Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical Utility of Ghrelin-O-Acyltransferase (GOAT) Enzyme as a Diagnostic Tool and Potential Therapeutic Target in Prostate Cancer

Recent data suggested that plasma Ghrelin O-Acyl Transferase enzyme (GOAT) levels could represent a new diagnostic biomarker for prostate cancer (PCa). In this study, we aimed to explore the diagnostic and prognostic/aggressiveness capacity of GOAT in urine, as well as to interrogate its putative pathophysiological role in PCa. We analysed urine/plasma levels of GOAT in a cohort of 993 patients. In vitro (i.e., cell-proliferation) and in vivo (tumor-growth in a xenograft-model) approaches were performed in response to the modulation of GOAT expression/activity in PCa cells. Our results demonstrate that plasma and urine GOAT levels were significantly elevated in PCa patients compared to controls. Remarkably, GOAT significantly outperformed PSA in the diagnosis of PCa and significant PCa in patients with PSA levels ranging from 3 to 10 ng/mL (the so-called PSA grey-zone). Additionally, urine GOAT levels were associated to clinical (e.g., Gleason-score, PSA levels) and molecular (e.g., CDK2/CDK6/CDKN2A expression) aggressiveness parameters. Indeed, GOAT overexpression increased, while its silencing/blockade decreased cell-proliferation in PCa cells. Moreover, xenograft tumors derived from GOAT-overexpressing PCa (DU145) cells were significantly higher than those derived from the mock-overexpressing cells. Altogether, our results demonstrate that GOAT could be used as a diagnostic and aggressiveness marker in urine and a therapeutic target in PCa.
The Anti-Aging Potential of Neohesperidin and Its Synergistic Effects with Other Citrus Flavonoids in Extending Chronological Lifespan of Saccharomyces Cerevisiae BY4742

The anti-aging activity of many plant flavonoids, as well as their mechanisms of action, have been explored in the current literature. However, the studies on the synergistic effects between the different flavonoid compounds were quite limited in previous reports. In this study, by using a high throughput assay, we tested the synergistic effects between different citrus flavonoids throughout the yeast’s chronological lifespan (CLS). We studied the effect of four flavonoid compounds including naringin, hesperedin, hesperitin, neohesperidin, as well as their different combinations on the CLS of the yeast strain BY4742. Their ROS scavenging ability, in vitro antioxidant activity and the influence on the extracellular pH were also tested. The results showed that neohesperidin extended the yeast’s CLS in a concentration-dependent manner. Especially, we found that neohesperidin showed great potential in extending CLS of budding yeast individually or synergistically with hesperetin. The neohesperidin exhibited the strongest function in decreasing the reactive oxygen species (ROS) accumulation in yeast. These findings clearly indicated that neohesperidin is potentially an anti-aging citrus flavonoid, and its synergistic effect with other flavonoids on yeast’s CLS will be an interesting subject for future research of the anti-aging function of citrus fruits.
A Malicious Behavior Awareness and Defense Countermeasure Based on LoRaWAN Protocol

Low power wide area network (LoRaWAN) protocol has been widely used in various fields. With its rapid development, security issues about the awareness and defense against malicious events in the Internet of Things must be taken seriously. Eavesdroppers can exploit the shortcomings of the specification and the limited consumption performance of devices to carry out security attacks such as replay attacks. In the process of the over-the-air-activation (OTAA) for LoRa nodes, attackers can modify the data because the data is transmitted in plain text. If the user’s root key is leaked, the wireless sensor network will not be able to prevent malicious nodes from joining the network. To solve this security flaw in LoRaWAN, we propose a countermeasure called Secure-Packet-Transmission scheme (SPT) which works based on the LoRaWAN standard v1.1 to prevent replay attacks when an attacker has obtained the root key. The proposed scheme redefines the format of join-request packet, add the new One Time Password (OTP) encrypted method and changes the transmission strategy in OTAA between LoRa nodes and network server. The security evaluation by using the Burrows-Abadi-Needham logic (BAN Logic) and the Scyther shows that the security goal can be achieved. This paper also conducts extensive experiments by simulations and a testbed to perform feasibility and performance analysis. All results demonstrate that SPT is lightweight, efficient and able to defend against malicious behavior.
Purification and Characterization of a Novel Antifungal Flagellin Protein from Endophyte Bacillus methylotrophicus NJ13 against Ilyonectria robusta

