Miracle-dz/UniFAR-FTUs huggingface dataset:
Biochemical and Biophysical Characterization of Recombinant Human 3-Phosphoglycerate Dehydrogenase

The human enzyme D-3-phosphoglycerate dehydrogenase (hPHGDH) catalyzes the reversible dehydrogenation of 3-phosphoglycerate (3PG) into 3-phosphohydroxypyruvate (PHP) using the NAD+/NADH redox cofactor, the first step in the phosphorylated pathway producing L-serine. We focused on the full-length enzyme that was produced in fairly large amounts in E. coli cells; the effect of pH, temperature and ligands on hPHGDH activity was studied. The forward reaction was investigated on 3PG and alternative carboxylic acids by employing two coupled assays, both removing the product PHP; 3PG was by far the best substrate in the forward direction. Both PHP and α-ketoglutarate were efficiently reduced by hPHGDH and NADH in the reverse direction, indicating substrate competition under physiological conditions. Notably, neither PHP nor L-serine inhibited hPHGDH, nor did glycine and D-serine, the coagonists of NMDA receptors related to L-serine metabolism. The investigation of NADH and phosphate binding highlights the presence in solution of different conformations and/or oligomeric states of the enzyme. Elucidating the biochemical properties of hPHGDH will enable the identification of novel approaches to modulate L-serine levels and thus to reduce cancer progression and treat neurological disorders.
Treatment Options for Motor and Non-Motor Symptoms of Parkinson’s Disease

Parkinson’s disease (PD) usually presents in older adults and typically has both motor and non-motor dysfunctions. PD is a progressive neurodegenerative disorder resulting from dopaminergic neuronal cell loss in the mid-brain substantia nigra pars compacta region. Outlined here is an integrative medicine and health strategy that highlights five treatment options for people with Parkinson’s (PwP): rehabilitate, therapy, restorative, maintenance, and surgery. Rehabilitating begins following the diagnosis and throughout any additional treatment processes, especially vis-à-vis consulting with physical, occupational, and/or speech pathology therapist(s). Therapy uses daily administration of either the dopamine precursor levodopa (with carbidopa) or a dopamine agonist, compounds that preserve residual dopamine, and other specific motor/non-motor-related compounds. Restorative uses strenuous aerobic exercise programs that can be neuroprotective. Maintenance uses complementary and alternative medicine substances that potentially support and protect the brain microenvironment. Finally, surgery, including deep brain stimulation, is pursued when PwP fail to respond positively to other treatment options. There is currently no cure for PD. In conclusion, the best strategy for treating PD is to hope to slow disorder progression and strive to achieve stability with neuroprotection. The ultimate goal of any management program is to improve the quality-of-life for a person with Parkinson’s disease.
Transcriptome profiles associated with selenium-deficiency-dependent oxidative stress identify potential diagnostic and therapeutic targets in liver cancer cells

Hepatocellular carcinoma (HCC) is one of the most common cancer types with high mortality rates and displays increased resistance to various stress conditions such as oxidative stress. Conventional therapies have low efficacies due to resistance and off-target effects in HCC. Here we aimed to analyze oxidative stress-related gene expression profiles of HCC cells and identify genes that could be crucial for novel diagnostic and therapeutic strategies. To identify important genes that cause resistance to reactive oxygen species (ROS), a model of oxidative stress upon selenium (Se) deficiency was utilized. The results of transcriptome-wide gene expression data were analyzed in which the differentially expressed genes (DEGs) were identified between HCC cell lines that are either resistant or sensitive to Se-deficiency-dependent oxidative stress. These DEGs were further investigated for their importance in oxidative stress resistance by network analysis methods, and 27 genes were defined to have key roles; 16 of which were previously shown to have impact on liver cancer patient survival. These genes might have Se-deficiency-dependent roles in hepatocarcinogenesis and could be further exploited for their potentials as novel targets for diagnostic and therapeutic approaches.
Women’s Perception of Male Involvement in Antenatal, Childbirth and Postnatal Care in Urban Slum Areas in Bangladesh: A Community-Based Cross-Sectional Study

