Miracle-dz/UniFAR-FTUs huggingface dataset:
Electrochemical Biochip Assays Based on Anti-idiotypic Antibodies for Rapid and Automated On-Site Detection of Low Molecular Weight Toxins

Phycotoxins and mycotoxins, such as paralytic shellfish poisoning toxins, type A trichothecenes, and aflatoxins are among the most toxic low molecular weight toxins associated with human poisoning incidents through the consumption of naturally contaminated food. Therefore, there is an utmost need for rapid and sensitive on-site detection systems. Herein, an electrochemical biochip for fast detection of saxitoxin, T-2 toxin as well as aflatoxin M1 and their corresponding congeners, respectively, using a portable and fully automated detection platform (pBDi, portable BioDetector integrated) was developed. Toxin analysis is facilitated upon the biochip via an indirect competitive immunoassay using toxin-specific antibodies combined with anti-idiotypic antibodies. The developed biochips enable detection in the low ng/mL-range within 17 min. Moreover, the assays cover a wide linear working range of 2–3 orders of magnitude above the limit of detection with an inter-chip coefficient of variation lower than 15%. The broad specificity of the employed antibodies which react with a large number of congeners within the respective toxin group allows efficient screening of contaminated samples for the presence of these low molecular weight toxins. With respect to the analysis of human urine samples, we focused here on the detection of saxitoxin, HT-2 toxin, and aflatoxin M1, all known as biomarkers of acute toxin exposure. Overall, it was proved that the developed biochip assays can be used to rapidly and reliably identify severe intoxications caused by these low molecular weight toxins.
Selection of Reference Genes for Expression Analysis in Chinese Medicinal Herb Huperzia serrata

Huperzine A (HupA) is a powerful and selective inhibitor of acetylcholinesterase. It has attracted widespread attention endangering the ultimate plant sources of Lycopodiaceae family. In this study, we used Huperzia serrata, extensively used in Traditional Chinese medicine (TCM), a slow growing vascular plant as the model plant of the Lycopodiaceae family to develop and validate the reference genes. We aim to use gene expression platform to understand the gene expression of different tissues and developmental stages of this medicinal herb. Eight candidate reference genes were selected based on RNA-seq data and evaluated with qRT-PCR. The expression of L/ODC and cytochrome P450s genes known for their involvement in lycopodium alkaloid biosynthesis, were also studied to validate the selected reference genes. The most stable genes were TBP, GAPDH, and their combination (TBP + GAPDH). We report for the first time the reference gene of H. serrata’s different tissues which would provide important insights into understanding their biological functions comparing other Lycopodiaceae plants and facilitate a good biopharming approach.
The Influence of Contrasting Microbial Lifestyles on the Pre-symbiotic Metabolite Responses of Eucalyptus grandis Roots

Plant roots co-inhabit the soil with a diverse consortium of microbes of which a number attempt to enter symbiosis with the plant. These microbes may be pathogenic, mutualistic or commensal. Hence, the health and survival of plants is heavily reliant on their ability to perceive different microbial lifestyles and respond appropriately. Emerging research suggests that there is a pivotal role for plant root secondary metabolites in responding to microbial colonization. However, it is largely unknown if plants are able to differentiate between microbes of different lifestyles and respond differently during the earliest stages of pre-symbiosis (i.e. prior to physical contact). By studying, here, plant responses to a range of microbial isolates, we questioned: (1) if individual microbes of different lifestyles and species caused alterations to the plant root metabolome during pre-symbiosis, and (2) if these early metabolite responses correlate with the outcome of the symbiotic interaction in later phases of colonization. We compared the changes of the root tip metabolite profile of the model tree Eucalyptus grandis during pre-symbiosis with two isolates of a pathogenic fungus (Armillaria luteobubalina), one isolate of a pathogenic oomycete (Phytophthora cinnamomi), two isolates of an incompatible mutualistic fungus (Suillus granulatus), and six isolates of a compatible mutualistic fungus (Pisolithus microcarpus). Untargeted metabolite profiling revealed predominantly positive root metabolite responses at the pre-symbiosis stage, prior to any observable phenotypical changes of the root tips. Metabolite responses in the host tissue that were specific to each microbial species were identified. A deeper analysis of the root metabolomic profiles during pre-symbiotic contact with six strains of P. microcarpus showed a connection between these early metabolite responses in the root with later colonization success. Further investigation using isotopic tracing revealed a portion of metabolites found in root tips originated from the fungus. RNA-sequencing also showed that the plant roots undergo complementary transcriptomic reprogramming in responses to the fungal stimuli. Taken together, our results demonstrate that the early metabolite responses of plant roots are partially selective towards the lifestyle of the interacting microbe, and that these responses can be crucial in determining the outcome of the interaction.
The Effects of Transcranial Direct Current Stimulation (tDCS) on Working Memory Training in Healthy Young Adults

