Miracle-dz/UniFAR-FTUs huggingface dataset:
Neuroimaging in amyotrophic lateral sclerosis: current and emerging uses

ABSTRACT Introduction: Several neuroimaging techniques have been used to define in vivo markers of pathological alterations underlying amyotrophic lateral sclerosis (ALS). Growing evidence supports the use of magnetic resonance imaging (MRI) and positron emission tomography (PET) for the non-invasive detection of central nervous system involvement in patients with ALS. Areas covered: A comprehensive overview of structural and functional neuroimaging applications in ALS is provided, focusing on motor and extra-motor involvement in the brain and the spinal cord. Implications for pathogenetic models, patient diagnosis, prognosis, monitoring, and the design of clinical trials are discussed. Expert commentary: State-of-the-art neuroimaging techniques provide fundamental instruments for the detection and quantification of upper motor neuron and extra-motor brain involvement in ALS, with relevance for both pathophysiologic investigation and clinical practice. Network-based analysis of structural and functional connectivity alterations and multimodal approaches combining several neuroimaging measures are promising tools for the development of novel diagnostic and prognostic markers to be used at the individual patient level.
Development and novel therapeutics in hepatocellular carcinoma: a review

This review summarizes the epidemiological trend, risk factors, prevention strategies such as vaccination, staging, current novel therapeutics, including the drugs under clinical trials, and future therapeutic trends for hepatocellular carcinoma (HCC). As HCC is the third most common cause of cancer-related death worldwide, its overall incidence remains alarmingly high in the developing world and is steadily rising across most of the developed and developing world. Over the past 15 years, the incidence of HCC has more than doubled and it increases with advancing age. Chronic infection with hepatitis B virus is the leading cause of HCC, closely followed by infection with hepatitis C virus. Other factors contributing to the development of HCC include alcohol abuse, tobacco smoking, and metabolic syndrome (including obesity, diabetes, and fatty liver disease). Treatment options have improved in the past few years, particularly with the approval of several molecular-targeted therapies. The researchers are actively pursuing novel therapeutic targets as well as predictive biomarker for treatment of HCC. Advances are being made in understanding the mechanisms underlying HCC, which in turn could lead to novel therapeutics. Nevertheless, there are many emerging agents still under clinical trials and yet to show promising results. Hence, future therapeutic options may include different combination of novel therapeutic interventions.
Embryology of the craniocervical junction and posterior cranial fossa, part II: Embryogenesis of the hindbrain

Although pathology of the hindbrain and its derivatives can have life altering effects on a patient, a comprehensive review on its embryology is difficult to find in the peer‐reviewed medical literature. Therefore, this review article, using standard search engines, seemed timely. The embryology of the hindbrain is complex and relies on a unique timing of various neurovascular and bony elements. Derailment of these developmental processes can lead to a wide range of malformations such as the Chiari malformations. Therefore, a good working knowledge of this embryology as outlined in this review of the hindbrain is important for those treating patients with involvement of this region of the central nervous system. Clin. Anat. 31:488–500, 2018. © 2018 Wiley Periodicals, Inc.
Shape Factor’s Effect on a Dynamic Cleaners Swarm

This work discusses an impossibility result for the Dynamic Cooperative Cleaners problem, and the relation of a specific geometric feature of the problem, known as the shape factor, to the efficiency of the operating swarm. The dynamic cooperative cleaners problem assumes a grid, having “contamination” points or tiles that form a connected region of the grid. Several agents move in this contaminated region, each having the ability to “clean” the place it is located in. The ”contaminated” tiles expand deterministically, simulating a spreading of contamination, or fire. This problem, as well as a cooperative cleaning protocol for it and its analysis, were first introduced in [1]. The equivalence of this problem to another interesting multi agents problem was demonstrated in [2] by utilizing results relevant to the problem in order to design a cooperative hunting protocol for a swarm of UAVs. The results of [1] contain a generic lower bound for the cleaning time of any multi agents system which is designed to entirely clean an expanding contaminated area. This work enhances this bound, while discussing the effect of the region’s shape factor (i.e. the ratio between the region’s boundary and its area) and the swarm’s cleaning efficiency. As a result, a tighter lower bound is produced, establishing a new and more generic impossibility result for the problem.
Identification of Psychoactive Degradants of Cannabidiol in Simulated Gastric and Physiological Fluid

