Miracle-dz/UniFAR-FTUs huggingface dataset:
DEF8 and Autophagy-Associated Genes are Altered in Mild Cognitive Impairment, Probable Alzheimer's Disease Patients and a Transgenic Model of the Disease.

BACKGROUND Disturbances in the autophagy/endolysosomal systems are proposed as early signatures of Alzheimer's disease (AD). However, few studies are available concerning autophagy gene expression in AD patients. OBJECTIVE To explore the differential expression of classical genes involved in the autophagy pathway, among them a less characterized one, DEF8 (Differentially expressed in FDCP 8), initially considered a Rubicon family member, in peripheralblood mononuclear cells (PBMCs) from individuals with mild cognitive impairment (MCI) and probable AD (pAD) and correlate the results with the expression of DEF8 in the brain of 5xFAD mice. METHOD By real-time PCR and flow cytometry, we evaluated autophagy genes levels in PBMCs from MCI and pAD patients. We evaluated DEF8 levels and its localization in brain samples of the 5xFAD mice by real-time PCR, western blot, and immunofluorescence. RESULTS Transcriptional levels of DEF8 were significantly reduced in PBMCs of MCI and pAD patients compared with healthy donors, correlating with the MoCA and MoCA-MIS cognitive tests scores. DEF8 protein levels were increased in lymphocytes from MCI but not pAD, compared to controls. In the case of brain samples from 5xFAD mice, we observed a reduced mRNA expression and augmented protein levels in 5xFAD compared to age-matched wild-type mice. DEF8 presented a neuronal localization. CONCLUSION DEF8, a protein proposed to act at the final step of the autophagy/endolysosomal pathway, is differentially expressed in PBMCs of MCI and pAD and neurons of 5xFAD mice. These results suggest a potential role for DEF8 in the pathophysiology of AD.
Formation of porous poly(ethylene‐co‐vinyl alcohol) membrane via thermally induced phase separation

Crystalline poly(ethylene-co-vinyl alcohol) (EVOH) membranes were prepared by a thermally induced phase separation (TIPS) process. The diluents used were 1,3-propanediol and 1,3-butanediol. The dynamic crystallization temperature was determined by DSC measurement. No structure was detected by an optical microscope in the temperature region higher than the crystallization temperature. This means that porous membrane structures were formed by solid–liquid phase separation (polymer crystallization) rather than by liquid–liquid phase separation. The EVOH/butanediol system showed a higher dynamic crystallization temperature and equilibrium melting temperature than those of the EVOH/propanediol system. SEM observation showed that the sizes of the crystalline particles in the membranes depended on the polymer concentration, cooling rate, and kinds of diluents. © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 79: 2449–2455, 2001
Quasi-Reversible Chloride Adsorption/Desorption through a Polycationic Organic Film on Cu(100)

Combined cyclic voltammetry and in situ scanning tunneling microscopy studies were employed to gain information about the interfacial structure of a chloride modified Cu(100) electrode surface exposed to an acidic electrolyte solution that contained redox-active dibenzylviologens (DBV, 1,1‘-dibenzyl-4,4‘-bipyridinium molecules). A particular focus of this contribution lies in the structural characterization of the electrode surface under nonequilibrium reactive conditions, for example, during the occurrence of an electron-transfer reaction. Typically, two pairs of clearly distinguishable current waves denoted as P1/P1‘ and P2/P2‘ appear in the cyclic voltammogram of Cu(100) in a mixture of 10 mM HCl and 0.1 mM DBVCl2, provided the cathodic potential limit remains restricted to values of Ework > −425 mV vs reversible hydrogen electrode. Systematic variations of the DBV solution concentration and the nature of the counterion strongly suggest that P1 has to be assigned to the first electron-transfer reaction.
Development and characterization of lyophilized cefpodoxime proxetil-Pluronic® F127/polyvinylpyrrolidone K30 solid dispersions with improved dissolution and enhanced antibacterial activity

