bluuebunny/crossref_metadata_2025 huggingface dataset:
Teachers’ Implicit Theories of Professional Abilities in the Domain of School Improvement
Authors: Rechsteiner Beat , Compagnoni Miriam , Wullschleger Andrea , Maag Merki Katharina
Published: March 2021

Numerous studies show positive effects of students’ malleable implicit theories of their abilities on their self-regulated learning and learning achievements (Yeager and Dweck, 2012;Burnette et al., 2013), especially when domain-specific implicit theories are assessed (Costa and Faria, 2018). Thinking of school improvement as a collective learning process for the teaching staff, it is reasonable to assume that this relationship also exists on the teacher level. Hence, this study aims to provide answers to the following overarching question: What role do teachers’ implicit theories of professional abilities play for school improvement? In a first step, a measurement instrument was developed to assess teachers’ implicit theories of professional abilities in the domain of school improvement. In a second step, we explored the link between these implicit theories and collective teacher learning in the area of further developing the school’s educational practices. In a sample ofN= 1,483 Swiss primary school teachers atN= 59 schools, we analyzed how teachers’ malleable (vs. fixed) implicit theories of professional abilities are related to collective metacognitive and emotional-motivational regulation activities and to the perception that the school is on the right track to improvement. Results show that teachers’ implicit theories of professional abilities can be assessed reliably. Structural equation modeling analyses revealed that the more teachers view professional abilities as malleable and developable, the more positive their perceptions of the schools’ improvement were. This relation was mediated by collective emotional-motivational regulation activities. However, no significant effect of a malleable implicit theory on collective metacognitive regulation was found. It can be concluded that teachers have varying beliefs about the malleability of teachers’ professional abilities that are linked to their collective regulation. It therefore acknowledges the domain-specific effects of teachers’ implicit theories in the area of school improvement.
Dietary Oxysterol, 7-Ketocholesterol Accelerates Hepatic Lipid Accumulation and Macrophage Infiltration in Obese Mice
Authors: Chang Jiuyang , Koseki Masahiro , Saga Ayami , Kanno Kotaro , Higo Tomoaki , Okuzaki Daisuke , Okada Takeshi , Inui Hiroyasu , Tanaka Katsunao , Asaji Masumi , Zhu Yinghong , Kamada Yoshihiro , Ono Masafumi , Saibara Toshiji , Ichi Ikuyo , Ohama Tohru , Nishida Makoto , Yamashita Shizuya , Sakata Yasushi
Published: March 2021

Non-alcoholic fatty liver disease is strongly associated with obese and type 2 diabetes. It has been reported that an oxidized cholesterol, 7-ketocholesterol (7KC), might cause inflammatory response in macrophages and plasma 7KC concentration were higher in patients with cardiovascular diseases or diabetes. Therefore, we have decided to test whether small amount of 7KC in diet might induce hepatic steatosis and inflammation in two types of obese models. We found that addition of 0.01% 7KC either in chow diet (CD, regular chow diet with 1% cholesterol) or western type diet (WD, high fat diet with 1% cholesterol) accelerated hepatic neutral lipid accumulation by Oil Red O staining. Importantly, by lipid extraction analysis, it has been recognized that triglyceride rather than cholesterol species was significantly accumulated in CD+7KC compared to CD as well as in WD+7KC compared to WD. Immunostaining revealed that macrophages infiltration was increased in CD+7KC compared to CD, and also in WD+7KC compared to WD. These phenotypes were accompanied by inducing inflammatory response and downregulating fatty acid oxidation. Furthermore, RNA sequence analysis demonstrated that 7KC reduced expression of genes which related to autophagy process. Levels of LC3-II protein were decreased in WD+7KC compared to WD. Similarly, we have confirmed the effect of 7KC on acceleration of steatohepatitis in db/db mice model. Collectively, our study has demonstrated that small amount of dietary 7KC contributed to accelerate hepatic steatosis and inflammation in obese mice models.
The Effect of 6 Months’ Treatment With Pasireotide LAR on Glucose Metabolism in Patients With Resistant Acromegaly in Real-World Clinical Settings
Authors: Witek Przemysław , Bolanowski Marek , Szamotulska Katarzyna , Wojciechowska-Luźniak Agnieszka , Jawiarczyk-Przybyłowska Aleksandra , Kałużny Marcin
Published: March 2021

Objective

The aim of the study was to evaluate glucose metabolism, as measured by glycated hemoglobin (HbA1c) levels and the need for antidiabetic medical treatment, in patients with acromegaly resistant to first-generation somatostatin receptors ligands (SRLs) treated with pasireotide long-acting release (LAR) in real-world clinical practice. Biochemical control of acromegaly, as measured by growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels, was also assessed.

Study Design

Two-center retrospective cohort of consecutive patients with acromegaly treated with first-generation SRLs at maximum doses, who had not achieved biochemical disease control. After SRLs were discontinued, patients were given pasireotide LAR 40 mg i.m. every 28 days. The dose was increased to 60 mg i.m. in patients for whom adequate control was not achieved after 3 months. Patients were given dietary and lifestyle advice, and antihyperglycemic treatment was modified as needed.

