bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractAmyotrophic 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

AbstractHepatitis 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

Abstract
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

Abstract
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

Abstract
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

Abstract
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).
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

AbstractBackgroundNDM-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.MethodsStreptomycin 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.ResultsStreptomycin 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.ConclusionsThe 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

AbstractAs 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.