bluuebunny/crossref_metadata_2025 huggingface dataset:
The pathological significance of LOXL2 in pre-metastatic niche formation of HCC and its related molecular mechanism
Authors: Wu Sifan , Xing Xiaoxia , Wang Yaohui , Zhang Xi , Li Miao , Wang Mimi , Wang Zhiming , Chen Jie , Gao Dongmei , Zhao Yan , Chen Rongxin , Ren Zhenggang , Zhang Kezhi , Cui Jiefeng
Published: May 2020

Background: The mechanisms underlying the contribution of primary tumor to pre-metastatic niche formation remains largely unknown in HCC. We previously reported that the released Lysyl oxidase like 2 (LOXL2) from HCC cells under higher stiffness stimulation facilitated the formation of lung pre-metastatic niche. Here we further clarified the pathological role of LOXL2 in promoting lung pre-metastatic niche formation in HCC and its relevant molecular mechanism. Methods: Lung pre-metastatic niche nude mouse model and LOXL2-overexpressed xenograft HCC models were respectively developed to validate the significance of LOXL2 in pre-metastatic niche formation and pulmonary metastasis. Simultaneously, a gel-based cell culture system mirroring lung tissue stiffness in normal and pathological state was constructed to investigate the underlying mechanism of LOXL2-induced pre-metastatic niche formation.Results: LOXL2 by tail vein injection had obvious inducting effects on CD11b+/CD45+ BMDCs recruitment and fibronectin expression in lung tissue during the development of lung pre-metastatic niche. Tumor-secreted LOXL2 also promoted the occurrence of pulmonary metastasis and the number of metastasis lesions remarkably in LOXL2-overexpressed xenograft HCC models. Applying a gel-based cell culture system, we discovered that LOXL2 and LOXL2-caused matrix stiffening all upregulated the expressions of MMP9 and fibronectin in lung fibroblasts significantly, but little effect on MMP2 expression. Moreover, the activation of PI3K-AKT pathway participated in the regulation of LOXL2-upregulated fibronectin. Additionally, LOXL2 and LOXL2-caused matrix stiffening also increased the number of adherent HCC cells evidently, as well as the expression of chemokine CXCL2. Clinical data analysis demonstrated that HCC patients in High-LOXL2 group had higher ratio of microvascular invasion (OR=10.563, P=0.005) and tumor recurrence (OR=8.556, P=0.013) than HCC patients in Low-LOXL2 group, also revealing a significance of LOXL2 in HCC progression and unfavorable outcomeConclusion: Primary tumor-released LOXL2 contributes to the formation of lung pre-metastatic niche and the occurrence of lung metastasis. LOXL2 and LOXL2-caused matrix stiffening work together to induce pre-metastatic niche formation through influencing matrix remodeling and cell colonization. This study sheds light on the pathological significance of LOXL2 in lung pre-metastatic niche formation in HCC, also implicates a new intervention approach for HCC metastasis through reversal of lung pre-metastatic niche.
Employment transitions for spouses of stroke survivors: Evidence from Swedish national registries
Authors: Persson Josefine , Hensing Gunnel
Published: May 2020

Background: The sudden occurrence of stroke often leads to impaired physical, emotional, and cognitive abilities. Many stroke survivors therefore require support from their family members. However, little is known about the effects of a stroke event on the spouses’ employment transition probabilities. Thus, the aim of this study was to investigate whether a first ever stroke has an effect on employment transition probabilities for employed and unemployed spouses. The aim was also to analyze whether heterogeneity with respect to age, gender, education and comorbidities influence the size of the effect. Method: Data for this population-based cohort study were extracted from Swedish national registries from 2005 to 2016. The national sample consisted of 1,818 spouses of first ever stroke survivors during 2010 and 2011, and 7,399 matched controls that were employed or unemployed during five years prior stroke onset. Effects of stroke on spousal employment transitions were analyzed using linear regression, stratified by employment status prior to stroke onset.Results: Employed spouses prior stroke onset reduced their employment by -1.3 percentage points (95% CI: -2.4, -0.2). The data also indicated that employed spouses with lower age, comorbid conditions, and low educational attainment may be at even greater risk of transitioning to unemployment. On the other hand, stroke events appear to have limited impact on spouses that were unemployed prior to stroke onset. Conclusion: The risk of transitioning to unemployment appears to increase after stroke onset for spouses of stroke survivors, and disadvantaged groups may be at even greater risk. Thus, it is important for policy-makers to implement interventions to ensure that these groups of spouses have the possibilities to combine their caregiving role and remaining in the labor market.
Self-Medication Practice and Associated Factors Among Teachers’ Education Training College Students in Amhara Region, Ethiopia: A Cross-Sectional Study
Authors: Mekuria Abebe Basazn , Birru Eshetie Melese , Tesfa Melkamu Teshome , Geta Mestayet , Bykeda Tsegaw Amare
Published: May 2020