Working memory (WM) is a fundamental cognitive ability to support complex thought, but it is limited in capacity. WM training has shown the potential benefit for those in need of a higher WM ability. Many studies have shown the potential of transcranial direct current stimulation (tDCS) to transiently enhance WM performance by delivering a low current to the brain cortex of interest, via electrodes on the scalp. tDCS has also been revealed as a promising intervention to augment WM training in a few studies. However, those few tDCS-paired WM training studies, focused more on the effect of tDCS on WM enhancement and its transferability after training and paid less attention to the variation of cognitive performance during the training procedure. The current study attempted to explore the effect of tDCS on the variation of performance, during WM training, in healthy young adults. All the participants received WM training with the load-adaptive verbal N-back task, for 5 days. During the training procedure, active/sham anodal high-definition tDCS (HD-tDCS) was used to stimulate the left dorsolateral prefrontal cortex (DLPFC). To examine the training effect, pre- and post-tests were performed, respectively, 1 day before and after the training sessions. At the beginning of each training session, stable-load WM tasks were performed, to examine the performance variation during training. Compared to the sham stimulation, higher learning rates of performance metrics during the training procedure were found when WM training was combined with active anodal HD-tDCS. The performance improvements (post–pre) of the active group, were also found to be higher than those of the sham group and were transferred to a similar untrained WM task. Further analysis revealed a negative relationship between the training improvements and the baseline performance. These findings show the potential that tDCS may be leveraged as an intervention to facilitate WM training, for those in need of a higher WM ability.
Dendritic Cell Regulation of Graft-Vs.-Host Disease: Immunostimulation and Tolerance

Graft-vs.-host disease (GVHD) remains a significant cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Significant progresses have been made in defining the dichotomous role of dendritic cells (DCs) in the development of GVHD. Host-derived DCs are important to elicit allogeneic T cell responses, whereas certain donor-types of DCs derived from newly engrafted hematopoietic stem/progenitor cells (HSPCs) can amply this graft-vs.-host reaction. In contrast, some DCs also play non-redundant roles in mediating immune tolerance. They induce apoptotic deletion of host-reactive donor T cells while promoting expansion and function of regulatory T cells (Treg). Unfortunately, this tolerogenic effect of DCs is impaired during GVHD. Severe GVHD in patients subject to allo-HSCT is associated with significantly decreased number of circulating peripheral blood DCs during engraftment. Existing studies reveal that GVHD causes delayed reconstitution of donor DCs from engrafted HSPCs, impairs the antigen presentation function of newly generated DCs and reduces the capacity of DCs to regulate Treg. The present review will discuss the importance of DCs in alloimmunity and the mechanism underlying DC reconstitution after allo-HSCT.
Energy Storage Sizing and Photovoltaic Self-Consumption in Selected Households in Qatar

In this paper, we present energy storage sizing and photovoltaic self-consumption calculations of four selected households in Qatar based on actual measurements. Four houses were chosen to represent different socioeconomic groups (one large villa-high income, two mid-size villas-middle class, and one low-income family) and their electricity consumption were recorded at every five minutes with non-intrusive energy monitors for a twelve month period from July 2017 to June 2018. Moreover, to estimate solar energy production, global horizontal index (GHI) values were obtained from the solar test facility located in Qatar. Energy storage size is calculated based on average reverse energy flow. The results show that due to the cooling load, residential electricity consumptions is quite high for the large building and no storage is needed. On the other hand, in medium-size buildings storage could be used in winter months when the local consumption is low. Finally, for the low-income family due to low electricity consumption, storage units can be used for twelve months. To the best of author’s knowledge, this is the first study in the GCC region to conduct such calculations with actual measurement numbers, and it will shed light on future research efforts.
Time Is Not More Abstract Than Space in Sound

