Miracle-dz/UniFAR-FTUs huggingface dataset:
A Three-Dimensional Printed Foot Orthosis for Flexible Flatfoot: An Exploratory Biomechanical Study on Arch Support Reinforcement and Undercut

The advancement of 3D printing and scanning technology enables the digitalization and customization of foot orthosis with better accuracy. However, customized insoles require rectification to direct control and/or correct foot deformity, particularly flatfoot. In this exploratory study, we aimed at two design rectification features (arch stiffness and arch height) using three sets of customized 3D-printed arch support insoles (R+U+, R+U−, and R−U+). The arch support stiffness could be with or without reinforcement (R+/−) and the arch height may or may not have an additional elevation, undercutting (U+/−), which were compared to the control (no insole). Ten collegiate participants (four males and six females) with flexible flatfoot were recruited for gait analysis on foot kinematics, vertical ground reaction force, and plantar pressure parameters. A randomized crossover trial was conducted on the four conditions and analyzed using the Friedman test with pairwise Wilcoxon signed-rank test. Compared to the control, there were significant increases in peak ankle dorsiflexion and peak pressure at the medial midfoot region, accompanied by a significant reduction in peak pressure at the hindfoot region for the insole conditions. In addition, the insoles tended to control hindfoot eversion and forefoot abduction though the effects were not significant. An insole with stronger support features (R+U+) did not necessarily produce more favorable outcomes, probably due to over-cutting or impingement. The outcome of this study provides additional data to assist the design rectification process. Future studies should consider a larger sample size with stratified flatfoot features and covariating ankle flexibility while incorporating more design features, particularly medial insole postings.
Hypothesizing Nutrigenomic-Based Precision Anti-Obesity Treatment and Prophylaxis: Should We Be Targeting Sarcopenia Induced Brain Dysfunction?

Background: The United States Centers for Disease Control and Prevention (CDC) estimates a total obesity rate of 30% for 12 states and a 20% obesity rate nationwide. The obesity epidemic continues to increase in spite of preventative measures undertaken worldwide. Pharmacological treatments promise to reduce total fat mass. However, medications may have significant side effects and can be potentially fatal. Data Retrieval: This brief review, based on a PUBMED search of the key terms “Obesity” and” Sarcopenia,” will present evidence to corroborate the existence of Reward Deficiency Syndrome (RDS) in obesity and the involvement of catecholaminergic pathways in substance seeking behavior, particularly as it relates to carbohydrates cravings. Expert Opinion: The genetic basis and future genetic testing of children for risk of aberrant generalized craving behavior are considered a prevention method. Here we present evidence supporting the use of precursor amino acid therapy and modulation of enkephalinase, MOA, and COMT inhibition in key brain regions. Such treatments manifest in improved levels of dopamine/norepinephrine, GABA, serotonin, and enkephalins. We also present evidence substantiating insulin sensitivity enhancement via Chromium salts, which affect dopamine neuronal synthesis regulation. We believe our unique combination of natural ingredients will influence many pathways leading to the promotion of well-being and normal healthy metabolic functioning. Sarcopenia has been shown to reduce angiogenesis and possible cerebral blood flow. Exercise seems to provide a significant benefit to overcome this obesity-promoting loss of muscle density. Conclusion: Utilization of proposed nutrigenomic formulae based on coupling genetic obesity risk testing promotes generalized anti-craving of carbohydrates and can inhibit carbohydrate bingeing, inducing significant healthy fat loss and relapse prevention.
Synthesis and Reactivity of Group 10 Silyl Pincer Complexes

xvii List of Abbreviations and Symbols Used . xviii Acknowledgments. xxi CHAPTER 1: Introduction . 1 1.1 Overview . 1 1.2 The Utility of Group 10 Metal Complexes in Synthesis. 2 1.3 Pincer-Type Ancillary Ligand Design for Tuning Transition Metal Reactivity . 6 1.4 Reactivity of Group 10 Metal Pincer Complexes . 9 1.4. 1 Pt Pincer complexes for arene C-H bond activation . 10 1.4. 2 Synthesis and reactivity of a pincer supported Pt-oxo complex. 17 1.4. 3 Intramolecular arene C-H bond activation mediated by (PNP)Ni species. 20 1.4. 4 Pd-mediated N-H and N-C bond cleavage reactions. 22 1.4. 5 Synthesis and reactivity of Pd hydride and hydroxide complexes. 25 1.5 The development of Group 10 metal LSiL-type pincer complexes (L = N, P) . 28
Source Identification of Klebsiella pneumoniae Causing Six Episodes of Recurrent Sepsis in an Adolescent That Underwent Hematopoietic Stem Cell Transplantation