Background Self-medication practice is the use of medications without health care professional request. It leads to irrational medication usage, wastage of resources, increased chance of microbial resistance and adverse drug reaction. Therefore, this study aimed at assessing the prevalence associated factors of self-medication practice among students teacher’s education training college students in Amhara region, Ethiopia.Methods A multicentre cross-sectional study was conducted on 344 teacher's education training college students in Amhara region, from January 1 to February 28, 2020. Systematic random sampling was used to select participants and data collected through structured questionnaire. Descriptive statistics, univariate and multivariate logistic regression analysis were done to determine various variables and factors associated with self-medication practice.Results Out of 344 respondents, 68.0% were practiced self- medication. The most commonly cited indication for self-medication practice was headache 75 (32.05%) followed by abdominal discomfort 53 (22.6%). The respondents with age of greater than 26 years (AOR: 2.47, 95% CI: 1.18–3.94), third years of study (AOR: 3.14, 95% CI: 1.94–5.79), urban residence (AOR: 2.97, 95% CI: 1.06–3.64), near accessibility of pharmacy (AOR: 2.12, 95% CI: 1.43–4.46) and who had peer/family pressure (AOR: 2.34, 95% Cl: 1.53–3.56) were significantly associated with self-medication practice.Conclusion More than two-thirds of the study participants practiced self-medication. Being from the urban area, having access to private pharmacy and increase year of study are positively affects the self-medication practice.
The Modules of Mental Health Programs Implemented in Schools in Low- and Middle-Income Countries: Findings from a Systematic Literature Review
Authors: Gimba Solomon Musa , Harris Paul , Saito Amornrat , Udah Hyacinth , Martin Averil , Wheeler Amanda J.
Published: May 2020

Background Secondary schools in low- and middle-income countries (LMICs) provide promotional, preventive, and early treatment services. But the literature indicates that the modules of these services are either adapted or modified from existing mental health programs in developed countries. The literature also highlights the provision of non-comprehensive services (mental health promotion, prevention, and early treatment), in LMIC’s such as Nigeria. These findings inform the need for undertaking this systematic literature review. The aim of the review was to identify modules of school based mental health programs that have been implemented in LMICs to guide the development of a culturally sensitive comprehensive mental health program for adolescents in a LMIC.Methods The Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) statement was used to guide this review. The following databases were searched in September 2018, to identify the relevant literature: PubMed, CINAHL, Scopus, Web of Science, PsycINFO, and ERIC. The search was conducted by one of the authors and reviewed by two of the authors.Results Following the screening process, a total of 11 papers were identified and reviewed for quality. The systematic review highlighted that the mental health programs provided in schools included: introduction module, communication and relationship module, psychoeducation module, cognitive skills module, behavioral skills module, establishing social networks for recovery and help seeking behavioral activities and a summary/conclusion module.Conclusion The review shed light on the characteristics of the programs in LMIC. Two programs were universal in nature. Five programs were directed at key risk factors or at-risk groups and four were early intervention programs. The review also revealed that only one programs out of the 11 programs, included modules for parents. The synthesis indicated that all the identified programs were adapted or modified from existing programs. The dearth of comprehensive programs in LMIC was also revealed. The review also revealed modules that can be useful for developing a school based mental health program.
Maternal Stress, Depressive Symptoms and Body Mass Index of Adolescents: A Prospective Study
Authors: Koning Maaike , Vink Jacqueline , Visscher Tommy L.S. , Larsen Junilla
Published: May 2020

Background Changes in adolescent dietary and sedentary behaviors contribute to adolescence being one of the most vulnerable periods for the development of overweight and overweight-related morbidity. Children become more autonomous during adolescence, particularly in regard to decision-making over their own health behaviors. Despite this expanding autonomy, parents still play a major role in shaping health behaviors of adolescents and can still have influence on children’s weight outcomes. There is rising evidence that maternal stress and depressive symptoms are associated with young children’s weight outcomes. Longitudinal studies that test whether maternal stress or depressive symptoms may precede the development of adolescents’ weight outcomes are rare. This study aimed to fill this gap.Methods In this longitudinal cohort study data from 336 mothers and adolescents aged 10–14 years was used. Adolescents height and weight were measured, and both parents and adolescents filled in questionnaires on perceived stress and depressive symptoms. Regression analyses were performed in R to examine longitudinal links between stress and depressive symptoms at baseline (T1) and adolescents’ zBMI 6 months later (T2).Results Maternal general perceived stress (β = .14, p = .01) at T1 preceded the development of higher adolescents’ zBMI at T2, after controlling for baseline zBMI and other covariates, whereas maternal depressive symptoms at T1 (β = .04, p = .40) and other domain specific stress did not (maternal financial stress, maternal stress at work, maternal stress at home). Additionally, lower educational level among adolescents was associated with a higher zBMI at T2 (β = .16, p = .001).Conclusions Results suggest that maternal general stress, but not depressive symptoms, may influence adolescents’ weight development. Our findings warrant future investigation on whether and how general stress among mothers, but also fathers, may predict weight increases of their adolescent offspring.
Measuring the Impact of Advertisement on Children Diet Choice in the Pediatric Population.
Authors: Ponce-Blandón José Antonio , Romero-Martín Macarena , Gómez-Salgado Juan , Jiménez-Picón Nerea , Ramírez-Baena Lucía , Lomas-Campos María de las Mercedes
Published: May 2020

Background: The aim of this study was to evaluate the test–retest reliability of the paired selection method for measuring the impact of food advertising on the consumption preferences of children.
Methods: In this study, 52 children aged 4 to 6 years participated in watching an advertisement style video showing four foodstuffs with low nutritional value. Two pollsters were introduced at two instances showing pairs of pictures of the advertised foodstuffs right next to similar products, so that children could express their preferences. The test–retest reliability was measured through the concordance and interclass co-relation between both answers.
Results: Kappa concordance indices of 0.71 (0.46–0.97), 0.88 (0.62–1.15), and 0.90 (0.64–1.16) were obtained for the three foodstuff pairs. The interclass correlation coefficient for the sum of manifested preferred scores was 0.72 (p = 0.0000).
Conclusions: The paired selection method has been demonstrated to be efficient with good or very good reliability, making it useful for measuring the impact of food advertising on this age group.
Keywords: food advertising; food habits; childhood obesity; television advertising; assessment.
Trajectory optimization for waste collection system using multi-objective evolutionary algorithm
Authors: Guachetá-Alba Juan C. , Prieto-Pedraza Diego A. , Hurtado-Duque Daniela M. , Mauledoux Mauricio , Avilés Oscar F.
Published: May 2020