Endophyte Bacillus methylotrophicus NJ13 was isolated from Panax ginseng. Its sterile fermentation liquid showed a significant inhibitory effect against Ilyonectria robusta, causing the rusty root rot of P. ginseng and P. quinquefolius. The antifungal protein was obtained after precipitation by 20% saturated ammonium sulfate, desalted by Sephadex G-25, weak anion exchange chromatography, and gel filtration chromatography. SDS-PAGE showed that the purified protein was approximately 29 KDa. The antifungal protein after desalting was not resistant to temperatures higher than 100 °C, resistant to acid conditions, and did not tolerate organic solvents and protease K. The amino acid sequence of purified antifungal protein had an identity of 76% to flagellin from Bacillus velezensis. The isoelectric point of the protein was 4.97 and its molecular mass was 27 KDa. Therefore, a specific primer G1 was designed based on the flagellin gene sequence, and a 770 bp gene sequence was cloned in NJ13 genomic DNA, which shared the same size of flagellin. There were ten base differences between the gene sequences of flagellin and the cloned gene, however, the amino acid sequence encoded by the cloned gene was identical to the flagellin. In conclusion, the antifungal protein produced by biocontrol agent NJ13 contained a flagellin protein.
Comparison of ultrasonic Doppler flow monitor, oscillometric, and direct arterial blood pressure measurements in anesthetized dogs

This study was performed to evaluate three different noninvasive blood pressure measurement methods (NIBP) in comparison with direct blood pressure measurements in anesthetized dogs. Ten normal healthy Beagle dogs (mean age; 3.7 ± 1.01 yrs, mean body weight 10.2 ± 1.15 kg) were enrolled in this study. The BP was measured by three different methods, i.e., Doppler (DOP), oscillometric and high density oscillometric (HDO), simultaneously for 5 times in each subject under anesthesia at three different locations (right, left front legs and tail). The blood pressure value measured by Doppler method was the most close to the value measured by the direct method. Although the accuracy and consistency of the BP measured by 3 different non-invasive methods were differed by the method, all methods except conventional oscillometric method were acceptable for monitoring systolic blood pressure in anesthetic dogs and the inter-measurement variations in DOP and HDO was minimal enough not to affect the consistency of test result.
The Efficiency of Color Space Channels to Quantify Color and Color Intensity Change in Liquids, pH Strips, and Lateral Flow Assays with Smartphones

Bottom-up, end-user based feed, and food analysis through smartphone quantification of lateral flow assays (LFA) has the potential to cause a paradigm shift in testing capabilities. However, most developed devices do not test the presence of and implications of inter-phone variation. Much discussion remains regarding optimum color space for smartphone colorimetric analyses and, an in-depth comparison of color space performance is missing. Moreover, a light-shielding box is often used to avoid variations caused by background illumination while the use of such a bulky add-on may be avoidable through image background correction. Here, quantification performance of individual channels of RGB, HSV, and LAB color space and ΔRGB was determined for color and color intensity variation using pH strips, filter paper with dropped nanoparticles, and colored solutions. LAB and HSV color space channels never outperformed the best RGB channels in any test. Background correction avoided measurement variation if no direct sunlight was used and functioned more efficiently outside a light-shielding box (prediction errors < 5%/35% for color/color intensity change). The system was validated using various phones for quantification of major allergens (i.e., gluten in buffer, bovine milk in goat milk and goat cheese), and, pH in soil extracts with commercial pH strips and LFA. Inter-phone variation was significant for LFA quantification but low using pH strips (prediction errors < 10% for all six phones compared). Thus, assays based on color change hold the strongest promise for end-user adapted smartphone diagnostics.
Airway Mucus Hyperconcentration in Non-Cystic Fibrosis Bronchiectasis.

