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It is folklore knowledge that nonconvex mixed-integer nonlinear optimization problems can be notoriously hard to solve in practice. In this paper we go one step further and drop analytical properties that are usually taken for granted in mixed-integer nonlinear optimization. First, we only assume Lipschitz continuity of the nonlinear functions and additionally consider multivariate implicit constraint functions that cannot be solved for any parameter analytically. For this class of mixed-integer problems we propose a novel algorithm based on an approximation of the feasible set in the domain of the nonlinear function—in contrast to an approximation of the graph of the function considered in prior work. This method is shown to compute approximate global optimal solutions in finite time and we also provide a worst-case iteration bound. In some first numerical experiments we show that the "cost of not knowing enough" is rather high by comparing our approach with the open-source global solver SCIP. This reveals that a lot of work is still to be done for this highly challenging class of problems and we thus finally propose some possible directions of future research. [ABSTRACT FROM AUTHOR]

Coordinative challenging exercises in changing environments referred to as open-skill exercises seem to be beneficial on cognitive function. Although electroencephalographic research allows to investigate changes in cortical processing during movement, information about cortical dynamics during open-skill exercise is lacking. Therefore, the present study examines frontal brain activation during table tennis as an open-skill exercise compared to cycling exercise and a cognitive task. 21 healthy young adults conducted three blocks of table tennis, cycling and n-back task. Throughout the experiment, cortical activity was measured using 64-channel EEG system connected to a wireless amplifier. Cortical activity was analyzed calculating theta power (4–7.5 Hz) in frontocentral clusters revealed from independent component analysis. Repeated measures ANOVA was used to identify within subject differences between conditions (table tennis, cycling, n-back; p <.05). ANOVA revealed main-effects of condition on theta power in frontal (p <.01, ηp2 = 0.35) and frontocentral (p <.01, ηp2 = 0.39) brain areas. Post-hoc tests revealed increased theta power in table tennis compared to cycling in frontal brain areas (p <.05, d = 1.42). In frontocentral brain areas, theta power was significant higher in table tennis compared to cycling (p <.01, d = 1.03) and table tennis compared to the cognitive task (p <.01, d = 1.06). Increases in theta power during continuous table tennis may reflect the increased demands in perception and processing of environmental stimuli during open-skill exercise. This study provides important insights that support the beneficial effect of open-skill exercise on brain function and suggest that using open-skill exercise may serve as an intervention to induce activation of the frontal cortex. [ABSTRACT FROM AUTHOR]

In the midst of the debate about vaccines against COVID-19 and vaccine mandates, there are a surprisingly large number of concerns coming from some churches centring on the dependence of some of the vaccines on historic abortions and limitations of freedom of choice. Although the ethical significance of separation between historic abortions and the vaccines has been widely accepted by most religious authorities, the pandemic has led to renewed concern by some. The emergence of vaccine mandates, with their potential negative impact on church attendance, has led some to oppose anything that would limit freedom of choice. Within this opposition is a medley of other messages, such as lack of trust in experts and human rights violations. Some regard vaccine passports as a form of 'medical apartheid' or 'therapeutic totalitarianism', coercing people's conscience. A countervailing perspective is provided by most church organizations that take a far more communitarian view based upon Jesus' teachings, identification with the poor and marginalized, and public health considerations. These Christians place far greater store on science as a gift from God, medical science as a means of transforming societies for good, and the potential of vaccines to control a rampant pandemic. Flexibility in imposing vaccine mandates is essential with onus placed on protecting the vulnerable, the community, and directed by the biblical precept of love for one's neighbour. [ABSTRACT FROM AUTHOR]

Cytoplasmic RNP condensates enriched in mRNAs and proteins are found in various cell types and associated with both buffering and regulatory functions. While a clear link has been established between accumulation of aberrant RNP aggregates and progression of aging-related neurodegenerative diseases, the impact of physiological aging on neuronal RNP condensates has never been explored. Through high-resolution imaging, we uncover that RNP components progressively cluster into large yet dynamic granules in the aging Drosophila brain. We further show that age-dependent clustering is caused by an increase in the stoichiometry of the conserved helicase Me31B/DDX6, and requires PKA kinase activity. Finally, our functional analysis reveals that mRNA species recruited to RNP condensates upon aging exhibit age-dependent translational repression, indicating that co-clustering of selected mRNAs and translation regulators into repressive condensates may contribute to the specific post-transcriptional changes in gene expression observed in the course of aging. Aberrant RNA condensates are a hallmark of age-related neurodegenerative diseases. Here, the authors show that RNA condensation increases in aging Drosophila brains, triggering translation repression. [ABSTRACT FROM AUTHOR]

People suffering from congenital anosmia show normal brain architecture although they do not have functional sense of smell. Some studies in this regard point to the changes in secondary olfactory cortex, orbitofrontal cortex (OFC), in terms of gray matter volume increase. However, diffusion tensor imaging has not been explored so far. We included 13 congenital anosmia subjects together with 15 controls and looked into various diffusion parameters like FA. Increased FA in bilateral OFC confirms the earlier studies reporting increased gray matter thickness. However, it is quite difficult to interpret FA in terms of gray matter volume. Increased FA has been seen with recovery after traumatic brain injury. Such changes in OFC point to the plastic nature of the brain. [ABSTRACT FROM AUTHOR]

The environmentally friendly behaviors (EFBs) play a conspicuous role achieving sustainable development due to encouraging citizens using green transportation modes. Assessing EFB among university students is one of the little-known subjects and important research area since they are not only likely to have leading roles in the future society, but also are potentially influential actors in encouraging policy makers to develop the green transportation infrastructure. The present study illustrates the empirical results of a survey of commuting behaviors and the degree of environmental awareness in a target community of students in a campus (Pardis) of University of Tehran, Iran. This paper aims to investigate linkage between students' environmental attitudes and their commuting patterns to the campus. The research method strategy is quantitative and questionnaire, and statistical analysis are deployed to assess the environmental awareness on travel behavior among postgraduate students of the university. Despite a high reliance on the use of public transport, empirical results document a relatively low level of EFB. These findings suggest how national policies should promote a higher level of environmental awareness in university students, stimulating a more environmentally sustainable performance of local systems. Surveyed students in Pardis campus recommended provision of a better functioning public transportation system, including a sharing-bike scheme as an alternative to private transportation. [ABSTRACT FROM AUTHOR]

