Miracle-dz/UniFAR-FTUs huggingface dataset:
Developing an optimized strategy with transcranial direct current stimulation to enhance the endogenous pain control system in fibromyalgia

ABSTRACT Introduction: Fibromyalgia affects more than 5 million people in the United States and has a detrimental impact on individuals’ quality of life. Current pharmacological treatments provide limited benefits to relieve the pain of fibromyalgia, along with a risk of adverse effects; a scenario that explains the increasing interest for multimodal approaches. A tailored strategy to focus on this dysfunctional endogenous pain inhibitory system is transcranial direct current stimulation (tDCS) of the primary motor cortex. By combining tDCS with aerobic exercise, the effects can be optimized. Areas covered: The relevant literature was reviewed and discussed the methodological issues for designing a mechanistic clinical trial to test this combined intervention. Also, we reviewed the neural control of different pathways that integrate the endogenous pain inhibitory system, as well as the effects of tDCS and aerobic exercise both alone and combined. In addition, potential neurophysiological assessments are addressed: conditioned pain modulation, temporal slow pain summation, transcranial magnetic stimulation, and electroencephalography in the context of fibromyalgia. Expert commentary: By understanding the neural mechanisms underlying pain processing and potential optimized interventions in fibromyalgia with higher accuracy, the field has an evident potential of advancement in the direction of new neuromarkers and tailored therapies.
Privacy For User Behavior Data

Tons of online user behavior data are being generated every day on the booming and ubiquitous Internet. Growing efforts have been devoted to mining the abundant behavior data to extract valuable information for research purposes or business interests. However, online users’ privacy is thus under the risk of being exposed to third-parties. The last decade has witnessed a body of research works trying to perform data aggregation in a privacy-preserving way. Most of existing methods guarantee strong privacy protection yet at the cost of very limited aggregation operations, such as allowing only summation, which hardly satisfies the need of behavior analysis. In this paper, we propose a scheme PPSA, which encrypts users’ sensitive data to prevent privacy disclosure from both outside analysts and the aggregation service provider, and fully supports selective aggregate functions for online user behavior analysis while guaranteeing differential privacy. We have implemented our method and evaluated its performance using a trace-driven evaluation based on a real online behavior dataset. Experiment results show that our scheme effectively supports both overall aggregate queries and various selective aggregate queries with acceptable computation and communication
Ready‐to‐use thermally stable mastermix pills for molecular biology applications

Rolling circle amplification (RCA), polymerase chain reaction (PCR), and loop‐mediated isothermal amplification (LAMP), are powerful tools that can be used for gene manipulation, pathogen detection, and infectious disease diagnostics. However, these techniques require trained personnel, as the pipetting steps involved can lead to contamination and, consequently, erroneous results. Furthermore, many of the reagents used in molecular biology are thermally labile and must be kept within a cold‐chain. In this article, we present a simple and cost‐effective method that allows molecular biology reagents to be thermally stabilized into ready‐to‐use mastermixes via drying in pullulan and trehalose films. Our experimental results demonstrate that this method is capable of preserving the activity of RCA, PCR, LAMP, ligase, polynucleotide kinase, and Klenow fragment mastermixes for at least 3 months at ambient conditions. Thus, stabilizing reagents via drying in pullulan and trehalose film may allow for a drastic reduction in the number of pipetting steps and the elimination of the need for a cold chain. © 2018 American Institute of Chemical Engineers Biotechnol. Prog. , 35: e2764, 2019.
Safety and Efficacy of Rituximab in Multiple Sclerosis: A Retrospective Observational Study

