Miracle-dz/UniFAR-FTUs huggingface dataset:
Production of ACE Inhibitory Peptides from Whey Proteins Modified by High Intensity Ultrasound Using Bromelain

High Intensity Ultrasound (HIUS) can induce modification of the protein structure. The combination of enzymatic hydrolysis and ultrasound is an interesting strategy to improve the release of the Angiotensin-Converting Enzyme (ACE) inhibitory peptides. In this study, whey proteins were pretreated with HIUS at two levels of amplitude (30 and 50%) for 10 min, followed by hydrolysis using the vegetable protease bromelain. The hydrolysates obtained were ultrafiltrated and their fractions were submitted to a simulated gastrointestinal digestion. The conformational changes induced by HIUS on whey proteins were analyzed using Fourier-transform infrared spectroscopy by attenuated total reflectance (FTIR-ATR) and intrinsic spectroscopy. It was found that both levels of ultrasound pretreatment significantly decreased the IC50 value (50% Inhibitory Concentration) of the hydrolysates in comparison with the control (α = 0.05). After this treatment, HIUS-treated fractions were shown as smaller in size and fractions between 1 and 3 kDa displayed the highest ACE inhibition activity. HIUS promoted significant changes in whey protein structure, inducing, unfolding, and aggregation, decreasing the content of α-helix, and increasing β-sheets structures. These findings prove that ultrasound treatment before enzymatic hydrolysis is an innovative and useful strategy that modifies the peptide profile of whey protein hydrolysates and enhances the production of ACE inhibitory peptides.
Crosstalk between PRLR and EGFR/HER2 Signaling Pathways in Breast Cancer

Simple Summary Prolactin receptor (PRLR) and epidermal growth factor receptor (EGFR/ERBB) signaling pathways have a crucial role in the development of mammary glands and breast carcinogenesis. In this review, we have provided ample evidence to support the significant role for PRLR and EGFR/HER2 signaling crosstalk in breast cancer. Recent studies from our lab and other finding also recognize how these two receptors work together to induce hyperactivation of their downstream signaling kinases that overlap with each other and in turn further induce target genes and other pro-oncogenic factors. Prolactin through PRLR can activate both EGFR and HER2 downstream signaling pathways which in turn leads to activation of other oncogenic growth factors that promote growth, survival, and proliferation of breast cancer cells. The crosstalk between PRLR and EGFR/HER2 signaling is an additional route that magnifies the actions of their ligands, and further promote tumor growth. This may be responsible for endocrine resistance in breast cancer patients resulting in tumor relapse. Abstract Prolactin receptor (PRLR) and epidermal growth factor receptor (EGFR/ERBB) signaling pathways activated by prolactin (PRL) and epidermal growth factor (EGF), have a major role in the mammary gland development and in the etiology of breast cancer, respectively. ER+ breast tumors comprise up to 75% of all breast cancers and 10% of these are HER2+. Elevated levels of PRLR in breast tumors, high circulating levels of PRL and increased expression of ERBB1/2 in patients that become resistant to endocrine therapy have shown to be associated with higher risk of cancer progression. In this review, we examine the role of crosstalk between PRLR and ERBB1/2 signaling pathways in the activation of unliganded ERα, cyclin-D1 and other oncogenic factors (MYC, FOS, JUN) in breast cancer. PRL/PRLR and EGF/EGFR induces phosphorylation of ERα through activation of MEK/MAPK and PI3K/AKT signaling pathways. PRL in breast cancer cells via PRLR/JAK2 can also induce phosphorylation of ERBB2/HER2, which in turn activates the downstream RAS/MEK/ERK pathway required for ERα phosphorylation. EGFR, independent of PRL/PRLR, can activate STAT5 indirectly via c-SRC and drive the expression of target genes involved in cell proliferation and survival. The crosstalk between PRLR and HER2, where PRL induces HER2 signaling can be an alternative route for ERα activation to induce transcription of PRLR and other ER target genes. We believe that overexpression of EGFR/HER2 and PRLR in breast tumors could maximize the actions of their ligands, and further induce cell proliferation promoting malignancy. This could also explain the resistance to endocrine therapy resulting in tumor growth.
Characteristics of Home-Visit Nursing Agencies That Closed after the 2012 Fee Revision for Home-Visit Nursing Services: A Nationwide Panel Data Analysis in Japan

