Miracle-dz/UniFAR-FTUs huggingface dataset:
Signaling Pathways in Bone Development and Their Related Skeletal Dysplasia

Bone development is a tightly regulated process. Several integrated signaling pathways including HH, PTHrP, WNT, NOTCH, TGF-β, BMP, FGF and the transcription factors SOX9, RUNX2 and OSX are essential for proper skeletal development. Misregulation of these signaling pathways can cause a large spectrum of congenital conditions categorized as skeletal dysplasia. Since the signaling pathways involved in skeletal dysplasia interact at multiple levels and have a different role depending on the time of action (early or late in chondrogenesis and osteoblastogenesis), it is still difficult to precisely explain the physiopathological mechanisms of skeletal disorders. However, in recent years, significant progress has been made in elucidating the mechanisms of these signaling pathways and genotype–phenotype correlations have helped to elucidate their role in skeletogenesis. Here, we review the principal signaling pathways involved in bone development and their associated skeletal dysplasia.
Treatment of Multiple Myeloma and the Role of Melphalan in the Era of Modern Therapies—Current Research and Clinical Approaches

Multiple myeloma (MM) accounts for 10% of all hematological malignancies, and it is the second most common hematological neoplasm for which chemotherapy is an important pharmacological treatment. High dose melphalan followed by autologous stem cell transplantation remains the standard of treatment for transplant-eligible patients with MM. In this review, we describe aspects of the pharmacokinetics and pharmacodynamics of melphalan therapy and related compounds. In addition, we describe the use of melphalan in innovative therapies for the treatment of MM, including the development of drug carriers to reduce systemic toxicity, combination therapy to improve the effectiveness of cancer therapy, and the chemical modification of the melphalan molecule to improve antitumor activity.
Association between Training Load and Well-Being Measures in Young Soccer Players during a Season

This study aimed to analyze the correlations among weekly (w) acute workload (wAW), chronic workload (wCW), acute/chronic workload ratio (wACWR), training monotony (wTM), training strain (wTS), sleep quality (wSleep), delayed onset muscle soreness (wDOMS), fatigue (wFatigue), stress (wStress), and Hooper index (wHI) in pre-, early, mid-, and end-of-season. Twenty-one elite soccer players (age: 16.1 ± 0.2 years) were monitored weekly on training load and well-being for 36 weeks. Higher variability in wAW (39.2%), wFatigue (84.4%), wStress (174.3%), and wHI (76.3%) at the end-of-season were reported. At mid-season, higher variations in wSleep (59.8%), TM (57.6%), and TS (111.1%) were observed. Moderate to very large correlations wAW with wDOMS (r = 0.617, p = 0.007), wFatigue, wStress, and wHI were presented. Similarly, wCW reported a meaningful large association with wDOMS (r = 0.526, p < 0.001); moderate to very large associations with wFatigue (r = 0.649, p = 0.005), wStress, and wHI. Moreover, wTM presented a large correlation with wSleep (r = 0.515, p < 0.001); and a negatively small association with wStress (r = −0.426, p = 0.003). wTS showed a small to large correlation with wSleep (r = 0.400, p = 0.005) and wHI; also, a large correlation with wDOMS (r = 0.556, p = 0.028) and a moderate correlation with wFatigue (r = 0.343, p = 0.017). Wellness status may be considered a useful tool to provide determinant elite players’ information to coaches and to identify important variations in training responses.
Expiration Date of Ready-to-Eat Salads: Effects on Microbial Load and Biochemical Attributes