Objective To evaluate the efficacy and safety of rituximab in multiple sclerosis in a clinical practice setting. Methods Clinical data for all adult patients with multiple sclerosis (MS) treated with off-label rituximab at a single MS center in Lebanon between March 2008 and April 2017 were retrospectively collected from medical charts. The main efficacy outcomes assessed were annualized relapse rate (ARR) and proportion of patients free from relapses, disability progression, or magnetic resonance imaging (MRI) activity. Results A total of 89 rituximab-treated patients were included: 59 relapsing-remitting MS (RRMS) and 30 progressive MS (PMS). Patients were treated with 1000 or 2000 mg rituximab IV every 6–12 months for a mean duration of 22.2 ± 24.8 months. The subjects were 65.2% females with a mean age of 40.5 ± 12.3 years and a mean disease duration of 7.9 ± 6.2 years. During treatment, the ARR decreased from 1.07 at baseline to 0.11 in RRMS (p < 0.0001) and from 0.25 to 0.16 in PMS patients (p = 0.593). The mean Expanded Disability Status Scale (EDSS) remained unchanged in both RRMS and PMS patients. Between baseline and the last follow-up, the percent of patients free from any new MRI lesions increased from 18.6% to 92.6% in the RRMS group and from 43.3% to 82% in the PMS group. No evidence of disease activity (NEDA) was achieved in 74% of patients at 1 year of treatment. A total of 64 adverse events (AEs) (71.9%) were recorded with the most common being infusion-related reactions in 25.8% of patients, all mild in nature. Two of our rituximab-treated patients experienced serious AEs requiring surgical interventions: pyoderma gangrenosum vaginalis with perianal abscess and fistula and an increase in the size of a meningioma. No case of progressive multifocal leukoencephalopathy (PML) was detected. Conclusion In our real-world cohort, rituximab was well-tolerated and effective in reducing relapse rate and disability progression in relapsing-remitting and progressive MS patients.
UvA-DARE (Digital Academic Repository) A Robust Functional Genomics Approach to Identify Effector Genes Required for Thrips (Frankliniella occidentalis) Reproductive Performance on Tomato Leaf

Thrips ( Frankliniella occidentalis ) is a persistent plant pest that is able to vector pathogenic viruses. Natural plant resistance to thrips has become a prominent breeding target in commercial crops. The main reason for this is the shift toward banning key pesticides used for controlling thrips infestations and the lack of effective alternatives. Despite this urgent need for crop plants that are resistant, or tolerant, to thrips infestation, the toolbox for studying genetic resistance to this insect is still underdeveloped. Essentially, there is a lack of robust protocols for the screening and identiﬁcation of thrips genes relevant to its performance on crop plants. To bridge this gap, we have developed a functional analysis screening method. Our approach relies on the, Agrobacterium tumefaciens -mediated, homogeneous, and transient ectopic expression of thrips genes in large tomato leaf discs followed by the assessment of thrips reproductive performance. The setup is designed to maintain gene expression during the course of the assay, where GFP signal in the control treatment is used as a reporter of expression. The screen is conducted in a climate box under controlled settings. As a result, multiple genes can be screened for their effect on thrips reproductive performance in a single experiment and in a relatively small space, without the need for generating stable transgenic plants. The method also eliminates the need for a greenhouse equipped to accommodate the combination of A. tumefaciens -inﬁltrations and thrips infestations. It is not only ﬂexible and convenient for screening genes encoding putative thrips effectors but also for plant resistance genes or effector-targets of host plants and can be adapted for other crop plants, or other herbivorous arthropods.
From nodes to networks: How methods for defining nodes influence inferences regarding network interactions

Functional connectivity (FC) analysis of fMRI data typically rests on prior identification of network nodes from activation profiles. We compared Activation Likelihood Estimate (ALE) and the Experimentally Derived Estimate (EDE) approaches to network node identification and functional inference for both verbal and visual forms of working memory. ALE arrives at canonical activation maxima that are assumed to reliably represent peaks of brain activity underlying a psychological process (e.g., working memory). By comparison, EDEs of activation maxima are typically derived from individual participant data, and are thus sensitive to individual participant activation profiles. Here, nodes were localized by both ALE and EDE methods for each participant, and subsequently extracted time series were compared using connectivity analysis. Two sets of significance tests were performed: (1) correlations computed between nodal time series of each method were compared, and (2) correlations computed between network edges (functional connections) of each network node pair were compared. Large proportions of edge correlations significantly differed between methods. ALE effectively summarizes working memory network node locations across studies and subjects, but the sensitivity to individual functional loci suggest that EDE methods provide individualized estimates of network connectivity. We suggest that a hybrid method incorporating both ALE and EDE is optimal for network inference.
Protective Factors Associated With Fewer Generalized Anxiety Disorder Symptoms Among Women Exposed to Intimate Partner Violence