The control and correct disposal of waste is a global need, promotes recycling and keeps cities clean. In Bogota, the waste collection system has not made any significant changes during the last years, and although it is not an obsolete system, it is a system that can be optimized. The identification of the type of waste and the disposition of the vehicles fleet according to this classification, allows to obtain a more efficient waste collection system. This paper implements a modification on the NSGA-II multiagent optimization algorithm and the Nash Bargaining, to find the best trajectories that the collection vehicles perform on test points in the city of Bogotá, Colombia.
Folic Acid Supplementation in Children with Sickle Cell Disease: Study Protocol for a Double-Blind Randomized Cross-Over Trial
Authors: Williams Brock A , McCartney Heather , Adams Erin , Devlin Angela M , Singer Joel , Vercauteren Suzanne , Wu John K , Karakochuk Crystal D
Published: May 2020

• Background: Sickle cell disease (SCD) is a genetic disorder which causes dysfunctional red blood cells (RBC) and is thought to increase requirements for folate, an essential B-vitamin, due to increased RBC production and turn-over in the disease. High-dose supplementation with 1-5mg/d folic acid, synthetic folate, has been the standard recommendation for children with SCD. There is concern about whether children with SCD need such high doses of folic acid, following mandatory folic acid fortification of enriched grains in Canada, and advancements in medical therapies which extend the average lifespan of RBCs. In animal and human studies, high folic acid intakes (1 mg/d)have been associated with accelerated growth of some cancers, and the biological effects of circulating unmetabolized folic acid (UMFA), which can occur with doses of folic acid ≥0.2mg/d, are not fully understood. The objective of this study is to determine efficacy and alterations in folate metabolism of high-dose folic acid in children with SCD during periods of folic acid supplementation versus no supplementation• Methods: In this double-blind randomized controlled cross-over trial, children with SCD (n=36, aged 2-19 y)will be randomized to either receive 1 mg/d folic acid, the current standard of care, or a placebo for 12-weeks. After a 12-week washout period, treatments will be reversed. Total folate concentrations (serum and RBC), different folate forms (including UMFA), folate-related metabolites, and clinical outcomes will be measured at baseline and after treatment periods. The sum of the values measured in the two periods will be calculated for each subject and compared across the two sequence groups by means of a test for independent samples for the primary (RBC folate concentrations) and secondary (UMFA) outcomes. Dietary intake will be measured at the beginning of each study period. • Discussion:As the first rigorously designed clinical trial in children with SCD, this trial will inform and assess current clinical practice, with the ultimate goal of improving nutritional status of children with SCD.• Trial registration: This trial was registered July 8, 2019 at clinicaltrials.gov: NCT04011345. https://clinicaltrials.gov/ct2/show/NCT04011345
Common carotid artery stiffness in patients with Spontaneous Coronary Artery Dissection (SCAD) is comparable to non-dissection controls
Authors: Almutairi *Fahad F , Al-hussaini *Abtehal , Marsh Anne-Marie , Samani Nilesh J , McCann Gerry P , Adlam David , Chung Emma , Ramnarine Kumar V
Published: May 2020

Background: Arterial dissection is a rare but potentially life-threatening condition, hypothesized to be linked to changes in vessel wall elasticity. This study aimed to provide an insight into the pathophysiology of arterial dissection by assessing whether elasticity of the common carotid artery (CCA) differs between patients with confirmed spontaneous coronary artery dissection (SCAD) and non-dissection controls. Methods: Ultrasound shear wave elastography (SWE) estimates of artery wall elasticity were obtained from the left and right CCAs of 89 confirmed SCAD patients and 38 non-dissection controls. SWE images obtained over multiple cardiac cycles were analysed by a blinded observer to estimate elasticity in the form of a Young’s Modulus (YM) value, across regions of interest (ROI) located within the anterior and posterior CCA walls. A confidence limit on the difference in mean YM between SCAD patients and non-dissection controls was estimated. Results: YM estimates ranged from 17 to 133 kPa in SCAD patients compared to 34 to 87 kPa in non-dissection controls. The mean YM of 55 [SD: 21] kPa in SCAD patients was not significantly different to the mean of 57 [SD: 12] kPa in controls, p= 0.32. The difference between groups was 2 kPa [95%CI: -11, 4]. Conclusions: We found no evidence of a significant difference in elasticity of the CCA between SCAD patients and non-dissection controls. This suggests that widespread changes in arterial compliance are not a major factor in the pathogenesis of arterial dissection.
Self-limited focal epilepsy in a young child with SARS-CoV-2: serendipity or causal association?
Authors: Silvagni Davide , Soloni Pietro , Darra Francesca , Biban Paolo
Published: May 2020