When minimally processed vegetables reach their expiration date, expose an increased microbial load. This includes mainly spoilage microorganisms but also foodborne pathogens, thus affecting the quality and safety of highly consumed ready-to-eat salads. A total of 144 ready-to-eat salads from the Cypriot market were analyzed in an attempt to determine the effects of the expiration date on the microbial load and plant metabolic variables of the salads. Possible correlations between them were also investigated for the first time. Furthermore, the impacts of the season (winter, summer), salad producing companies and type of salad and/or their interactions with the tested parameters were investigated. Results revealed that the microbial load (mainly spoilage microorganisms, such as Pseudomonas spp., yeasts and molds) increased towards the end of the shelf life. The microbial load was differentiated among the five salad producers and/or the salad types, highlighting the importance of a common and safe sanitation-processing chain in the preparation of ready-to-eat salads. Summer was the season in which Escherichia coli counts were found to be higher for plain lettuce, while Staphylococcus spp. was increased numbers for the lettuce+endive/radicchio, lettuce+rocket and lettuce+chives type of salads. Additionally, an increased Staphylococcus spp. was observed for plain rocket salads in winter. All samples examined were found negative for Salmonella enterica and Listeria monocytogenes. Moreover, carbon dioxide production and damage indexes (hydrogen peroxide and lipid peroxidation) increased on expiration date on both winter and summer seasons, indicating plant tissue stress at the end of shelf life. These findings indicate that the expiration date and relevant shelf life of processed vegetables are important parameters to be considered when postharvest management is applied to these products, ensuring safety and quality.
Antiglycating Effect of Phenolics from the Chilean Currant Ribes cucullatum under Thermal Treatment

Numerous dietary polyphenols possess antiglicating activity, but the effects of thermal treatment on this activity are mostly unknown. The effect of thermal treatment in the antiglycating activity of polyphenolic enriched extracts (PEEs) from Ribes cucullatum towards glyoxal-induced glycation of sarcoplasmic proteins was assessed. Sarcoplasmic proteins from chicken, beef, salmon, and turkey, were incubated 2 h at 60 °C with and without glyoxal and different concentrations of PEEs (0.25, 0.5, 1, and 5 mg/mL). The antiglycating activity was evaluated by: (1) Lys and Arg consumption, (2) Carboxymethyl lysine (CML) generation, and (3) lipid-derived electrophiles inhibition in a gastric digestion model. Protective effects were observed against CML generation in proteins and a decrease of electrophiles in the gastric digestion model. A dose-dependent consumption of Lys and Arg in proteins/PEEs samples, indicated the possible occurrence of quinoproteins generation from the phenolics. Protein/PEEs incubations were assessed by: (1) High pressure liquid chromatography analysis, (2) Gel electrophoresis (SDS-PAGE), and (3) Redox cycling staining of quinoproteins. Protein/PEEs incubations produced: (1) Decrease in phenolics, (2) increase of protein crosslinking, and (3) dose-dependent generation of quinoproteins. We demonstrate that phenolic compounds from R. cucullatum under thermal treatment act as antiglycating agents, but oxidative reactions occurs at high concentrations, generating protein crosslinking and quinoproteins.
Iron Deficiency in Obesity and after Bariatric Surgery

Iron deficiency (ID) is particularly frequent in obese patients due to increased circulating levels of acute-phase reactant hepcidin and adiposity-associated inflammation. Inflammation in obese subjects is closely related to ID. It induces reduced iron absorption correlated to the inhibition of duodenal ferroportin expression, parallel to the increased concentrations of hepcidin. Obese subjects often get decreased inflammatory response after bariatric surgery, accompanied by decreased serum hepcidin and therefore improved iron absorption. Bariatric surgery can induce the mitigation or resolution of obesity-associated complications, such as hypertension, insulin resistance, diabetes mellitus, and hyperlipidemia, adjusting many parameters in the metabolism. However, gastric bypass surgery and sleeve gastrectomy can induce malabsorption and may accentuate ID. The present review explores the burden and characteristics of ID and anemia in obese patients after bariatric surgery, accounting for gastric bypass technique (Roux-en-Y gastric bypass—RYGB) and sleeve gastrectomy (SG). After bariatric surgery, obese subjects’ iron status should be monitored, and they should be motivated to use adequate and recommended iron supplementation.
Current trends in the application of causal inference methods to pooled longitudinal observational infectious disease studies—A protocol for a methodological systematic review