Generalized anxiety disorder (GAD) has received minimal empirical attention in the context of intimate partner violence (IPV). Furthermore, factors related to lower levels of GAD symptoms in this population have received limited focus. This study evaluated the protective role of four forms of support, spiritual, family, friend, and community, in predicting levels of generalized anxiety among women who have experienced recent IPV. Participants included 116 women who were recruited from local agencies serving IPV-exposed individuals. Participants completed measures of IPV, GAD, stressful life events, spiritual support, social support, and community support during a 1-hr interview. Findings from a hierarchical multiple regression analysis indicated that after accounting for age, income, mental health service utilization, stressful life events, and severity of IPV, lower GAD symptoms were only associated with higher spiritual support (β = −0.20, p = .02) and community support (β = −0.25, p = .01), not friend or family support, F(9, 114) = 5.10; p < . 001; R2 = . 30. These findings indicate that alternative sources of support (i.e., spiritual and community) may be more accessible for IPV-exposed women, contributing to their association with reduced GAD symptomatology. The current study highlights the potential for spiritual and community support to serve a beneficial role above and beyond standard social support proffered by friends and family on symptoms of GAD. Results reinforce the examination of a broad range of multiple supports among women experiencing IPV. This thorough examination of different support systems may provide further insight into novel resources that can be strengthened among IPV-exposed populations.
Decoding the ocean's microbiological secrets for marine enzyme biodiscovery

Abstract A global census of marine microbial life has been underway over the past several decades. During this period, there have been scientific breakthroughs in estimating microbial diversity and understanding microbial functioning and ecology. It is estimated that the ocean, covering 71% of the earth's surface with its estimated volume of about 2 × 1018 m3 and an average depth of 3800 m, hosts the largest population of microbes on Earth. More than 2 million eukaryotic and prokaryotic species are thought to thrive both in the ocean and on its surface. Prokaryotic cell abundances can reach densities of up to 1012 cells per millilitre, exceeding eukaryotic densities of around 106 cells per millilitre of seawater. Besides their large numbers and abundance, marine microbial assemblages and their organic catalysts (enzymes) have a largely underestimated value for their use in the development of industrial products and processes. In this perspective article, we identified critical gaps in knowledge and technology to fast-track this development. We provided a general overview of the presumptive microbial assemblages in oceans, and an estimation of what is known and the enzymes that have been currently retrieved. We also discussed recent advances made in this area by the collaborative European Horizon 2020 project ‘INMARE’.
Time-effect relationship of acupuncture on histopathology, ultrastructure, and neuroethology in the acute phase of cerebral hemorrhage

Many clinical studies have addressed the treatment of acute cerebral hemorrhage using acupuncture. However, few studies have examined the relationship between time of acupuncture and curative effect on cerebral hemorrhage. By observing the effect of acupuncture on changes in histopathology, ultrastructure, and neuroethology in a cerebral hemorrhage model of rats, we have directly examined the time-effect relationship of acupuncture. The rat model of cerebral hemorrhage was produced by slowly injecting autologous blood to the right caudate nucleus. The experimental groups were: 3-, 9-, 24-, and 48-hour model groups; and 3-, 9-, 24-, and 48-hour acupuncture groups. The sham-operation group was used for comparison. Acupuncture was performed at the Neiguan (PC6) and Renzhong (DU26) acupoints, twice a day, 6 hours apart, for 5 consecutive days. Brain tissue changes were observed by light microscopy and transmission electron microscopy. Neuroethology was assessed using Bederson and Longa scores. Our results show that compared with the sham-operation and model groups, Bederson and Longa scores were lower in each acupuncture group, with visibly improved histopathology and brain tissue ultrastructure. Further, the results were better in the 3- and 9-hour acupuncture groups than the 24- and 48-hour acupuncture groups. Our findings show that acupuncture treatment can relieve pathological and ultrastructural deterioration and neurological impairment caused by the acute phase of cerebral hemorrhage, and may protect brain tissue during this period. In addition, earlier acupuncture intervention following cerebral hemorrhage (by 3 or 9 hours) is associated with a better treatment outcome.
Social networking site addiction and undergraduate students’ irrational procrastination: The mediating role of social networking site fatigue and the moderating role of effortful control