Main Outcome Measures

Biochemical disease control parameters (GH and IGF-1 concentration), as well as HbA1c level at baseline and after 6 months.

Results

In total, 39 patients with acromegaly were enrolled. GH concentration decreased (Δme =-1.56 µg/L, range -21.38–3.62, p <0.001) during 6 months of pasireotide LAR treatment. A worsening of metabolic status was observed, with an increase of median HbA1c (Δme =0.40%, range -0.20%–2.30%, p <0.001), and antihyperglycemic treatment intensification in 23 (59.0%) patients. The median decline in IGF-1 concentration was: -283.0 µg/L, range -682.7–171.6, p <0.001. IGF-1 reached the age- and gender-specific upper level of normal in 23 (59%) patients.

Conclusions

Pasireotide LAR is an effective therapeutic option in patients with acromegaly refractory to first-generation SRLs. However, this therapy may result in pasireotide LAR-associated hyperglycemia, which requires early and aggressive antidiabetic medical therapy to prevent glucose homeostasis alterations.
Improved Patient Dosimetry at Radioiodine Therapy by Combining the ICRP Compartment Model and the EANM Pre-Therapeutic Standard Procedure for Benign Thyroid Diseases
Authors: Andersson Martin , Mattsson Sören
Published: March 2021

Radioactive iodine is commonly used for the treatment of different thyroid conditions since the 1940s. The EANM has developed a standard pre-therapeutic procedure to estimate patient specific thyroid uptake at treatment of benign thyroid diseases. The procedure which models the time dependent fractional thyroid uptake is based on a two-compartment fitting system, one representing the thyroid and the other the blood. The absorbed dose is however only estimated for the thyroid and not for any other organ in the body. A more detailed biokinetic model for iodine is given by the ICRP and includes an iodide transport in the whole body. The ICRP model has 30 different compartments and 48 transfer coefficients to model the biokinetics of iodide and to model different transfer for inorganic iodide and organic iodine. The ICRP model is a recirculation iodine model, and the optimization is performed on the whole model and not exclusively on the thyroid as in the EANM procedure. Combining the EANM method and the ICRP model gives both patient specific estimations of thyroid uptake and retention and include most organs in the body. The new software gives both an improved patient specific dosimetry for the thyroid and an estimation of the absorbed dose to non-target organs and tissues like kidneys, urinary bladder, stomach wall, and uterus. Using the method described in this paper, the repercussions on the daily routines will be minimal.
Identifying and Regulating the Environmental Risks in the Development and Utilization of Natural Gas as a Low-Carbon Energy Source
Authors: Fu Jiaxin , Liu Yingqi , Sun FeiHong
Published: March 2021

In response to climate change and energy transition, natural gas has been rapidly developed as a relatively low-carbon energy source by many countries. However, there remain environmental risks at different stages in the entire process from exploitation to utilization. Firstly, this article identifies various environmental risks and benefits of natural gas along the entire industry chain from upstream exploitation and midstream transportation to downstream utilization. It is found that, during upstream exploitation, hydraulic fracturing has the worst environmental impact. During the midstream storage and transportation stage, methane leakage is the biggest environmental risk. In the downstream combustion and utilization stage, the risk to environment is less than other energy sources, although there are some greenhouse gas effects and water pollution issues. Thus, this article puts forward some policy recommendations for different stages from exploitation to utilization. In the upstream stage, especially hydraulic fracturing activity, we suggest strengthening environmental assessment management, improving policy standards, creating a water quality monitoring plan, and promoting the innovation of key technologies. In terms of the midstream, besides pipeline laying and site selection, we focus on monitoring the system, including leak detection, quality management of engineering materials, and risk identification and management. When it comes to the downstream, we encourage the application of advanced technologies to improve thermal efficiency and reduce emissions, such as gas-fired related technologies, natural gas recycling technologies, distributed energy technologies, and green and low-carbon service technologies.
Machine Learning Analysis of Naïve B-Cell Receptor Repertoires Stratifies Celiac Disease Patients and Controls
Authors: Shemesh Or , Polak Pazit , Lundin Knut E. A. , Sollid Ludvig M. , Yaari Gur
Published: March 2021

Celiac disease (CeD) is a common autoimmune disorder caused by an abnormal immune response to dietary gluten proteins. The disease has high heritability. HLA is the major susceptibility factor, and the HLA effect is mediated via presentation of deamidated gluten peptides by disease-associated HLA-DQ variants to CD4+ T cells. In addition to gluten-specific CD4+ T cells the patients have antibodies to transglutaminase 2 (autoantigen) and deamidated gluten peptides. These disease-specific antibodies recognize defined epitopes and they display common usage of specific heavy and light chains across patients. Interactions between T cells and B cells are likely central in the pathogenesis, but how the repertoires of naïve T and B cells relate to the pathogenic effector cells is unexplored. To this end, we applied machine learning classification models to naïve B cell receptor (BCR) repertoires from CeD patients and healthy controls. Strikingly, we obtained a promising classification performance with an F1 score of 85%. Clusters of heavy and light chain sequences were inferred and used as features for the model, and signatures associated with the disease were then characterized. These signatures included amino acid (AA) 3-mers with distinct bio-physiochemical characteristics and enriched V and J genes. We found that CeD-associated clusters can be identified and that common motifs can be characterized from naïve BCR repertoires. The results may indicate a genetic influence by BCR encoding genes in CeD. Analysis of naïve BCRs as presented here may become an important part of assessing the risk of individuals to develop CeD. Our model demonstrates the potential of using BCR repertoires and in particular, naïve BCR repertoires, as disease susceptibility markers.
Platelet-Mediated Protection of Cancer Cells From Immune Surveillance – Possible Implications for Cancer Immunotherapy
Authors: Schmied Laurent , Höglund Petter , Meinke Stephan
Published: March 2021