Introduction Pooling (or combining) and analysing observational, longitudinal data at the individual level facilitates inference through increased sample sizes, allowing for joint estimation of study- and individual-level exposure variables, and better enabling the assessment of rare exposures and diseases. Empirical studies leveraging such methods when randomization is unethical or impractical have grown in the health sciences in recent years. The adoption of so-called “causal” methods to account for both/either measured and/or unmeasured confounders is an important addition to the methodological toolkit for understanding the distribution, progression, and consequences of infectious diseases (IDs) and interventions on IDs. In the face of the Covid-19 pandemic and in the absence of systematic randomization of exposures or interventions, the value of these methods is even more apparent. Yet to our knowledge, no studies have assessed how causal methods involving pooling individual-level, observational, longitudinal data are being applied in ID-related research. In this systematic review, we assess how these methods are used and reported in ID-related research over the last 10 years. Findings will facilitate evaluation of trends of causal methods for ID research and lead to concrete recommendations for how to apply these methods where gaps in methodological rigor are identified. Methods and analysis We will apply MeSH and text terms to identify relevant studies from EBSCO (Academic Search Complete, Business Source Premier, CINAHL, EconLit with Full Text, PsychINFO), EMBASE, PubMed, and Web of Science. Eligible studies are those that apply causal methods to account for confounding when assessing the effects of an intervention or exposure on an ID-related outcome using pooled, individual-level data from 2 or more longitudinal, observational studies. Titles, abstracts, and full-text articles, will be independently screened by two reviewers using Covidence software. Discrepancies will be resolved by a third reviewer. This systematic review protocol has been registered with PROSPERO (CRD42020204104).
Unlocking the Health Potential of Microalgae as Sustainable Sources of Bioactive Compounds

Microalgae are known to produce a plethora of compounds derived from the primary and secondary metabolism. Different studies have shown that these compounds may have allelopathic, antimicrobial, and antipredator activities. In addition, in vitro and in vivo screenings have shown that several compounds have interesting bioactivities (such as antioxidant, anti-inflammatory, anticancer, and antimicrobial) for the possible prevention and treatment of human pathologies. Additionally, the enzymatic pathways responsible for the synthesis of these compounds, and the targets and mechanisms of their action have also been investigated for a few species. However, further research is necessary for their full exploitation and possible pharmaceutical and other industrial applications. Here, we review the current knowledge on the chemical characteristics, biological activities, mechanism of action, and the enzymes involved in the synthesis of microalgal metabolites with potential benefits for human health.
A Special View of What Was Almost Forgotten: p38δ MAPK

Simple Summary p38δ MAPK, as well as the other p38 isoforms, was proposed as a drug target for cancer therapy, owing to its critical roles in cellular signaling. However, herein, we show that p38δ inhibition may be therapeutically beneficial for treatment of specific cancer types, such as skin carcinoma, hepatocellular carcinoma (HCC), head and neck squamous cell carcinoma (HNSCC), cholangiocarcinoma (CC), and breast cancer. This review aims to discuss the roles of p38δ in cancer and summarize the findings of molecules with potential to inhibit p38δ in order to guide the search for new target cancer therapies based on p38δ inhibitors. Abstract The p38δ mitogen-activated protein kinase is an important signal transduction enzyme. p38δ has recently emerged as a drug target due to its tissue-specific expression patterns and its critical roles in regulation of cellular processes related to cancer and inflammatory diseases, such as cell proliferation, cell migration, apoptosis, and inflammatory responses. However, potent and specific p38δ inhibitors have not been defined so far. Moreover, in cancer disease, p38δ appears to act as a tumor suppressor or tumor promoter according to cancer and cell type studied. In this review, we outline the current understanding of p38δ roles in each cancer type, to define whether it is possible to delineate new cancer therapies based on small-molecule p38δ inhibitors. We also highlight recent advances made in the design of molecules with potential to inhibit p38 isoforms and discuss structural approaches to guide the search for p38δ inhibitors.
Advax-CpG Adjuvant Provides Antigen Dose-Sparing and Enhanced Immunogenicity for Inactivated Poliomyelitis Virus Vaccines