RATIONALE Non-cystic fibrosis bronchiectasis (NCFB) is characterized by airway mucus accumulation and sputum production, but the role of mucus concentration in the pathogenesis of these abnormalities has not been characterized. OBJECTIVES This study was designed to: (a) measure mucus concentration and biophysical properties of bronchiectasis mucus; (b) identify the secreted mucins contained in bronchiectasis sputum; (c) relate mucus properties to airway epithelial mucin RNA/protein expression; and (d) explore relationships between mucus hyperconcentration and disease severity. METHODS Sputum samples were collected from bronchiectasis subjects, with and without chronic erythromycin administration, and healthy controls. Sputum percent solid concentrations, total and individual mucin concentrations, osmotic pressures, rheological properties, and inflammatory mediators were measured. Intracellular mucins were measured in endobronchial biopsies by immunohistochemistry and gene expression. MUC5B polymorphisms were identified by qPCR. In a replication bronchiectasis cohort, spontaneously expectorated and hypertonic saline induced sputa were collected and mucus/mucin concentrations measured. MEASUREMENTS AND MAIN RESULTS Bronchiectasis sputum exhibited increased percent solids, total and individual (MUC5B and MUC5AC) mucin concentrations, osmotic pressure, and elastic and viscous moduli compared with healthy sputum. Within bronchiectasis subjects, sputum percent solids correlated inversely with FEV1 and positively with bronchiectasis extent, as measured by high-resolution computerized tomography, and inflammatory mediators. No difference was detected in MUC5B rs35705950 SNP allele frequency between bronchiectasis and healthy individuals. Hypertonic saline inhalation acutely reduced NCFB mucus concentration by 25%. CONCLUSIONS Hyper-concentrated airway mucus is characteristic of bronchiectasis subjects, likely contributes to disease pathophysiology, and may be a target for pharmacotherapy.
It’s Time to Replace the Term “Heavy Metals” with “Potentially Toxic Elements” When Reporting Environmental Research

Even if the Periodic Table of Chemical Elements is relatively well defined, some controversial terms are still in use. Indeed, the term “heavy metal” is a common term used for decades in the natural sciences, and even more in environmental sciences, particularly in studies of pollution impacts. As the use of the term appears to have increased, we highlight the relevance of the use of the term “Potentially Toxic Element(s)”, which needs more explicit endorsement, and we illustrate the chemical elements that need to be considered.
A qualitative investigation into how physiotherapists currently review people with Multiple Sclerosis and their opinions of telephone reviews in this population

A qualitative investigation into how physiotherapists’ currently review people with Multiple Sclerosis and their opinions of telephone reviews in this population Authors: Marie Condon, Dr Susan Coote Background: Guidelines recommend people with Multiple Sclerosis (PwMS) receive regular physiotherapy reviews (NICE, 2003). However little is known about how PwMS are currently reviewed. Reviews can be face-to-face, telephone or postal. The telephone is increasingly used to improve access to healthcare systems (Car, 2003). Yet no research is available on using telephone reviews with PwMS. Objectives: To explore: (i) how physiotherapists currently review PwMS and (ii) physiotherapists‟ opinions of telephone reviews in this population. Methods: Three focus groups were conducted with physiotherapists working with PwMS in urban (n=4) and rural (n=2) primary care settings and an acute hospital (n=3). Sessions were audio-recorded, transcribed verbatim and thematic analysis was performed. Results: Physiotherapists conversed that reviewing PwMS is not regularly done due to service constraints and inconsistencies in patient review pathways. Despite this, service provision was enhanced mainly by MS Ireland. Telephone reviews were perceived as beneficial. However concerns regarding compromised quality of care arose due to loss of visual cues, patients‟ ability to self-report and confidentiality issues. Concerns were allayed somewhat if a reliable self-reporting patient was chosen, reviews were structured and based on function. Conclusion: Physiotherapists are not regularly reviewing PwMS due to cutbacks in health services and problems with patient pathways. Due to the current economic climate further research is best aimed at refining patient pathways. Used appropriately, telephone reviews with PwMS have the potential to beneficial. Further research is required to ascertain benefits in reality and to ensure the safety of telephone reviews in this population.
Use of Fermented Hemp, Chickpea and Milling By-Products to Improve the Nutritional Value of Semolina Pasta

