and sensitivity in acute and chronic CSC cases with only mild or moderate RPE defects. However, this laser treatment has very limited outcome in CSC eyes with more severe RPE defects.