Abstract Introduction: In recent research, orally administered cannabidiol (CBD) showed a relatively high incidence of somnolence in a pediatric population. Previous work has suggested that when CBD is exposed to an acidic environment, it degrades to Δ9-tetrahydrocannabinol (THC) and other psychoactive cannabinoids. To gain a better understanding of quantitative exposure, we completed an in vitro study by evaluating the formation of psychoactive cannabinoids when CBD is exposed to simulated gastric fluid (SGF). Methods: Materials included synthetic CBD, Δ8-THC, and Δ9-THC. Linearity was demonstrated for each component over the concentration range used in this study. CBD was spiked into media containing 1% sodium dodecyl sulfate (SDS). Samples were analyzed using chromatography with UV and mass spectrometry detection. An assessment time of 3 h was chosen as representative of the maximal duration of exposure to gastric fluid. Results: CBD in SGF with 1% SDS was degraded about 85% after 60 min and more than 98% at 120 min. The degradation followed first-order kinetics at a rate constant of −0.031 min−1 (R2=0.9933). The major products formed were Δ9-THC and Δ8-THC with less significant levels of other related cannabinoids. CBD in physiological buffer performed as a control did not convert to THC. Confirmation of THC formation was demonstrated by comparison of mass spectral analysis, mass identification, and retention time of Δ9-THC and Δ8-THC in the SGF samples against authentic reference standards. Conclusions: SGF converts CBD into the psychoactive components Δ9-THC and Δ8-THC. The first-order kinetics observed in this study allowed estimated levels to be calculated and indicated that the acidic environment during normal gastrointestinal transit can expose orally CBD-treated patients to levels of THC and other psychoactive cannabinoids that may exceed the threshold for a physiological response. Delivery methods that decrease the potential for formation of psychoactive cannabinoids should be explored.
Local adaptive dictionary based image denoising

In this paper, the problem of balancing the noise removing and the image details preserving is considered. To remove noise adaptively, local dictionaries and sparse coding techniques are used. For a noised image patch, the local dictionary corresponding to it and the sparse coding technique are used to generate the sparse coding vector of the given patch. Then the noise of the given patch can be removed without any information on noise level by setting all components be zero but preserving largest component of the sparse coding vector. Because too much information on image details are removed with noise by the above process, a local weighted regression is adopted to refine the denoising image with the help of the information on the local geometry structure of noised image. Various experiments have been accomplished and prove our method to be effective in balancing the noise removing and the image details preserving.
Assessing Predicted HIV-1 Replicative Capacity in a Clinical Setting

HIV-1 replicative capacity (RC) provides a measure of within-host fitness and is determined in the context of phenotypic drug resistance testing. However it is unclear how these in-vitro measurements relate to in-vivo processes. Here we assess RCs in a clinical setting by combining a previously published machine-learning tool, which predicts RC values from partial pol sequences with genotypic and clinical data from the Swiss HIV Cohort Study. The machine-learning tool is based on a training set consisting of 65000 RC measurements paired with their corresponding partial pol sequences. We find that predicted RC values (pRCs) correlate significantly with the virus load measured in 2073 infected but drug naïve individuals. Furthermore, we find that, for 53 pairs of sequences, each pair sampled in the same infected individual, the pRC was significantly higher for the sequence sampled later in the infection and that the increase in pRC was also significantly correlated with the increase in plasma viral load and with the length of the time-interval between the sampling points. These findings indicate that selection within a patient favors the evolution of higher replicative capacities and that these in-vitro fitness measures are indicative of in-vivo HIV virus load.
Molecular changes during TGF β‐mediated lung fibroblast‐myofibroblast differentiation: implication for glucocorticoid resistance

