Miracle-dz/UniFAR-FTUs huggingface dataset:
Microbiota Signals during the Neonatal Period Forge Life-Long Immune Responses

The microbiota regulates immunological development during early human life, with long-term effects on health and disease. Microbial products include short-chain fatty acids (SCFAs), formyl peptides (FPs), polysaccharide A (PSA), polyamines (PAs), sphingolipids (SLPs) and aryl hydrocarbon receptor (AhR) ligands. Anti-inflammatory SCFAs are produced by Actinobacteria, Bacteroidetes, Firmicutes, Spirochaetes and Verrucomicrobia by undigested-carbohydrate fermentation. Thus, fiber amount and type determine their occurrence. FPs bind receptors from the pattern recognition family, those from commensal bacteria induce a different response than those from pathogens. PSA is a capsular polysaccharide from B. fragilis stimulating immunoregulatory protein expression, promoting IL-2, STAT1 and STAT4 gene expression, affecting cytokine production and response modulation. PAs interact with neonatal immunity, contribute to gut maturation, modulate the gut–brain axis and regulate host immunity. SLPs are composed of a sphingoid attached to a fatty acid. Prokaryotic SLPs are mostly found in anaerobes. SLPs are involved in proliferation, apoptosis and immune regulation as signaling molecules. The AhR is a transcription factor regulating development, reproduction and metabolism. AhR binds many ligands due to its promiscuous binding site. It participates in immune tolerance, involving lymphocytes and antigen-presenting cells during early development in exposed humans.
Role of the Renin–Angiotensin–Aldosterone and Kinin–Kallikrein Systems in the Cardiovascular Complications of COVID-19 and Long COVID

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the virus responsible for the COVID-19 pandemic. Patients may present as asymptomatic or demonstrate mild to severe and life-threatening symptoms. Although COVID-19 has a respiratory focus, there are major cardiovascular complications (CVCs) associated with infection. The reported CVCs include myocarditis, heart failure, arrhythmias, thromboembolism and blood pressure abnormalities. These occur, in part, because of dysregulation of the Renin–Angiotensin–Aldosterone System (RAAS) and Kinin–Kallikrein System (KKS). A major route by which SARS-CoV-2 gains cellular entry is via the docking of the viral spike (S) protein to the membrane-bound angiotensin converting enzyme 2 (ACE2). The roles of ACE2 within the cardiovascular and immune systems are vital to ensure homeostasis. The key routes for the development of CVCs and the recently described long COVID have been hypothesised as the direct consequences of the viral S protein/ACE2 axis, downregulation of ACE2 and the resulting damage inflicted by the immune response. Here, we review the impact of COVID-19 on the cardiovascular system, the mechanisms by which dysregulation of the RAAS and KKS can occur following virus infection and the future implications for pharmacological therapies.
Mechanisms of Central Hypogonadism

Reproductive function depends upon an operational hypothalamo–pituitary–gonadal (HPG) axis. Due to its role in determining survival versus reproductive strategies, the HPG axis is vulnerable to a diverse plethora of signals that ultimately manifest with Central Hypogonadism (CH) in all its many guises. Acquired CH can result from any pituitary or hypothalamic lesion, including its treatment (such as surgical resection and/or radiotherapy). The HPG axis is particularly sensitive to the suppressive effects of hyperprolactinaemia that can occur for many reasons, including prolactinomas, and as a side effect of certain drug therapies. Physiologically, prolactin (combined with the suppressive effects of autonomic neural signals from suckling) plays a key role in suppressing the gonadal axis and establishing temporary CH during lactation. Leptin is a further key endocrine regulator of the HPG axis. During starvation, hypoleptinaemia (from diminished fat stores) results in activation of hypothalamic agouti-related peptide neurons that have a dual purpose to enhance appetite (important for survival) and concomitantly suppresses GnRH neurons via effects on neural kisspeptin release. Obesity is associated with hyperleptinaemia and leptin resistance that may also suppress the HPG axis. The suppressibility of the HPG axis also leaves it vulnerable to the effects of external signals that include morphine, anabolic-androgenic steroids, physical trauma and stress, all of which are relatively common causes of CH. Finally, the HPG axis is susceptible to congenital malformations, with reports of mutations within >50 genes that manifest with congenital CH, including Kallmann Syndrome associated with hyposmia or anosmia (reduction or loss of the sense of smell due to the closely associated migration of GnRH with olfactory neurons during embryogenesis). Analogous to the HPG axis itself, patients with CH are often vulnerable, and their clinical management requires both sensitivity and empathy.
Inhibition of Bacterial Efflux Pumps by Crude Extracts and Essential Oil from Myristica fragrans Houtt. (Nutmeg) Seeds against Methicillin-Resistant Staphylococcus aureus