Despite the 2012 fee revision raising fees for home-visit nursing services to increase their supply in Japan, 300 to 500 home-visit nursing agencies (VNA) are still being closed annually. This study aims to identify the regional and organizational characteristics of the VNAs that closed after the 2012 fee revision. A longitudinal observational study was conducted using nationwide panel data of VNAs from 2014 to 2017 (N = 6496). Multiple logistic regression models stratified by years of operation were used for the analysis. We identified 821 closed agencies (12.6%). In this study, many important factors related to VNA closures were found. In the less than three years group, there were regional factors (lower aging rate and larger number of clinics) and an organizational factor (higher proportion of users under 40 years of age). In the 3–14 years group, there was a regional factor (larger number of clinics) and organizational factors (smaller number of FTE nurses, smaller number of users per FTE nurse, and smaller number of medical care types that can be provided). In the over 15 years group, there was an organizational factor (smaller number of FTE nurses). The findings provide valuable insights for policymakers in avoiding VNA closures.
The Sound of Silence: How Silenced Chromatin Orchestrates the Repair of Double-Strand Breaks

The eukaryotic nucleus is continuously being exposed to endogenous and exogenous sources that cause DNA breaks, whose faithful repair requires the activity of dedicated nuclear machineries. DNA is packaged into a variety of chromatin domains, each characterized by specific molecular properties that regulate gene expression and help maintain nuclear structure. These different chromatin environments each demand a tailored response to DNA damage. Silenced chromatin domains in particular present a major challenge to the cell’s DNA repair machinery due to their specific biophysical properties and distinct, often repetitive, DNA content. To this end, we here discuss the interplay between silenced chromatin domains and DNA damage repair, specifically double-strand breaks, and how these processes help maintain genome stability.
Comparison of the Vibration Damping of the Wood Species Used for the Body of an Electric Guitar on the Vibration Response of Open-Strings

Research show that the vibrations of the strings and the radiated sound of the solid body electric guitar depend on the vibrational behavior of its structure in addition to the extended electronic chain. In this regard, most studies focused on the vibro-mechanical properties of the neck of the electric guitar and neglected the coupling of the vibrating strings with the neck and the solid body of the instrument. Therefore, the aim of the study was to understand how the material properties of the solid body could affect the stiffness and vibration damping of the whole instrument when comparing ash (Fraxinus excelsior L.) and walnut (Juglans regia L.) wood. In the electric guitar with identical components, higher modal frequencies were confirmed in the structure of the instrument when the solid body was made of the stiffer ash wood. The use of ash wood for the solid body of the instrument due to coupling effect resulted in a beneficial reduction in the vibration damping of the neck of the guitar. The positive effect of the low damping of the solid body of the electric guitar made of ash wood was also confirmed in the vibration of the open strings. In the specific case of free-free vibration mode, the decay time was longer for higher harmonics of the E2, A2 and D3 strings.
Effects of Intensive and Semi-Intensive Production on Sheep Milk Chemical Composition, Physicochemical Characteristics, Fatty Acid Profile, and Nutritional Indices

Simple Summary Intensive and semi-intensive sheep farming are the two farming systems usually employed in Greece. Several studies have been conducted on the effect of the farming system on sheep milk fatty acid composition. This study simultaneously examines milk basic composition, physicochemical characteristics, fatty acid composition, and nutritional value according to the production system. Bulk tank milk from farms using the intensive and semi-intensive production systems was analyzed. The results show that grazing can improve the fatty acid composition of milk. Thus, pasture-based feeding strategies could improve the fatty acid composition and the nutritional properties of sheep dairy products. Abstract Dairy sheep farming is a vital sector of the agricultural economy in Greece. Information on the effect of the farming system on sheep milk characteristics is critical for producing dairy products with improved nutritional value according to the current guidelines for healthy food consumption. This study aimed to investigate the basic composition, physicochemical characteristics, fatty acid composition, and nutritional indices of milk produced in intensive and semi-intensive sheep farms. Bulk tank milk samples from 20 intensive and 20 semi-intensive sheep farms were examined. Sheep in the intensive farms were kept indoors and were fed with roughage, silage, and concentrates. Sheep in the semi-intensive farms were kept indoors during the night and were moved to the pastures during the day. Sheep were fed with roughage, silage, and concentrates in combination with grazing. Milk composition and somatic cell count were determined with automatic analyzers. The physicochemical characteristics were determined with standard laboratory methods. The fatty acid composition was analyzed by gas chromatography. The farming system did not affect milk chemical composition and physicochemical characteristics. However, milk fatty acid composition and nutritional value were significantly improved in milk from farms using the semi-intensive production system, and this favorable effect was attributed to the inclusion of pasture in sheep diet.
Impacts of Hypoxia on Osteoclast Formation and Activity: Systematic Review