The objective of this study was to assess the diagnostic value of plasma neutrophil gelatinase-associated lipocalin (pNGAL) for the early diagnosis of acute kidney injury (AKI) in adult patients following cardiac surgery requiring cardiopulmonary bypass (CPB). Electronic databases and other resources were systematically searched for relevant studies. Risk of bias was assessed using the Quality Assessment for Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Studies were assigned to a sub-group based on the timing of the pNGAL sample in relation to the cessation of CPB. These were < 4 h, 4–8 h, 12 h or 24 h post-cessation of CPB. Summary values for sensitivity and specificity were estimated using the hierarchical summary receiver operator characteristic (ROC) curve model. A random-effects meta-analysis of each pair of sensitivity and specificity estimates from each included study was performed. In total, 3131 patients from 16 studies were included. When taken at 4–8 h following CPB, pNGAL had superior performance for the diagnosis of AKI in the defined population when compared to earlier and later time points. Prediction regions and confidence intervals, however, demonstrated significant variability in pooled estimates of sensitivity and specificity. This is likely due to population and study design heterogeneity, lack of standardisation of assays and thresholds, and inability to distinguish the different molecular forms of NGAL. In conclusion, the diagnostic utility of pNGAL in this clinical setting is inconclusive and large individual studies of representative populations of cardiac surgery patients using assays that specifically detect NGAL in its monomeric form are required. [ABSTRACT FROM AUTHOR]

Background: Resting-state EEG microstates are thought to reflect brief activations of several interacting components of resting-state brain networks. Surprisingly, we still know little about the role of these microstates in migraine. In the present study, we attempted to address this issue by examining EEG microstates in patients with migraine without aura (MwoA) during the interictal period and comparing them with those of a group of healthy controls (HC). Methods: Resting-state EEG was recorded in 61 MwoA patients (50 females) and 66 HC (50 females). Microstate parameters were compared between the two groups. We computed four widely identified canonical microstate classes A-D. Results: Microstate classes B and D displayed higher time coverage and occurrence in the MwoA patient group than in the HC group, while microstate class C exhibited significantly lower time coverage and occurrence in the MwoA patient group. Meanwhile, the mean duration of microstate class C was significantly shorter in the MwoA patient group than in the HC group. Moreover, among the MwoA patient group, the duration of microstate class C correlated negatively with clinical measures of headache-related disability as assessed by the six-item Headache Impact Test (HIT-6). Finally, microstate syntax analysis showed significant differences in transition probabilities between the two groups, primarily involving microstate classes B, C, and D. Conclusions: By exploring EEG microstate characteristics at baseline we were able to explore the neurobiological mechanisms underlying altered cortical excitability and aberrant sensory, affective, and cognitive processing, thus deepening our understanding of migraine pathophysiology. [ABSTRACT FROM AUTHOR]

Infections with parasitic helminths cause severe debilitating and sometimes lethal diseases in humans and domestic animals on a global scale. Unable to synthesize de novo their own fatty acids and sterols, helminth parasites (nematodes, trematodes, cestodes) rely on their hosts for their supply. These organisms produce and secrete a wide range of lipid binding proteins that are, in most cases, structurally different from the ones found in their hosts, placing them as possible novel therapeutic targets. In this sense, a lot of effort has been made towards the structure determination of these proteins, but their precise function is still unknown. In this review, we aim to present the current knowledge on the functions of LBPs present in parasitic helminths as well as novel members of this highly heterogeneous group of proteins. [ABSTRACT FROM AUTHOR]

Chronic diseases, as stated by the WHO, are a threat to human health which kill 3 out of every 5 people worldwide. Therapeutics for such illnesses can be developed using traditional medicine. However, it is not an easy path from natural products to Western pharmacological and pharmaceutical methods. For several decades, chronic inflammatory disorders, especially in Westernized countries, have increased incidence and prevalence. Several NSAIDs are used to decrease inflammation and pain; however, there are numerous negative consequences of these anti-inflammatory medications, whereas plant-based natural products have anti-inflammatory therapeutic benefits that have little or no adverse effects. Nanoparticles are a new type of drug delivery device that may be designed to provide excellent target selectivity for certain cells and tissues while also having a high drug loading capacity, resulting in better pharmacokinetics, pharmacodynamics (PKPD), and therapeutic bioavailability. The size and polarity of phytochemical compounds make it hard to pass the blood–brain barrier (BBB), blood-vessel endothelial lining, gastrointestinal tract and mucosa. In addition, the gastrointestinal system is enzymatically destroyed. Therefore, nanoparticles or nanocrystals might also be used for encapsulation or conjugation of these chemicals as a method to improve their organic effectiveness through their gastrointestinal stability, absorption rate and dispersion. The therapy of numerous inflammatory illnesses, including arthritis, gastritis, Nephritis, Hepatitis (Type A, B &C), ulcerative colitis, Alzheimer's disease, atherosclerosis, allergic responses (asthma, eczema) or autoimmune disorders, is characterised by nanoparticles. This review paper provides information on the numerous nanosystem described with their probable mechanism to treat chronic inflammatory diseases. [ABSTRACT FROM AUTHOR]

Background: Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease that ultimately leads to cirrhosis and hepatocellular carcinoma. Intermittent fasting has been proposed as a nonpharmacological dietary approach against metabolic diseases, including NAFLD. In this study, we aimed to investigate the effect of alternate day fasting (ADF) on high-fat diet (HFD)-induced NAFLD in C57BL/6 mice. Methods: A mouse model of fatty liver disease was established by feeding the mice a HFD for 16 weeks. The mice were administered by body weight, lipid accumulation and inflammation. PPARα, FGF21, serum triglycerides (TG), total cholesterol (TC), transaminase and lipogenesis were assessed. Results: The results showed that long-term ADF can attenuate fatty liver disease by reducing hepatic inflammation and lipid accumulation in a mouse model. Meanwhile, fasting elevated the expression of serum and hepatic fibroblast growth Factor 21 (Fgf21), a circulating hormone produced predominantly in the liver, and could effectively prevent and ameliorate the pathogenesis of NAFLD. Serum starvation also enhanced Fgf21 expression and reduced free fatty acid (FFA)-induced lipid storage in hepatocytes. Moreover, refeeding inhibited the increase in Fgf21 expression induced by fasting. This fasted-to-refed transition is closely related to the expression of Fgf21. Further in vitro and in vivo studies showed that fasting-sensitive PPARα is indispensable for the expression of Fgf21 and its protective effect on NAFLD. Conclusion: These findings indicated that long-term ADF protects mouse livers against HFD induced fatty liver disease through controlling PPARα/Fgf21 signaling. In conclusion, ADF can emerge as a non-pharmacological dietary approach against fatty liver disease. [ABSTRACT FROM AUTHOR]