Septicemia or bacteremia is one of the leading causes of death worldwide. Long-term tunneled central venous catheters (CVCs) are usually placed in children undergoing chemotherapy or hematopoietic stem cell transplantation (HSCT) for underlying hemato–oncologic malignancies. However, catheter-related complications have been reported frequently, and there is high morbidity and mortality related to catheter-line-associated bloodstream infections (CLABSIs). We report a rare case of six episodes of recurrent K. pneumoniae sepsis within a 6-month period in a 12-year-old male adolescent that underwent HSCT for acute lymphoblastic leukemia, despite treatment with susceptible antibiotics. The patient received extensive diagnostic evaluations to find the hidden source; however, failure to discover the primary source led to multiple recurrences. Through enterobacterial repetitive intergenic consensus (ERIC)-PCR, we were able to identify the relationship between the six episodes and recognize the source of bacteremia.
Effects of Absorption Kinetics on the Catabolism of Melatonin Released from CAP-Coated Mesoporous Silica Drug Delivery Vehicles

Melatonin (MLT) is a pineal hormone involved in the regulation of the sleep/wake cycle. The efficacy of exogenous MLT for the treatment of circadian and sleep disorders is variable due to a strong liver metabolism effect. In this work, MLT is encapsulated in mesoporous silica (AMS-6) with a loading capacity of 28.8 wt%, and the mesopores are blocked using a coating of cellulose acetate phthalate (CAP) at 1:1 and 1:2 AMS-6/MLT:CAP ratios. The release kinetics of MLT from the formulations is studied in simulated gastrointestinal fluids. The permeability of the MLT released from the formulations and its 6-hydroxylation are studied in an in vitro model of the intestinal tract (Caco-2 cells monolayer). The release of MLT from AMS-6/MLT:CAP 1:2 is significantly delayed in acidic environments up to 40 min, while remaining unaffected in neutral environments. The presence of CAP decreases the absorption of melatonin and increases its catabolism into 6-hydroxylation by the cytochrome P450 enzyme CYP1A2. The simple confinement of melatonin into AMS-6 pores slightly affects the permeability and significantly decreases melatonin 6-hydroxylation. Measurable amounts of silicon in the basolateral side of the Caco-2 cell monolayer might suggest the dissolution of AMS-6 during the experiment.
Synergistic Effect of Simultaneous versus Sequential Combined Treatment of Histone Deacetylase Inhibitor Valproic Acid with Etoposide on Melanoma Cells

Melanoma is the most lethal form of skin cancer, which is intrinsically resistant to conventional chemotherapy. Combination therapy has been developed to overcome this challenge and show synergistic anticancer effects on melanoma. Notably, the histone deacetylase inhibitor, valproic acid (VPA), has been indicated as a potential sensitizer of chemotherapy drugs on various metastatic cancers, including advanced melanoma. In this study, we explored whether VPA could serve as an effective sensitizer of chemotherapy drug etoposide (ETO) on B16-F10 and SK-MEL-2-Luc melanoma cell lines in response to drug-induced DNA damages. Our results demonstrated that the VPA-ETO simultaneous combined treatment and ETO pretreated sequential combined treatment generated higher inhibitory effectivities than the individual treatment of each drug. We found the VPA-ETO simultaneous combined treatment contributed to the synergistic inhibitory effect by the augmented DNA double-strand breaks, accompanied by a compromised homologous recombination activity. In comparison, the ETO pretreated sequential combined treatment led to synergistic inhibitory effect via enhanced apoptosis. Surprisingly, the enhanced homologous recombination activity and G2/M phase arrest resulted in the antagonistic effect in both cells under VPA pretreated sequential combined treatment. In summary, our findings suggested that sequential order and effective dose of drug administration in VPA-ETO combination therapy could induce different cellular responses in melanoma cells. Such understanding might help potentiate the effectiveness of melanoma treatment and highlight the importance of sequential order and effective dose in combination therapy.
B Cells and Autoantibodies in AIRE Deficiency