Myristicafragrans Houtt. (Nutmeg) is a widely known folk medicine across several parts of Asia, particularly used in antimicrobial treatment. Bacterial resistance involves the expression of efflux pump systems (chromosomal norA and mepA) in methicillin-resistant Staphylococcus aureus (MRSA). Crude extract (CE) and essential oil (EO) obtained from nutmeg were applied as efflux pump inhibitors (EPIs), thereby enhancing the antimicrobial activity of the drugs they were used in. The major substances in CE and EO, which function as EPIs, in a descending order of % peak area include elemicin, myristicin, methoxyeugenol, myristicin, and asarone. Here, we investigated whether the low amount of CE and EO used as EPIs was sufficient to sensitize MRSA killing using the antibiotic ciprofloxacin, which acts as an efflux system. Interestingly, synergy between ciprofloxacin and CE or EO revealed the most significant viability of MRSA, depending on norA and mepA, the latter being responsible for EPI function of EO. Therefore, CE and EO obtained from nutmeg can act as EPIs in combination with substances that act as efflux systems, thereby ensuring that the MRSA strain is susceptible to antibiotic treatment.
Memantine Prevents the WIN 55,212-2 Evoked Cross-Priming of Ethanol-Induced Conditioned Place Preference (CPP)

The activation of the endocannabinoid system controls the release of many neurotransmitters involved in the brain reward pathways, including glutamate. Both endocannabinoid and glutamate systems are crucial for alcohol relapse. In the present study, we hypothesize that N-methyl-D-aspartate (NMDA) glutamate receptors regulate the ability of a priming dose of WIN 55,212-2 to cross-reinstate ethanol-induced conditioned place preference (CPP). To test this hypothesis, ethanol-induced (1.0 g/kg, 10% w/v, i.p.) CPP (unbiased method) was established using male adult Wistar rats. After CPP extinction, one group of animals received WIN 55,212-2 (1.0 and 2.0 mg/kg, i.p.), the cannabinoid receptor 1 (CB1) agonist, or ethanol, and the other group received memantine (3.0 or 10 mg/kg, i.p.), the NMDA antagonist and WIN 55,212-2 on the reinstatement day. Our results showed that a priming injection of WIN 55,212-2 (2.0 mg/kg, i.p.) reinstated (cross-reinstated) ethanol-induced CPP with similar efficacy to ethanol. Memantine (3.0 or 10 mg/kg, i.p.) pretreatment blocked this WIN 55,212-2 effect. Furthermore, our experiments indicated that ethanol withdrawal (7 days withdrawal after 10 days ethanol administration) down-regulated the CNR1 (encoding CB1), GRIN1/2A (encoding GluN1 and GluN2A subunit of the NMDA receptor) genes expression in the prefrontal cortex and dorsal striatum, but up-regulated these in the hippocampus, confirming the involvement of these receptors in ethanol rewarding effects. Thus, our results show that the endocannabinoid system is involved in the motivational properties of ethanol, and glutamate may control cannabinoid induced relapse into ethanol seeking behavior.
Phenolic Profiles of Ten Australian Faba Bean Varieties

Although Australia is the largest exporter of faba bean globally, there is limited information available on the levels of bioactive compounds found in current commercial faba bean varieties grown in this country. This study profiled the phenolic acid and flavonoid composition of 10 Australian faba bean varieties, grown at two different locations. Phenolic profiling by HPLC-DAD revealed the most abundant flavonoid to be catechin, followed by rutin. For the phenolic acids, syringic acid was found in high concentrations (72.4–122.5 mg/kg), while protocatechuic, vanillic, p-hydroxybenzoic, chlorogenic, p-coumaric, and trans-ferulic acid were all found in low concentrations. The content of most individual phenolics varied significantly with the variety, while some effect of the growing location was also observed. This information could be used by food processors and plant breeders to maximise the potential health benefits of Australian-grown faba bean.
1H-NMR-Based Metabolomics: An Integrated Approach for the Detection of the Adulteration in Chicken, Chevon, Beef and Donkey Meat