Human activities follow daily, weekly, and seasonal rhythms. The emergence of these rhythms is related to physiology and natural cycles as well as social constructs. The human body and its biological functions undergo near 24-h rhythms (circadian rhythms). While their frequencies are similar across people, their phases differ. In the chronobiology literature, people are categorized into morning-type, evening-type, and intermediate-type groups called chronotypes based on their tendency to sleep at different times of day. Typically, this typology builds on carefully designed questionnaires or manually crafted features of time series data on people's activity. Here, we introduce a method where time-stamped data from smartphones are decomposed into components using non-negative matrix factorization. The method does not require any predetermined assumptions about the typical times of sleep or activity: the results are fully context-dependent and determined by the most prominent features of the activity data. We demonstrate our method by applying it to a dataset of mobile phone screen usage logs of 400 university students, collected over a year. We find four emergent temporal components: morning activity, night activity, evening activity and activity at noon. Individual behavior can be reduced to weights on these four components. We do not observe any clear categories of people based on the weights, but individuals are rather placed on a continuous spectrum according to the timings of their phone activities. High weights for the morning and night components strongly correlate with sleep and wake-up times. Our work points towards a data-driven way of characterizing people based on their full daily and weekly rhythms of activity and behavior, instead of only focusing on the timing of their sleeping periods. [ABSTRACT FROM AUTHOR]

The pregnane X receptor (PXR) is a nuclear receptor that plays an important role in regulating the expression of biotransformation and metabolism enzymes, as well as transporter proteins. There are contradictory data in the literature on the effect of oxidative stress on the amount of PXR. The purpose of this study was to evaluate the effect of oxidative stress on the functioning of PXR. The work was performed on the Caco-2 cell line. Oxidative stress was modeled with hydrogen peroxide at concentrations of 0.1, 0.5, 1, 5, 10, 50, and 100 μM and incubation duration of 3, 24, and 72 h. The amount of PXR was estimated by Western blot method. H2O2 at all concentrations during incubation for 3 h did not significantly affect the amount of PXR. An increase in the exposure up to 24 h at prooxidant concentrations of 10, 50, and 100 μM led to an increase in the amount of PXR, which was combined with an increase in the content of lipid peroxidation products (LPPs). Continued exposure to hydrogen peroxide for up to 72 h was accompanied by an increase in the concentration of LPPs and a decrease in the amount of PXR to control values (at the H2O2 concentration of 10 μM) or below it (at H2O2 concentrations of 50 and 100 μM). Incubation of the cells with malonic dialdehyde, the final product of lipid peroxidation, at a concentration of 10 μM for 24 h led to an increase in the amount of PXR. Thus, exposure to hydrogen peroxide for 24 h led to an increase in the amount of PXR and was associated with the inducing effect of LPPs. An increase in the exposure to 72 h leveled this inducing effect. [ABSTRACT FROM AUTHOR]

Amniotic membrane (AM) is a biological tissue that surrounds the fetus in the mother's womb. It has pluripotent cells, immune modulators, collagen, cytokines with anti-fibrotic and anti-inflammatory effect, matrix proteins, and growth factors. In spite of the biological characteristics, some results have been released in preventing the adhesion on traumatized surfaces. Application of the AM as a scaffold is limited due to its low biomechanical resistance and rapid biodegradation. Therefore, for using the AM during surgery, its modification by different methods such as cross-linking of the membrane collagen is necessary, because the cross-linking is an effective way to reduce the rate of biodegradation of the biological materials. In addition, their cross-linking is likely an efficient way to increase the tensile properties of the material, so that they can be easily handled or sutured. In this regard, various methods related to cross-linking of the AM subsuming the composite materials, physical cross-linking, and chemical cross-linking with the glutraldehyde, carbodiimide, genipin, aluminum sulfate, etc. are reviewed along with its advantages and disadvantages in the current work. [ABSTRACT FROM AUTHOR]

Kidney exchange is among the effective methods that may permanently supply an important platform for incompatible donor-candidate pairs to exchange organs to achieve mutual benefit and guarantee treatment to people with kidney failure. However, building a dynamic model for Kidney Paired Exchange has become an increasingly urgent issue for augmenting the number of available kidneys in the field of organ transplantation. There has not been made a lot of research on the kidney exchange problem in a dynamic situation. Mathematically, maximizing the possible kidney exchanges for a given pool can be considered as an optimization problem and has attracted the attention of the community of researchers in the past few years. Thus, optimization approaches, like natural-inspired algorithms, can help Kidney paired exchange in defining which transplants should be made among all incompatible pairs according to some objectives. In this paper, a new natural stochastic-based algorithm called a Multiverse Optimizer is introduced to develop advanced dynamic approaches for kidney paired exchange. The objective of the proposed approach is to maximize the number of feasible cycles and chains among the pool pairs over time. The effectiveness of the proposed method is confirmed by providing the best performance compared to the results of genetic and antlion algorithms which are the only stochastic-based optimization algorithms applied to the kidney exchange. Furthermore, we applied more stochastic-based optimization algorithms for Kidney paired exchange to confirm the overall performance superiority of our proposed method. The performance of the proposed method in a dynamic situation demonstrates the competitiveness of the proposed method. [ABSTRACT FROM AUTHOR]

Given the concerns raised regarding the effects of prenatal exposure to methadone and buprenorphine on the developmental outcomes of the children, this study assessed mental health and use of services in a national sample of school-aged children (N = 78) born to women enrolled in opioid maintenance treatment during pregnancy, compared with a group of foster children (N = 140). The majority of the opioid-exposed children lived with their birth parent(s) at the time of assessment (N = 62), while 16 lived in foster homes. Caregivers completed the Strengths and Difficulties Questionnaire (SDQ) and the Reactive Attachment Disorder scale. Teachers completed the SDQ. Three kinds of services were included in measuring service use: school-based education services, child mental health services, and hospital-based habilitation services. The main finding of the study is that children prenatally exposed to methadone or buprenorphine living with their family of origin had significantly better mental health status than their foster-placed counterparts and that of the comparison group of foster children. In addition, the exposed children living at home had less child welfare involvement, and only half of them were using any of the three services measured. The odds for using services increased significantly in accordance with increasing mental health problems, independent of group affiliation, indicating a need-based access to services. In line with other studies, we found that the odds for using one or more services was 2.3 times greater for boys than for girls. Our results contribute to a more-nuanced understanding of the developmental outcomes of prenatal exposure to methadone and buprenorphine, and factors associated with increased service use in groups of at-risk children. [ABSTRACT FROM AUTHOR]

The effect of lithium chloride (LiCl) on the dose–response performance of the N-(3-methoxypropyl)acrylamide polymer-gel dosimeter (NMPAGAT) was studied for 3-D dose measurements. The NMPAGAT-LiCl dosimeters were irradiated for various doses using a 6 MV medical linear accelerator. A 0.5 Tesla nuclear magnetic resonance (NMR) instrument was used to scan the signal development of the irradiated dosimeters in terms of the spin–spin relaxation rate (R2 = 1/T2) of hydrogen protons within the water molecule. The results show that the R2 dose–response of NMPAGAT-LiCl gels improved with increasing the concentration of LiCl. The R2 sensitivity of dosimeter with a concentration of 1000 mM LiCl was 4 times higher than the same gel without LiCl in the range dose–response of 0–4 Gy. In addition, no significant effects were introduced to the LiCl gel formulation by varying the dose rate and photon energy. R2 of the gel dosimeter was not affected by changing irradiation temperature in the range of 15–25 °C. The dose–response decreased with increasing scanning temperature and was stable for up to 4 days after irradiation. [ABSTRACT FROM AUTHOR]