The growing insights in the complex interactions between metastatic cancer-cells and platelets have revealed that platelet tumor cell interactions in the blood stream are an important factor supporting tumor metastasis. An increased coagulability of platelets facilitates the vascular evasion and establishment of solid tumor metastasis. Furthermore, platelets can support an immunosuppressive tumor microenvironment or shield tumor cells directly from engagement of cytotoxic lymphocytes as e.g., natural killer (NK) cells. Platelets are both in the tumor microenvironment and systemically the quantitatively most important source of TGF-β, which is a key cytokine for immunosuppression in the tumor microenvironment. If similar platelet-tumor interactions are of physiological relevance in hematological malignancies remains less well-studied. This might be important, as T- and NK cell mediated graft vs. leukemia effects (GvL) are well-documented and malignant hematological cells have a high exposure to platelets compared to solid tumors. As NK cell-based immunotherapies gain increasing attention as a therapeutic option for patients suffering from hematological and other malignancies, we review the known interactions between platelets and NK cells in the solid tumor setting and discuss how these could also apply to hematological cancers. We furthermore explore the possible implications for NK cell therapy in patients with solid tumors and patients who depend on frequent platelet transfusions. As platelets have a protective and supportive effect on cancer cells, the impact of platelet transfusion on immunotherapy and the combination of immunotherapy with platelet inhibitors needs to be evaluated.
Metabolomic Signatures of Autoimmune Hepatitis in the Development of Cirrhosis
Authors: Li Shan-shan , Niu Ming , Jing Jing , Huang Ying , Zhang Zi-teng , Chen Shuai-shuai , Shi Ge-zi , He Xian , Zhang Hai-zhu , Xiao Xiao-he , Zou Zheng-sheng , Yu Yue-cheng , Wang Jia-bo
Published: March 2021

Objectives: Autoimmune hepatitis (AIH) can progress into severe outcomes, i.e., decompensated cirrhosis, from remarkable and persistent inflammation in the liver. Considering the energy-expending nature of inflammation, we tried to define the metabolomics signatures of AIH to uncover the underlying mechanisms of cirrhosis development and its metabolic biomarkers.

Methods: Untargeted metabolomics analysis was performed on sera samples from 79 AIH patients at the stages (phenotypes) of non-cirrhosis (n = 27), compensated cirrhosis (n = 22), and decompensated cirrhosis (n = 30). Pattern recognition was used to find unique metabolite fingerprints of cirrhosis with or without decompensation.

Results: Out of the 294 annotated metabolites identified, 2 metabolic fingerprints were found associated with the development of cirrhosis (independent of the decompensated state, 42 metabolites) and the evolution of decompensated cirrhosis (out of 47 metabolites), respectively. The cirrhosis-associated fingerprints (eigenmetabolite) showed better capability to differentiate cirrhosis from non-cirrhosis patients than the aminotransferase-to-platelet ratio index. From the metabolic fingerprints, we found two pairs of metabolites (Mesobilirubinogen/6-Hydroxynicotinic acid and LysoPA(8:0/0:0)/7alpha-Hydroxycholesterol) calculated as ratio of intensities, which revealed robust abilities to identify cirrhosis or predict decompensated patients, respectively. These phenotype-related fingerprint metabolites featured fundamental energy supply disturbance along with the development of AIH cirrhosis and progression to decompensation, which was characterized as increased lipolysis, enhanced proteolysis, and increased glycolysis.

Conclusions: Remodeling of metabolism to meet the liver inflammation-related energy supply is one of the key signatures of AIH in the development of cirrhosis and decompensation. Therefore, drug regulation metabolism has great potential in the treatment of AIH.
Hepatitis E 3ra Genotype Infection in People Living With HIV in Spain
Authors: Rivero-Juarez Antonio , Frias Mario , Lopez-Lopez Pedro , Berenguer Juan , García Federico , Macias Juan , Alcaraz Begoña , Castro-Iglesias Angeles , Caballero-Gomez Javier , Rivero Antonio
Published: March 2021

Background

The objective of our study was to assess the prevalence and incidence of HEV in people living with HIV (PLWH) in a Spanish national cohort.

Methods

Retrospective longitudinal study including PLWH recruited in the cohort of adult HIV-infected patients of the AIDS Research Network in follow-up at 28 Spanish hospitals with available serum samples in 2014 and 2015. All samples were tested for HEV IgG, IgM, and RNA. Samples with detectable HEV viral loads were genotyped. Prevalence and incidence of HEV infection were calculated.