Global immunization campaigns have resulted in a major decline in the global incidence of polio cases, with wild-type poliovirus remaining endemic in only two countries. Live oral polio vaccine (OPV) played a role in the reduction in polio case numbers; however, the risk of OPV developing into circulating vaccine-derived poliovirus makes it unsuitable for eradication programs. Trivalent inactivated polio virus (TIPV) vaccines which contain formalin-inactivated antigens produced from virulent types 1, 2 and 3 reference polio strains grown in Vero monkey kidney cells have been advocated as a replacement for OPV; however, TIPVs have weak immunogenicity and multiple boosts are required before peak neutralizing titers are reached. This study examined whether the incorporation of the novel polysaccharide adjuvant, Advax-CpG, could boost the immunogenicity of two TIPV vaccines, (i) a commercially available polio vaccine (IPOL®, Sanofi Pasteur) and (ii) a new TIPV formulation developed by Statens Serum Institut (SSI). Mice were immunized intramuscularly based on recommended vaccine dosage schedules and serum antibody titers were followed for 12 months post-immunization. Advax-CpG significantly enhanced the long-term immunogenicity of both TIPV vaccines and had at least a 10-fold antigen dose-sparing effect. An exception was the poor ability of the SSI TIPV to induce serotype type 1 neutralizing antibodies. Immunization with monovalent IPVs suggested that the low type 1 response to TIPV may be due to antigen competition when the type 1 antigen was co-formulated with the type 2 and 3 antigens. This study provides valuable insights into the complexity of the formulation of multivalent polio vaccines and supports the further development of adjuvanted antigen-sparing TIPV vaccines in the fight to eradicate polio.
State-of-the-Art and Opportunities for Forward Osmosis in Sewage Concentration and Wastewater Treatment

The application of membrane technologies for wastewater treatment to recover water and nutrients from different types of wastewater can be an effective strategy to mitigate the water shortage and provide resource recovery for sustainable development of industrialisation and urbanisation. Forward osmosis (FO), driven by the osmotic pressure difference between solutions divided by a semi-permeable membrane, has been recognised as a potential energy-efficient filtration process with a low tendency for fouling and a strong ability to filtrate highly polluted wastewater. The application of FO for wastewater treatment has received significant attention in research and attracted technological effort in recent years. In this review, we review the state-of-the-art application of FO technology for sewage concentration and wastewater treatment both as an independent treatment process and in combination with other treatment processes. We also provide an outlook of the future prospects and recommendations for the improvement of membrane performance, fouling control and system optimisation from the perspectives of membrane materials, operating condition optimisation, draw solution selection, and multiple technologies combination.
A Review of Colorectal Cancer in Terms of Epidemiology, Risk Factors, Development, Symptoms and Diagnosis

Simple Summary According to the available data, colorectal cancer (CRC) is one of the most common malignant neoplasms. Depending on the location, type of cancer or gender, it is ranked 2nd to 4th in terms of incidence in the world. CRC, year by year, shows an increasing tendency in terms of both morbidity and deaths. Many factors may be responsible for the development of this disease, including genetic and environmental factors. Considering all the aspects, we made efforts to systematize the available literature data in terms of epidemiology, risk factors, type and nature of symptoms, development stages, available and future diagnosis of colorectal cancer. Abstract This review article contains a concise consideration of genetic and environmental risk factors for colorectal cancer. Known risk factors associated with colorectal cancer include familial and hereditary factors and lifestyle-related and ecological factors. Lifestyle factors are significant because of the potential for improving our understanding of the disease. Physical inactivity, obesity, smoking and alcohol consumption can also be addressed through therapeutic interventions. We also made efforts to systematize available literature and data on epidemiology, diagnosis, type and nature of symptoms and disease stages. Further study of colorectal cancer and progress made globally is crucial to inform future strategies in controlling the disease’s burden through population-based preventative initiatives.
The ability of Achromobacter sp. KW1 strain to biodegrade isomers of chlorotoluene