Neurological manifestations have been reported in adults with COVID-19. In children with COVID-19, data on neurological symptoms are scarce. A 4-year-old girl was assisted at home for prolonged afebrile seizures. She was unresponsive, with a conjugate eye right deviation lasting > 20 minutes. Intravenous midazolam was administered. Before arrival in our Emergency Department, EMS providers excluded risk factors for COVID-19, such as fever, respiratory symptoms, other signs of viral infections, or recent contacts with suspected COVID-19 cases. Upon her arrival, seizures had resolved, GCS was 12. Temperature was 36,6°C. Chest was clear (SatO2 100%). Blood tests did not show signs of infection. We collected a nasopharyngeal swab, which tested positive for SARS-CoV-2. The patient rapidly recovered her neurological function. A pediatric neurological examination and video-EEG recording produced a possible diagnosis of self-limited focal epilepsy, with temporo-occipital spikes. Family history revealed her father had occasional seizures during fever episodes, at 14 and 21 years. The child was discharged home, scheduling further neurological investigations once the swab was negative. Our case emphasizes that keeping a high suspicion for SARS-CoV-2 infection is pivotal in hot spots, regardless of the absence of typical COVID-19 symptoms. As for the seizures episode, we know infections and fever are leading seizure precipitating factors in children. To our knowledge, this is the first case of focal status epilepticus in new onset focal self-limited epilepsy in an afebrile child with SARS-CoV-2. We speculate that SARS-CoV-2 infection may have triggered the onset of self-limited focal epilepsy in our patient.
Fighting the storm: novel anti- TNFα and anti-IL-6 C. sativa lines to tame cytokine storm in COVID-19
Authors: Kovalchuk Anna , Rodriguez-Juarez Rocio , Ilnytskyy Slava , Li Dongping , Wang Bo , Kovalchuk Igor , Kovalchuk Olga
Published: May 2020

The main aspects of severe COVID-19 disease pathogenesis include the increasing hyper-induction of proinflammatory cytokines, also known as ‘cytokine storm’, that precedes acute respiratory distress syndrome (ARDS) and often leads to death. COVID-19 patients often suffer from lung fibrosis, a serious and untreatable condition. There remains no effective treatment for these complications. Out of the cytokines, TNFα and IL-6 play crucial roles in cytokine storm pathogenesis and are likely responsible for the escalation in disease severity. These cytokines also partake in the molecular pathogenesis of fibrosis. Therefore, new approaches are urgently needed that can efficiently and swiftly block TNFα, IL-6, and the inflammatory cytokine cascade in order to curb inflammation and prevent fibrosis, and lead to disease remission.Cannabis sativa has been proposed to modulate gene expression and inflammation and is under investigation for several potential therapeutic applications against autoinflammatory diseases and cancer. Here, we hypothesized that the extracts of our novel C. sativa lines may be used to modulate the expression of pro-inflammatory cytokines and pathways involved in inflammation and fibrosis. To analyze the anti-inflammatory effects of novel C. sativa lines, we used a well-established full thickness human 3D skin artificial EpiDermFTTM tissue model, whereby tissues were exposed to UV to induce inflammation and then treated with extracts of seven new cannabis lines.We noted that out of seven studied extracts of novel C. sativa lines, three (#4, #8 and #14) were the most effective, causing profound and concerted down-regulation of TNFα, IL-6, CCL2, and other cytokines and pathways related to inflammation and fibrosis. Most importantly, one of the tested extracts had no effects at all, and one exerted effects that may be deleterious, signifying that cannabis is not generic and cultivar selection must be based on thorough pre-clinical studies.The observed pronounced inhibition of TNFα and IL-6 is the most important finding, as these molecules are currently considered to be the main actionable targets in COVID-19 cytokine storm and ARDS pathogenesis. Many currently trialed agents, such as anti-TNFα and anti-IL-6 biologics are expensive and cause an arrays of side effects. On the other hand, anti-TNFα and anti-IL-6 cannabis extracts that are generally regarded as safe (GRAS) modalities can be a useful addition to the current anti-inflammatory regimens to treat COVID-19, as well as various rheumatological diseases and conditions, and ‘inflammaging’ - the inflammatory underpinning of aging and frailty.
Identification of SARS-CoV-2 preclinical (in vivo) compounds targeting COVID-19 main protease: A scoping review, meta-analysis and molecular docking studies
Authors: Ebenezer Oluwakemi , Jordaan Maryam Amra , Damoyi Nkululeko , Ogunsakin Ropo , Shapi Michael
Published: May 2020

Due to the migratory flow of infected people with severe acute respiratory syndrome virus (SARS-CoV-2), the numbers of confirmed cases of coronavirus 2019 (COVID-19) infections is accelerating worldwide and pre-clinical evidence of antiviral agents that can combat this pandemic is still elusive. We identified published SAR-CoV efficacy experiments in which some selected compounds were used to test the reduction of the virus load in mice. We then developed a combined model based on scoping review, meta-analyses, and molecular docking studies to evaluate the effect size of preclinical studies of compounds that have been tested against SARS-CoV. Molecular docking studies of the inhibitors in the active pocket of COVID-19 protease were also performed. Our results identified three SARS-CoV inhibitors i.e. EIDD-2801, GS-5734 and amodiaquine that are excellent options for optimization and drug development to treat or cure COVID-19.
Advice from a systems-biology model of the Corona epidemics
Authors: Westerhoff Hans V. , Kolodkin Alexey N.
Published: May 2020

Using standard systems biology methodologies a 14-compartment dynamic model was developed for the Corona virus epidemic. The model predicts that: (i) it will be impossible to limit lockdown intensity such that sufficient herd immunity develops for this epidemic to die down, (ii) the death toll from the SARS-CoV-2 virus decreases very strongly with increasing intensity of the lockdown, but (iii) the duration of the epidemic increases at first with that intensity and then decreases again, such that (iv) it may be best to begin with selecting a lockdown intensity beyond the intensity that leads to the maximum duration, (v) an intermittent lockdown strategy should also work and might be more acceptable socially and economically, (vi) an initially intensive but adaptive lockdown strategy should be most efficient, both in terms of its low number of casualties and shorter duration, (vii) such an adaptive lockdown strategy offers the advantage of being robust to unexpected imports of the virus, e.g. due to international travel, (viii) the eradication strategy may still be superior as it leads to even fewer deaths and a shorter period of economic, but should have the adaptive strategy as backup in case of unexpected infection imports (ix) earlier detection of infections is the most effective way in which the epidemic can be controlled, whilst waiting for vaccines.
Ferric-ferrous iron ratios of experimental majoritic garnet and clinopyroxene as a function of oxygen fugacity
Authors: Rzehak Laura J.A. , Rohrbach Arno , Vollmer Christian , Höfer Heidi E. , Berndt Jasper , Klemme Stephan
Published: May 2020