Time is talked about in terms of space more frequently than the other way around. Some have suggested that this asymmetry runs deeper than language. The idea that we think about abstract domains (like time) in terms of relatively more concrete domains (like space) but not vice versa can be traced to Conceptual Metaphor Theory. This theoretical account has some empirical support. Previous experiments suggest an embodied basis for space-time asymmetries that runs deeper than language. However, these studies frequently involve verbal and/or visual stimuli. Because vision makes a privileged contribution to spatial processing it is unclear whether these results speak to a general asymmetry between time and space based on each domain’s general level of relative abstractness, or reflect modality-specific effects. The present study was motivated by this uncertainty and what appears to be audition’s privileged contribution to temporal processing. In Experiment 1, using an auditory perceptual task, temporal duration and spatial displacement were shown to be mutually contagious. Irrelevant temporal information influenced spatial judgments and vice versa with a larger effect of time on space. Experiment 2 examined the mutual effects of space, time, and pitch. Pitch was investigated because it is a fundamental characteristic of sound perception. It was reasoned that if space is indeed less relevant to audition than time, then spatial distance judgments should be more easily contaminated by variations in auditory frequency, while variations in distance should be less effective in contaminating pitch perception. While time and pitch were shown to be mutually contagious in Experiment 2, irrelevant variation in auditory frequency affected estimates of spatial distance while variations in spatial distance did not affect pitch judgments. Results overall suggest that the perceptual asymmetry between spatial and temporal domains does not necessarily generalize across modalities, and that time is not generally more abstract than space.
Development and preliminary evaluation of a short self-report measure of generalized pain hypersensitivity

Purpose Generalized pain hypersensitivity is frequently observed in chronic pain conditions. Currently, identification is based on expert clinical opinion, and in very few cases combined with quantitative sensory testing. The objectives of this study were to develop and evaluate a short self-report measure of generalized pain hypersensitivity: a generalized pain questionnaire (GPQ). Methods Items for the GPQ were developed based on a literature review, followed by an interview study with ten rheumatic patients with suspected pain hypersensitivity. We examined the psychometric properties of the preliminary items in a sample of 212 outpatients suffering from either fibromyalgia (FM; n=98) or rheumatoid arthritis (n=114). Additionally, self-reported data were gathered on sociodemographics, fibromyalgia-survey criteria, health status, and neuropathic-like pain features. Results Mokken-scale analyses demonstrated a unidimensional seven-item scale with strong homogeneity (H=0.65) and high reliability (r=0.90). Correlations between total GPQ scores and relevant external measures, such as the FM-survey criteria and neuropathic-like pain features, were consistent with a priori expectations, supporting its external construct validity. Furthermore, the GPQ had good accuracy in distinguishing between patients with FM (generally assumed to be the result of central nervous system hypersensitization) and patients with RA (assumed to result mostly in local nociceptive or inflammatory pain), with an area under the receiver-operating characteristic curve of 0.89. A cutoff value >10 had the highest combination of sensitivity (82.7%) and specificity (77.2%). Conclusion The GPQ is psychometrically sound and appears promising for measuring the presence and severity of generalized pain hypersensitivity in chronic pain patients.
RAP80 expression in breast cancer and its relationship with apoptosis in breast cancer cells