Background The isomers of chlorotoluene (2-chlorotoluene, 3-chlorotoluene and 4-chlorotoluene) are considered to be toxic and have a negative impact on humans and the environment. Therefore, issues related to their removal from the natural environment have become of increasing interest. Results The morphology of cells and colonies after long-term metabolic stress was significantly modified. Metabolic stress is suggested to be a determinant of bacteria cell surface properties. The chlorine atom position in chlorotoluenes has a strong impact on cell surface modification. When the chlorine atom was at the ortho or para position, a large increase in hydrophobicity (from 40% to 73% and from 29% to 49% respectively) and a decrease in the inner membrane permeability (from 0.31 to 0.24 μM min−1 and from 0.52 to 0.13 μM min−1) were observed. Moreover, Achromobacter sp. KW1 strain was found to exhibit good ability to degrade chlorotoluenes. The greatest difference in biodegradation between the stressed and non-stressed strains was observed for the cultures grown on toluene and 3-chlorotoluene. Conclusions Both long-term contact with hydrocarbons and the addition of surfactants demonstrated a beneficial effect on the biodegradation process. However, as a result of long-term contact with hydrocarbons, the bacteria studied were able to degrade chlorotoluenes faster and more effectively.
Entropy-Driven Heterogeneous Crystallization of Hard-Sphere Chains under Unidimensional Confinement

We investigate, through Monte Carlo simulations, the heterogeneous crystallization of linear chains of tangent hard spheres under confinement in one dimension. Confinement is realized through flat, impenetrable, and parallel walls. A wide range of systems is studied with respect to their average chain lengths (N = 12 to 100) and packing densities (φ = 0.50 to 0.61). The local structure is quantified through the Characteristic Crystallographic Element (CCE) norm descriptor. Here, we split the phenomenon into the bulk crystallization, far from the walls, and the projected surface crystallization in layers adjacent to the confining surfaces. Once a critical volume fraction is met, the chains show a phase transition, starting from regions near the hard walls. The established crystal morphologies consist of alternating hexagonal close-packed or face-centered cubic layers with a stacking direction perpendicular to the confining walls. Crystal layer perfection is observed with an increasing concentration. As in the case of the unconstrained phase transition of athermal polymers at high densities, crystal nucleation and growth compete with the formation of sites of a fivefold local symmetry. While surface crystallites show perfection with a predominantly triangular character, the morphologies of square crystals or of a mixed type are also formed. The simulation results show that the rate of perfection of the surface crystallization is not significantly faster than that of the bulk crystallization.
Nutritional Potentials of Atypical Feed Ingredients for Broiler Chickens and Pigs

Simple Summary Common feed ingredients such as corn, barley, wheat, soybean meal, and canola meal are used to feed broiler chickens and pigs in various countries around the world. However, due to rising costs and the need to practice sustainable animal husbandry, concerted efforts have been aimed at identifying and examining the nutritional potentials of atypical feed ingredients for pigs and chickens. Although there are some articles and reviews that discuss the potential of a single or few feed ingredients for either chickens or pigs, there has not been an extensive review that integrates information from several alternative feed ingredients for both species in one place. Therefore, this review aims to enumerate several feed ingredients that have shown prospects in supplying either one or more nutrients to pigs and chickens while reducing the dependence on commonly used feedstuff. In addition, feeding practices, merits, and limitations associated with these uncommon feed ingredients are discussed. Furthermore, practical applications of these alternative feed ingredients in relation to either pigs or chickens are briefly examined. Abstract Diets play an important part in monogastric nutrition. This is because diets are comprised of various feed ingredients that supply energy and nutrients required by broiler chickens or pigs for normal growth and development. The main feed ingredients used for formulating diets for pigs and chickens are comprised of cereals and oilseed meals. Corn and soybean meal (SBM) are mostly used in North America for animal feeds. However, due to geographical locations, availability, and cost, ingredients such as wheat, barley, and canola meal are often used for feeding pigs and chickens. Overdependence on common ingredients such as corn and SBM for decades has resulted in rising costs of animal production. Therefore, the need has risen to examine the potentials of alternative feed ingredients capable of supplying the required energy and nutrients for monogastric animals. Research has been carried out to identify and evaluate several uncommon feed ingredients and their utilization by broiler chickens and pigs. Thus, this review enumerates the nutritional potentials of feed ingredients in 4 main nutritional classes using information from articles in peer-reviewed journals. Feeding practices, advantages, and limitations of using certain uncommon feed ingredients are discussed. In addition, species-specific factors in terms of practical applications are explored.