Hypoxia is evident in several bone diseases which are characterized by excessive bone resorption by osteoclasts, the bone-resorbing cells. The effects of hypoxia on osteoclast formation and activities are widely studied but remain inconclusive. This systematic review discusses the studies reporting the effect of hypoxia on osteoclast differentiation and activity. A literature search for relevant studies was conducted through SCOPUS and PUBMED MEDLINE search engines. The inclusion criteria were original research articles presenting data demonstrating the effect of hypoxia or low oxygen on osteoclast formation and activity. A total of 286 studies were identified from the search, whereby 20 studies were included in this review, consisting of four in vivo studies and 16 in vitro studies. In total, 12 out of 14 studies reporting the effect of hypoxia on osteoclast activity indicated higher bone resorption under hypoxic conditions, 14 studies reported that hypoxia resulted in more osteoclasts, one study found that the number remained unchanged, and five studies indicated that the number decreased. In summary, examination of the relevant literature suggests differences in findings between studies, hence the impact of hypoxia on osteoclasts remains debatable, even though there is more evidence to suggest it promotes osteoclast differentiation and activity.
ANTIOXIDANT PROFILE AND PHYTOCHEMICAL CONTENT OF DIFFERENT PARTS OF SUPER RED DRAGON FRUIT (HYLOCEREUS COSTARICENSIS) COLLECTED FROM WEST JAVA-INDONESIA

Objectives : The goals of this research were to observe antioxidant properties from different parts of super red dragon fruit ( Hylocereus costaricensis ) using two antioxidant testing methods which were 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2’-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) (ABTS). Methods: Antioxidant activities were determined using DPPH and ABTS assays, total phenolic content (TPC) using Folin–Ciocalteu reagent, flavonoid content by Chang’s method. Results: Inhibitory concentration 50% (IC50) of DPPH scavenging activity of all of the extracts in the range of 2.69 μg/ml was −94.17 μg/ml. The ethyl acetate peel extract of super red dragon fruit expressed the highest TPC (4.56 g GAE/100 g) and the highest total flavonoid content (12.63 g QE/100 g). TPC in flesh extract of super red dragon fruit had a negative and significant correlation with their IC50 of ABTS. The IC50 of DPPH and IC50 of ABTS of flesh extract of super red dragon fruit showed positive and significant correlation. Conclusion: All different parts extracts of super red dragon fruit (except n-hexane flesh extract) were categorized as a very strong antioxidant by DPPH method. Phenolic compounds in flesh extract of super red dragon fruit were the major contributor in antioxidant activities by ABTS method. DPPH and ABTS showed linear results in antioxidant activities of super red dragon fruit flesh extract.
Transcriptional Landscaping Identifies a Beige Adipocyte Depot in the Newborn Mouse

The present study sought to identify gene networks that are hallmarks of the developing inguinal subcutaneous adipose tissue (iWAT) and the interscapular brown adipose tissue (BAT) in the mouse. RNA profiling revealed that the iWAT of postnatal (P) day 6 mice expressed thermogenic and lipid catabolism transcripts, along with the abundance of transcripts associated with the beige adipogenesis program. This was an unexpected finding, as thermogenic BAT was believed to be the only site of nonshivering thermogenesis in the young mouse. However, the transcriptional landscape of BAT in P6 mice suggests that it is still undergoing differentiation and maturation, and that the iWAT temporally adopts thermogenic and lipolytic potential. Moreover, P6 iWAT and adult (P56) BAT were similar in their expression of immune gene networks, but P6 iWAT was unique in the abundant expression of antimicrobial proteins and virus entry factors, including a possible receptor for SARS-CoV-2. In summary, postnatal iWAT development is associated with a metabolic shift from thermogenesis and lipolysis towards fat storage. However, transcripts of beige-inducing signal pathways including β-adrenergic receptors and interleukin-4 signaling were underrepresented in young iWAT, suggesting that the signals for thermogenic fat differentiation may be different in early postnatal life and in adulthood.
Metabolism of Phenolics of Tetrastigma hemsleyanum Roots under In Vitro Digestion and Colonic Fermentation as Well as Their In Vivo Antioxidant Activity in Rats