Results

The study sample comprised 845 PLWH. At baseline, 101 patients were positive for HEV IgG antibodies (11.9%), none had HEV IgM antibodies, and 2 presented detectable HEV RNA (0.23%). Forty-two seroconverted for IgG, supposing a cumulative incidence of 5.7%. One subject was positive for IgM (0.13%), and 2 showed detectable HEV RNA (0.27%). One case was infected by the emergent HEV genotype 3ra.

Conclusion

Our study identifies one case of HEV 3ra genotype infection, the main host of which is rabbit, showing a potential zoonotic role of this emerging genotype in Spain.
Case Report: Bayesian Statistical Inference of Experimental Parameters via Biomolecular Simulations: Atomic Force Microscopy
Authors: Fuchigami Sotaro , Niina Toru , Takada Shoji
Published: March 2021

The atomic force microscopy (AFM) is a powerful tool for imaging structures of molecules bound on surfaces. To gain high-resolution structural information, one often superimposes structure models on the measured images. Motivated by high flexibility of biomolecules, we previously developed a flexible-fitting molecular dynamics (MD) method that allows protein structural changes upon superimposing. Since the AFM image largely depends on the AFM probe tip geometry, the fitting process requires accurate estimation of the parameters related to the tip geometry. Here, we performed a Bayesian statistical inference to estimate a tip radius of the AFM probe from a given AFM image via flexible-fitting molecular dynamics (MD) simulations. We first sampled conformations of the nucleosome that fit well the reference AFM image by the flexible-fitting with various tip radii. We then estimated an optimal tip parameter by maximizing the conditional probability density of the AFM image produced from the fitted structure.
Intelligent Badminton Training Robot in Athlete Injury Prevention Under Machine Learning
Authors: Xie Jun , Chen Guohua , Liu Shuang
Published: March 2021

This study was developed to explore the role of the intelligent badminton training robot (IBTR) to prevent badminton player injuries based on the machine learning algorithm. An IBTR is designed from the perspectives of hardware and software systems, and the movements of the athletes are recognized and analyzed with the hidden Markov model (HMM) under the machine learning. After the design was completed, it was simulated with the computer to analyze its performance. The results show that after the HMM is optimized, the recognition accuracy or data pre-processing algorithm, based on the sliding window segmentation at the moment of hitting reaches 96.03%, and the recognition rate of the improved HMM to the robot can be 94.5%, showing a good recognition effect on the training set samples. In addition, the accuracy rate is basically stable when the total size of the training data is 120 sets, after the accuracy of the robot is analyzed through different data set sizes. Therefore, it was found that the designed IBTR has a high recognition rate and stable accuracy, which can provide experimental references for injury prevention in athlete training.
Dietary Management of Children With Super-Refractory Status Epilepticus: A Systematic Review and Experience in a Single UK Tertiary Centre
Authors: Schoeler Natasha E. , Simpson Zoe , Zhou Runming , Pujar Suresh , Eltze Christin , Cross J. H.
Published: March 2021

Ketogenic diet therapies (KDT) are high-fat, low carbohydrate diets used as an effective treatment option for drug-resistant epilepsy. There is limited research on the efficacy of KDT for super-refractory status epilepticus (SRSE). We systematically review evidence for use of KDT in children with SRSE and present a single UK tertiary centre's experience. Thirty one articles were included, of which 24 were “medium” or “low” quality. One hundred and forty seven children with SRSE started KDT, of which 141 (96%) achieved ketosis. KDT was started mean 5.3 days (range 1–420) after status epilepticus (SE) started. SRSE resolved in 85/141 (60%) children after mean 6.3 days (range 0–19) post SE onset, but it is unclear whether further treatments were initiated post-KDT. 13/141 (9%) children died. Response to KDT was more likely when initiated earlier (p = 0.03) and in females (p = 0.01). Adverse side effects were reported in 48/141 (34%), mostly gastrointestinal; potentially serious adverse effects occurred in ≤4%. Eight children with SRSE, all diagnosed with febrile infection-related epilepsy syndrome, were treated with KDT at Great Ormond Street Hospital for Children. KDT was initiated enterally at mean day 13.6+/− 5.1 of admission. Seven of 8 (88%) children reported adverse side effects, which were potentially serious in 4/8 (50%), including metabolic acidosis, hypoglycaemia and raised amylase. SE ceased in 6/8 (75%) children after mean 25+/− 9.4 days post onset, but other treatments were often started concomitantly and all children started other treatments post-KDT. Two of 8 (25%) children died during admission and another died post-admission. Four of the remaining 5 children continue to have drug-resistant seizures, one of whom remains on KDT; seizure burden was unknown for one child. Our findings indicate that KDT is possible and safe in children with SRSE. Cessation of SRSE may occur in almost two-thirds of children initiated with KDT, but a causal effect is difficult to determine due to concomitant treatments, treatments started post-KDT and the variable length of time post-KDT onset when SRSE cessation occurs. Given that serious adverse side effects seem rare and response rates are (cautiously) favorable, KDT should be considered as an early treatment option in this group.
Changes in Resting-State Functional Connectivity of Cerebellum in Amnestic Mild Cognitive Impairment and Alzheimer’s Disease: A Case-Control Study
Authors: Zhou Zhi , Zhu Rui , Shao Wen , Zhang Shu-juan , Wang Lei , Ding Xue-jiao , Peng Dan-tao
Published: March 2021