The oxidation state of iron in upper mantle minerals is widely used to constrain the Earth mantle's oxidation state. Previous studies showed high levels of ferric iron in high-pressure majoritic garnets and pyroxenes despite reducing conditions. To disentangle the effects of pressure and increasing oxygen fugacity on the Fe3+/ΣFe ratios of garnet and clinopyroxene, we performed high-pressure experiments at a pressure of 10 GPa in a 1000-ton Walker-type multi-anvil apparatus at the University of Münster. We synthesized majoritic garnets and clinopyroxenes with a total iron content close to natural mantle values at different oxygen fugacities, ranging from IW+4.7 to metal saturation at IW+0.9. We analyzed the iron oxidation state in garnets with the electron microprobe “flank method.” Furthermore, we investigated the oxidation state of iron in garnets and clinopyroxenes with transmission electron microscopy (TEM) electron energy loss spectroscopy (EELS). Although the flank method measurements are systematically lower than the EELS measurements, Fe3+/ΣFe obtained with both methods agree well within 2σ errors. The “flank method” has the advantage of being much faster and more easily to set up, whereas TEM-EELS has a much higher spatial resolution and can be applied to various non-cubic minerals such as orthopyroxenes and clinopyroxenes. We used our experimental results to compare two geobarometers that contain a term for ferric iron in garnet (Beyer and Frost 2017; Tao et al. 2018) with two geobarometers that do not account for ferric iron (Collerson et al. 2010; Wijbrans et al. 2016). We found that for garnets with low total Fe and Fe3+ (like many natural garnets), the pressures can be calculated without including the ferric iron content.
Magma oxygen fugacity of mafic-ultramafic intrusions in convergent margin settings: Insights for the role of magma oxidation states on magmatic Ni-Cu sulfide mineralization
Authors: Cao Yonghua , Wang Christina Yan , Wei Bo
Published: May 2020

Oxygen fugacities (fO2) of mantle-derived mafic magmas have important controls on the sulfur status and solubility of the magmas, which are key factors to the formation of magmatic Ni-Cu sulfide deposits, particularly those in convergent margin settings. To investigate the fO2 of mafic magmas related to Ni-Cu sulfide deposits in convergent margin settings, we obtained the magma fO2 of several Ni-Cu sulfide-bearing mafic-ultramafic intrusions in the Central Asian Orogenic Belt (CAOB), North China, based on the olivine-spinel oxygen barometer and the modeling of V partitioning between olivine and melt. We also calculated the mantle fO2 on the basis of V/Sc ratios of primary magmas of these intrusions.

Ni-Cu sulfide-bearing mafic-ultramafic intrusions in the CAOB include arc-related Silurian-Carboniferous ones and post-collisional Permian-Triassic ones. Arc-related intrusions formed before the closure of the paleo-Asian ocean and include the Jinbulake, Heishan, Kuwei, and Erbutu intrusions. Post-collisional intrusions were emplaced in extensional settings after the closure of the paleo-Asian ocean and include the Kalatongke, Baixintan, Huangshandong, Huangshan, Poyi, Poshi, Tulaergen, and Hongqiling No. 7 intrusions. It is clear that the magma fO2 values of all these intrusions in both settings range mostly from FMQ+0.5 (FMQ means fayalite-magnetite-quartz oxygen buffer) to FMQ+3 and are generally elevated with the fractionation of magmas, much higher than that of MORBs (FMQ-1 to FMQ+0.5). However, the mantle fO2 values of these intrusions vary from ~FMQ to ~FMQ+1.0, just slightly higher than that of mid-ocean ridge basalts (MORBs) (≤FMQ). This slight difference is interpreted as the intrusions in the CAOB may have been derived from the metasomatized mantle wedges where only minor slab-derived, oxidized components were involved. Therefore, the high-magma fO2 values of most Ni-Cu sulfide-bearing mafic-ultramafic intrusions in the CAOB were attributed to the fractionation of magmas derived from the slightly oxidized metasomatized mantle. In addition, the intrusions that host economic Ni-Cu sulfide deposits in the CAOB usually have magma fO2 of >FMQ+1.0 and sulfides with mantle-like δ34S values (–1.0 to +1.1‰), indicating that the oxidized mafic magmas may be able to dissolve enough mantle-derived sulfur to form economic Ni-Cu sulfide deposits. Oxidized mafic magmas derived from metasomatized mantle sources may be an important feature of major orogenic belts.
Investigation of the crystal structure of a low water content hydrous olivine to 29.9 GPa: A high-pressure single-crystal X-ray diffraction study
Authors: Xu Jingui , Fan Dawei , Zhang Dongzhou , Li Bo , Zhou Wenge , Dera Przemyslaw K.
Published: May 2020