Airway remodeling is an important process in response to repetitive inflammatory‐mediated airway wall injuries. This is characterized by profound changes and reorganizations at the cellular and molecular levels of the lung tissue. It is of particular importance to understand the mechanisms involved in airway remodeling, as this is strongly associated with severe asthma leading to devastating airway dysfunction. In this study, we have investigated the transforming growth factor‐β (TGFβ, a proinflammatory mediator)‐activated fibroblast to myofibroblast transdifferentiation pathway, which plays a key role in asthma‐related airway remodeling. We show that TGFβ induces fibroblast to myofibroblast transdifferentiation by the expression of αSMA, a specific myofibroblast marker. Furthermore, Smad2/Smad3 gene and protein expression patterns are different between fibroblasts and myofibroblasts. Such a change in expression patterns reveals an important role of these proteins in the cellular phenotype as well as their regulation by TGFβ during cellular transdifferentiation. Interestingly, our data show a myofibroblastic TGFβ‐mediated increase in glucocorticoid receptor (GR) expression and a preferential localization of GR in the nucleus, compared to in fibroblasts. Furthermore, the GRβ (nonfunctional GR isoform) is increased relative to GRα (functional isoform) in myofibroblasts. These results are interesting as they support the idea of a GRβ‐mediated glucocorticoid resistance observed in the severe asthmatic population. All together, we provide evidence that key players are involved in the TGFβ‐mediated fibroblast to myofibroblast transdifferentiation pathway in a human lung fibroblast cell line. These players could be the targets of new treatments to limit airway remodeling and reverse glucocorticoid resistance in severe asthma.
Chapter 4 Wine Spoilage Yeasts : Control Strategy

Traditionally in winemaking, sulphur dioxide (SO 2 ) is chemically the most widely used for microflora control as antimicrobial preservative. Other tested compounds for selective yeast control are sorbic and benzoic acids. Herein, we discuss the effectiveness and the application of traditional and novel treatments and biotechnologies for chemical and biological control of wine spoilage yeasts. The versatility of the killer toxins and the antimicrobial properties of natural compounds such as carvacrol, essential oils and bioactive peptides will be considered. Some of the wine spoilage yeasts that are intended to control belong to the genera Zygosaccharomyces, Saccharomycodes and Dekkera/Brettanomyces, but also the non-Saccharomyces yeasts species dominating the first phase of fermentation (Hanseniaspora uvarum, Hansenula anomala, Metschnikowia pulcherrima, Wickerhamomyces anomalus) and some others, such as Schizosaccharomyces pombe, depending on the kind of wine to be produced.
Weather Sentiment - Amazon Mechanical Turk dataset

Dataset re-collected using Amazon Mechanical Turk from an original dataset provided by CrowdFlower as part of the 2013 Crowdsourcing at Scale shared task challenge. The dataset contains 6000 classifications of the sentiment of 300 tweets, with gold-standard sentiment labels, provided by 110 workers. The sentiment judgements are provided in the following categories: negative (0), neutral (1), positive (2), tweet not related to weather (3) and can't tell (4). Each row contains workerID, taskID, Worker label, gold label, time spent by the worker to produce the judgment
Fetal heart size measurements as new predictors of homozygous &agr;‐thalassemia‐1 in mid‐pregnancy

OBJECTIVE To evaluate the efficacy of using fetal heart size measurements derived from axial echocardiography to predict homozygous α-thalassemia-1. DESIGN Prospective diagnostic study. SETTING The carrier rate of α-thalassemia-1 (-/αα) in China's Guangxi Zhuang Autonomous Region is approximately 15%. If both parents are carriers, the risk of homozygous α-thalassemia-1 in one pregnancy is 25%. PATIENTS Singleton mid-pregnancies at risk of homozygous α-thalassemia-1 were enrolled. OUTCOME MEASURES Fetal heart measurements, including heart diameter (HD), heart length (HL), heart circumference (HC), and heart area (HA), were measured. The z-scores for these heart parameters were then calculated separately based on previously constructed z-score models. Finally, the accuracy of these predictive variables was analyzed and compared to that achieved by cardiothoracic ratio (CTR) using a receiver operating characteristic (ROC) curves analysis. RESULTS A total of 214 singleton pregnancies were recruited. The discriminatory power of HA and HD z-scores was better (z-test P< .01) while that of HC and HL z-scores was comparable to (z-test P>.05) that of CTR. HD combined with HA z-scores had the highest sensitivity (100%), and the specificity of HD and/or HA z-scores was 100%. CONCLUSION Fetal heart size measurements are novel, effective and noninvasive predictors of homozygosity for α-thalassemia-1 in mid-pregnancy. The discriminatory power of HD and HA z-scores was better than while that of HC and HL z-scores was comparable to that of CTR. Further investigation is needed to understand the effectiveness of these predictors.
Platelets expressing IgG receptor FcγRIIA/CD32A determine the severity of experimental anaphylaxis