Background RAP80 is a member of BRCA1-A complex, which plays an important role in regulating the cell cycle checkpoint and DNA damage repair in the nucleus. Method We investigated RAP80 expression in breast cancer and its paired normal breast tissues to further analyze its role in the biological behavior of breast cancer cells. Results RAP80 expression in breast cancer (62.3%, 101/162) was significantly lower than that in adjacent normal breast tissues (P<0.05). RAP80 expression was related to tumor size, lymph node metastasis, TNM stage, and molecular subtype (P<0.05). RAP80 mRNA expression was significantly lower in triple-negative breast cancer than other types. The mRNA and protein of RAP80 were obvious in MCF-7 and very weak in ZR-75 or MDA-MB-231, so we picked MCF-7 to be transfected with RAP80 siRNA. The survival rate of both cells decreased in a dose-dependent manner and the IC50 value for cisplatin in MCF-7 RAP80 siRNA cells was 0.83 µg/mL, and 1.69 µg/mL in wild-type MCF-7 according to MTT. RAP80 siRNA transfection upregulated the apoptosis and downregulated invasive or migrating ability of MCF-7. RAP80 siRNA also upregulated the protein expression of Caspase-3, cleaved Caspase-3, Apaf-1, Cytochrome C, Bax, and Fas, and downregulated the protein expression of Bcl-2. Conclusion RAP80 expression was related to ER or PR activity. Inhibition of RAP80 expression can induce apoptosis in breast cancer cells and improve chemosensitivity to cisplatin. Tumor cells can activate protective responses to inhibit cell cycle progression, which may be related to RAP80, and repair cisplatin-induced DNA damage. RAP80 is related to BRCA1’s effect, which can be used as an interesting target for pharmacological modulation that can increase the efficiency of cisplatin chemotherapy.
Effects of low-dose ketamine infusion on remifentanil-induced acute opioid tolerance and the inflammatory response in patients undergoing orthognathic surgery

Purpose Remifentanil is associated with acute opioid tolerance that can lead to increased postoperative consumption of opioid analgesics. The purpose of this study was to determine whether a low dose of ketamine prevents remifentanil-induced acute opioid tolerance and affects the neutrophil–lymphocyte ratio (NLR), a newly recognized biomarker of inflammation. Materials and methods Forty patients undergoing orthognathic surgery were enrolled in this prospective, randomized, double-blind study and randomly assigned to intraoperative administration of one of the following anesthetic regimens: high-dose remifentanil (0.6 µg/kg/minute); low-dose remifentanil (0.2 µg/kg/minute); or high-dose remifentanil with ketamine (remifentanil 0.6 µg/kg/minute with 0.5 mg/kg ketamine just after induction followed by an intraoperative infusion of ketamine 5 µg/kg/minute until wound closure). Fentanyl by intravenous patient-controlled analgesia was used for postoperative pain control. Visual Analog Scale pain scores and fentanyl consumption were recorded in the first 24 hours postoperatively. Perioperative serum C-reactive protein level and NLR were also determined. Results Baseline characteristics were similar in the three study groups. There were no between-group differences in Visual Analog Scale pain scores during the study period. The high-dose remifentanil group had a significantly higher requirement for fentanyl than the other two groups. Addition of ketamine did not affect the C-reactive protein level but increased the NLR; this increase was associated with decreased fentanyl consumption. Conclusion High-dose intraoperative remifentanil induced postoperative acute opioid tolerance that was prevented by infusion of low-dose ketamine. Ketamine increased the postoperative NLR associated with decreased fentanyl requirement for postoperative pain control.
Will endoscopic submucosal dissection (ESD) become the gold standard for laterally spreading tumors (LST)?

Laterally spreading tumors (LST) have become a recognizable proportion of all pre-cancerous colorectal lesions, particularly with the advent of population-based bowel cancer screening. Since Kudo’s first description in 1993 which analyzed how best to remove flat and depressed types of early colorectal cancer via endoscopic mucosal resection (EMR), there has been much debate as to the definition of these lesions and how they should be excised [1]. The 2002 Paris Consensus established boundaries of LST morphology. EMR is currently the mainstream technique for treating LST, but debate has emerged as to whether especially piecemeal EMR should be replaced by newer modalities such as endoscopic submucosal dissection (ESD) [2]. A key point is that en-bloc resection with EMR is usually limited to lesions < 20 mm diameter in the colon or < 25 mm in the rectum [3]. Although piecemeal EMR has proven to be a reliable option, this may come with reduced cost-effectiveness over the entire treatment course for the lesion, less good pathological assessment, and increased risks of local recurrence. Because of this, a substantial body of opinion suggests that ESD should be the future in LST treatment. However, when considering ESD as “gold standard,” we cannot overlook its downsides of technical intricacy, prolonged time of procedure and increased chances of perforation and overnight hospital admission.
Effects of duodenal–jejunal bypass surgery in ameliorating nonalcoholic steatohepatitis in diet-induced obese rats