This case-control study is aimed to investigate the correlation of altered functional connectivity (FC) in cerebellum with cognitive impairment in amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD). The morphometric and resting-state FC MRI analysis including 46 participants with AD, 32 with aMCI and 42 age-matched normal controls (NCs) were conducted. We compared the cerebellar gray matter volume and cerebellar FC with cerebral cortical regions among three groups. To investigate the relationship of cerebellar FC with cognition, we measure the correlation of significant altered FC and individual cognitive domain. No significant morphometric differences of cerebellum was observed across three groups. The patients with AD had weaker cerebral cortical FCs in bilateral Crus I and left VIIb compared to NCs, and in bilateral Crus I compared to patients with aMCI. For patients with aMCI, the weaker FC were found between right Crus I, left VIIb and cerebral cortical regions compared to NCs. The strength of left cerebellar FC positively correlated with specific cognitive subdomains, including memory, executive function, visuospatial function, and global cognition in AD and aMCI. These findings demonstrated the alteration of cerebellar FC with cerebral cortical regions, and the correlation of cerebellar FC and cognitive impairment in AD and aMCI.
Volumetric Quantitative Ablation Margins for Assessment of Ablation Completeness in Thermal Ablation of Liver Tumors
Authors: Sandu Raluca-Maria , Paolucci Iwan , Ruiter Simeon J. S. , Sznitman Raphael , de Jong Koert P. , Freedman Jacob , Weber Stefan , Tinguely Pascale
Published: March 2021

Background

In thermal ablation of liver tumors, complete coverage of the tumor volume by the ablation volume with a sufficient ablation margin is the most important factor for treatment success. Evaluation of ablation completeness is commonly performed by visual inspection in 2D and is prone to inter-reader variability. This work aimed to introduce a standardized approach for evaluation of ablation completeness after CT-guided thermal ablation of liver tumors, using volumetric quantitative ablation margins (QAM).

Methods

A QAM computation metric based on volumetric segmentations of tumor and ablation areas and signed Euclidean surface distance maps was developed, including a novel algorithm to address QAM computation in subcapsular tumors. The code for QAM computation was verified in artificial examples of tumor and ablation spheres simulating varying scenarios of ablation margins. The applicability of the QAM metric was investigated in representative cases extracted from a prospective database of colorectal liver metastases (CRLM) treated with stereotactic microwave ablation (SMWA).

Results

Applicability of the proposed QAM metric was confirmed in artificial and clinical example cases. Numerical and visual options of data presentation displaying substrata of QAM distributions were proposed. For subcapsular tumors, the underestimation of tumor coverage by the ablation volume when applying an unadjusted QAM method was confirmed, supporting the benefits of using the proposed algorithm for QAM computation in these cases. The computational code for developed QAM was made publicly available, encouraging the use of a standard and objective metric in reporting ablation completeness and margins.

Conclusion

The proposed volumetric approach for QAM computation including a novel algorithm to address subcapsular liver tumors enables precision and reproducibility in the assessment of ablation margins. The quantitative feedback on ablation completeness opens possibilities for intra-operative decision making and for refined analyses on predictability and consistency of local tumor control after thermal ablation of liver tumors.
ZNF213 Facilitates ER Alpha Signaling in Breast Cancer Cells
Authors: Yang Huijie , Lv Xulei , Li Xin , Mao Lanzhi , Niu Zhiguo , Wang Ting , Zhuang Ting , Huang Qingsong
Published: March 2021

Background

Breast cancer is the most common women malignancy worldwide, while estrogen receptor alpha positive type accounts for two third of all breast cancers. Although ER alpha positive breast cancer could be effectively controlled by endocrine therapy, more than half of the cases could develop endocrine resistance, making it an important clinical issue in breast cancer treatment. Thus, decoding the detailed mechanism, which controls ER alpha signaling activation and ER alpha protein stability, is of great importance for the improvement of breast cancer therapy. Several zinc finger proteins were shown to mediate the ubiquitination process and modulate protein stability. Thus, we further explore the function of Zinc finger protein 213 on ER alpha protein stability and tamoxifen resistance.

Methods

CCK8 and Edu assay was used to measure cell proliferation. RNA sequence was performed by Ingenuity pathway analysis. The ER alpha signaling activities were measured with luciferase assay, real-time quantitative PCR, and western blotting. Protein stability assay and ubiquitin assay were used to determine ER alpha protein degradation and ubiquitination. The immuno-precipitation was utilized to determine ER alpha and ZNF213 interaction. The ubiquitin-based immuno-precipitation assay was sued to detect specific ubiquitination manner on ER alpha.

Results

We identified ZNF213 as a novel zinc finger protein, which modulated ER alpha protein. ZNF213 expression correlated with poor outcome in endocrine treated patients. ZNF213 depletion inhibited ER alpha signaling and proliferation in breast cancer cells. Further mechanistic studies showed ZNF213 located in cytosol and nuclear, which modulated ER alpha stability via inhibiting ER alpha K48-linked ubiquitination.