Platelet-derived serotonin contributes to FcγRIIA/CD32A-induced IgG-dependent anaphylaxis. Potent platelets Anaphylaxis results from inappropriate immune responses to allergens. Human platelets express the IgG receptor FcγRIIA/CD32A and release inflammatory mediators in response to their engagement, but their contribution to anaphylaxis is not well understood. Beutier et al. developed mouse models that express either human FcγRIIA/CD32A alone or the full human IgG receptor complexity to understand the role of platelets in anaphylaxis. Anaphylaxis induced a marked decrease in platelet levels, but preventive platelet depletion reduced anaphylaxis severity. A clinical study of patients with drug-induced anaphylaxis revealed that a severe reaction was likewise associated with fewer circulating platelets. Activated platelets released serotonin, which contributed to anaphylaxis severity. These results reveal a critical role for platelets in IgG-mediated anaphylaxis. Platelets are key regulators of vascular integrity; however, their role in anaphylaxis, a life-threatening systemic allergic reaction characterized by the loss of vascular integrity and vascular leakage, remains unknown. Anaphylaxis is a consequence of inappropriate cellular responses triggered by antibodies to generally harmless antigens, resulting in a massive mediator release and rapidly occurring organ dysfunction. Human platelets express receptors for immunoglobulin G (IgG) antibodies and can release potent mediators, yet their contribution to anaphylaxis has not been previously addressed in mouse models, probably because mice do not express IgG receptors on platelets. We investigated the contribution of platelets to IgG-dependent anaphylaxis in human IgG receptor–expressing mouse models and a cohort of patients suffering from drug-induced anaphylaxis. Platelet counts dropped immediately and markedly upon anaphylaxis induction only when they expressed the human IgG receptor FcγRIIA/CD32A. Platelet depletion attenuated anaphylaxis, whereas thrombocythemia substantially worsened its severity. FcγRIIA-expressing platelets were directly activated by IgG immune complexes in vivo and were sufficient to restore susceptibility to anaphylaxis in resistant mice. Serotonin released by activated platelets contributed to anaphylaxis severity. Data from a cohort of patients suffering from drug-induced anaphylaxis indicated that platelet activation was associated with anaphylaxis severity and was accompanied by a reduction in circulating platelet numbers. Our findings identify platelets as critical players in IgG-dependent anaphylaxis and provide a rationale for the design of platelet-targeting strategies to attenuate the severity of anaphylactic reactions.
Containment control for multi-agent systems via intermittent sampled data algorithm

In this paper, the containment control problem in second-order multi-agent systems for static and dynamic leaders under directed and undirected topologies are studied. We propose the periodic intermittent containment control algorithm, which both reduces the load of updating rates of controller and cuts down the working time of the controller in each sampling interval. Some necessary and sufficient conditions depending on the eigenvalues of the Laplacian matrix associated with the communication graph, the communication width, sampling period and the gain parameters, are obtained to guarantee the containment control. Finally, some simulations are conducted to verify the effectiveness of the proposed algorithms.
Interferon-Gamma Impairs Maintenance and Alters Hematopoietic Support of Bone Marrow Mesenchymal Stromal Cells