Abstract The aim of this study was the development of hard-cellulose capsules containing cefpodoxime proxetil (CEF) (BCS Class II) loaded novel Pluronic® F127 (P127)/Polyvinylpyrrolidone K30 (PVP) solid dispersions (SDs) using ultrasonic probe induced solvent-lyophilization method for effective antibacterial treatment by means of improved saturated aqueous solubility, dissolution rate, reduced particle size, and wettability. SDs were evaluated for physical and solid-state analyses. The solubility of pure CEF was calculated as 0.269 ± 0.005 mg/mL, SDs formulated with P127/PVP exhibited increased solubility from 3.5- to 8-fold. Molecular distribution of CEF in SDs and formation of CEF loaded amorphous polymeric network were confirmed with morphological study, thermal analysis, Fourier-transform infrared spectroscopy (FT-IR), and 1H-NMR studies. Staphylococcus aureus (ATCC 29213), Escherichia coli (ATCC 25922), and Klebsiella pneumoniae (ATCC 700603) were used to investigate the antibacterial effectiveness of the SDs. The minimum inhibitory concentration (MIC) values of the P127/PVP SDs were found 2–8 times lower than the pure CEF. All SDs from hard-cellulose capsules exhibited significantly faster release than unprocessed CEF. The profiles of SDs and reference were detected to be dissimilar according to difference (f1) and similarity factor (f2). Hard-cellulose capsules containing CEF loaded P127/PVP SDs appear to be feasible alternative to commercially available CEF tablets for effective antibacterial therapy at lowest dose. Graphical Abstract
Reactions of cysteine with N-methyl-N-nitroso-p-toluenesulfonamide and N-methyl-N′-nitro-N-nitrosoguanidine

The reaction between cysteine and N-methyl-N-nitroso-p-toluenesulfonamide affords almost quantitative yields of cystine and N-methyl-p-toluenesulfonamide. A mechanism based on the intermediacy of the S-nitroso derivative of cysteine and the intermediate formation of nitric oxide is proposed. Nitrous oxide is shown to be a final product. In the reaction of cysteine with N-methyl-N′-nitro-N-nitrosoguanidine a substantial yield of 2-nitramino-4-carboxyl-thiazoline is obtained. Cystine, N-methyl-N′-nitro-guanidine and S-methylcysteine are formed in lesser amounts. The major product arises from nucleophilic attack on the imino carbon of N-methyl-N′-nitro-N-nitrosoguanidine. Concomitant elimination of the methylnitrosamino group accounts for the mathylating ability of the system.
Clinical Outcomes, Structure, and Function Improve With Both Heavy and Moderate Loads in the Treatment of Patellar Tendinopathy: A Randomized Clinical Trial

Background: Loading interventions have become a predominant treatment strategy for tendinopathy, and positive clinical outcomes and tendon tissue responses may depend on the exercise dose and load magnitude. Purpose/Hypothesis: The purpose was to investigate if the load magnitude influenced the effect of a 12-week loading intervention for patellar tendinopathy in the short term (12 weeks) and long term (52 weeks). We hypothesized that a greater load magnitude of 90% of 1 repetition maximum (RM) would yield a more positive clinical outcome, tendon structure, and tendon function compared with a lower load magnitude of 55% of 1 RM when the total exercise volume was kept equal in both groups. Study Design: Randomized clinical trial; Level of evidence, 1. Methods: A total of 44 adult participants with chronic patellar tendinopathy were included and randomized to undergo moderate slow resistance (MSR group; 55% of 1 RM) or heavy slow resistance (HSR group; 90% of 1 RM). Function and symptoms (Victorian Institute of Sport Assessment–Patella questionnaire [VISA-P]), tendon pain during activity (numeric rating scale [NRS]), and ultrasound findings (tendon vascularization and swelling) were assessed before the intervention, at 6 and 12 weeks during the intervention, and at 52 weeks from baseline. Tendon function (functional tests) and tendon structure (ultrasound and magnetic resonance imaging) were investigated before and after the intervention period. Results: The HSR and MSR interventions both yielded significant clinical improvements in the VISA-P score (mean ± SEM) (HSR: 0 weeks, 58.8 ± 4.3; 12 weeks, 70.5 ± 4.4; 52 weeks, 79.7 ± 4.6) (MSR: 0 weeks, 59.9 ± 2.5; 12 weeks, 72.5 ± 2.9; 52 weeks, 82.6 ± 2.5), NRS score for running, NRS score for squats, NRS score for preferred sport, single-leg decline squat, and patient satisfaction after 12 weeks, and these were maintained after 52 weeks. HSR loading was not superior to MSR loading for any of the measured clinical outcomes. Similarly, there were no differences in functional (strength and jumping ability) or structural (tendon thickness, power Doppler area, and cross-sectional area) improvements between the groups undergoing HSR and MSR loading. Conclusion: There was no superior effect of exercising with a high load magnitude (HSR) compared with a moderate load magnitude (MSR) for the clinical outcome, tendon structure, or tendon function in the treatment of patellar tendinopathy in the short term. Both HSR and MSR showed equally good, continued improvements in outcomes in the long term but did not reach normal values for healthy tendons. Registration: NCT03096067 (ClinicalTrials.gov identifier)
Increased risk for prostate cancer related mortality among childless men in a population-based cohort followed for up to 40 years