Conclusions

Our study reveals an interesting post-translational mechanism between ER alpha and ZNF213 in breast cancer. Targeting ZNF213 could be an appealing strategy for ER alpha positive breast cancer.
The Thrombopoietin Receptor, MPL, Is a Therapeutic Target of Opportunity in the MPN
Authors: Spivak Jerry L. , Moliterno Alison R.
Published: March 2021

The myeloproliferative neoplasms, polycythemia vera, essential thrombocytosis and primary myelofibrosis share driver mutations that either activate the thrombopoietin receptor, MPL, or indirectly activate it through mutations in the gene for JAK2, its cognate tyrosine kinase. Paradoxically, although the myeloproliferative neoplasms are classified as neoplasms because they are clonal hematopoietic stem cell disorders, the mutations affecting MPL or JAK2 are gain-of-function, resulting in increased production of normal erythrocytes, myeloid cells and platelets. Constitutive JAK2 activation provides the basis for the shared clinical features of the myeloproliferative neoplasms. A second molecular abnormality, impaired posttranslational processing of MPL is also shared by these disorders but has not received the recognition it deserves. This abnormality is important because MPL is the only hematopoietic growth factor receptor expressed in hematopoietic stem cells; because MPL is a proto-oncogene; because impaired MPL processing results in chronic elevation of plasma thrombopoietin, and since these diseases involve normal hematopoietic stem cells, they have proven resistant to therapies used in other myeloid neoplasms. We hypothesize that MPL offers a selective therapeutic target in the myeloproliferative neoplasms since impaired MPL processing is unique to the involved stem cells, while MPL is required for hematopoietic stem cell survival and quiescent in their bone marrow niches. In this review, we will discuss myeloproliferative neoplasm hematopoietic stem cell pathophysiology in the context of the behavior of MPL and its ligand thrombopoietin and the ability of thrombopoietin gene deletion to abrogate the disease phenotype in vivo in a JAK2 V617 transgenic mouse model of PV.
Evaluation of Bone Age in Children: A Mini-Review
Authors: Cavallo Federica , Mohn Angelika , Chiarelli Francesco , Giannini Cosimo
Published: March 2021

Bone age represents a common index utilized in pediatric radiology and endocrinology departments worldwide for the definition of skeletal maturity for medical and non-medical purpose. It is defined by the age expressed in years that corresponds to the level of maturation of bones. Although several bones have been studied to better define bone age, the hand and wrist X-rays are the most used images. In fact, the images obtained by hand and wrist X-ray reflect the maturity of different types of bones of the skeletal segment evaluated. This information, associated to the characterization of the shape and changes of bone components configuration, represent an important factor of the biological maturation process of a subject. Bone age may be affected by several factors, including gender, nutrition, as well as metabolic, genetic, and social factors and either acute and chronic pathologies especially hormone alteration. As well several differences can be characterized according to the numerous standardized methods developed over the past decades. Therefore, the complete characterization of the main methods and procedure available and particularly of all their advantages and disadvantages need to be known in order to properly utilized this information for all its medical and non-medical main fields of application.
Ghrelin Inhibits Intestinal Epithelial Cell Apoptosis Through the Unfolded Protein Response Pathway in Ulcerative Colitis
Authors: Zhang Lin , Cheng Jian , Shen Jie , Wang Sheng , Guo Chuanyong , Fan Xiaoming
Published: March 2021

Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD) that occurs in the lining of the rectum and colon. Apoptosis of the intestinal epithelial cells (IECs) is common in active UC patients. Ghrelin is reported to be downregulated in apoptosis of IECs induced by tumor necrosis factor-α (TNF-α). Therefore, we hypothesized that ghrelin might play an antiapoptotic role in UC progression, which was investigated using in vitro and in vivo studies. The TNF-α-treated Caco-2 cell model and mouse colitis model induced by dextran sulfate sodium (DSS) or 2,4,6-trinitrobenzenesulfonic acid (TNBS) were established and employed. We found that ghrelin could inhibit the apoptosis of Caco-2 cells induced by TNF-α, which could be disturbed by [D-lys3]-GHRP-6, the antagonist of ghrelin receptor GHS-R1a. Similarly, in the DSS- and TNBS-induced mouse colitis models, ghrelin could also protect intestinal tissues from apoptosis in DSS- and TNBS-induced colitis depending on GHS-R1a. Furthermore, ghrelin modulated the unfolded protein response (UPR) pathway and regulated the expressions of caspase-3, BAX, and Bcl-2, which contributed to the inhibition of cell apoptosis. In conclusion, ghrelin protects IECs from apoptosis during the pathogenesis of colitis by regulating the UPR pathway.
PAR2 Activation on Human Kidney Tubular Epithelial Cells Induces Tissue Factor Synthesis, That Enhances Blood Clotting
Authors: Iyer Abishek , Humphries Tyrone L. R. , Owens Evan P. , Zhao Kong-Nan , Masci Paul P. , Johnson David W. , Nikolic-Paterson David , Gobe Glenda C. , Fairlie David P. , Vesey David A.
Published: March 2021