Autoimmune polyendocrine syndrome type 1 (APS-1) is a rare but severe monogenetic autoimmune endocrine disease caused by failure of the Autoimmune Regulator (AIRE). AIRE regulates the negative selection of T cells in the thymus, and the main pathogenic mechanisms are believed to be T cell-mediated, but little is known about the role of B cells. Here, we give an overview of the role of B cells in thymic and peripheral tolerance in APS-1 patients and different AIRE-deficient mouse models. We also look closely into which autoantibodies have been described for this disorder, and their implications. Based on what is known about B cell therapy in other autoimmune disorders, we outline the potential of B cell therapies in APS-1 and highlight the unresolved research questions to be answered.
Fungi and Algae as Sources of Medicinal and Other Biologically Active Compounds: A Review

Many species of fungi including lichenized fungi (lichens) and algae have the ability to biosynthesize biologically active compounds. They produce, among others, polysaccharides with anticancer and immunostimulatory properties: (1) Background: This paper presents the characteristics of the most important bioactive compounds produced by fungi and algae; (2) Methods: Based on the example of the selected species of mushrooms, lichens and algae, the therapeutic properties of the secondary metabolites that they produce and the possibilities of their use are presented; (3) Results: The importance of fungi, especially large-fruited mushrooms, lichens and algae, in nature and human life is discussed, in particular, with regard to their use in the pharmaceutical industry and their nutritional value; (4) Conclusions: The natural organisms, such as fungi, lichenized fungi and algae, could be used as supplementary medicine, in the form of pharmaceutical preparations and food sources. Further advanced studies are required on the pharmacological properties and bioactive compounds of these organisms.
Improved Large-Scale Homology Search by Two-Step Seed Search Using Multiple Reduced Amino Acid Alphabets

Metagenomic analysis, a technique used to comprehensively analyze microorganisms present in the environment, requires performing high-precision homology searches on large amounts of sequencing data, the size of which has increased dramatically with the development of next-generation sequencing. NCBI BLAST is the most widely used software for performing homology searches, but its speed is insufficient for the throughput of current DNA sequencers. In this paper, we propose a new, high-performance homology search algorithm that employs a two-step seed search strategy using multiple reduced amino acid alphabets to identify highly similar subsequences. Additionally, we evaluated the validity of the proposed method against several existing tools. Our method was faster than any other existing program for ≤120,000 queries, while DIAMOND, an existing tool, was the fastest method for >120,000 queries.
Iron Oxide Nanoparticles in Regenerative Medicine and Tissue Engineering

In recent years, many promising nanotechnological approaches to biomedical research have been developed in order to increase implementation of regenerative medicine and tissue engineering in clinical practice. In the meantime, the use of nanomaterials for the regeneration of diseased or injured tissues is considered advantageous in most areas of medicine. In particular, for the treatment of cardiovascular, osteochondral and neurological defects, but also for the recovery of functions of other organs such as kidney, liver, pancreas, bladder, urethra and for wound healing, nanomaterials are increasingly being developed that serve as scaffolds, mimic the extracellular matrix and promote adhesion or differentiation of cells. This review focuses on the latest developments in regenerative medicine, in which iron oxide nanoparticles (IONPs) play a crucial role for tissue engineering and cell therapy. IONPs are not only enabling the use of non-invasive observation methods to monitor the therapy, but can also accelerate and enhance regeneration, either thanks to their inherent magnetic properties or by functionalization with bioactive or therapeutic compounds, such as drugs, enzymes and growth factors. In addition, the presence of magnetic fields can direct IONP-labeled cells specifically to the site of action or induce cell differentiation into a specific cell type through mechanotransduction.
A Qualitative and Comprehensive Analysis of Caries Susceptibility for Dental Fluorosis Patients