Proper evaluation of water quality is pertinent to estuarine habitat restoration. Identifying the degrading factors of the water environment and predicting the trend of eutrophication are key to restore the habitat. Through trophic level index (TLI), water quality index (WQI), modified Nemerow pollution index (NPI), and the Random Forest (RF) model, water samples collected from various estuaries of Taihu Lake from 2017 to 2019 were evaluated. To predict the water quality development, four scenarios were set viz. S1: add or remove an ecological buffer, S2: increase or reduce the external nutrients, S3: open or close the dam/gate, and S4: increase or decrease the internal release. In Wuli Lake, the nutrient concentrations in the river regions were higher than in the lake regions, while a contrary trend was observed in Gonghu Bay. The estuarine water quality in the dry season (WQI = 40.91, NPI = 1.73) was merely worse than that in the wet season (WQI = 47.27, NPI = 1.67). On the other hand, the eutrophic status in the wet season (TLIWet = 57.93) was worse than that in the dry season (TLIDry = 57.23). The estuarine water quality of Taihu Lake has improved from 2017 to 2019 but still belongs to medium level. The principal component analysis (PCA) revealed that dam construction, land use types, unstable hydrodynamic conditions, and trumpet-shaped estuary were the main factors that aggravated the water quality degradation. The RF model has strong forecasting capabilities for estuarine water quality. When the estuaries are close to residential and industrial districts, controlling the surface runoff and improving sewage treatment efficiency are the most effective measures to improve the water quality. In the estuaries, the sediments are usually disturbed by the wind-waves. Conclusively, reducing sediment disturbance and internal contamination accumulation via biological and engineering measures is the key to estuarine restoration. [ABSTRACT FROM AUTHOR]

Over the past few years, it has become standard to describe brain anatomical and functional organisation in terms of complex networks, wherein single brain regions or modules and their connections are respectively identified with network nodes and the links connecting them. Often, the goal of a given study is not that of modelling brain activity but, more basically, to discriminate between experimental conditions or populations, thus to find a way to compute differences between them. This in turn involves two important aspects: defining discriminative features and quantifying differences between them. Here we show that the ranked dynamical stability of network features, from links or nodes to higher-level network properties, discriminates well between healthy brain activity and various pathological conditions. These easily computable properties, which constitute local but topographically aspecific aspects of brain activity, greatly simplify inter-network comparisons and spare the need for network pruning. Our results are discussed in terms of microstate stability. Some implications for functional brain activity are discussed. [ABSTRACT FROM AUTHOR]

Background: Lupus erythematosus is an autoimmune disease that causes damage to multiple organs ranging from skin lesions to systemic manifestations. Cutaneous lupus erythematosus (CLE) is a common type of lupus erythematosus (LE), but its molecular mechanisms are currently unknown. The study aimed to explore changes in the gene expression profiles and identify key genes involved in CLE, hoping to uncover its molecular mechanism and identify new targets for CLE. Method: We analyzed the microarray dataset (GSE109248) derived from the Gene Expression Omnibus (GEO) database, which was a transcriptome profiling of CLE cutaneous lesions. The differentially expressed genes (DEGs) were identified, and the functional annotation of DEGs was performed with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Protein–protein interaction (PPI) network was also constructed to identify hub genes involved in CLE. Result: A total of 755 up-regulated DEGs and 405 down-regulated DEGs were identified. GO enrichment analysis showed that defense response to virus, immune response, and type I interferon signaling pathway were the most significant enrichment items in DEGs. The KEGG pathway analysis identified 51 significant enrichment pathways, which mainly included systemic lupus erythematosus, osteoclast differentiation, cytokine-cytokine receptor interaction, and primary immunodeficiency. Based on the PPI network, the study identified the top 10 hub genes involved in CLE, which were CXCL10, CCR7, FPR3, PPARGC1A, MMP9, IRF7, IL2RG, SOCS1, ISG15, and GSTM3. By comparison between subtypes, the results showed that ACLE had the least DEGs, while CCLE showed the most gene and functional changes. Conclusion: The identified hub genes and functional pathways found in this study may expand our understanding on the underlying pathogenesis of CLE and provide new insights into potential biomarkers or targets for the diagnosis and treatment of CLE. Key Points • The bioinformatics analysis based on CLE patients and healthy controls was performed and 1160 DEGs were identified • The 1160 DEGs were mainly enriched in biological processes related to immune responses, including innate immune response, type I interferon signaling pathway, interferon-γ-mediated signaling pathway, positive regulation of T cell proliferation, regulation of immune response, antigen processing, and presentation via MHC class Ib and so on • KEGG pathway enrichment analysis indicated that DEGs were mainly enriched in several immune-related diseases and virus infection, including systemic lupus erythematosus, primary immunodeficiency, herpes simplex infection, measles, influenza A, and so on • The hub genes such as CXCL10, IRF7, MMP9, CCR7, and SOCS1 may become new markers or targets for the diagnosis and treatment of CLE [ABSTRACT FROM AUTHOR]

Psychological science has spent many years attempting to understand the impact of new technology on people and society. However, the frequent use of self-report methods to quantify patterns of usage struggle to capture subtle nuances of human–computer interaction. This has become particularly problematic for devices like smartphones that are used frequently and for a variety of purposes. While commercial apps can provide an element of objectivity, these are 'closed' and cannot be adapted to deliver a researcher-focused 'open' platform that allows for straightforward replication. Therefore, we have developed an Android app that provides accurate, highly detailed, and customizable accounts of smartphone usage without compromising participants' privacy. Further recommendations and code are provided to assist with data analysis. All source code, materials, and data are freely available (see links in supplementary materials section). [ABSTRACT FROM AUTHOR]

The Xuancheng ore district is a newly discovered ore district within the Middle-Lower Yangtze River Metallogenic Belt (MYRMB) of Eastern China. Here we investigated the major and trace element concentrations of apatite crystallizes in ore-related intrusions from three skarn deposits with distinctive metal endowments in this region to further reveal their implications for petrogenesis, metallogenesis, and potential for polymetallic mineralization. The studied apatite samples identified as fluorapatite, display identical contents of F (2.04–3.25 wt%), whereas distinctive variations of Cl (0.04–1.42 wt%). The different correlations between Sr contents and (La/ Yb)N, (La/Sm)N, and (Sm/Yb)N reflect the differentiation process of the magma evolution in the Xuancheng area. Furthermore, the negative Eu/Eu* and Ce/Ce* correlation, and high log fO2 values (−10.02 to −17.40) of apatite studied, further indicate more oxidized and moderate oxidized environments. Apatite chemistry is characterized by LREE enriched patterns and has high (La/Yb)N ratios with a moderate negative Eu anomaly, suggesting that these plutons originated from enriched mantle mixing with various degrees of crustal components. Meanwhile, the visible differences in apatites among skarn Cu fertile, Cu-Mo fertile, and Cu-W fertile plutons were attributed to distinctive source affinities that ultimately control their metal endowments. Also, our study demonstrates that the Cl, F/Cl, and Eu/Eu* ratios in apatite can act as powerful pointers for ore varieties and mineral exploration. [ABSTRACT FROM AUTHOR]