Coagulation abnormalities and increased risk of atherothrombosis are common in patients with chronic kidney diseases (CKD). Mechanisms that alter renal hemostasis and lead to thrombotic events are not fully understood. Here we show that activation of protease activated receptor-2 (PAR2) on human kidney tubular epithelial cells (HTECs), induces tissue factor (TF) synthesis and secretion that enhances blood clotting. PAR-activating coagulation-associated protease (thrombin), as well as specific PAR2 activators (matriptase, trypsin, or synthetic agonist 2f-LIGRLO-NH2(2F), induced TF synthesis and secretion that were potently inhibited by PAR2 antagonist, I-191. Thrombin-induced TF was also inhibited by a PAR1 antagonist, Vorapaxar. Peptide activators of PAR1, PAR3, and PAR4 failed to induce TF synthesis. Differential centrifugation of the 2F-conditoned medium sedimented the secreted TF, together with the exosome marker ALG-2 interacting protein X (ALIX), indicating that secreted TF was associated with extracellular vesicles. 2F-treated HTEC conditioned medium significantly enhanced blood clotting, which was prevented by pre-incubating this medium with an antibody for TF. In summary, activation of PAR2 on HTEC stimulates synthesis and secretion of TF that induces blood clotting, and this is attenuated by PAR2 antagonism. Thrombin-induced TF synthesis is at least partly mediated by PAR1 transactivation of PAR2. These findings reveal how underlying hemostatic imbalances might increase thrombosis risk and subsequent chronic fibrin deposition in the kidneys of patients with CKD and suggest PAR2 antagonism as a potential therapeutic strategy for intervening in CKD progression.
The Deficit of Early Selective Attention in Adults With Sluggish Cognitive Tempo: In Comparison With Those With Attention-Deficit/Hyperactivity Disorder
Authors: Park Yelin , Lee Jang-Han
Published: March 2021

Sluggish cognitive tempo (SCT) is a cluster of attentional symptoms characterized by slow information processing and behavior, distractibility, mental confusion, absent-mindedness, and hypoactivity. The present study aimed to compare early and late selective attention in the information processing speed of adults with SCT to those with attention-deficit/hyperactivity disorder (ADHD) and adults without any attentional problems. The participants were screened using Barkley Adult ADHD Rating Scale-IV and divided into the following groups: SCT (N = 24), ADHD (N = 24), and controls (N = 25). All participants completed the irrelevant distractor task measuring early and late selective attention under load condition (low vs. high) and distractor condition (no-distractor vs. distractor). The inefficiency index was calculated by subtracting the reaction time of no-distractor condition of correct trials from the reaction time of distractor condition to control the impact of accuracy. Upon analysis, the SCT group showed a lower efficiency compared to the ADHD group under high load, while the ADHD group showed lower efficiency under low load than high load. This meant that the ADHD group had increased efficiency of selective attention with higher load, while the SCT group had low efficiency of selective attention even under high loads. These results suggest that the symptoms of “slow” or “distracted” in SCT could be attributed to the reduced speed and efficiency of selective attention in early information processing and the problem can be pronounced in situations with distractors. The results of the study imply that the attention-deficit-like symptoms shown in those with SCT and ADHD can be distinguished in specific stage of information processing.
Tourette Syndrome Risk Genes Regulate Mitochondrial Dynamics, Structure, and Function
Authors: Clarke Raymond A. , Furlong Teri M. , Eapen Valsamma
Published: March 2021

Gilles de la Tourette syndrome (GTS) is a neurodevelopmental disorder characterized by motor and vocal tics with an estimated prevalence of 1% in children and adolescents. GTS has high rates of inheritance with many rare mutations identified. Apart from the role of the neurexin trans-synaptic connexus (NTSC) little has been confirmed regarding the molecular basis of GTS. The NTSC pathway regulates neuronal circuitry development, synaptic connectivity and neurotransmission. In this study we integrate GTS mutations into mitochondrial pathways that also regulate neuronal circuitry development, synaptic connectivity and neurotransmission. Many deleterious mutations in GTS occur in genes with complementary and consecutive roles in mitochondrial dynamics, structure and function (MDSF) pathways. These genes include those involved in mitochondrial transport (NDE1, DISC1, OPA1), mitochondrial fusion (OPA1), fission (ADCY2, DGKB, AMPK/PKA, RCAN1, PKC), mitochondrial metabolic and bio-energetic optimization (IMMP2L, MPV17, MRPL3, MRPL44). This study is the first to develop and describe an integrated mitochondrial pathway in the pathogenesis of GTS. The evidence from this study and our earlier modeling of GTS molecular pathways provides compounding support for a GTS deficit in mitochondrial supply affecting neurotransmission.
The Burden of Antipsychotic-Induced Weight Gain and Metabolic Syndrome in Children
Authors: Libowitz Mark R. , Nurmi Erika L.
Published: March 2021

