Miracle-dz/UniFAR-FTUs huggingface dataset:
All d-Lysine Analogues of the Antimicrobial Peptide HPA3NT3-A2 Increased Serum Stability and without Drug Resistance

Novel antibiotic drugs are urgently needed because of the increase in drug-resistant bacteria. The use of antimicrobial peptides has been suggested to replace antibiotics as they have strong antimicrobial activity and can be extracted from living organisms such as insects, marine organisms, and mammals. HPA3NT3-A2 ([Ala1,8] HPA3NT3) is an antimicrobial peptide that is an analogue of the HP (2–20) peptide derived from Helicobacter pylori ribosomal protein L1. Although this peptide was shown to have strong antimicrobial activity against drug-resistant bacteria, it also showed lower toxicity against sheep red blood cells (RBCs) and HaCaT cells compared to HPA3NT3. The l-Lys residues of HPA3NT3-A2 was substituted with d-Lys residues (HPA3NT3-A2D; [d-Lys2,5,6,9,10,15] HPA3NT3-A2) to prevent the cleavage of peptide bonds by proteolytic enzymes under physiological conditions. This peptide showed an increased half-life and maintained its antimicrobial activity in the serum against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) (pathogen). Furthermore, the antimicrobial activity of HPA3NT3-A2D was not significantly affected in the presence of mono- or divalent ions (Na+, Mg2+, Ca2+). Finally, l- or d-HPA3NT3-A2 peptides exhibited the strongest antimicrobial activity against antibiotic-resistant bacteria and failed to induce resistance in Staphylococcus aureus after 12 passages.
Biventricular myocardial adaptation in patients with repaired tetralogy of Fallot: Mechanistic insights from magnetic resonance imaging tissue phase mapping

Background The myocardial adaptive mechanism in patients with repaired tetralogy of Fallot (rTOF) is less understood. We aimed to investigate biventricular myocardial adaptive remodeling in rTOF patients. Methods We recruited 32 rTOF patients and 38 age- and sex-matched normal controls. The pulmonary stenosis of rTOF patients was measured using catheterized pressure gradient between right ventricle (RV) and pulmonary artery (PGRVPA). rTOF patients with PGRVPA < 15 mmHg and ≥15 mmHg were classified as low pulmonary stenosis (rTOFlow, n = 19) and high pulmonary stenosis (rTOFhigh, n = 13) subgroups, respectively. Magnetic resonance imaging tissue phase mapping was employed to evaluate the voxelwise biventricular myocardial motion in longitudinal (Vz), radial (Vr), and circumferential (Vφ) directions. Results The rTOFlow subgroup presented higher pulmonary regurgitation fraction than rTOFhigh subgroup (p < 0.001). Compared with the normal group, only rTOFlow subgroup presented a decreased RV ejection fraction (RVEF) (p < 0.05). The rTOFlow subgroup showed decreased systolic and diastolic Vz in RV and LV, whereas rTOFhigh subgroup showed such change only in RV. In rTOFlow subgroup, RVEF significantly correlated with RV systolic Vr (r = 0.56, p < 0.05), whereas LVEF correlated with LV systolic Vz (r = 0.51, p = 0.02). Prolonged QRS correlated with RV systolic Vr (r = -0.58, p < 0.01) and LV diastolic Vr (r = 0.81, p < 0.001). No such correlations occurred in rTOFhigh subgroup. Conclusions The avoidance of unfavorable functional interaction in RV and LV in rTOFhigh subgroup suggested that adequate pulmonary stenosis (PGRVPA ≥ 15 mmHg in this sereis) has a protective effect against pulmonary regurgitation.
Transcriptome Analysis Reveals That Abeliophyllum distichum Nakai Extract Inhibits RANKL-Mediated Osteoclastogenensis Mainly through Suppressing Nfatc1 Expression

Abeliophyllum distichum Nakai is known as a monotypic genus endemic to South Korea. Currently, several pharmacological studies have revealed that A. distichum extract exhibits diverse biological functions, including anti-cancer, anti-diabetic, anti-hypertensive, and anti-inflammatory activities. In this study, we present the anti-osteoporotic activity of A. distichum extract by inhibiting osteoclast formation. First, we show that the methanolic extract of the leaves of A. distichum, but not extracts of the branches or fruits, significantly inhibits receptor activator of the NF-κB ligand (RANKL)-induced osteoclast differentiation. Second, our transcriptome analysis revealed that the leaf extract (LE) blocks sets of RANKL-mediated osteoclast-related genes. Third, the LE attenuates the phosphorylation of extracellular signal-related kinase. Finally, treatment with the LE effectively prevents postmenopausal bone loss in ovariectomized mice and glucocorticoid-induced osteoporosis in zebrafish. Our findings show that the extract of A. distichum efficiently suppressed osteoclastogenesis by regulating osteoclast-related genes, thus offering a novel therapeutic strategy for osteoporosis.
The Role of Receptor Tyrosine Kinases in Lassa Virus Cell Entry