Male participation in reproductive health issues has been considered to be an effective and promising strategy to address the women’s reproductive health problems since the 1990s. Under this background, we aim to explore the women’s perception of men’s involvement in antenatal care (ANC), delivery and postnatal care (PNC) in the slum community of Bangladesh where various sexual and reproductive health problems exist. A community-based cross-sectional study was conducted among women and their husbands living in 12 slums of Chattogram city. Cross-tabulation with chi-square tests and multivariate logistic regression analyses were performed to examine the predictors of husbands’ support in wives’ antenatal, delivery and postnatal care. The study demonstrates that the education and economic level of most women and their husbands were very low although husbands seemed to have a better status than wives in these aspects. Almost all men (~90%) had never accessed services related to reproductive and maternal health. Only 10% of respondents gave birth to their last baby in government hospitals or private clinics. In addition, 60% of the husbands took care of their wives during pregnancy with 44% during childbirth and about 30% providing help in receiving postpartum care. Moreover, husbands’ discussions with a health worker regarding maternal and reproductive health were the most important predictors for support of their wives during pregnancy, childbirth and postpartum care (p < 0.05). Study participants’ perception of a satisfying spousal relationship also appeared to be a significant factor for husbands’ responsible role regarding wives’ antenatal care, delivery and postnatal care (p < 0.05). This study found that pregnant women living in slums received poorer health-related services when there was a low involvement of men; specifically, the husbands of pregnant women. In addition, men’s involvement was influenced by many aspects, particularly awareness-related factors (e.g., knowledge, communication and access to reproductive health services). Therefore, awareness creation is important for active involvement in antenatal, delivery and postnatal care. Strategies should be designed to provide men living in the slums with adequate information, education and communication to gain their interest and support about reproductive and maternal health.
The Urokinase Receptor: A Multifunctional Receptor in Cancer Cell Biology. Therapeutic Implications

Proteolysis is a key event in several biological processes; proteolysis must be tightly controlled because its improper activation leads to dramatic consequences. Deregulation of proteolytic activity characterizes many pathological conditions, including cancer. The plasminogen activation (PA) system plays a key role in cancer; it includes the serine-protease urokinase-type plasminogen activator (uPA). uPA binds to a specific cellular receptor (uPAR), which concentrates proteolytic activity at the cell surface, thus supporting cell migration. However, a large body of evidence clearly showed uPAR involvement in the biology of cancer cell independently of the proteolytic activity of its ligand. In this review we will first describe this multifunctional molecule and then we will discuss how uPAR can sustain most of cancer hallmarks, which represent the biological capabilities acquired during the multistep cancer development. Finally, we will illustrate the main data available in the literature on uPAR as a cancer biomarker and a molecular target in anti-cancer therapy.
In Situ Atomic-Scale Observation of Silver Oxidation Triggered by Electron Beam Irradiation

Understanding the mechanism of metal oxidation processes is critical for maintaining the desired properties of metals and catalysts, as well as for designing advanced materials. In this work, we investigate the electron beam induced oxidation of silver using in situ transmission electron microscopy. The additions of Ag-O columns on {111} and {110} planes were captured with atomic resolution. Interestingly, oscillatory growth on {110} planes was observed, which resulted from the double effect of electron beam irradiation. It was found that not only thermodynamic factors but also kinetic factors played significant roles in morphology evolutions. These results can facilitate the fundamental understanding of the oxidation process of Ag and provide a promising approach for the fabrication of desired nanostructures.
Motor Performance in Male Youth Soccer Players: A Systematic Review of Longitudinal Studies

The aim of this systematic review was to identify and synthesize the available information regarding longitudinal data addressing young soccer players’ motor performance changes. Following the Preferred Reporting Items for Systematic and Meta-analyses (PRISMA) statement, literature searches were performed in three databases: PubMed, ISI Web of Science and SCOPUS. The following descriptors were used: football, soccer, youth, young, player, athlete, physical performance, motor performance, longitudinal. The inclusion criteria were original articles in English with longitudinal data of young males (aged 10–18 years), with the aim to investigate motor performance serial changes. The initial search returned 211 records, and the final sample comprised 32 papers. These papers covered the European continent, and used mixed and pure longitudinal design with variation in sample size and age range. The reviewed studies tended to use different tests to assess the motor performance and aimed to identify changes in motor performance in several ways. In general, they indicated motor performance improvements with age, with a marked influence of biological maturity, body composition, and training stimuli. This review highlights the need for coaches and stakeholders to consider players’ motor performance over time whilst considering biological maturation, biological characteristics, and training stimuli.
Emergency Department as the Entry Point to Inpatient Care: A Nationwide, Population-Based Study in South Korea, 2016–2018