Antipsychotic medications are critical to child and adolescent psychiatry, from the stabilization of psychotic disorders like schizophrenia, bipolar disorder, and psychotic depression to behavioral treatment of autism spectrum disorder, tic disorders, and pediatric aggression. While effective, these medications carry serious risk of adverse events—most commonly, weight gain and cardiometabolic abnormalities. Negative metabolic consequences affect up to 60% of patients and present a major obstacle to long-term treatment. Since antipsychotics are often chronically prescribed beginning in childhood, cardiometabolic risk accumulates. An increased susceptibility to antipsychotic-induced weight gain (AIWG) has been repeatedly documented in children, particularly rapid weight gain. Associated cardiometabolic abnormalities include central obesity, insulin resistance, dyslipidemia, and systemic inflammation. Lifestyle interventions and medications such as metformin have been proposed to reduce risk but remain limited in efficacy. Furthermore, antipsychotic medications touted to be weight-neutral in adults can cause substantial weight gain in children. A better understanding of the biological underpinnings of AIWG could inform targeted and potentially more fruitful treatments; however, little is known about the underlying mechanism. As yet, modest genetic studies have nominated a few risk genes that explain only a small percentage of the risk. Recent investigations have begun to explore novel potential mechanisms of AIWG, including a role for gut microbiota and microbial metabolites. This article reviews the problem of AIWG and AP metabolic side effects in pediatric populations, proposed mechanisms underlying this serious side effect, and strategies to mitigate adverse impact. We suggest future directions for research efforts that may advance the field and lead to improved clinical interventions.
Duration of Neurocognitive Impairment With Medical Cannabis Use: A Scoping Review
Authors: Eadie Lauren , Lo Lindsay A. , Christiansen April , Brubacher Jeffrey R. , Barr Alasdair M. , Panenka William J. , MacCallum Caroline A.
Published: March 2021

While the recreational use of cannabis has well-established dose-dependent effects on neurocognitive and psychomotor functioning, there is little consensus on the degree and duration of impairment typically seen with medical marijuana use. Compared to recreational cannabis users, medical cannabis patients have distinct characteristics that may modify the presence and extent of impairment. The goal of this review was to determine the duration of acute neurocognitive impairment associated with medical cannabis use, and to identify differences between medical cannabis patients and recreational users. These findings are used to gain insight on how medical professionals can best advise medical cannabis patients with regards to automobile driving or safety-sensitive tasks at work. A systematic electronic search for English language randomized controlled trials (RCTs), clinical trials and systematic reviews (in order to capture any potentially missed RCTs) between 2000 and 2019 was conducted through Ovid MEDLINE and EMBASE electronic databases using MeSH terms. Articles were limited to medical cannabis patients using cannabis for chronic non-cancer pain or spasticity. After screening titles and abstracts, 37 relevant studies were subjected to full-text review. Overall, seven controlled trials met the inclusion/exclusion criteria and were included in the qualitative synthesis: six RCTs and one observational clinical trial. Neurocognitive testing varied significantly between all studies, including the specific tests administered and the timing of assessments post-cannabis consumption. In general, cognitive performance declined mostly in a THC dose-dependent manner, with steady resolution of impairment in the hours following THC administration. Doses of THC were lower than those typically reported in recreational cannabis studies. In all the studies, there was no difference between any of the THC groups and placebo on any neurocognitive measure after 4 h of recovery. Variability in the dose-dependent relationship raises the consideration that there are other important factors contributing to the duration of neurocognitive impairment besides the dose of THC ingested. These modifiable and non-modifiable factors are individually discussed.
A Dietary Assessment Training Course Path: The Italian IV SCAI Study on Children Food Consumption
Authors: Turrini Aida , Catasta Giovina , Censi Laura , Comendador Azcarraga Francisco Javier , D'Addezio Laura , Ferrari Marika , Le Donne Cinzia , Martone Deborah , Mistura Lorenza , Pettinelli Antonella , Piccinelli Raffaela , Saba Anna , Sette Stefania , Barbina Donatella , Guerrera Debora , Carbone Pietro , Mazzaccara Alfonso
Published: March 2021

The eating patterns in a population can be estimated through dietary surveys in which open-ended assessment methods, such as diaries and interviews, or semi-quantitative food frequency questionnaires are administered. A harmonized dietary survey methodology, together with a standardized operational procedure, in conducting the study is crucial to ensure the comparability of the results and the accuracy of information, thus reducing uncertainty and increasing the reliability of the results. Dietary patterns (i) include several target variables (foods, energy and nutrients, other food components), (ii) require several explanatory variables (age, gender, anthropometric measurements, socio-cultural and economic characteristics, lifestyle, preferences, attitudes, beliefs, organization of food-related activities, etc.), and (iii) have impacts in several domains: imbalance diets; acute and chronic exposures affect health, specifically non-communicable diseases; and then sanitary expenditure. On the other hand, food demand has impacts on the food system: production, distribution, and food services system; food wastes and other wastes generated by food-related activities of the households (e.g., packaging disposal) have consequences on the “health of the planet” which in turn can have effects on human health. Harmonization and standardization of measurement methods and procedures in such a complex context require an ad hoc structured information system made by databases (food nomenclatures, portion sizes, food atlas, recipes) and methodological tools (quantification methods, food coding systems, assessment of nutritional status, data processing to extrapolate what we consider validated dietary data). Establishing a community of professionals specialized in dietary data management could lead to build a surveillance system for monitoring eating habits in the short term, thus reducing costs, and to arrange a training re-training system. Creating and maintaining the dietary data managers community is challenging but possible. In this context, the cooperation between the CREA Research Centre for Food and Nutrition and the Italian National Health Institute (ISS) promoted and supported by the Italian Ministry of Health may represent a model of best practice that can ensure a continuous training for the professional community carrying out a nutritional study.