With the popularity of social networking sites (SNSs), the problems of SNS addiction have been increasing. Research has revealed the association between SNS addiction and irrational procrastination. However, the mechanism underlying this relation is still unclear. The present study aimed to examine the mediating role of social networking site fatigue and the moderating role of effortful control in this link among Chinese undergraduate students. The Social Networking Site Addiction Scale, Social Networking Service Fatigue Scale, Effortful Control Scale and Irrational Procrastination Scale were completed by 1,085 Chinese undergraduate students. Results indicated that SNS addiction, SNS fatigue and irrational procrastination were positively correlated with each other, and negatively correlated with effortful control. Further analyses revealed that, SNS addiction has a direct effect on irrational procrastination. SNS fatigue mediated the relationship between SNS addiction and irrational procrastination. Both direct and indirect effects of SNS addiction on irrational procrastination were moderated by effortful control. Specifically, this effect was stronger for people with lower effortful control. These findings help clarify the mechanism underlying the association between SNS addiction and irrational procrastination, which have potential implications for intervention.
3D Bioprinting: Fundamentals, Principles and Applications

3D Bioprinting: Fundamentals, Principles and Applications provides the latest information on the fundamentals, principles, physics, and applications of 3D bioprinting. It contains descriptions of the various bioprinting processes and technologies used in additive biomanufacturing of tissue constructs, tissues, and organs using living cells. The increasing availability and decreasing costs of 3D printing technologies are driving its use to meet medical needs, and this book provides an overview of these technologies and their integration. Each chapter discusses current limitations on the relevant technology, giving future perspectives. Professor Ozbolat has pulled together expertise from the fields of bioprinting, tissue engineering, tissue fabrication, and 3D printing in his inclusive table of contents. Topics covered include raw materials, processes, machine technology, products, applications, and limitations. The information in this book will help bioengineers, tissue and manufacturing engineers, and medical doctors understand the features of each bioprinting process, as well as bioink and bioprinter types. In addition, the book presents tactics that can be used to select the appropriate process for a given application, such as tissue engineering and regenerative medicine, transplantation, clinics, or pharmaceutics.Describes all aspects of the bioprinting process, from bioink processing through design for bioprinting, bioprinting techniques, bioprinter technologies, organ printing, applications, and future trendsProvides a detailed description of each bioprinting technique with an in-depth understanding of its process modeling, underlying physics and characteristics, suitable bioink and cell types printed, and major accomplishments achieved thus farExplains organ printing technology in detail with a step-by-step roadmap for the 3D bioprinting of organs from isolating stem cells to the post-transplantation of organsPresents tactics that can be used to select the appropriate process for a given application, such as tissue engineering and regenerative medicine, transplantation, clinics, or pharmaceutics
Validation of NAD synthase inhibitors for inhibiting the cell viability of Leishmania donovani: In silico and in vitro approach