Supraventricular tachycardia (SVT) is considered the most common cause of arrhythmia in children and infants. Regarding the likelihood of a spontaneous resolution of SVTs during the first years of life, drug treatment aims to bridge the time until children 'grow out' out of the arrhythmia. The choice of antiarrhythmic agents and the planning of maintenance therapy are mainly based on clinical experience and retrospective single- and multi-institutional analyses and databases from all over the world approaching differently to this topic. The current study aimed to evaluate the clinical course, pharmacological treatment strategies, and constellations of risk for recurrences in the management of SVTs in children aged 3 < years. The database of the Heart Center Leipzig, Department of Pediatric cardiology, was searched for pediatric patients aged < 3 years with a clinically documented SVT between 2000 and 2019 that received pharmacologic treatment. Patients with complex congenital heart disease or arrhythmias following cardiac surgery were excluded. 69 patients were included. Pharmacologic treatment, follow-up schedule, recurrences, outcomes, and risk factors for complicated courses are reported. Drug therapy of SVTs in young children remains a controversial topic with heterogeneous treatment and follow-up strategies applied. Risk factors for recurrences and/or stubborn clinical courses are difficult rhythm control with 3 or more antiarrhythmic drugs, ectopic atrial tachycardias, and a first occurrence of the SVT in the fetal period. Prospective studies are needed to sufficiently evaluate optimal treatment strategies. [ABSTRACT FROM AUTHOR]

A novel low toxic normoxic polymer gel dosimeter containing acrylic acid monomer is prepared and characterized for dosimetry in radiotherapy. Gel samples were fabricated under normal atmospheric conditions. The gels were irradiated to different doses using a medical linear accelerator at 6 MV X-ray energy to investigate the dose response and other characteristics. The dose response was evaluated in terms of relaxation rate using NMR relaxometry, which was carried out using a 0.5 T NMR technique. The sample temperature during the NMR relaxometry was fixed at 20.0 ± 0.1 °C using a thermostatic circulating water bath connected to the NMR relaxometry. A significant improvement in the performance of the dosimeter was noticed for acrylic acid gel with the addition of MgCl2 salt. The sensitivity of gel with 0.6 M MgCl2 was about 4.6 times of the same gel without MgCl2. The total uncertainty of the R2 measurements was about 5%. Different important parameters such as dose rate, beam quality, NMR scanning temperature, and stability of the dose response were investigated in this study. [ABSTRACT FROM AUTHOR]

In bacteria and other microorganisms, the cells within a population often show extreme phenotypic variation. Different species use different mechanisms to determine how distinct phenotypes are allocated between individuals, including coordinated, random, and genetic determination. However, it is not clear if this diversity in mechanisms is adaptive—arising because different mechanisms are favoured in different environments—or is merely the result of non-adaptive artifacts of evolution. We use theoretical models to analyse the relative advantages of the two dominant mechanisms to divide labour between reproductives and helpers in microorganisms. We show that coordinated specialisation is more likely to evolve over random specialisation in well-mixed groups when: (i) social groups are small; (ii) helping is more "essential"; and (iii) there is a low metabolic cost to coordination. We find analogous results when we allow for spatial structure with a more detailed model of cellular filaments. More generally, this work shows how diversity in the mechanisms to produce phenotypic heterogeneity could have arisen as adaptations to different environments. In microorganisms, the cells within a population often show extreme phenotypic variation with different mechanisms used to determine how distinct phenotypes are allocated. This study uses theoretical models to examine the relative advantages of the two dominant mechanisms, coordinated and random determination, in dividing labour between reproductives and helpers in microorganisms. [ABSTRACT FROM AUTHOR]

Phytoestrogens are naturally plant-derived compounds that could bind to estrogen receptors and mimic estrogenic effects. Previous studies showed a positive association between phytoestrogens and hypothyroidism; however, little is known on phytoestrogens and thyroid hormones. This study was designed to investigate the associations between urinary phytoestrogens and thyroid hormone levels. Based on the US National Health and Nutrition Examination Survey (NHANES) 2007–2010, 4103 participants were recruited in this cross-sectional study. Linear regression models and multiple linear regressions models were applied to examine the relationships between urinary phytoestrogens and thyroid hormone levels. Urinary O-desmethylangolensin (O-DMA) was found to be correlated with serum FT4 levels in the female 20–60-year-of-age group (β=0.018, 95% CI: 0.006, 0.031). Higher enterolactone (ENT) levels were significantly positively associated with TSH levels in the 12–19-year-of-age female group (β=0.196, 95% CI: 0.081, 0.311). In the male group, enterodiol (END) was significantly positively correlated with TSH and TT3 in the 12–19-year-of-age group, respectively (TT3: β=3.444, 95% CI: 0.150, 6.737; TSH: β=0.104, 95% CI: 0.005, 0.203). However, equol (EQU) levels were negatively associated with TT4 (12–19-year-of-age: β=− 0.166, 95% CI: − 0.279, − 0.034; 20–60-year-of-age: β=− 0.132, 95% CI: − 0.230, − 0.034). Our study provided epidemiological evidence that urinary phytoestrogens were powerfully associated with thyroid hormone levels. The results also supported that phytoestrogens acted as endocrine disruptors. It is imperative and important to pay attention to the intake of phytoestrogens. [ABSTRACT FROM AUTHOR]

The quantification of supramolecular host–guest interactions is important for finely modulating supramolecular systems. Previously, most host–guest interactions quantified using force spectroscopic techniques have been reported in force units. However, accurately evaluating the adhesion energies of host–guest pairs remains challenging. Herein, using a surface forces apparatus, we directly quantify the interaction energies between cyclodextrin (CD)-modified surfaces and ditopic adamantane (DAd) molecules in water as a function of the DAd concentration and the CD cavity size. The adhesion energy of the β-CD–DAd complex drastically increased with increasing DAd concentration and reached saturation. Moreover, the molecular adhesion energy of a single host–guest inclusion complex was evaluated to be ~9.51 kBT. This approach has potential for quantifying fundamental information toward furthering the understanding of supramolecular chemistry and its applications, such as molecular actuators, underwater adhesives, and biosensors, which require precise tuning of specific host–guest interactions. Quantification of supramolecular host–guest interactions is important for modulating supramolecular systems but accurately evaluating the adhesion energies of host–guest pairs remains challenging. Here, the authors directly quantify the interaction energies between cyclodextrin modified surfaces and ditopic adamantane using a surface force apparatus. [ABSTRACT FROM AUTHOR]