Tetrastigma hemsleyanum Diels et Gilg is a herbaceous perennial species distributed mainly in southern China. The Tetrastigma hemsleyanum root (THR) has been prevalently consumed as a functional tea or dietary supplement. In vitro digestion models, including colonic fermentation, were built to evaluate the release and stability of THR phenolics with the method of HPLC-QqQ-MS/MS and UPLC-Qtof-MS/MS. From the oral cavity, the contents of total phenolic and flavonoid began to degrade. Quercetin-3-rutinoside, quercetin-3-glucoside, kaempferol-3-rutinoside, and kaempferol-3-glucoside were metabolized as major components and they were absorbed in the form of glycosides for hepatic metabolism. On the other hand, the total antioxidant capacity (T-AOC), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activity, and glutathione (GSH) content were significantly increased, while malondialdehyde (MDA) content was decreased in plasma and tissues of rats treated with THR extract in the oxidative stress model. These results indicated that the THR extract is a good antioxidant substance and has good bioavailability, which can effectively prevent some chronic diseases caused by oxidative stress. It also provides a basis for the effectiveness of THR as a traditional functional food.
3D-Printed Oral Dosage Forms: Mechanical Properties, Computational Approaches and Applications

The aim of this review is to present the factors influencing the mechanical properties of 3D-printed oral dosage forms. It also explores how it is possible to use specific excipients and printing parameters to maintain the structural integrity of printed drug products while meeting the needs of patients. Three-dimensional (3D) printing is an emerging manufacturing technology that is gaining acceptance in the pharmaceutical industry to overcome traditional mass production and move toward personalized pharmacotherapy. After continuous research over the last thirty years, 3D printing now offers numerous opportunities to personalize oral dosage forms in terms of size, shape, release profile, or dose modification. However, there is still a long way to go before 3D printing is integrated into clinical practice. 3D printing techniques follow a different process than traditional oral dosage from manufacturing methods. Currently, there are no specific guidelines for the hardness and friability of 3D printed solid oral dosage forms. Therefore, new regulatory frameworks for 3D-printed oral dosage forms should be established to ensure that they meet all appropriate quality standards. The evaluation of mechanical properties of solid dosage forms is an integral part of quality control, as tablets must withstand mechanical stresses during manufacturing processes, transportation, and drug distribution as well as rough handling by the end user. Until now, this has been achieved through extensive pre- and post-processing testing, which is often time-consuming. However, computational methods combined with 3D printing technology can open up a new avenue for the design and construction of 3D tablets, enabling the fabrication of structures with complex microstructures and desired mechanical properties. In this context, the emerging role of computational methods and artificial intelligence techniques is highlighted.
RNA-Sequencing Based microRNA Expression Signature of Colorectal Cancer: The Impact of Oncogenic Targets Regulated by miR-490-3p

To elucidate novel aspects of the molecular pathogenesis of colorectal cancer (CRC), we have created a new microRNA (miRNA) expression signature based on RNA-sequencing. Analysis of the signature showed that 84 miRNAs were upregulated, and 70 were downregulated in CRC tissues. Interestingly, our signature indicated that both guide and passenger strands of some miRNAs were significantly dysregulated in CRC tissues. These findings support our earlier data demonstrating the involvement of miRNA passenger strands in cancer pathogenesis. Our study focused on downregulated miR-490-3p and investigated its tumor-suppressive function in CRC cells. We successfully identified a total of 38 putative oncogenic targets regulated by miR-490-3p in CRC cells. Among these targets, the expression of three genes (IRAK1: p = 0.0427, FUT1: p = 0.0468, and GPRIN2: p = 0.0080) significantly predicted 5-year overall survival of CRC patients. Moreover, we analyzed the direct regulation of IRAK1 by miR-490-3p, and its resultant oncogenic function in CRC cells. Thus, we have clarified a part of the molecular pathway of CRC based on the action of tumor-suppressive miR-490-3p. This new miRNA expression signature of CRC will be a useful tool for elucidating new molecular pathogenesis in this disease.
Clinical Course, Myopathology and Challenge of Therapeutic Intervention in Pediatric Patients with Autoimmune-Mediated Necrotizing Myopathy