Dental fluorosis (DF) is an endemic disease caused by excessive fluoride exposure during childhood. Previous studies mainly focused on the acid resistance of fluorotic enamel and failed to reach a consensus on the topic of the caries susceptibility of DF patients. In this review, we discuss the role of DF classification in assessing this susceptibility and follow the “four factors theory” in weighing the pros and cons of DF classification in terms of host factor (dental enamel and saliva), food factor, bacteria factor, and DF treatment factor. From our analysis, we find that susceptibility is possibly determined by various factors such as the extent of structural and chemical changes in fluorotic enamel, eating habits, fluoride levels in diets and in the oral cavity, changes in quantity and quality of saliva, and/or oral hygiene. Thus, a universal conclusion regarding caries susceptibility might not exist, instead depending on each individual’s situation.
The 5HTOL/5HIAA Ratio as a Biomarker of Alcohol Hangover

Assessment of the presence and severity of alcohol hangovers relies on the subjective method of self-report. Therefore, there is a need of adequate biomarkers that (1) correlate significantly with hangover severity, and (2) correspond to the level of hangover-related performance impairment objectively. In this naturalistic study, n = 35 social drinkers participated. Urine samples were obtained the morning after alcohol consumption and after an alcohol-free control day. Concentrations of 5-hydroxytryptophol (5-HTOL), 5-hydroxyindoleacetic acid (5-HIAA) and the 5-HTOL/5-HIAA ratio were determined. The results confirm previous findings that 5-HTOL and the 5HTOL/5-HIAA ratio are useful biomarkers of recent alcohol consumption. Significant correlations were found with the amount of alcohol consumed, total drink time, and estimated BAC. However, urine concentrations of 5-HTOL and 5-HIAA (and their ratio 5HTOL/5-HIAA) did not significantly correlate with hangover severity. In conclusion, urine 5-HTOL, 5-HIAA, and the 5HTOL/5-HIAA ratio cannot be considered to be suitable biomarkers of alcohol hangover.
Behavioral Observation Procedures and Tests to Characterize the Suitability of Sows for Loose-Housed Farrowing Systems

Simple Summary In this study, different behavior tests were developed and applied to characterize the behavior of sows against humans and piglets in systems with short-term fixation only. In loose-housed sows, it is of extreme importance that the sows neither attack the stockpersons nor crush their piglets through carelessness. Selecting the sows for the respective traits might show positive effects in a successful realization of these husbandry systems. For example, the Dummy Arm Test simulated catching the piglets. In the Towel Test, the general reaction to unknown stress situations was tested by throwing a towel towards the sow during a resting phase. Another test simulated the emptying of the trough to simulate interaction with humans during a routine procedure. The study showed that the majority of the sows reacted calmly. Nesting and lying behavior were also analyzed, as was the behavior of sows when their litters returned after a short separation. This study showed that the behavioral observation procedures and designed tests are suitable to characterize sows’ behavior towards humans and piglets with regard to traits that are particularly important in systems without fixation. Abstract The objective of the study was to evaluate behavioral observation procedures and tests to characterize sows’ behavior for their suitability for free farrowing systems. Nest building activity (NB), lying-down behavior (LDB), and position after lying down (PLD) were assessed. Four tests were designed to characterize the reaction of sows to a novel object and an unexpected situation (Towel Test, TT), behavior towards humans (Dummy Arm Test, DAT; Trough Cleaning Test, TCT), and behavior towards piglets (Reunion Test, RT). The study was performed on a nucleus farm in 37 batches including 771 purebred landrace sows housed in farrowing pens with short-term fixation. The assessment of NB started 2 days before the expected date of the farrowing. In 56.2% of the observations, the sows showed increased chewing activity on gunnysacks. The LDB and PLD were assessed on days 3 and 19 post partum (p.p.). In 49.1% of the observations, sows showed careful lying-down behavior. In 50.1% of cases, sows preferred the stomach-teats-position when lying down. With the DAT on day 4 p.p., in 89.3% of observations, no or only slight reactions of the sow were documented. The TT and TCT were performed on days 3 and 10 p.p. Strong defensive reactions of animals towards humans were recorded in 4.5% of the observations in the TT, and in 4.0% of the observations in the TCT. In the RT on day 3 p.p., in 61.8%, a joyful response of the sows to the reunion with their piglets was observed. This study showed that the behavioral observation procedures and designed tests are suitable to characterize sows’ behavior towards humans and piglets with regard to traits that are particularly important in systems without fixation.
Expression of the Malus sieversii NF-YB21 Encoded Gene Confers Tolerance to Osmotic Stresses in Arabidopsis thaliana