Abstract Based on a nationwide register data we recently reported a link between male infertility and increased risk of early onset prostate cancer. However, mortality due to prostate cancer, which can be regarded as the ultimate proxy for its clinical significance, especially in the context of over-diagnosis and over-treatment, could not be explored in the previous study, since the follow-up period in most cases was too short. Data therefore must be retrieved from other cohorts, with longer follow-up. We sourced data from a population-based prospective cohort including 11,343 men aged over 45 years, enrolled in the 1970s. The results showed that childless men have higher risk for prostate cancer related mortality (HR: 1.49, 95% CI: 1.09–2.03, p = 0.01) compared to men with children, in particular when only married men, who most probably are involuntary childless, were considered (HR 1.54, 95% CI 1.13 − 2.10, p = 0.006). However, the prostate cancer incidence did not differ (HR = 1.04, 95% CI: 0.88–1.24). In conclusion, our results show that childless men are at higher risk for dying from prostate cancer, probably due to a more aggressive form of the disease.
Ferroelectricity in Sodium Nitrite Thin Films

Investigations have been conducted on the ferroelectric property of thin films of NaNO2. The thin films were prepared with the dip coating technique. The phase transition was investigated by observing the change in the dielectric constant with temperature change. The presence of ferro-electricity was investigated with a Sawyer-Tower Bridge. UV-VIS absorbance spectroscopy was used to determine the energy band gap and the extinction coefficient at room temperature. It was observed thatNaNO2 thin film undergoes a first order transition from the disordered paraelectric phase to an ordered ferroelectric phase at 162.3�C. Ferroelectricity was confirmed in the NaNO2 thin films by the appearance of a hysteresis loop below the transition temperature. The band gap of the thin film was 3.102 eV. The ferroelectric property exhibited by the NaNO2 thin films do not make it a favourable choice for modern day ferroelectric devices. However, this may be im-proved by doping the thin film with chlorine ions.
Influence of poultry manure and inorganic nitrogen fertilizer on grain yield and proximate component of two cultivars of cowpea ( Vigna unguiculata (L.) Walps)

A study on the influence of poultry manure and inorganic nitrogen fertilizer on grain yield and proximate composition of two cultivars of cowpea (Ife Brown and IT86D - 719) was carried out at the Teaching and Research (TR thus having significant influence on the final yield of the two cultivars; while pod length (PL), number of pods per peduncle (PPE), number of seeds per pod (NSP), 100SW were not. The crude protein, percent crude fibre, total nitrogen and carbohydrate content of the grains varied among cultivars and were significantly improved by fertilizer source, especially IFPM and PM. The significant response observed in the nutritional composition indicated differential utilization of nutrients under different treatments. The differential response of Ife Brown and IT86D-719 to poultry manure and inorganic fertilizer is clearly manifested on the grain yield, crude protein, percent crude fibre, total nitrogen and carbohydrate content of the grains of the two cultivars. Key Words: cowpea; cultivars; nutrient source; poultry manure; proximate composition; yield Moor J. Agric. Res. Vol.4(1) 2003:37-45
Combined therapy with conventional trans-arterial chemoembolization (cTACE) and microwave ablation (MWA) for hepatocellular carcinoma >3–<5 cm