(1) Background: Immune–mediated necrotizing myopathy (IMNM) is a rare form of inflammatory muscle disease which is even more rare in pediatric patients. To increase the knowledge of juvenile IMNM, we here present the clinical findings on long-term follow-up, myopathological changes, and therapeutic strategies in two juvenile patients. (2) Methods: Investigations included phenotyping, determination of antibody status, microscopy on muscle biopsies, MRI, and response to therapeutic interventions. (3) Results: Anti-signal recognition particle (anti-SRP54) and anti- 3-hydroxy-3-methylglutarly coenzyme A reductase (anti-HMGCR) antibodies (Ab) were detected in the patients. Limb girdle presentation, very high CK-levels, and a lack of skin rash at disease-manifestation and an absence of prominent inflammatory signs accompanied by an abnormal distribution of α-dystroglycan in muscle biopsies initially hinted toward a genetically caused muscle dystrophy. Further immunostaining studies revealed an increase of proteins involved in chaperone-assisted autophagy (CASA), a finding already described in adult IMNM-patients. Asymmetrical muscular weakness was present in the anti-SRP54 positive Ab patient. After initial stabilization under therapy with intravenous immunoglobulins and methotrexate, both patients experienced a worsening of their symptoms and despite further therapy escalation, developed a permanent reduction of their muscle strength and muscular atrophy. (4) Conclusions: Diagnosis of juvenile IMNM might be complicated by asymmetric muscle weakness, lack of cutaneous features, absence of prominent inflammatory changes in the biopsy, and altered α-dystroglycan.
Factors Influencing Turnover Intention among Male Nurses in Korea

The study examined predictors of male nurse turnover intention in Korea using data collected from Korean hospitals. The results were obtained based on a secondary analysis of data previously collected from 306 male nurses in 16 regions of Korea from December 2014 to February 2015. Our findings suggest that male nurse turnover intention is predicted by (1) individual factors: single (B = 0.93, p = 0.008); (2) organizational factors: organizational commitment (B = −0.36, p < 0.001), job satisfaction (B = −0.27, p = 0.001), and job stress (B = 0.24, p < 0.001); and (3) social factors: hospital location in medium-categorized cities (B = 0.70, p = 0.012) and kinship responsibility (B = 0.13, p = 0.026). These factors accounted for 56.9% of the total variance. To lower the rate of turnover intention among male nurses, strategic interventions should be implemented based on the factors identified in this study.
The NIH Lipo-COVID Study: A Pilot NMR Investigation of Lipoprotein Subfractions and Other Metabolites in Patients with Severe COVID-19

A complex interplay exists between plasma lipoproteins and inflammation, as evidenced from studies on atherosclerosis. Alterations in plasma lipoprotein levels in the context of infectious diseases, particularly respiratory viral infections, such as SARS-CoV-2, have become of great interest in recent years, due to their potential utility as prognostic markers. Patients with severe COVID-19 have been reported to have low levels of total cholesterol, HDL-cholesterol, and LDL-cholesterol, but elevated levels of triglycerides. However, a detailed characterization of the particle counts and sizes of the different plasma lipoproteins in patients with COVID-19 has yet to be reported. In this pilot study, NMR spectroscopy was used to characterize lipoprotein particle numbers and sizes, and various metabolites, in 32 patients with severe COVID-19 admitted to the intensive care unit. Our study revealed markedly reduced HDL particle (HDL-P) numbers at presentation, especially low numbers of small HDL-P (S-HDL-P), and high counts of triglyceride-rich lipoprotein particle (TRL-P), particularly the very small and small TRL subfractions. Moreover, patients with severe COVID-19 were found to have remarkably elevated GlycA levels, and elevated levels of branched-chain amino acids and beta-hydroxybutyrate. Finally, we detected elevated levels of lipoproteins X and Z in most participants, which are distinct markers of hepatic dysfunction, and that was a novel finding.