Bone marrow (BM) mesenchymal stromal cells (MSCs) provide microenvironmental support to hematopoietic stem and progenitor cells (HSPCs). Culture-expanded MSCs are interesting candidates for cellular therapies due to their immunosuppressive and regenerative potential which can be further enhanced by pretreatment with interferon-gamma (IFN-γ). However, it remains unknown whether IFN-γ can also influence hematopoietic support by BM-MSCs. In this study, we elucidate the impact of IFN-γ on the hematopoietic support of BM-MSCs. We found that IFN-γ increases expression of interleukin (IL)-6 and stem cell factor by human BM-MSCs. IFN-γ-treated BM-MSCs drive HSPCs toward myeloid commitment in vitro, but impair subsequent differentiation of HSPC. Moreover, IFN-γ-ARE-Del mice with increased IFN-γ production specifically lose their BM-MSCs, which correlates with a loss of hematopoietic stem cells' quiescence. Although IFN-γ treatment enhances the immunomodulatory function of MSCs in a clinical setting, we conclude that IFN-γ negatively affects maintenance of BM-MSCs and their hematopoietic support in vitro and in vivo.
Reply: Interaction between Brassinosteroids and Gibberellins: Synthesis or Signaling? In Arabidopsis, Both![OPEN]

Brassinosteroids (BRs) are plant hormones with versatile roles. Among other functions, the BRs control cell elongation, division, and differentiation events ([Gudesblat and Russinova, 2011][1]), fulfill roles in adaptive growth processes ([Wang et al., 2012][2]; [Fridman and Savaldi-Goldstein, 2013
Comparison of Arterial Spin Labeling and Dynamic Susceptibility Contrast Perfusion MRI in Patients with Acute Stroke

Background The aim of this study was to evaluate whether arterial spin labeling (ASL) perfusion magnetic resonance imaging (MRI) can reliably quantify perfusion deficit as compared to dynamic susceptibility contrast (DSC) perfusion MRI. Methods Thirty-nine patients with acute ischemic stroke in the anterior circulation territory were recruited. All underwent ASL and DSC MRI perfusion scans within 30 hours after stroke onset and 31 patients underwent follow-up MRI scans. ASL cerebral blood flow (CBF) and DSC time to maximum (Tmax) maps were used to calculate the perfusion defects. The ASL CBF lesion volume was compared to the DSC Tmax lesion volume by Pearson's correlation coefficient and likewise the ASL CBF and DSC Tmax lesion volumes were compared to the final infarct sizes respectively. A repeated measures analysis of variance and least significant difference post hoc test was used to compare the mean lesion volumes among ASL CBF, DSC Tmax >4–6 s and final infarct. Results Mean patient age was 72.6 years. The average time from stroke onset to MRI was 13.9 hours. The ASL lesion volume showed significant correlation with the DSC lesion volume for Tmax >4, 5 and 6 s (r = 0.81, 0.82 and 0.80; p<0.001). However, the mean lesion volume of ASL (50.1 ml) was significantly larger than those for Tmax >5 s (29.2 ml, p<0.01) and Tmax >6 s (21.8 ml, p<0.001), while the mean lesion volumes for Tmax >5 or 6 s were close to mean final infarct size. Conclusion Quantitative measurement of ASL perfusion is well correlated with DSC perfusion. However, ASL perfusion may overestimate the perfusion defects and therefore further refinement of the true penumbra threshold and improved ASL technique are necessary before applying ASL in therapeutic trials.
Resolving Alliance Ruptures from an Attachment-Informed Perspective

In this article, we examine how the different attachment patterns enable or hinder the resolution of ruptures in the therapeutic alliance. We try to show that secure and insecure patients alike may experience ruptures in the therapeutic alliance, but that their ability to participate in resolving such ruptures differ markedly. Recent findings with the Patient Attachment Coding System (PACS) show that attachment classifications manifest in psychotherapy as distinct ways of communicating about present internal experience. Secure patients disclose their present experience openly and invite attunement from the therapist, while insecure patients either minimize their contributions to the dialogue (avoidant) or the contributions of the therapist (preoccupied). Using examples from session transcripts, we demonstrate how secure patients are particularly responsive to resolution strategies that focus on here-and-now experience, while insecure patients’ characteristic ways of communicating pose significant challenges to the resolution process.