The zoonotic Old World mammarenavirus Lassa (LASV) causes severe hemorrhagic fever with high mortality and morbidity in humans in endemic regions. The development of effective strategies to combat LASV infections is of high priority, given the lack of a licensed vaccine and restriction on available treatment to off-label use of ribavirin. A better understanding of the fundamental aspects of the virus’s life cycle would help to improve the development of novel therapeutic approaches. Host cell entry and restriction factors represent major barriers for emerging viruses and are promising targets for therapeutic intervention. In addition to the LASV main receptor, the extracellular matrix molecule dystroglycan (DG), the phosphatidylserine-binding receptors of the Tyro3/Axl/Mer (TAM), and T cell immunoglobulin and mucin receptor (TIM) families are potential alternative receptors of LASV infection. Therefore, the relative contributions of candidate receptors to LASV entry into a particular human cell type are a complex function of receptor expression and functional DG availability. Here, we describe the role of two receptor tyrosine kinases (RTKs), Axl and hepatocyte growth factor receptor (HGFR), in the presence and absence of glycosylated DG for LASV entry. We found that both RTKs participated in the macropinocytosis-related LASV entry and, regardless of the presence or absence of functional DG, their inhibition resulted in a significant antiviral effect.
Genetic Impairment of Cellulose Biosynthesis Increases Cell Wall Fragility and Improves Lipid Extractability from Oleaginous Alga Nannochloropsis salina

In microalgae, photosynthesis provides energy and sugar phosphates for the biosynthesis of storage and structural carbohydrates, lipids, and nitrogenous proteins. The oleaginous alga Nannochloropsis salina does not preferentially partition photoassimilates among cellulose, chrysolaminarin, and lipids in response to nitrogenous nutrient deprivation. In the present study, we investigated whether genetic impairment of the cellulose synthase gene (CesA) expression would lead to protein accumulation without the accumulation of storage C polymers in N. salina. Three cesA mutants were generated by the CRISPR/Cas9 approach. Cell wall thickness and cellulose content were reduced in the cesA1 mutant, but not in cesA2 or cesA4 cells. CesA1 mutation resulted in a reduction of chrysolaminarin and neutral lipid contents, by 66.3% and 37.1%, respectively, but increased the soluble protein content by 1.8-fold. Further, N. salina cells with a thinned cell wall were susceptible to mechanical stress, resulting in a 1.7-fold enhancement of lipid extractability. Taken together, the previous and current studies strongly suggest the presence of a controlling mechanism that regulates photoassimilate partitioning toward C and N metabolic pathways as well as the cellulose metabolism as a potential target for cost-effective microalgal cell disruption and as a useful protein production platform.
Simultaneous separation of naproxen and 6-O-desmethylnaproxen metabolite in saliva samples by liquid chromatography–tandem mass spectrometry: Pharmacokinetic study of naproxen alone and associated with esomeprazole

Naproxen is a widely used non-steroidal anti-inflammatory drug for the control of postoperative inflammatory signs and symptoms in dentistry. Its association with esomeprazole has been widely studied and has yielded good results for the control of acute pain, even with the delayed absorption of naproxen owing to the presence of esomeprazole. To further understand the absorption, distribution, and metabolism of this drug alone and in combination with esomeprazole, we will analyze the pharmacokinetic parameters of naproxen and its major metabolite, 6-O-desmethylnaproxen, in saliva samples. A rapid, sensitive, and selective liquid chromatography-tandem mass spectrometric method for the simultaneous determination of naproxen and 6-O-desmethylnaproxen in saliva will be developed and validated. Sequential saliva samples from six patients will be analyzed before and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6 8, 11, 24, 48, 72, and 96 h after the ingestion of one naproxen tablet (500 mg) and esomeprazole-associated naproxen tablets (500 + 20 mg), at two different times. After liquid-liquid extraction with ethyl acetate and HCl, the samples will be analyzed using an 8040 Triple Quadrupole Mass Spectrometer (Shimadzu, Kyoto, Japan). Separation of naproxen and its major metabolic products will be performed using a Shim-Pack XR-ODS 75Lx2.0 column and C18 pre-column (Shimadzu, Kyoto, Japan) at 40°C using a mixture of methanol and 10 mM ammonium acetate (70:30, v/v) with an injection flow of 0.3 mL/min. The total analytical run time will be 5 min. The detection and quantification of naproxen and its metabolite will be validated, which elucidate the pharmacokinetics of this drug, thereby contributing to its proper prescription for the medical and dental interventions that cause acute pain.
Development of [18F]ICMT-11 for Imaging Caspase-3/7 Activity during Therapy-Induced Apoptosis