A biotechnological approach including enzymatic treatment (protease and xylanase) and lactic acid bacteria fermentation has been evaluated to enhance the nutritional value of semolina pasta enriched with hemp, chickpea and milling by-products. The intense (up to circa, (ca.) 70%) decrease in the peptide profile area and (up to two-fold) increase in total free amino acids, compared to the untreated raw materials, highlighted the potential of lactic acid bacteria to positively affect their in vitro protein digestibility. Fermented and unfermented ingredients have been characterized and used to fortify pasta made under pilot-plant scale. Due to the high contents of protein (ca. 13%) and fiber (ca. 6%) and according to the Regulation of the European Community (EC) No. 1924/2006 fortified pasta can be labelled as a “source of fiber” and a “source of protein”. The use of non-wheat flours increased the content of anti-nutritional factors as compared to the control pasta. Nevertheless, fermentation with lactic acid bacteria led to significant decreases in condensed tannins (ca. 50%), phytic acid and raffinose (ca. ten-fold) contents as compared to the unfermented pasta. Moreover, total free amino acids and in vitro protein digestibility values were 60% and 70%, respectively, higher than pasta made only with semolina. Sensory analysis highlighted a strong effect of the fortification on the sensory profile of pasta.
Miniaturized Intracavitary Forward-Looking Ultrasound Transducer for Tissue Ablation

Objective: This paper aims to develop a miniaturized forward-looking ultrasound transducer for intracavitary tissue ablation, which can be used through an endoscopic device. The internal ultrasound (US) delivery is capable of directly interacting with the target tumor, resolving adverse issues of currently available US devices, such as unintended tissue damage and insufficient delivery of acoustic power. Methods: To transmit a high acoustic pressure from a small aperture (<3 mm), a double layer transducer (1.3 MHz) was designed and fabricated based on numerical simulations. The electric impedance and the acoustic pressure of the actual device was characterized with an impedance analyzer and a hydrophone. Ex vivo tissue ablation tests and temperature monitoring were then conducted with porcine livers. Results: The acoustic intensity of the transducer was 37.1 W/cm2 under 250 Vpp and 20% duty cycle. The tissue temperature was elevated to 51.8 °C with a 67 Hz pulse-repetition frequency. The temperature profile in the tissue indicated that ultrasound energy was effectively absorbed inside the tissue. During a 5-min sonification, an approximate tissue volume of 2.5 × 2.5 × 1.0 mm3 was ablated, resulting in an irreversible lesion. Conclusion: This miniaturized US transducer is a promising medical option for the precise tissue ablation, which can reduce the risk of unintended tissue damage found in noninvasive US treatments. Significance: Having a small aperture (2 mm), the intracavitary device is capable of ablating a bio tissue in 5 min with a relatively low electric power (<17 W).
Transcriptome analysis of apple leaves infected by the rust fungus Gymnosporangium yamadae at two sporulation stages reveals detoxication and secondary metabolite host responses and fungal pathogenesis-related genes.

Apple rust disease caused by Gymnosporangium yamadae is one of the major threats to apple orchards. In this study, dual RNA-seq analysis was conducted to simultaneously monitor gene expression profiles of G. yamadae and infected apple leaves during the formation of rust spermogonia and aecia. The molecular mechanisms underlying this compatible interaction at 10 and 30 days post inoculation (dpi) indicate a significant reaction from the host plant and comprise detoxication pathways at the earliest stage and the induction of secondary metabolism pathways at 30dpi. Such host reactions have been previously reported in other rust pathosystems and may represent a general reaction to rust infection. G. yamadae transcript profiling indicates a conserved genetic program in spermogonia and aecia that is shared with other rust fungi, whereas secretome prediction reveals the presence of specific secreted candidate effector proteins expressed during apple infection. Unexpectedly, the survey of fungal unigenes in the transcriptome assemblies of inoculated and mock-inoculated apple leaves reveals that G. yamadae infection may modify the fungal community composition in the apple phyllosphere at 30 dpi. Collectively, our results provide novel insights into the compatible apple-G. yamadae interaction and advance the knowledge of this heteroecious demicyclic rust fungus.
Solid-Phase Insertion of N-mercaptoalkylglycine Residues into Peptides