Background Duodenal–jejunal bypass (DJB) is an important component of many types of current bariatric surgery including Roux-en-Y gastric bypass, mini-gastric bypass, biliopancreatic diversion, duodenal switch, and DJB plus sleeve gastrectomy. Surgery is often observed to ameliorate nonalcoholic steatohepatitis (NASH), but without a clearly delineated mechanism. In this study, we investigated the effects of DJB in diet-induced obese rats with NASH. Materials and methods Male Wistar rats were divided into four groups and fed the following diets over 6 months: A) normal chow (NC group, n=6); B) methionine–choline-deficient (MCD)–high-fat (HF) diet (HF group, n=6); C) MCD–HF diet for 3 months followed by DJB and MCD–HF diet for subsequent 3 months (DJB group, n=6); and D) MCD–HF diet for 3 months followed by treatment with pioglitazone (PGZ) with MCD–HF diet for subsequent 3 months (PGZ group, n=6). Body weight, glucose tolerance, the homeostatic model assessment-insulin resistance index, and lipid profiles were compared. Liver and visceral adipose tissue histology, inflammatory marker and hepatic stellate cell (HSC) activity, and hepatocyte autophagy were assessed. Results Compared with the HF group, the DJB group showed improved body weight, insulin sensitivity, lipid metabolism, and steatosis severity. The DJB group exhibited a significantly lower nonalcoholic fatty liver disease activity score than the HF and PGZ group (P<0.001 and P=0.003, respectively). Furthermore, DJB significantly reduced fat mass and adipocyte size. These effects were also observed in the PGZ group. Therefore, we speculated that the improvements induced by DJB are closely related to an alteration in insulin sensitivity. Moreover, DJB reduced HSC activity and TNF-α expression and enhanced hepatocyte autophagy. Conclusion DJB improves NASH through several mechanisms, particularly by altering insulin sensitivity, inflammatory responses, HSC activity, and hepatocyte autophagy.
Screening of novel HSP-inducing compounds to conserve cardiomyocyte function in experimental atrial fibrillation

Background The heat shock protein (HSP) inducer, geranylgeranylacetone (GGA), was previously found to protect against atrial fibrillation (AF) remodeling in experimental model systems. Clinical application of GGA in AF is limited, due to low systemic concentrations owing to the hydrophobic character of GGA. Objectives To identify novel HSP-inducing compounds, with improved physicochemical properties, that prevent contractile dysfunction in experimental model systems for AF. Methods Eighty-one GGA-derivatives were synthesized and explored for their HSP-inducing properties by assessment of HSP expression in HL-1 cardiomyocytes pretreated with or without a mild heat shock (HS), followed by incubation with 10 µM GGA or GGA-derivative. Subsequently, the most potent HSP-inducers were tested for preservation of calcium transient (CaT) amplitudes or heart wall contraction in pretreated tachypaced HL-1 cardiomyocytes (with or without HSPB1 siRNA) and Drosophilas, respectively. Finally, CaT recovery in tachypaced HL-1 cardiomyocytes posttreated with GGA or protective GGA-derivatives was determined. Results Thirty GGA-derivatives significantly induced HSPA1A expression after HS, and seven showed exceeding HSPA1A expression compared to GGA. GGA and nine GGA-derivatives protected significantly from tachypacing (TP)-induced CaT loss, which was abrogated by HSPB1 suppression. GGA and four potent GGA-derivatives protected against heart wall dysfunction after TP compared to non-paced control Drosophilas. Of these compounds, GGA and three GGA-derivatives induced a significant restoration from CaT loss after TP of HL-1 cardiomyocytes. Conclusion We identified novel GGA-derivatives with improved physicochemical properties compared to GGA. GGA-derivatives, particularly GGA*-59, boost HSP expression resulting in prevention and restoration from TP-induced remodeling, substantiating their role as novel therapeutics in clinical AF.