Insufficient apoptosis is a recognised hallmark of cancer. A strategy to quantitatively measure apoptosis in vivo would be of immense value in both drug discovery and routine patient management. The first irreversible step in the apoptosis cascade is activation of the “executioner” caspase-3 enzyme to commence cleavage of key structural proteins. One strategy to measure caspase-3 activity is Positron Emission Tomography using isatin-5-sulfonamide radiotracers. One such radiotracer is [18F]ICMT-11, which has progressed to clinical application. This review summarises the design and development process for [18F]ICMT-11, suggesting potential avenues for further innovation.
Treatment outcomes among children treated for uncomplicated severe acute malnutrition: a retrospective study in Accra, Ghana

Abstract Objectives: The objectives of the study were to describe outcomes of children with uncomplicated severe acute malnutrition (SAM) attending community-based management of acute malnutrition (CMAM) treatment centres in Accra Metropolitan Area (AMA) and explore factors associated with non-adherence to clinic visits and defaulting from the treatment programme. Design: A retrospective cohort study analysing routinely collected data on children with uncomplicated SAM enrolled into CMAM in 2017 was conducted. Setting: Study was conducted at seven sites comprising Princess Marie Louise Children’s Hospital, three sub-metropolitan health facilities and three community centres, located in five sub-metropolitan areas in AMA. Participants: Children with uncomplicated SAM aged 6–59 months, enrolled from community-level facilities (pure uncomplicated SAM, PUSAM) or transferred after completing inpatient care (post-stabilisation uncomplicated SAM, PSSAM), participated in the study. Results: Out of 174 cases studied (105 PUSAM, sixty-nine PSSAM), 56·3 % defaulted, 34·5 % recovered and 8·6 % were not cured by 16 weeks. No deaths were recorded. Mid-upper arm circumference (MUAC) increased by 2·2 (95 % CI 1·8, 2·5) mm/week with full compliance and 0·9 (95 % CI 0·6, 1·2) mm/week with more than two missed visits. In breast-feeding children, MUAC increased at a slower rate than in other children by 1·3 (95 % CI 1·0, 1·5) mm/week. Independent predictors of subsequent missed visits were diarrhoea and fever, while children with MUAC < 110 mm on enrolment were at increased risk of defaulting. Conclusion: A high default rate and a long time to recovery are challenges for CMAM in AMA. Efforts must be made to improve adherence to treatment to improve outcomes.
Establishing a 130-Bed Field Intensive Care Unit to Prepare for COVID-19 in 7 Days in Bahrain Military Hospital

ABSTRACT This article reports the establishment of an isolated, fully functional field intensive care unit (FICU) unit equipped with all necessary critical care facilities as a part of the national pre-emptive preparedness to treat an unexpected surge outbreak of coronavirus disease 2019 (COVID-19) patients in Bahrain. One floor of an existing car parking structure was converted into a 130-bed FICU set-up by the in-house project implementation team comprised of multidisciplinary departments. The setting was a military hospital in the Kingdom of Bahrain, and the car park was on the hospital premises. The FICU contained a 112-bed fully equipped ICU and an 18-bed step-down ICU, and was built in 7 d to cater to the intensive care of COVID-19 patients in Bahrain.
Estimation of between-Cow Variability in Nutrient Digestion of Lactating Dairy Cows Fed Corn-Based Diets