The possibilities of the synthesis of nanodiamond/amorphous carbon composite structures (a-C:ND) by the pulsed mode of direct current magnetron sputtering are analyzed in the current paper. We showed that the ion-induced microarcing on the substrate surface caused the transfer of nanodiamond particles of an average size of 4.5 nm, whose size distribution is close to one of the precursor particles. According to the structural investigations carried out by transmission electron microscopy, electron diffraction, Raman spectroscopy and electron energy loss spectroscopy, the coatings with uniformly distributed nanodiamond inclusions can be obtained at a low number of discharge pulses. The particles transferred at 10 pulses preserve their luminescence properties and become encapsulated in the sp3-rich carbon matrix. However, with a higher number of pulses, graphitization and agglomeration of the particles induced by microarcing and ion irradiation are observed. [ABSTRACT FROM AUTHOR]

A convenient one-step method for the synthesis of new bisacridine derivatives, containing fragments of 5-arylisoxazoles, 4,5-dichloroisothiazole, as well as isonicotinic acid residues covalently attached by ester groups to various positions of the aromatic core, was developed. A three-component cascade condensation of 1,5-naphthalenediamine, aldehydes, and cyclic β-dicarbonyl compounds was carried out by refluxing in butanol. Quaternary ammonium salts of synthesized bisacridine derivatives were obtained. It was shown that the synthesized bisacridine compounds form complexes with palladium LPdCl2, which exhibit high catalytic activity in the model Suzuki reaction in water in the absence of organic co-solvent. [ABSTRACT FROM AUTHOR]

Innovation Management Software can promote Entrepreneurial Ecosystems by consolidating an organization's innovation programs, stakeholders, and resources in one place. In this study, we highlighted the digitalization of innovation processes. We focus particularly on the factors influencing the adoption of a specific class of software tools called Innovation Management Software (IMS) or Digital Innovation Management System to support innovation management methods and activities. Specifically, we address the two questions (a) which specific functionality drives the adoption of IMS tools, and (b) which services of IMS providers are valuable in supporting the adoption of IMS by organizations aiming to digitalize their innovation processes. By using an online questionnaire, we gathered survey data from 199 innovation managers of German firms. We used regression analysis to test our hypotheses. While the overall IMS adoption is considered to positively affect the new product development (NPD) efficiency, our results indicate that especially idea management functionalities and services for updates and upgrades improve the IMS adoption. Surprisingly, offering complementary consulting services together with IMS offerings to support the digitalization of innovation processes reduces the likelihood of IMS adoption. These findings are important for managers, consultants, and developers in order to choose and leverage the right options for improving the adoption of IT tools in the NPD process and therefore increase NPD performance and thus also promote Entrepreneurial Ecosystems. [ABSTRACT FROM AUTHOR]

Purpose: c-MYC plays an important role in regulating cellular growth and apoptosis, and it is aberrantly expressed in many human malignancies. Although c-MYC has been extensively investigated in Burkitt lymphoma and diffuse large B cell lymphoma, little has been reported in anaplastic large cell lymphoma (ALCL). The aim of this study was to investigate the expression and genetic alterations of c-MYC in primary systemic ALCL, characterize its clinicopathologic features and immunophenotypes, and discuss their implications in prognosis. Methods: Tissue microarrays using samples from 85 ALCL patients were used to evaluate expression of c-MYC and anaplastic lymphoma kinase (ALK). c-MYC and ALK genetic alterations were detected using fluorescence in situ hybridization. The Kaplan–Meier and multivariate Cox regression methods were used for survival analysis. Results: c-MYC was expressed in 24 of 85 samples (28.2%), and ALK was expressed in 54 (63.5%). c-MYC and ALK were co-expressed in 16 samples (18.8%). c-MYC expression and c-MYC and ALK co-expression increased with ALCL clinical stages and the International Prognostic Index (IPI) score (p < 0.05). Fifty of the samples (58.8%) had ALK rearrangement, and 18 (22.1%) had aneuploidy. c-MYC rearrangement was not detected, but aneuploidy was observed in 19 cases (22.4%). c-MYC aneuploidy was significantly different based on c-MYC expression and the IPI score (p < 0.05). c-MYC was a significant independent prognostic factor for progression-free survival and overall survival in patients with ALCL. Conclusion: c-MYC protein expression and c-MYC aneuploidy could predict worse survival in patients with ALCL. [ABSTRACT FROM AUTHOR]

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Objective: Treatment of implants with peri-implantitis is often unsuccessful due to residual microbial biofilm hindering re-osseointegration. The aim of this study was to treat biofilm-grown titanium (Ti) implants with different modalities involving air abrasion (AA) and cold atmospheric plasma (CAP) to compare the effectiveness in surface decontamination and the alteration/preservation of surface topography. Materials and methods: Saliva collected from a peri-implantitis patient was used to in vitro develop human biofilm over 35 implants with moderately rough surface. The implants were then mounted onto standardized acrylic blocks simulating peri-implantitis defects and treated with AA (erythritol powder), CAP in a liquid medium, or a combination (COM) of both modalities. The remaining biofilm was measured by crystal violet (CV). Surface features and roughness before and after treatment were assessed by scanning electron microscope (SEM). The data were statistically analyzed using Kruskal-Wallis followed by Tukey's multiple comparison test. Results: In the present peri-implantitis model, the human complex biofilm growth was successful as indicated by the statistical significance between the negative and positive controls. All the treatment groups resulted in a remarkable implant surface decontamination, with values very close to the negative control for AA and COM. Indeed, statistically significant differences in the comparison between the positive control vs. all the treatment groups were found. SEM analysis showed no post-treatment alterations on the implant surface in all the groups. Conclusions: Decontamination with AA delivering erythritol with or without CAP in liquid medium demonstrated compelling efficacy in the removal of biofilm from implants. All the tested treatments did not cause qualitative alterations to the Ti surface features. No specific effects of the CAP were observed, although further studies are necessary to assess its potential as monotherapy with different settings or in combination with other decontamination procedures. Clinical relevance: CAP is a promising option in the treatment of peri-implantitis because it has potential to improve the elimination of bacterial plaque from implant surfaces, in inaccessible pockets or during open-flap debridement, and should stimulate the process of the re-osseointegration of affected dental implants by not altering surface features and roughness. [ABSTRACT FROM AUTHOR]