Olivine is the most abundant mineral in the Earth's upper mantle and subducting slabs. Studying the structural evolution and equation of state of olivine at high-pressure is of fundamental importance in constraining the composition and structure of these regions. Hydrogen can be incorporated into olivine and significantly influence its physical and chemical properties. Previous infrared and Raman spectroscopic studies indicated that local structural changes occur in Mg-rich hydrous olivine (Fo ≥ 95; 4883–9000 ppmw water) at high-pressure. Since water contents of natural olivine are commonly <1000 ppmw, it is inevitable to investigate the effects of such water contents on the equation of state (EoS) and structure of olivine at high-pressure. Here we synthesized a low water content hydrous olivine (Fo95; 1538 ppmw water) at low SiO2 activity and identified that the incorporated hydrogens are predominantly associated with the Si sites. We performed high-pressure single-crystal X-ray diffraction experiments on this olivine to 29.9 GPa. A third-order Birch-Murnaghan equation of state (BM3 EoS) was fit to the pressure-volume data, yielding the following EoS parameters: VT0 = 290.182(1) Å3, KT0 = 130.8(9) GPa, and K′T0 = 4.16(8). The KT0 is consistent with those of anhydrous Mg-rich olivine, which indicates that such low water content has negligible effects on the bulk modulus of olivine. Furthermore, we carried out the structural refinement of this hydrous olivine as a function of pressure to 29.9 GPa. The results indicate that, similar to the anhydrous olivine, the compression of the M1-O and M2-O bonds are comparable, which are larger than that of the Si-O bonds. The compression of M1-O and M2-O bonds of this hydrous olivine are comparable with those of anhydrous olivine, while the Si-O1 and Si-O2 bonds in the hydrous olivine are more compressible than those in the anhydrous olivine. Therefore, this study suggests that low water content has negligible effects on the EoS of olivine, though the incorporation of water softens the Si-O1 and Si-O2 bond.
Test of capital market integration using Fama-French three-factor model: empirical evidence from India
Authors: Sehrawat Neeraj , Kumar Amit , Kumar Nigam Narander , Singh Kirtivardhan , Goyal Khushi
Published: May 2020

Integration or segmentation of markets determines whether substantial advantages in risk reduction can be attained through portfolio diversification in foreign securities. In an integrated market, investors face risk from country-specific factors and factors, which are common to all countries, but price only the later, as country-specific risk is diversifiable. The aim of this study is two-fold, firstly, investigating the superiority of the Fama-French three-factor model over Capital Asset Pricing Model (CAPM) and later using the superior model to test for integration of Indian and US equity markets (a proxy for global markets). Based on a sample of Bombay Stock Exchange 500 non-financial companies for the period 2003–2019, the data suggest the superiority of Fama-French three-factor model over CAPM. Using the Non-Linear Seemingly Unrelated Regression technique, the first half of the sample period (2003–2010) shows evidence of market segmentation; however, the second sub-period (2011–2019) shows weak signs of market integration, which is supported by the Johansen test of cointegration, suggesting that Indian market is gradually getting integrated with global markets.
A polemical handwritten manuscript in the milieu of the Płock cathedral at the time of the Hussite disputes
Authors: Marszalska Jolanta M.
Published: May 2020

W XV - wiecznym kościelnym środowisku płockim obecne były dyskusje dotyczące spraw koncyliaryzmu, reformy Kościoła i husytyzmu, który w tym czasie stał się poważnym zagrożeniem jedności religijnej w Polsce. To, że interesowano się w Płocku sprawami husyckimi świadczą pozostawione na marginesach kart liczne glosy związane z zamieszczonymi w kodeksach traktatami (mowami) i kazaniami.  Przechowywane kodeksy zawierały traktaty polemiczne i mowy antyhusyckie skierowane przeciw czterem artykułom praskim, których autorami byli zwolennicy Husa: Jan z Raguzy (Ioannis de Ragusio), z traktatem: De communione sub utraque specie oraz Septem regulae ad habendum verum sensum sacrarum scripturarum, Hieronim z Pragi zwany Mniszek, (Hieronymi Pragensis) z traktatem kazanodziejskim: Sermo, Gilles Charlier (Aegidus Carlerii), z traktatem: De punitione peccatorum publicorum, Henryk Kalteis, (Henrici Kalteisen), z traktatem: Oratio de libera predicatione verbi Dei, Jan de Palomar,(Ioannis de Palomar), z traktatem: De civili domino clericorum, nadto zamieszczono pisma: Excerpta ex Summa Benedicti abbatis Massiliae contra errores haereticorum; Responsiones ad obiectiones et pictura Ioannis Hus, traktat kardynała Juliana Cesarini, Oratio ad convertendos Bohemos oraz traktat Jana de Bachenstein decretorum doctoris, Sermo in concilio Basiliensi. O tym że husytyzm jako prąd myślowy z ukierunkowaniem religijno-społecznym dotarł na Mazowsze, dobitnie świadczą przechowywane księgi i zachowane na nich wpisy marginalne i proweniencyjne, rozczytane przez Adama Vetulaniego jeszcze przed 1939 rokiem. Wprawdzie nie są to traktaty, które zajmują się doktryną Kościoła w ujęciu husyckim, co raczej polemiczne w stosunku do tego ruchu. Zatem książka rękopiśmienna w kręgu kościelnym (katedralnym) płockim w XIV stuleciu, poprzez swoją tematykę służyła również w obronie obowiązującej doktryny katolickiej, niż z nią prowadzonej polemiki. Jednocześnie poprzez wspomniane księgi widoczny jest fakt zainteresowania nowym prądem religijnym w znacznie odległym od ośrodka akademickiego krakowskiego - Płocka i jego duchowieństwa związanego z kapitułą katedralną.
“De heresibusetextirpacionehereticorum in dioecesiplocensi”. Was there an organized Hussite movement in the Mazovian part of the Płockdiocese in the mid-15th century?
Authors: Graczyk Waldemar
Published: May 2020