Simple Summary Cow variability present in nutrient digestibility studies differs for different diets and nutrients. It is a major factor determining adequate sample size so that studies are not under-powered or over-powered. The objective of the current study was to develop cow variability estimates that can be used to determine the optimal sample size for digestibility trials having randomized block designs using mid-lactation dairy cows when fed corn-based diets having different neutral detergent fiber:starch ratio (0.7, 1.0, and 1.3). Cow variability is greater for digestibility of fiber and dry matter and less for starch. Estimated cow variability as standard deviations for digestibility of dry matter, neutral detergent fiber and starch were 3.8 g/kg, 5.1 g/kg and 3.3 g/kg, respectively. A major implication of this study is that cow variability is greatest for fiber digestibility and the use of a minimum of 12 cows per dietary treatment is adequate to reliably detect treatment effects on the digestibility of fiber, starch and dry matter using lactating dairy cows fed in groups with randomized block design under current experimental conditions. Abstract The objective of this study was to estimate cow variability that can be used to determine the optimal sample size for digestibility trials using lactating dairy cows. Experimental design was randomized complete block design having three blocks and three dietary treatments. Three similarly managed nearby intensive farms were considered as blocks, and three diets were formulated to have 0.7, 1.0, and 1.3 neutral detergent fiber (NDF): starch ratio. In each farm, 18 cows were assigned for each dietary treatment and five sample sizes per each treatment group were simulated by simple random sampling of data from 18, 15, 12, 9 and 6 cows respectively. Intake was not affected by diet or sample size (p > 0.05). Estimated cow variability (as standard deviation) for digestibility of dry matter, NDF and starch were 3.8 g/kg, 5.1 g/kg and 3.3 g/kg, respectively. A major implication of this study is that cow variability is greatest for NDF digestibility and the use of a minimum of 12 cows per dietary treatment is adequate to reliably detect treatment effects on the digestibility of NDF, starch and dry matter using cows fed in groups with randomized block design under these experimental conditions.
Prevalence and Characteristics of Undiagnosed COPD in Adults 40 Years and Older – Reports from the Tunisian Population-Based Burden of Obstructive Lung Disease Study

Abstract This study aimed to investigate the underdiagnosis of COPD and its determinants based on the Tunisian Burden of Obstructive Lung Disease study. We collected information on respiratory history symptoms and risk factors for COPD. Post-bronchodilator (Post-BD) FEV1/FVC < the lower limit of normal (LLN) was used to define COPD. Undiagnosed COPD was considered when participants had post-BD FEV1/FVC < LLN but were not given a diagnosis of emphysema, chronic bronchitis or COPD. 730 adults aged ⩾40 years selected from the general population were interviewed, 661 completed spirometry, 35 (5.3%) had COPD and 28 (80%) were undiagnosed with the highest prevalence in women (100%). When compared with patients with an established COPD diagnosis, undiagnosed subjects had a lower education level, milder airway obstruction (Post-BD FEV1 z-score −2.2 vs. −3.7, p < 0.001), fewer occurrence of wheezing (42.9% vs. 100%, p = 0.009), less previous lung function test (3.6% vs. 42.8%, p = 0.019) and less visits to the physician (32.1% vs. 85.7%, p = 0.020) in the past year. Multivaried analysis showed that the probability of COPD underdiagnosis was higher in subjects who had mild to moderate COPD and in those who did not visit a clinician and did not perform a spirometry in the last year. Collectively, our results highlight the need to improve the diagnosis of COPD in Tunisia. Wider use of spirometry should reduce the incidence of undiagnosed COPD. Spirometry should also predominately be performed not only in elderly male smokers but also in younger women in whom the prevalence of underdiagnosis is the highest.
Comparison of the Safety Profiles of 3 Different Hymenoptera Venom Immunotherapy Protocols: A Retrospective 2-Center Study of 143 Patients