Drought is the main environmental factor that limits the yield and quality of apples (Malus × domestica) grown in arid and semi-arid regions. Nuclear factor Ys (NF-Ys) are important transcription factors involved in the regulation of plant growth, development, and various stress responses. However, the function of NF-Y genes is poorly understood in apples. Here, we identified 43 NF-Y genes in the genome of apples and conducted an initial functional characterization of the apple NF-Y. Expression analysis of NF-Y members in M. sieversii revealed that a large number of NF-Ys were highly expressed in the roots compared with the leaves, and a large proportion of NF-Y genes responded to drought treatment. Furthermore, heterologous expression of MsNF-YB21, which was significantly upregulated by drought, led to a longer root length and, thus, conferred improved osmotic and salt tolerance in Arabidopsis. Moreover, the physiological analysis of MsNF-YB21 overexpression revealed enhanced antioxidant systems, including antioxidant enzymes and compatible solutes. In addition, genes encoding catalase (AtCAT2, AtCAT3), superoxide dismutase (AtFSD1, AtFSD3, AtCSD1), and peroxidase (AtPER12, AtPER42, AtPER47, AtPER51) showed upregulated expression in the MsNF-YB21 overexpression lines. These results for the MsNF-Y gene family provide useful information for future studies on NF-Ys in apples, and the functional analysis of MsNF-YB21 supports it as a potential target in the improvement of apple drought tolerance via biotechnological strategies.
In Silico-Based Design and In Vivo Evaluation of an Anthranilic Acid Derivative as a Multitarget Drug in a Diet-Induced Metabolic Syndrome Model

Metabolic syndrome (MetS) is a complex disease that affects almost a quarter of the world’s adult population. In MetS, diabetes, obesity, hyperglycemia, high cholesterol, and high blood pressure are the most common disorders. Polypharmacy is the most used strategy for managing conditions related to MetS, but it has drawbacks such as low medication adherence. Multitarget ligands have been proposed as an interesting approach to developing drugs to treat complex diseases. However, suitable preclinical models that allow their evaluation in a context closer to a clinical situation of a complex disease are needed. From molecular docking studies, compound 1b, a 5-aminoanthranilic acid derivative substituted with 4′-trifluoromethylbenzylamino and 3′,4′-dimethoxybenzamide moieties, was identified as a potential multitarget drug, as it showed high in silico affinity against targets related to MetS, including PPAR-α, PPAR-γ, and HMG-CoA reductase. It was evaluated in a diet-induced MetS rat model and simultaneously lowered blood pressure, glucose, total cholesterol, and triglyceride levels after a 14-day treatment. No toxicity events were observed during an acute lethal dose evaluation test at 1500 mg/kg. Hence, the diet-induced MetS model is suitable for evaluating treatments for MetS, and compound 1b is an attractive starting point for developing multitarget drugs.
Insights into Growth Factors in Liver Carcinogenesis and Regeneration: An Ongoing Debate on Minimizing Cancer Recurrence after Liver Resection

Hepatocellular carcinoma has become a leading cause of cancer-associated mortality throughout the world, and is of great concern. Currently used chemotherapeutic drugs in the treatment of hepatocellular carcinoma lead to severe side effects, thus underscoring the need for further research to develop novel and safer therapies. Liver resection in cancer patients is routinely performed. After partial resection, liver regeneration is a perfectly calibrated response apparently sensed by the body’s required liver function. This process hinges on the effect of several growth factors, among other molecules. However, dysregulation of growth factor signals also leads to growth signaling autonomy and tumor progression, so control of growth factor expression may prevent tumor progression. This review describes the role of some of the main growth factors whose dysregulation promotes liver tumor progression, and are also key in regenerating the remaining liver following resection. We herein summarize and discuss studies focused on partial hepatectomy and liver carcinogenesis, referring to hepatocyte growth factor, insulin-like growth factor, and epidermal growth factor, as well as their suitability as targets in the treatment of hepatocellular carcinoma. Finally, and given that drugs remain one of the mainstay treatment options in liver carcinogenesis, we have reviewed the current pharmacological approaches approved for clinical use or research targeting these factors.