(1) Background: The emergency department provides lifesaving treatment and has become an entry point to hospital admission. The purpose of our study was to describe the characteristics and outcomes of patients who were admitted through the emergency department to the intensive care unit or general ward. (2) Methods: We performed a retrospective, cross-sectional, descriptive analysis using the National Emergency Department Information System, analyzing patient data including disease category, diagnosis, and mortality from 1 January 2016, to 31 December 2018. (3) Results: During the study period, about 13.6% were admitted through the emergency department. Of these, the overall in-hospital mortality was 4.6%. The frequent disease class for the intensive care unit admissions was the cardiovascular system, and the classes for the general ward admissions were as follows: injury and toxicology, digestive system, and respiratory system. Cardiovascular system-related emergencies were the predominant cause of death among patients admitted to the intensive care unit; however, oncologic complications were the leading cause of death in the general ward. (4) Conclusions: Emergency departments are incrementally utilized as the entry point for hospital admission. Health care providers need to understand emergency department admission epidemiology and prepare for managing patients with certain common diagnoses.
The Increasing Impact of Translational Research in the Molecular Diagnostics of Neuromuscular Diseases

The diagnosis of neuromuscular diseases (NMDs) has been progressively evolving from the grouping of clinical symptoms and signs towards the molecular definition. Optimal clinical, biochemical, electrophysiological, electrophysiological, and histopathological characterization is very helpful to achieve molecular diagnosis, which is essential for establishing prognosis, treatment and genetic counselling. Currently, the genetic approach includes both the gene-targeted analysis in specific clinically recognizable diseases, as well as genomic analysis based on next-generation sequencing, analyzing either the clinical exome/genome or the whole exome or genome. However, as of today, there are still many patients in whom the causative genetic variant cannot be definitely established and variants of uncertain significance are often found. In this review, we address these drawbacks by incorporating two additional biological omics approaches into the molecular diagnostic process of NMDs. First, functional genomics by introducing experimental cell and molecular biology to analyze and validate the variant for its biological effect in an in-house translational diagnostic program, and second, incorporating a multi-omics approach including RNA-seq, metabolomics, and proteomics in the molecular diagnosis of neuromuscular disease. Both translational diagnostics programs and omics are being implemented as part of the diagnostic process in academic centers and referral hospitals and, therefore, an increase in the proportion of neuromuscular patients with a molecular diagnosis is expected. This improvement in the process and diagnostic performance of patients will allow solving aspects of their health problems in a precise way and will allow them and their families to take a step forward in their lives.
Sesame Oil-Based Nanostructured Lipid Carriers of Nicergoline, Intranasal Delivery System for Brain Targeting of Synergistic Cerebrovascular Protection

Nicergoline (NIC) is a semisynthetic ergot alkaloid derivative applied for treatment of dementia and other cerebrovascular disorders. The efficacy of sesame oil to slow and reverse the symptoms of neurodegenerative cognitive disorders has been proven. This work aimed to formulate and optimize sesame oil-based NIC-nanostructured lipid carriers (NIC–NLCs) for intranasal (IN) delivery with expected synergistic and augmented neuroprotective properties. The NIC–NLC were prepared using sesame oil as a liquid lipid. A three-level, three-factor Box–Behnken design was applied to statistically optimize the effect of sesame oil (%) of the total lipid, surfactant concentration, and sonication time on particle size, zeta potential, and entrapment efficacy as responses. Solid-state characterization, release profile, and ex vivo nasal permeation in comparison to NIC solution (NIC–SOL) was studied. In vivo bioavailability from optimized NIC–NLC and NIC–SOL following IN and IV administration was evaluated and compared. The optimized NIC–NLC formula showed an average particle size of 111.18 nm, zeta potential of −15.4 mV, 95.11% entrapment efficacy (%), and 4.6% loading capacity. The NIC–NLC formula showed a biphasic, extended-release profile (72% after 48 h). Permeation of the NIC–NLC formula showed a 2.3 enhancement ratio. Bioavailability studies showed a 1.67 and 4.57 fold increase in plasma and brain following IN administration. The results also indicated efficient direct nose-to-brain targeting properties with the brain-targeting efficiency (BTE%) and direct transport percentage (DTP%) of 187.3% and 56.6%, respectively, after IN administration. Thus, sesame oil-based NIC–NLC can be considered as a promising IN delivery system for direct and efficient brain targeting with improved bioavailability and expected augmented neuroprotective action for the treatment of dementia.
Hydration Status, Fluid Intake, Sweat Rate, and Sweat Sodium Concentration in Recreational Tropical Native Runners