Meat is a rich source of energy that provides high-value animal protein, fats, vitamins, minerals and trace amounts of carbohydrates. Globally, different types of meats are consumed to fulfill nutritional requirements. However, the increasing burden on the livestock industry has triggered the mixing of high-price meat species with low-quality/-price meat. This work aimed to differentiate different meat samples on the basis of metabolites. The metabolic difference between various meat samples was investigated through Nuclear Magnetic Resonance spectroscopy coupled with multivariate data analysis approaches like principal component analysis (PCA) and orthogonal partial least square-discriminant analysis (OPLS-DA). In total, 37 metabolites were identified in the gluteal muscle tissues of cow, goat, donkey and chicken using 1H-NMR spectroscopy. PCA was found unable to completely differentiate between meat types, whereas OPLS-DA showed an apparent separation and successfully differentiated samples from all four types of meat. Lactate, creatine, choline, acetate, leucine, isoleucine, valine, formate, carnitine, glutamate, 3-hydroxybutyrate and α-mannose were found as the major discriminating metabolites between white (chicken) and red meat (chevon, beef and donkey). However, inosine, lactate, uracil, carnosine, format, pyruvate, carnitine, creatine and acetate were found responsible for differentiating chevon, beef and donkey meat. The relative quantification of differentiating metabolites was performed using one-way ANOVA and Tukey test. Our results showed that NMR-based metabolomics is a powerful tool for the identification of novel signatures (potential biomarkers) to characterize meats from different sources and could potentially be used for quality control purposes in order to differentiate different meat types.
Additive Manufacturing of Ti-Based Intermetallic Alloys: A Review and Conceptualization of a Next-Generation Machine

TiAl-based intermetallic alloys have come to the fore as the preferred alloys for high-temperature applications. Conventional methods (casting, forging, sheet forming, extrusion, etc.) have been applied to produce TiAl intermetallic alloys. However, the inherent limitations of conventional methods do not permit the production of the TiAl alloys with intricate geometries. Additive manufacturing technologies such as electron beam melting (EBM) and laser powder bed fusion (LPBF), were used to produce TiAl alloys with complex geometries. EBM technology can produce crack-free TiAl components but lacks geometrical accuracy. LPBF technology has great geometrical precision that could be used to produce TiAl alloys with tailored complex geometries, but cannot produce crack-free TiAl components. To satisfy the current industrial requirement of producing crack-free TiAl alloys with tailored geometries, the paper proposes a new heating model for the LPBF manufacturing process. The model could maintain even temperature between the solidified and subsequent layers, reducing temperature gradients (residual stress), which could eliminate crack formation. The new conceptualized model also opens a window for in situ heat treatment of the built samples to obtain the desired TiAl (γ-phase) and Ti3Al (α2-phase) intermetallic phases for high-temperature operations. In situ heat treatment would also improve the homogeneity of the microstructure of LPBF manufactured samples.
Prognostic Value of Palliative Prognostic Index for Hospitalized Patients With End-of-Life Hematologic Malignancies in a Japanese University Hospital

PURPOSE: Uncertainty of prognosis is one reason patients with hematologic malignancies receive aggressive therapy near end of life more often than those with advanced solid tumors. It is unknown whether end-of-life prognosis prediction models are useful for patients with hematologic malignancies, especially hospitalized patients receiving chemotherapy, because most prognostic models were developed for patients with solid tumors. The purpose of this study was to evaluate the prognostic accuracy of the Palliative Prognostic Index (PPI) for end-of-life patients with advanced hematologic malignancies. METHODS: We retrospectively reviewed the records of 143 patients who became resistant to standard chemotherapy and died of disease progression in our university hospital hematology ward between May 2015 and November 2019. Patients were classified according to PPI scores (groups: A, PPI ≤ 2.0; B, 2.0 < PPI ≤ 4.0; and C, PPI > 4.0) based on their clinical charts at admission. The median overall survival for each patient (95% confidence interval) was calculated using the Kaplan-Meier method. Log-rank tests were used to determine significant differences between survival curves. RESULTS: Median patient age was 76 years (range: 39-92 years), and 59% were men. Median overall survival times in the PPI groups A, B, and C were 58 days, 36 days, and 10 days, respectively. Statistically significant differences in survival time were observed between the groups (P < .01); prediction accuracy was similar to that for patients with different diagnoses. CONCLUSION: The usefulness of PPI was validated for near-end-of-life hospitalized patients with hematologic malignancies.
The Layered Anatomy of the Nose: An Ultrasound-Based Investigation.