Abstract Purpose To compare safety and efficacy of combined therapy with conventional transarterial chemoembolization (cTACE)+microwave ablation (MWA) versus only TACE or MWA for treatment of hepatocellular carcinoma (HCC) >3–<5 cm. Methods This randomized controlled trial (NCT04721470) screened 278 patients with HCC >3–<5 cm. Patients were randomized into three groups: 90 underwent TACE (Group 1); 95 underwent MWA (Group 2); and 93 underwent combined therapy (Group 3). Patients were followed-up with contrast-enhanced CT or MRI. Images were evaluated and compared for treatment response and adverse events based on modified response evaluation criteria in solid tumor. Serum alpha-fetoprotein (AFP) concentration was measured at baseline and during every follow-up visit. Results Final analysis included 265 patients (154 men, 111 women; mean age = 54.5 ± 11.8 years; range = 38–76 years). Complete response was achieved by 86.5% of patients who received combined therapy compared with 54.8% with only TACE and 56.5% with only MWA (p = 0.0002). The recurrence rate after 12 months was significantly lower in Group 3 (22.47%) than Groups 1 (60.7%) and 2 (51.1%) (p = 0.0001). The overall survival rate (three years after therapy) was significantly higher in Group 3 (69.6%) than Groups 1 (54.7%) and 2 (54.3%) (p = 0.02). The mean progression-free survival was significantly higher in Group 3 than groups 1 and 2 (p < 0.001). A decrease in AFP concentration was seen in 75%, 63%, and 48% patients of Group 3, 2, and 1, respectively. Conclusions Combined therapy with cTACE + MWA is safe, well-tolerated, and more effective than TACE or MWA alone for treatment of HCC >3–<5 cm.
Adrenomedullin Receptor Antagonists as Novel Angiogenesis Inhibitors

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“You Should Maybe Work Together a Little Bit”: Formulating Requests in Interprofessional Interactions

Based on an empirical analysis of video-recorded collaborative practice situations, this article looks at different ways in which a health professional can direct a request to another professional with the aim that he or she performs an action. Using a corpus of video-recorded interactions in different institutional settings and types of situations, it looks at how requests are formulated, showing that they can range from authoritative to mitigated, direct to indirect, and explicit to implicit. The study shows that professionals use a great deal of strategies to preserve politeness and each other’s right not to be told what to do, aiming at mitigating the “face-threatening” aspect of requests. However, by doing so, they frequently produce unclear statements which can impede good communication and professional collaboration.
A long reads-based de-novo assembly of the genome of the Arlee homozygous line reveals chromosomal rearrangements in rainbow trout.

Currently, there is still a need to improve the contiguity of the rainbow trout reference genome and to use multiple genetic backgrounds that will represent the genetic diversity of this species. The Arlee doubled haploid line was originated from a domesticated hatchery strain that was originally collected from the northern California coast. The Canu pipeline was used to generate the Arlee line genome de-novo assembly from high coverage PacBio long-reads sequence data. The assembly was further improved with Bionano optical maps and Hi-C proximity ligation sequence data to generate 32 major scaffolds corresponding to the karyotype of the Arlee line (2 N = 64). It is composed of 938 scaffolds with N50 of 39.16 Mb and a total length of 2.33 Gb, of which ∼95% was in 32 chromosome sequences with only 438 gaps between contigs and scaffolds. In rainbow trout the haploid chromosome number can vary from 29 to 32. In the Arlee karyotype the haploid chromosome number is 32 because chromosomes Omy04, 14 and 25 are divided into six acrocentric chromosomes. Additional structural variations that were identified in the Arlee genome included the major inversions on chromosomes Omy05 and Omy20 and additional 15 smaller inversions that will require further validation. This is also the first rainbow trout genome assembly that includes a scaffold with the sex-determination gene (sdY) in the chromosome Y sequence. The utility of this genome assembly is demonstrated through the improved annotation of the duplicated genome loci that harbor the IGH genes on chromosomes Omy12 and Omy13.
Macrophage targeting with the novel carbopol-based miltefosine-loaded transfersomal gel for the treatment of cutaneous leishmaniasis: in vitro and in vivo analyses

Abstract Objective The purpose of this study was to develop novel carbopol-based miltefosine-loaded transfersomal gel (HePCTG) for the treatment of cutaneous leishmaniasis (CL) via efficient targeting of leishmania infected macrophages. Methods Miltefosine-loaded transfersomes (HePCT) were prepared by ethanol injection method followed by their incorporation into carbopol gel to form HePCTG. The prepared HePCT were assessed for physicochemical properties including mean particle size, polydispersity index, zeta potential, entrapment efficiency, morphology, and deformability. Similarly, HePCTG was evaluated for physiochemical and rheological attributes. The in vitro release, skin permeation, skin irritation, anti-leishmanial activity, and in vivo efficacy in BALB/c mice against infected macrophages were also performed for HePCT. Results The optimized HePCT displayed a particle size of 168 nm with entrapment efficiency of 92%. HePCTG showed suitable viscosity, pH, and sustained release of the incorporated drug. Furthermore, HePCT and HePCTG demonstrated higher skin permeation than drug solution. The results of macrophage uptake study indicated improved drug intake by passive diffusion. The lower half maximal inhibitory concentration value, selectivity index and higher 50% cytotoxic concentration value of HePCT compared to that of HePC solution demonstrated the improved anti-leishmanial efficacy and non-toxicity of the formulation. This was further confirmed by the notable reduction in parasite load and lesion size observed in in vivo anti-leishmanial study. Conclusion It can be stated that the formulated HePCTG can effectively be used for the treatment of CL.
Protective effects of dietary carnosine during in-vitro digestion of pork differing in fat content and cooking conditions.