Introduction: Venom immunotherapy (VIT) is highly effective and the treatment of choice for patients with a history of systemic anaphylactic reactions to a Hymenoptera sting. It has been assumed that VIT protocols with a rapid dose increase during the induction phase are associated with a higher frequency of systemic reactions (SR); however, study data addressing this issue are conflicting. Objective: The aim of this study was to compare the safety of 3 different Hymenoptera VIT protocols (half-day ultra-rush, 3-day rush, 3-week cluster). Methods: This retrospective 2-center study included 143 Hymenoptera venom-allergic patients, who underwent 147 VIT procedures during the years 2015–2018. Twenty cluster, 75 rush, and 52 ultra-rush VIT protocols were performed with honeybee (54 protocols) and wasp (93 protocols) venom. All documented side effects were classified into large local and SR (Ring and Messmer classification). Results: SR were observed during 11 (7.5%) VIT procedures and did not exceed severity grade II. SR occurred more frequently in cluster compared to accelerated protocols. This result was observed for both honeybee (cluster: 25%, rush: 8.7%, and ultra-rush: 15.8%) and wasp VIT (cluster: 12.5%, rush: 0%, and ultra-rush: 6.1%), though the differences were statistically significant only in the wasp VIT subgroup. Honeybee venom elicited more SR than wasp venom (14.8 and 3.2%, respectively, p = 0.01). The risk for SR did not depend on age, sex, concomitant antihypertensive medication, hypertryptasemia, or severity of the index sting reaction. Conclusion: Accelerated VIT protocols, namely, rush and ultra-rush protocols are safe therapeutic options for Hymenoptera venom-allergic patients and displayed fewer SR than cluster VIT protocols in our study.
Cystic Fibrosis Defective Response to Infection Involves Autophagy and Lipid Metabolism

Cystic fibrosis (CF) is a hereditary disease, with 70% of patients developing a proteinopathy related to the deletion of phenylalanine 508. CF is associated with multiple organ dysfunction, chronic inflammation, and recurrent lung infections. CF is characterized by defective autophagy, lipid metabolism, and immune response. Intracellular lipid accumulation favors microbial infection, and autophagy deficiency impairs internalized pathogen clearance. Myriocin, an inhibitor of sphingolipid synthesis, significantly reduces inflammation, promotes microbial clearance in the lungs, and induces autophagy and lipid oxidation. RNA-seq was performed in Aspergillusfumigatus-infected and myriocin-treated CF patients’ derived monocytes and in a CF bronchial epithelial cell line. Fungal clearance was also evaluated in CF monocytes. Myriocin enhanced CF patients’ monocytes killing of A. fumigatus. CF patients’ monocytes and cell line responded to infection with a profound transcriptional change; myriocin regulates genes that are involved in inflammation, autophagy, lipid storage, and metabolism, including histones and heat shock proteins whose activity is related to the response to infection. We conclude that the regulation of sphingolipid synthesis induces a metabolism drift by promoting autophagy and lipid consumption. This process is driven by a transcriptional program that corrects part of the differences between CF and control samples, therefore ameliorating the infection response and pathogen clearance in the CF cell line and in CF peripheral blood monocytes.
DSC Performance Evaluation and Exploration Case of TMS320F28335

— The rapid advanced of microelectronics and semiconductor technologies has enabled to increase the capacity of digital circuits like Application-Specific Integrated Circuits (ASICs), microcontrollers (MCUs), Digital Signal Processors (DSPs) and Field Programmable Gate Array (FPGAs). Recently, a new digital circuits termed "Digital Signal Controller" (DSCs) has emerged. DSC combines the processing power of the DSP and the functionality of the MCU with several peripheral modules that make it an attractive proposition for practically all embedded systems applications, including communication, audio, medical, aerospace, defence and industrial control. The performance analysis of DSCs processors, presents one of the consideration metric in the choice the best processing element for a special application. In this paper, we will focus on the performance analysis of the TMS320F28335 DSC, basing on benchmarking.
Expression analysis of the DkNCED1, DkNCED2 and DkCYP707A1 genes that regulate homeostasis of abscisic acid during the maturation of persimmon fruit

Summary To reveal details of the role(s) of abscisic acid (ABA) during fruit ripening and the regulation of ABA levels, two 9-cis-epoxycarotenoid dioxygenase genes (DkNCED1 and DkNCED2) and the DkCYP707A1 gene for ABA 8'-hydroxylase were isolated from unripened persimmon fruit. Expression of DkNCED1 increased at the start of fruit maturation and peaked 20 d before harvest, which was consistent with the accumulation of ABA during ripening in persimmon. Expression of the DkNCED2 gene was high in fruit at the immature stage, then declined continuously throughout ripening. Compared to the DkNCED genes, expression of DkCYP707A1 peaked 145 d after full-bloom (DAFB), then declined. Ethylene release decreased gradually from 65 DAFB to 115 DAFB, then peaked at 10 d after harvest. Water-deficit stress enhanced the expression of DkNCED1, but down-regulated transcript levels of DkCYP707A1 in the calyx. These results suggest that endogenous ABA content is modulated by a dynamic balance between ABA biosynthesis and catabolism, which is regulated by expression of the DkNCED1 and DkCYP707A1 genes, respectively, during persimmon fruit development and under drought stress.