BACKGROUND An increasing number of soft tissue filler procedures in the nasal region has been reported. Concomitant with demand, the number of complications has risen due to the difficulty in administering filler in a region where soft tissue layering is complex. OBJECTIVES To describe the layered soft tissue arrangement of the nose as it relates to the underlying arterial vasculature and to define safer zones for nasal filler enhancement. METHODS A total of 60 (28 males and 32 females) study participants were investigated with respect to their layered anatomy in the midline of the nose using ultrasound imaging. The presence and extent of the layered arrangement was examined as well as the depth of the arterial vasculature. RESULTS In the mid-nasal dorsum, a 5-layer arrangement was observed in 100% (n= 60) of all investigated cases, whereas it was found to be absent in the nasal radix and tip. The 5-layer arrangement showed an average extent of 26.7% - 67.5% in relation to nasal length. The nasal arteries coursed superficially in 91.7% of all cases in the nasal radix, in 80% in the mid-nasal dorsum, and in 98.3% in the nasal tip. CONCLUSIONS Soft tissue filler administration in the nose carries the highest risk for irreversible vision loss compared to any other facial region. The safety of soft tissue filler rhinoplasty procedures is enhanced by knowledge of the layered anatomy of the nose, the location and depth of the major nasal vasculature, and employment of maneuvers to decrease the risk of blindness.
Biodiversity of Secondary Metabolites Compounds Isolated from Phylum Actinobacteria and Its Therapeutic Applications

The current review aims to summarise the biodiversity and biosynthesis of novel secondary metabolites compounds, of the phylum Actinobacteria and the diverse range of secondary metabolites produced that vary depending on its ecological environments they inhabit. Actinobacteria creates a wide range of bioactive substances that can be of great value to public health and the pharmaceutical industry. The literature analysis process for this review was conducted using the VOSviewer software tool to visualise the bibliometric networks of the most relevant databases from the Scopus database in the period between 2010 and 22 March 2021. Screening and exploring the available literature relating to the extreme environments and ecosystems that Actinobacteria inhabit aims to identify new strains of this major microorganism class, producing unique novel bioactive compounds. The knowledge gained from these studies is intended to encourage scientists in the natural product discovery field to identify and characterise novel strains containing various bioactive gene clusters with potential clinical applications. It is evident that Actinobacteria adapted to survive in extreme environments represent an important source of a wide range of bioactive compounds. Actinobacteria have a large number of secondary metabolite biosynthetic gene clusters. They can synthesise thousands of subordinate metabolites with different biological actions such as anti-bacterial, anti-parasitic, anti-fungal, anti-virus, anti-cancer and growth-promoting compounds. These are highly significant economically due to their potential applications in the food, nutrition and health industries and thus support our communities’ well-being.
Neurally-Adjusted Ventilatory Assist (NAVA) versus Pneumatically Synchronized Ventilation Modes in Children Admitted to PICU

Traditionally, invasively ventilated children in the paediatric intensive care unit (PICU) are weaned using pneumatically-triggered ventilation modes with a fixed level of assist. The best weaning mode is currently not known. Neurally adjusted ventilatory assist (NAVA), a newer weaning mode, uses the electrical activity of the diaphragm (Edi) to synchronise ventilator support proportionally to the patient’s respiratory drive. We aimed to perform a systematic literature review to assess the effect of NAVA on clinical outcomes in invasively ventilated children with non-neonatal lung disease. Three studies (n = 285) were included for analysis. One randomised controlled trial (RCT) of all comers showed a significant reduction in PICU length of stay and sedative use. A cohort study of acute respiratory distress syndrome (ARDS) patients (n = 30) showed a significantly shorter duration of ventilation and improved sedation with the use of NAVA. A cohort study of children recovering from cardiac surgery (n = 75) showed significantly higher extubation success, shorter duration of ventilation and PICU length of stay, and a reduction in sedative use. Our systematic review presents weak evidence that NAVA may shorten the duration of ventilation and PICU length of stay, and reduce the requirement of sedatives. However, further RCTs are required to more fully assess the effect of NAVA on clinical outcomes and treatment costs in ventilated children.
Organ Specific Differences in Alteration of Aquaporin Expression in Rats Treated with Sennoside A, Senna Anthraquinones and Rhubarb Anthraquinones