The safety and efficacy of landiolol have not been fully elucidated in pediatric patients. This study aimed to clarify the safety and efficacy of landiolol in a pediatric cohort. We retrospectively assessed the clinical features of 21 pediatric patients who were administered landiolol at our hospital. We also investigated the rates of sinus rhythm conversion and heart rate response. The median patient age was 7 months (interquartile range 1–13 months). The etiology of tachyarrhythmia was junctional ectopic tachycardia in 10 patients (47.6%), atrial tachycardia in 10 patients (47.6%), and ventricular tachycardia in 1 patient (4.8%). Of the 21 children, 18 (85.7%) had congenital heart defects, including 14 (77.8%) in whom a landiolol infusion was performed perioperatively. The landiolol infusion was effective in 18 pediatric patients (85.7%), as measured by the conversion to sinus rhythm or a reduced heart rate. Atrial tachycardia in the perioperative period was terminated in all patients. Of 7 patients with tachyarrhythmias unrelated to the perioperative period, landiolol was effective in 5. No adverse effects were reported in any patient. Landiolol infusion is effective and safe in pediatric patients with tachyarrhythmia of various etiologies, especially those with atrial tachyarrhythmia during the perioperative period. [ABSTRACT FROM AUTHOR]

The impact of lithium chloride inorganic salt (LiCl) on the response of radiated N-(Hydroxymethyl) acrylamide (NHMA) polymer gel dosimeters was presented in this article. The NHMA-LiCl polymer dosimeters were positioned in a cubic water-phantom and then irradiated by a linac to different dose ranging from 0 to 10 Gy. The response of gel to X-ray radiation was evaluated using NMR spin–spin relaxation rate (R2 = 1/T2). Linearity relationship of dose–response s were obtained in the dose-range of 0–6 Gy. The polymer showed a significant increase in dose-sensitivity (about 50%) when LiCl concentration was increased from 0 to 2.1wt% in the linearity region of 0–6 Gy. The dependency of irradiated gel on the dose rate and the photon beam energy were not observed by adding LiCl over the range studied (less than 5%). The R2 values were decreased with increasing the scanning temperature. The gel was fairly stable after four days of irradiation. The LiCl acts as an excellent sensitizer to the polymerization of irradiated gel dosimeters. [ABSTRACT FROM AUTHOR]

Fuchs endothelial corneal dystrophy (FECD) is one of the main causes for corneal endothelial blindness, which is characterized by the progressive decline of corneal endothelial cells. Poly (ADP-ribose) polymerase (PARP) was reported to be involved in cell death and apoptosis of several diseases. However, the role of PARP1 in the progression of FECD remains elusive. In the present study, we reported that UVA irradiation caused the corneal endothelial damage and corneal edema in mice, which was accompanied with the elevated activity of PARP1 and PAR. The PARP1 inhibitor PJ34 resolved the corneal edema and protected corneal endothelium from UVA-induced oxidative damage, mitochondrial dysfunction, and cell apoptosis. Mechanistically, PARP1 inhibition exerted its anti-apoptotic effects through downregulation of the phosphorylation levels of JNK1/2 and p38 MAPK and subsequently the increase of MKP-1. Our results suggest that PARP1 inhibition protects corneal endothelium from UVA-induced oxidative damage, which provides a potential alternative strategy for the therapy of FECD. [ABSTRACT FROM AUTHOR]

We evaluated whether and how rapidly temperate forest tree species able to stimulate or inhibit nitrification (through biological nitrification inhibition, BNI) also influence denitrifier activity and abundance in soil and identified the main determinants of changes in denitrification. A reciprocal soil core transfer approach was implemented at a long-term experimental site between Douglas fir, a species assumed to stimulate nitrification, and stands of tree species with (spruce and Nordmann fir) or without (Corsican pine and beech) BNI capacity. Sixteen months after soil transfer, potential denitrification decreased in soils transferred from Douglas fir to another tree species and increased in soil cores transferred from any species to Douglas fir. The change in denitrification was not related to the BNI capacity of the tree species 'receiving' the soil cores. Structural equation modelling revealed that in soil cores transferred between Douglas fir and BNI species, changes in denitrification were mainly correlated to nitrifier abundances, i.e. AOA and Nitrobacter, nitrification rates, and soil NO3− availability, whereas in soil cores transferred between Douglas fir and non-BNI species denitrification changes were well correlated to C availability and the abundance of nirK-harbouring denitrifiers. Overall, our results indicate that denitrification rates can change strongly and quickly following soil transfers between tree stands. Particularly, when Douglas fir replaces BNI tree species, this quickly results in both increased nitrification and denitrification rates, thus exacerbating the ensuing risk of increased NO3− leaching and N2O emission from soil. [ABSTRACT FROM AUTHOR]

We developed an enantioselective voltammetric sensor based on a carbon-paste electrode modified by enantiomorphic crystals of bromotriphenylmethane for the recognition and determination of tryptophan enantiomers. Enantiomorphic crystals of bromotriphenylmethane were obtained under the condition of Viedma ripening. The electrochemical and analytical characteristics of the sensor were studied. The proposed sensor was used to recognize and determine the enantiomers of L- and D-tryptophan in model solutions of pharmaceutical preparations and in human urine and blood plasma samples. The sensor is easy to manufacture and exhibits high reproducibility and stability. It was shown that, in using chemometric data processing, the presence of even slight differences between the voltammograms of enantiomers recorded using the proposed carbon-paste electrode is sufficient for their reliable recognition. [ABSTRACT FROM AUTHOR]

Miniaturization is one of the principal trends in the evolution of winged insects (Pterygota), in many groups of which miniature forms with body sizes comparable to those of unicellular protists have evolved independently. Microinsects are capable of active flight, the mechanics of which differs considerably from those of larger representatives of related taxa. Many miniature insects have convergently acquired wings with a narrow blade and a peripheral fan of long bristles: a condition known as ptiloptery. Due to low air permeability, the bristled wing shows almost the same aerodynamic efficiency as the membranous wing and at the same time has a much smaller mass and inertia. The unsteady aerodynamic mechanisms that provide lift during the flapping flight typical of large insects, birds, and bats are not efficient enough when viscous forces are comparable to inertial forces. Correspondingly, miniature insects use the rowing type of flight, during which the wings move with high angles of attack, and a significant part of the aerodynamic force is generated by their drag. The study of the locomotion of miniature insects is not only essential for understanding their biology, but also poses new problems in the field of motion mechanics at ultralow Reynolds numbers. Data on the structure and functional morphology of the wings of miniature insects and the mechanics of their flight have been actively accumulated in recent years. The available publications on the issue are covered in this review. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to estimate the prevalence of pain, the extent of analgesics intake and the mental health status of German pre-hospital emergency medical service (EMS) personnel. Methods: We conducted a nationwide online survey, which consisted of sociodemographic and job-related items, questions on pain and analgesics intake and the short-version of the validated Depression–Anxiety–Stress Scale (DASS-21). Results: A total of 774 EMS personnel with a mean age of 33.03 (standard error [SE] 0.37) years were included into the final analysis of which 23.77% were female. Pain was reported by 58.64% (454 of 774) of the study participants with 10.72% (95% confidence interval [CI] 8.54%; 13.29%) suffering from chronic, 1.68% (95% CI 0.89%; 2.87%) from acute and 46.25% (95% CI 41.49%; 51.30%) from recurrent pain, respectively. Most frequent location of pain was lumbar spine. Analgesics were used by 52.76% (239 of 454) of pre-hospital EMS personnel with pain (acute 76.92% / chronic 69.88% / recurrent 47.90%). Moreover, participants with chronic and recurrent pain indicated significantly higher depression (p ≤ 0.001), anxiety (p ≤ 0.001), and stress (p ≤ 0.001) levels compared to those without pain, respectively. Conclusion: This study indicates a high prevalence of pain and analgesics usage in participating German pre-hospital EMS personnel and a poorer mental health in those with chronic and recurrent pain. Therefore, disease prevention and health promotion measures are needed to preserve health of pre-hospital EMS personnel. [ABSTRACT FROM AUTHOR]