Muscle carnosine represents an important health advantage of meat. Ground pork samples with intrinsic or added carnosine; fat content; and cooked under low or high intensity as a 2 × 2 × 2 factorial were digested in-vitro. Changes in free carnosine and in markers of lipid (hexanal, 4-hydroxynonenal (4-HNE), malondialdehyde (MDA) and protein (protein-carbonyls, thiols) oxidation, and of advanced glycation end-products (AGEs) Nε -(carboxymethyl)lysine (CML) were determined in the saliva, gastric, and duodenal digests. During digestion, the different markers overall indicated increased oxidation and decreased free carnosine. Increasing pork carnosine level significantly reduced protein carbonyls, loss of thiols, and 4-HNE during in-vitro gastric digestion, irrespective of fat and cooking level of the meat. Increased carnosine also significantly reduced hexanal, MDA and CML up to the duodenum phase in moderately cooked lean pork. Besides substantiating the formation of AGEs during digestion, these results show a potentially important role of dietary carnosine occurring in the gastrointestinal tract. PRACTICAL APPLICATIONS: The ailments epidemiologically associated with red meat consumption could be counteracted by ingesting carnosine into meat. The health advantages of dietary carnosine, however, have never been demonstrated during digestion, a unique and complex oxidative environment compounded by the composition and cooking of the meat. The results obtained substantiated that AGEs formation occurred in-vitro in the GIT. They also showed that increased carnosine had an immediate health beneficial role during pork digestion in reducing the formation of different harmful molecules, including AGEs, modulated by the composition and cooking of the meat. However, in exerting this protective role in the GIT, the remaining free level of carnosine, gradually decreased during digestion. Carnosine, as an important meat compositional factor may, depending on the fat content and cooking conditions, change the image of meat from representing a health risk to a health benefit. Carnosine level may also explain discrepancies observed in the literature.
In vitro evaluation of bioburden, three-dimensional stability, and accuracy of surgical templates without metallic sleeves after routinely infection control activities.

BACKGROUND Surgical templates are classified as noncritical devices, and they do not need to be sterile. AIM Primary aim of this study was to assess the microbiological burden present on the surgical templates without metallic sleeves after disinfection. Furthermore, to evaluate trueness after disinfection and steam sterilization at 121°C/15 min, and over a 8-week storage period. Finally, to assess their accuracy after in vitro implant placement simulation. MATERIALS AND METHODS Forty surgical templates were printed and divided in five groups of eight templates each. Groups A to C were disinfected with 0.5% Chlorhexidine Gluconate and 70% ethyl alcohol base solution for 15 min. Templates in the group D were steam sterilized at 121°C for 15 min, while, the templates in the group E were used as control. Implant simulation was performed in the group A. Outcome measures were determination of bioburden, trueness assessment using GOM Inspect Professional software, and accuracy evaluated thought the mean angular deviation of simulated implants. RESULTS Total microbic charge measured as colony forming units (CFU) for sample, was 24.40 in the control group (group E; n = 8), and <4.40 in the test group (group C; n = 8), with a reduction of 84%. Colored representation from GOM inspection showed no differences after disinfection and implant simulation, disinfection alone, and steam sterilization, compared to the control group. A very small difference in the surface and volume dimensions was reported 1 month after templates fabrication. The mean roundness tolerances of the tested templates improved of 0.96 ± 0.56° (95% CI 0.57-1.35). CONCLUSION Surgical templates without metallic sleeves can be safely used after disinfection, demonstrating high level of accuracy, even when the surgical procedures should be postponed within a couple of weeks. Further in vivo study are needed to confirm these preliminary results.