Senna and rhubarb are often used as routine laxatives, but there are differences in mechanism of action and potential side effects. Here, we studied metabolites of senna anthraquinones (SAQ), rhubarb anthraquinones (RAQ) and their chemical marker, sennoside A (SA), in a rat diarrhea model. In in vitro biotransformation experiments, SAQ, RAQ and SA were incubated with rat fecal flora solution and the metabolites produced were analyzed using HPLC. In in vivo studies, the same compounds were investigated for purgation induction, with measurement of histopathology and Aqps gene expression in six organs. The results indicated that SAQ and RAQ had similar principal constituents but could be degraded into different metabolites. A similar profile of Aqps down-regulation for all compounds was seen in the colon, suggesting a similar mechanism of action for purgation. However, in the kidneys and livers of the diarrhea-rats, down-regulation of Aqps was found in the RAQ-rats whereas up-regulation of Aqps was seen in the SAQ-rats. Furthermore, the RAQ-rats showed lower Aqp2 protein expression in the kidneys, whilst the SA-rats and SAQ-rats had higher Aqp2 protein expression in the kidneys. This may have implications for side effects of SAQ or RAQ in patients with chronic kidney or liver diseases.
Alternative Approach for Specific Tyrosinase Inhibitor Screening: Uncompetitive Inhibition of Tyrosinase by Moringa oleifera

Tyrosinase (TYR) is a type III copper oxidase present in fungi, plants and animals. The inhibitor of human TYR plays a vital role in pharmaceutical and cosmetic fields by preventing synthesis of melanin in the skin. To search for an effective TYR inhibitor from various plant extracts, a kinetic study of TYR inhibition was performed with mushroom TYR. Among Panax ginseng, Alpinia galanga, Vitis vinifera and Moringa oleifera, the extracts of V. vinifera seed, A. galanga rhizome and M. oleifera leaf reversibly inhibited TYR diphenolase activity with IC50 values of 94.8 ± 0.2 µg/mL, 105.4 ± 0.2 µg/mL and 121.3 ± 0.4 µg/mL, respectively. Under the same conditions, the IC50 values of the representative TYR inhibitors of ascorbic acid and kojic acid were found at 235.7 ± 1.0 and 192.3 ± 0.4 µg/mL, respectively. An inhibition kinetics study demonstrated mixed-type inhibition of TYR diphenolase by A. galanga and V. vinifera, whereas a rare uncompetitive inhibition pattern was found from M. oleifera with an inhibition constant of Kii 73 µg/mL. Phytochemical investigation by HPLC-MS proposed luteolin as a specific TYR diphenolase ES complex inhibitor, which was confirmed by the inhibition kinetics of luteolin. The results clearly showed that studying TYR inhibition kinetics with plant extract mixtures can be utilized for the screening of specific TYR inhibitors.
Fly Ash-Based Eco-Efficient Concretes: A Comprehensive Review of the Short-Term Properties

Development of sustainable concrete as an alternative to conventional concrete helps in reducing carbon dioxide footprint associated with the use of cement and disposal of waste materials in landfill. One way to achieve that is the use of fly ash (FA) as an alternative to ordinary Portland cement (OPC) because FA is a pozzolanic material and has a high amount of alumina and silica content. Because of its excellent mechanical properties, several studies have been conducted to investigate the use of alkali-activated FA-based concrete as an alternative to conventional concrete. FA, as an industrial by-product, occupies land, thereby causing environmental pollution and health problems. FA-based concrete has numerous advantages, such as it has early strength gaining, it uses low natural resources, and it can be configurated into different structural elements. This study initially presents a review of the classifications, sources, chemical composition, curing regimes and clean production of FA. Then, physical, fresh, and mechanical properties of FA-based concretes are studied. This review helps in better understanding of the behavior of FA-based concrete as a sustainable and eco-friendly material used in construction and building industries.