Na Mazowszu, w latach 20 - tych XV wieku nie zauważamy jeszcze przejawów zainteresowania się ruchem husyckim, choć spotyka go się w tym czasie w Wielkopolsce i na Kujawach.Pierwsze sygnały o osobach sympatyzujących z reformą husycką pojawiły się w końcu trzeciej dekady XV wieku. Na przestrzeni niespełna dwudziestu lat (1440-1457) należy odnotować kilka miejscowości (Płock, Ciechanów, Strzegowo, Baboszewo, Bulkowo), gdzie spotykamy jakieś formy zainteresowania nauką Jana Husa. W większości byli to duchowni, duszpasterze miejscowych parafii, a w jednym przypadku płocki skryptor, który być może tą drogą zaznajomił się z programem reformy proponowanej przez praskiego teologa. Czy na podstawie wyżej omówionych przykładów można mówić o zjawisku husytyzmu na Mazowszu? Sadzę, że nie. Nie był to zorganizowany ruch, mający swoich przywódców i oczywiście zwolenników. Przypadki te bardziej odzwierciedlają religijną wrażliwość niektórych duchownych, która być może pobudzona przez docierające ze świata informacje, znajdowała ujście w takich formach pobożności jak choćby częstsze praktykowanie wystawiania Najświętszego Sakramentu w monstrancji dla ożywienia pobożności wiernych. Po drugie niedostatki w wykształceniu duchownych a tym samym rażące braki w nieznajomości zagadnień teologicznych, zawierały pułapki popadnięcia w religijny subiektywizm. Chyba wystarczyło zaproszenie podejrzanego przez biskupa, złożenie wyjaśnień i zapewne zobowiązanie się do zaniechania nietypowych praktyk religijnych, by sprawę uznać za załatwioną. Akta posiedzeń kapituły katedralnej nie informują o mających miejsce debatach teologicznych, próbach obrony własnego stanowiska – jak będzie to miało miejsce sto lat później za sprawą reformy Marcina Lutra. W tym przypadku wystarczyło opracowanie przez Mikołaja z Mirzyńca zbioru podstawowych zasad wiary katolickiej, zaznajomienie z nim przede wszystkim duchownych na zwoływanych przez biskupa synodach i problem został załatwiony.
The Nitric Oxide Pathway in Pulmonary Arterial Hypertension: Pathomechanism, Biomarkers and Drug Targets
Authors: Lázár Zsófia , Mészáros Martina , Bikov Andras
Published: May 2020

The altered Nitric Oxide (NO) pathway in the pulmonary endothelium leads to increased
vascular smooth muscle tone and vascular remodelling, and thus contributes to the
development and progression of pulmonary arterial hypertension (PAH). The pulmonary NO
signalling is abrogated by the decreased expression and dysfunction of the endothelial NO
synthase (eNOS) and the accumulation of factors blocking eNOS functionality. The NO deficiency
of the pulmonary vasculature can be assessed by detecting nitric oxide in the exhaled
breath or measuring the degradation products of NO (nitrite, nitrate, S-nitrosothiol) in blood
or urine. These non-invasive biomarkers might show the potential to correlate with changes in
pulmonary haemodynamics and predict response to therapies. Current pharmacological therapies
aim to stimulate pulmonary NO signalling by suppressing the degradation of NO (phosphodiesterase-
5 inhibitors) or increasing the formation of the endothelial cyclic guanosine
monophosphate, which mediates the downstream effects of the pathway (soluble guanylate
cyclase sensitizers). Recent data support that nitrite compounds and dietary supplements rich
in nitrate might increase pulmonary NO availability and lessen vascular resistance. This review
summarizes current knowledge on the involvement of the NO pathway in the pathomechanism
of PAH, explores novel and easy-to-detect biomarkers of the pulmonary NO.
Aberrant β-catenin Activity in Hepatoid Adenocarcinoma of the Stomach
Authors: Wang Nan , Kong Rui , Han Wei , Lu Jie
Published: May 2020

Background:

Hepatoid adenocarcinoma of the stomach (HAS) has been
recognized as a rare primary gastric tumor characterized by hepatocellular carcinomalike
histology. HAS often causes diagnostic confusion with conventional gastric
adenocarcinoma (CGA) due to the difficulty to detect hepatoid differentiation solely
based on findings from hematoxylin and eosin (H&E) staining. β-catenin is highly
expressed in hepatocellular carcinoma (HCC), which is involved in the maintenance of
tumor initiating cells, drug resistance, tumor progression, and metastasis. Due to the
scarcity of confirmed cases of HAS, there are few studies on β-catenin.

Objectives:

14 patients diagnosed in our hospital were selected.

Methods:

The clinical characteristics of 14 patients were statistically studied, and
pathological specimens were analyzed by immunohistochemistry.

Results:

We detected statistically significant difference in the expression of β-catenin (P
= 0.000), glypican3 (P = 0.019), and hepar-1 (P = 0.007) between HAS cancer tissues
and normal tissues. Furthermore, a significant correlation was found between the
expression of β-catenin in HAS cancer tissue and normal tissue (Pearson correlation
coefficient: 0.686, P = 0.007). Meanwhile, a significant correlation was observed
between the expression of β-catenin and survival time (Spearman correlation
coefficient= - 0.482, P = 0.003). However, we found the expression of β-catenin did not
correlate with the tumor differentiation and size, age, gender, serum AFP levels,
microinvasion, and metastasis (P > 0.05).