N-mercaptoalkylglycine residues were inserted into peptides by reacting N-free amino groups of peptides, which were initially synthesized on 2-chlorotrityl resin (Cltr) using the Fmoc/tBu method, with bromoacetic acid and subsequent nucleophilic replacement of the bromide by reacting with S-4-methoxytrityl- (Mmt)/S-trityl- (Trt) protected aminothiols. The synthesized thiols containing peptide–peptoid hybrids were cleaved from the resin, either protected by treatment with dichloromethane (DCM)/trifluoroethanol (TFE)/acetic acid (AcOH) (7:2:1), or deprotected (fully or partially) by treatment with trifluoroacetic acid (TFA) solution using triethylsilane (TES) as a scavenger.
Role of electrolyte concentrations and renin‐angiotensin‐aldosterone activation in the staging of canine heart disease

Abstract Background Refractory congestive heart failure (CHF) and associated diuretic resistance are not well defined. Objectives To characterize renal function, electrolyte concentrations, indices of diuretic efficacy, and renin‐angiotensin‐aldosterone system (RAAS) activation in dogs with naturally occurring heart disease (HD) in American College of Veterinary Internal Medicine stages B1, B2, C, and D and to determine their usefulness in defining HD stages. Animals Group 1:149 dogs with HD stages B1, B2, C, and D. Group 2:22 dogs with HD stages C and D. Methods Group 1: Renal parameters, serum and urine electrolyte and diuretic concentrations, and urine aldosterone concentrations were measured. Medication dosages and measured variables were compared among stages. Correlation of furosemide dosages to serum concentrations was explored. Group 2: Angiotensin‐converting enzyme activity and RAAS components were measured and compared among CHF stages. Results Serum chloride concentration was the best differentiator of HD stage. Furosemide PO dosages (≤6 mg/kg/day) were weakly correlated with serum furosemide concentrations, whereas higher dosages were not significantly correlated. Angiotensin‐converting enzyme inhibitor dosage and RAAS inhibition were greater in stage D, compared to stage C dogs. Conclusions and Clinical Importance Hypochloremia is a useful marker for stage D HD in dogs. Poor furosemide dosage correlation to serum concentration may indicate variable and poor absorption, especially at higher dosages, advanced disease, or both. A small number of stage D dogs met proposed criteria for diuretic resistance. Greater RAAS inhibition in stage D versus stage C indicates effectiveness of RAAS‐suppressive treatments in this group of dogs with refractory CHF.
Impact of Different Mucoadhesive Polymeric Nanoparticles Loaded in Thermosensitive Hydrogels on Transcorneal Administration of 5-Fluorouracil

In a previous paper a thermosensitive hydrogel formulation based on chitosan or its derivatives (TSOH), containing medicated chitosan nanoparticles (Ch NP) for transcorneal administration of 5-fluorouracil (5-FU) was described. The Ch NP-containing TSOH allowed a time-constant 5-FU concentration in the aqueous for 7 h from instillation. The aim of the present work was to study the impact of the surface characteristics of new NP contained in TSOH on ocular 5-FU bioavailability. The Ch derivatives used to prepare NP were quaternary ammonium-Ch conjugate (QA-Ch), S-protected derivative thereof (QA-Ch-S-pro), and a sulphobutyl chitosan derivative (SB-Ch). All NP types had 300–400 nm size, 16–18% encapsulation efficiency, and retained the entrapped drug for at least 15 h. Drug release from TSOH containing NP based on QA-Ch or QA-Ch-S-pro was virtually equal, whereas with TSOH containing NP based on SB-Ch was significantly slower. Instillation, in rabbit eyes, of NP-containing TSOH based on QA-Ch or SB-Ch led to a plateau in the aqueous concentration vs. time plot in the 1–10 h range with significantly enhanced area under curve (AUC). Negative charges on the NP surface slowed down 5-FU release from TSOH while positive charges increased NP contact with the negatively charged ocular surface. Either results in enhanced ocular bioavailability.