Abstract NAD (nicotinamide adenine dinucleotide) synthase catalyses the biochemical synthesis of NAD, from nicotinic acid adenine dinucleotide (NAAD). NAD may be synthesized through the de novo pathways and/or the salvage pathways in cells. However, in Leishmania parasite, the synthesis of NAD solely depends on the salvage pathways. NAD synthetase is widely explored as a drug target in various microorganisms. In Bacillus anthracis, a group of sulphonamides 5599, 5617 and 5824 and complex amide 5833 were reported to have activity at micromolar range against NAD synthetase. Hence, in the present study, the same group of sulphonamides and complex amide were validated through in silico and in vitro studies for its efficiency towards Leishmania donovani NAD synthase. In silico study revealed the ligands 5824 and 5833 to have better docking score. Molecular dynamics simulation for a duration of 50 ns of all the ligand–protein complexes suggested that the complexes with the ligands 5824 and 5833 were stable and interacting. In vitro and ex vivo studies have shown that 5824 and 5833 inhibit the cell viability of the organism at a lower concentration than 5599 and 5617. Hence, with further in vivo validation, 5824 (or its synthetic analogues) and 5833 could be the choice that may work synergistically with other potential drugs in treating drug-resistant cases of leishmaniasis. Communicated by Ramaswamy H. Sarma
New insights into the evolution of wheat avenin-like proteins in wild emmer wheat (Triticum dicoccoides)

Significance Wheat grain avenin-like proteins (ALPs) have functions for dough quality and antifungal activities. A genome-wide characterization of ALP encoding genes in bread wheat is conducted. Results showed that most ALPs are transcriptionally active in developing grains and are up-regulated upon Bgt infection. The allelic diversity of ALPs in 21 natural populations of wild emmer wheat (WEW) in Israel were studied. Many ALP allelic variations in WEW were associated with regional environmental adaption. Our findings demonstrate that the diversifying natural selection through climatic and edaphic factors was a major driving force for the allelic diversity of ALP genes. The results indicate that WEW harbors a high genetic diversity of ALPs utilizable for wheat improvement. Fifteen full-length wheat grain avenin-like protein coding genes (TaALP) were identified on chromosome arms 7AS, 4AL, and 7DS of bread wheat with each containing five genes. Besides the a- and b-type ALPs, a c type was identified in the current paper. Both a and b types have two subunits, named x and y types. The five genes on each of the three chromosome arms consisted of two x-type genes, two y-type genes, and one c-type gene. The a-type genes were typically of 520 bp in length, whereas the b types were of 850 bp in length, and the c type was of 470 bp in length. The ALP gene transcript levels were significantly up-regulated in Blumeria graminis f. sp. tritici (Bgt)-infected wheat grain caryopsis at early grain filling. Wild emmer wheat [(WEW), Triticum dicoccoides] populations were focused on in our paper to identify allelic variations of ALP genes and to study the influence of natural selection on certain alleles. Consequently, 25 alleles were identified for TdALP-bx-7AS, 13 alleles were identified for TdALP-ax-7AS, 7 alleles were identified for TdALP-ay-7AS, and 4 alleles were identified for TdALP-ax-4AL. Correlation studies on TdALP gene diversity and ecological stresses suggested that environmental factors contribute to the ALP polymorphism formation in WEW. Many allelic variants of ALPs in the endosperm of WEW are not present in bread wheat and therefore could be utilized in breeding bread wheat varieties for better quality and elite plant defense characteristics.
Several clock genes polymorphisms are meaningful risk factors in the development and severity of cannabis addiction

ABSTRACT Circadian rhythms have been related to psychiatric diseases and regulation of dopaminergic transmission, especially in substance abusers. The relationship between them remained enigmatic and no data on the role of clock genes on cannabis dependence have been documented. We aimed at exploring the role of clock gene genotypes as potential predisposing factor to cannabis addiction, using a high throughput mass spectrometry methodology that enables the large-scale analysis of the known relevant polymorphisms of the clock genes. We have conducted a case-control study on 177 Caucasians categorizing between cannabis-addicted subjects and casual consumers based on structured interviews recorded socio-demographic data, AUDIT, Fagerström test, MINI, and medical examinations. Alcohol, opiates, and stimulants’ consumption was as exclusion criteria. We report an association between several Single Nucleotide Polymorphism (SNP)s in main circadian genes SNPs, especially the gene locus HES7/PER1 on chromosome 17 and cannabis consumption as well as the development of neuropsychiatric and social disorders. This SNP’s signature that may represent a meaningful risk factor in the development of cannabis dependence and its severity requires to be deeply explored in a prospective study.