Conclusion:

Our findings establish β-catenin as a useful marker that can distinguish
HAS from CGA and may improve the early diagnosis to guide the appropriate and timely
treatment of HAS patients.
Transcriptional Factors and Protein Biomarkers as Target Therapeutics in Traumatic Spinal Cord and Brain Injury
Authors: Kumar Suneel , Fritz Zachary , Sulakhiya Kunjbihari , Theis Thomas , Berthiaume Francois
Published: May 2020

Traumatic injury to the spinal cord (SCI) and brain (TBI) are serious health problems and affect many people every year throughout the world. These devastating injuries are affecting not only patients but also their families socially as well as financially. SCI and TBI lead to neurological dysfunction besides continuous inflammation, ischemia, and necrosis followed by progressive neurodegeneration. There are well-established changes in several other processes such as gene expression as well as protein levels that are the important key factors to control the progression of these diseases. We are not yet able to collect enough knowledge on the underlying mechanisms leading to the altered gene expression profiles and protein levels in SCI and TBI. Cell loss is hastened by the induction or imbalance of pro- or anti-inflammatory expression profiles and transcription factors for cell survival after or during trauma. There is a sequence of events of dysregulation of these factors from early to late stages of trauma that opens a therapeutic window for new interventions to prevent/ restrict the progression of these diseases. There has been increasing interest in the modulation of these factors for improving the patient’s quality of life by targeting both SCI and TBI. Here, we review some of the recent transcriptional factors and protein biomarkers that have been developed and discovered in the last decade in the context of targeted therapeutics for SCI and TBI patients.
Plant-Derived Butters as Lipid Nanocarriers: A Systematic and Prospective Review
Authors: Coelho Angélica G. , dos Santos Webysten R.P. , dos Santos Andressa A. , da Silva Maisa G. , Cunha Francisco V. Macedo , Mendes Anderson N. , Arcanjo Daniel D.R.
Published: May 2020

Background:

Pharmaceutical nanotechnology represents an efficient alternative for the delivery
of pharmacologically active plant-derived compounds, considering their protective capacity, oral
bioavailability and drug vectorization capacity. In this context, butters obtained from plant seeds have
emerged as promising products for the development of pharmacologically active nanostructures. They
possess a complex lipid composition, allowing the formation of different emulsion systems with solid
cores, since this mixture of different triglycerides is solid at room temperature and body temperature.
Therefore, the systematic mapping around the technological development of nanostructures produced
from plant-derived butters is potentially valuable for researchers interested in novel alternative formulations
for pharmacological therapy, with potential industrial, economic, health and societal impacts.

Methods:

Systematic review was carried out by the search of scientific papers and patents deposited in
official databases concerning the development of nanostructured pharmaceutical products using plantderived
butters as starting material. The publications obtained were subjected to sorting and analysis
by applying the following inclusion/exclusion criteria.

Results:

The Solid Lipid Nanoparticle (SLN) was the type of nanostructure produced in all the analyzed
scientific papers, due to the physicochemical characteristics of the lipid constituents of plantderived
butters. In this sense, 54% of the articles have reported the use of Cocoa Butter for the production
of nanostructures; 28% for Shea Butter; 6% for Cupuacu Butter, 6% for Murumuru Butter and 6%
for Bacuri Butter.

Discussion:

In the technological prospection, only two patents exhibited SLN as an invention based on
cocoa butter and on shea butter, respectively. The production methods employed have included: phase
inversion temperature, microemulsion, hot high pressure homogenization, high shear homogenization
and ultrasonication.

Conclusion:

In light of this prospective review, the encouragement of novel studies in lipids-based
nanotechnology is evident, considering the small number of findings so far, in order to stimulate new
research involving plant-derived butters from easily cultivated fruits in tropical regions, then stimulating
the pharmaceutical development of new therapeutic alternatives using biocompatible and sustainable
raw materials.
Therapist-Supported Online Interventions for Children and Young People With Tic Disorders: Lessons Learned From a Randomized Controlled Trial and Considerations for Future Practice
Authors: Chamberlain Liam R , Hall Charlotte L , Andrén Per , Davies E Bethan , Kilgariff Joseph , Kouzoupi Natalia , Murphy Tara , Hollis Chris
Published: May 2020

In recent years, research into internet-based cognitive behavioral therapy (iCBT) has suggested that therapist-guided digital interventions have greater engagement, adherence, and effectiveness than self-directed digital therapies. While research has focused on the effectiveness of, and adherence to, these interventions, less attention has been paid to their implementation in practice and what aspects of the therapist role support success. An understanding of the key factors related to the therapist role and intervention delivery is required if these iCBTs are to be applied in routine clinical care and outcomes optimized. In light of the coronavirus disease 2019 (COVID-19) pandemic, there is greater emphasis on allowing patients access to remote therapies. We report the experiences and reflections of 4 therapists and their 2 supervisors in delivering an online, therapist-supported intervention in a randomized controlled trial for children and young people with tic disorders (the Online Remote Behavioural Intervention for Tics [ORBIT] trial). Themes discussed include the importance of training, supervision, creating support documents/manuals, and record keeping. Alongside this are communication strategies used by therapists to encourage patient adherence and treatment effectiveness. These include rapport building, treatment personalization, and suggestions for overcoming non-engagement. These reflections offer important considerations for the delivery of iCBTs as well as implications associated with the implementation of these interventions in existing services and future research studies. We share thoughts on where iCBTs may sit in a stepped care model, how services may deal with comorbid conditions, and the potential role of iCBTs in collecting clinical data.