The article presents a case-study of a 25-year-old patient, who was referred for the investigation of polyglobulia. Sequence analysis of the erythropoietin receptor (EPO-R) gene was performed, which showed a mutation in exon 8. The patient with low-dose aspirin and phlebotomies to achieve a hematocrit of less than 55 percent. It also discusses primary congenital erythrocytosis, which is associated with low erythropoietin levels and results from mutations in EPO-R gene.

Self-learning chips to implement many popular ANN (artificial neural network) algorithms are very difficult to design. We explain why this is so and say what lessons previous work teaches us in the design of self-learning systems. We offer a contribution to the “biologically-inspired” approach, explaining what we mean by this term and providing an example of a robust, self-learning design that can solve simple classical-conditioning tasks. We give details of the design of individual circuits to perform component functions, which can then be combined into a network to solve the task. We argue that useful conclusions as to the future of on-chip learning can be drawn from this work. [ABSTRACT FROM AUTHOR]

Viruses need cells for their replication and, therefore, ways to hijack cellular functions. Mitochondria play fundamental roles within the cell in metabolism, immunity and regulation of homeostasis due to which some viruses aim to alter mitochondrial functions. Herein we show that the nucleoprotein (NP) of arenaviruses enters the mitochondria of infected cells, affecting the mitochondrial morphology. Reptarenaviruses cause boid inclusion body disease (BIBD) that is characterized, especially in boas, by the formation of cytoplasmic inclusion bodies (IBs) comprising reptarenavirus NP within the infected cells. We initiated this study after observing electron-dense material reminiscent of IBs within the mitochondria of reptarenavirus infected boid cell cultures in an ultrastructural study. We employed immuno-electron microscopy to confirm that the mitochondrial inclusions indeed contain reptarenavirus NP. Mutations to a putative N-terminal mitochondrial targeting signal (MTS), identified via software predictions in both mamm- and reptarenavirus NPs, did not affect the mitochondrial localization of NP, suggesting that it occurs independently of MTS. In support of MTS-independent translocation, we did not detect cleavage of the putative MTSs of arenavirus NPs in reptilian or mammalian cells. Furthermore, in vitro translated NPs could not enter isolated mitochondria, suggesting that the translocation requires cellular factors or conditions. Our findings suggest that MTS-independent mitochondrial translocation of NP is a shared feature among arenaviruses. We speculate that by targeting the mitochondria arenaviruses aim to alter mitochondrial metabolism and homeostasis or affect the cellular defense. [ABSTRACT FROM AUTHOR]

Background: The MIDAS is the most used questionnaire to evaluate migraine-related disability, but its utility to assess treatment response remains unclear. Our aim was to estimate the MIDAS' minimal important change (MIC) value and its responsiveness. Methods: A total of 103 patients were enrolled in a non-pharmacological, preference-based clinical trial. MIDAS and global rating of self-perceived change (GRoC) scores were collected at baseline, after 5 weeks of treatment, 4-weeks and 3-months follow-up after treatment. Anchor-based approaches were used to establish MIC values and responsiveness. Findings: In all 3 timepoint comparisons, MIDAS presented a MIC of 4.5 points. A moderate positive correlation was identified between the MIDAS change and GRoC scores. The area under the curve ranged from 0.63 to 0.68. Conclusions: This study showed that MIDAS has a limited responsiveness to change. A change of 4.5 points or more represents a clinically important change for patients with high frequent migraine and chronic migraine receiving non-pharmacological treatment. [ABSTRACT FROM AUTHOR]

We study combinatorial structures in large-scale mixed-integer (nonlinear) programming problems arising in gas network optimization. We propose a preprocessing strategy exploiting the observation that a large part of the combinatorial complexity arises in certain subnetworks. Our approach analyzes these subnetworks and the combinatorial structure of the flows within these subnetworks in order to provide alternative models with a stronger combinatorial structure that can be exploited by off-the-shelve solvers. In particular, we consider the modeling of operation modes for complex compressor stations (i.e., ones with several in- or outlets) in gas networks. We propose a refined model that allows to precompute tighter bounds for each operation mode and a number of model variants based on the refined model exploiting these tighter bounds. We provide a procedure to obtain the refined model from the input data for the original model. This procedure is based on a nontrivial reduction of the graph representing the gas flow through the compressor station in an operation mode. We evaluate our model variants on reference benchmark data, showing that they reduce the average running time between 10% for easy instances and 46% for hard instances. Moreover, for three of four considered networks, the average number of search tree nodes is at least halved, showing the effectivity of our model variants to guide the solver's search. [ABSTRACT FROM AUTHOR]

For the past two decades, growing research has been pointing to multiple repercussions of bisphenol A (BPA) exposure to human health. BPA is a synthetic oestrogen which primarily targets the endocrine system; however, the compound also disturbs other systemic organ functions, in which the magnitude of impacts in those other systems is as comparable to those in the endocrine system. To date, the discoveries on the association between BPA and health outcomes mainly came from animal and in vitro studies, with limited human studies which emphasised on children's health. In this comprehensive review, we summarised studies on human, in vivo and in vitro models to understand the consequences of pre-, post- and perinatal BPA exposure on the perinatal, children and adult health, encompassing cardiovascular, neurodevelopmental, endocrine and reproductive effects. Conclusion: Evidence from in vitro and animal studies may provide further support and better understanding on the correlation between environmental BPA exposure and its detrimental effects in humans and child development, despite the difficulties to draw direct causal relations of BPA effects on the pathophysiology of the diseases/syndromes in children, due to differences in body system complexity between children and adults, as well as between animal and in vitro models and humans. What is known: • Very limited reviews are available on how BPA adversely affects children's health. • Previous papers mainly covered two systems in children. What is new: • Comprehensive review on the detrimental effects of BPA on children health outcomes, including expectations on adult health outcomes following perinatal BPA exposure, as well as covering a small part of BPA alternatives. • Essentially, BPA exposure during pregnancy has huge impacts on the foetus in which it may cause changes in foetal epigenetic programming, resulting in disease onsets during childhood as well as adulthood. [ABSTRACT FROM AUTHOR]