Aim: The purpose of this study was to evaluate hydration status, fluid intake, sweat rate, and sweat sodium concentration in recreational tropical native runners. Methods: A total of 102 males and 64 females participated in this study. Participants ran at their self-selected pace for 30–100 min. Age, environmental conditions, running profiles, sweat rates, and sweat sodium data were recorded. Differences in age, running duration, distance and pace, and physiological changes between sexes were analysed. A p-value cut-off of 0.05 depicted statistical significance. Results: Males had lower relative fluid intake (6 ± 6 vs. 8 ± 7 mL·kg−1·h−1, p < 0.05) and greater relative fluid balance deficit (−13 ± 8 mL·kg−1·h−1 vs. −8 ± 7 mL·kg−1·h−1, p < 0.05) than females. Males had higher whole-body sweat rates (1.3 ± 0.5 L·h−1 vs. 0.9 ± 0.3 L·h−1, p < 0.05) than females. Mean rates of sweat sodium loss (54 ± 27 vs. 39 ± 22 mmol·h−1) were higher in males than females (p < 0.05). Conclusions: The sweat profile and composition in tropical native runners are similar to reported values in the literature. The current fluid replacement guidelines pertaining to volume and electrolyte replacement are applicable to tropical native runners.
Biological Response Induced in Primary Human Gingival Fibroblasts upon Exposure to Various Types of Injectable Astringent Retraction Agents

Traditional chemo-mechanical retraction/displacement materials can impact the gingival margin tissues. This study was undertaken to analyze biological responses induced in human gingival fibroblasts (HGFs) upon application of injectable astringent-based agents used in the cordless retraction technique. HGFs were exposed to hemostatic agents (five gels, three pastes, and one foam) based on aluminium chloride, aluminium sulphate and ferric sulphate. Changes in cell viability and proliferation were evaluated using an MTT assay and a BrdU assay. The cytoskeleton structure organization (zyxin and F-actin) was visualized by confocal laser scanning microscopy. Oxidative stress was determined using the Griess Reagent System. The RNA expression levels of antioxidant enzymes were quantified by real-time RT-PCR. The statistical significance was evaluated using Student’s t-test and one-way ANOVA with post-hoc Tukey HSD test. The evaluated agents did not downregulate fibroblast viability or proliferation. No significant cytoskeleton reorganization was observed. Only one agent (Expasyl) induced oxidative stress, demonstrated by the increased level of nitrites. Incubation with the studied agents significantly increased the RNA expression of some antioxidant enzymes (SOD1, SOD3, GPX1). However, no significant influence on the expression of SOD2 and HMOX1 was detected. The injectable forms of chemical retraction agents revealed biocompatibility with HGFs, suggesting their potential clinical usefulness in gingival margin retraction.
ERIC and WGS Typing of Paenibacillus larvae in Slovenia: Investigation of ERIC I Outbreaks

Simple Summary American foulbrood is a serious disease of honeybees caused by Paenibacillus larvae. ERIC-PCR is a widely used method for typing of P. larvae that currently divides it into five ERIC types (ERIC I–V); these differ in certain phenotypic characteristics—most importantly, virulence. In the first part of the study, we assessed the distribution of ERIC types in Slovenia in the period 2017–2019 on a set of 506 P. larvae isolates. We identified ERIC II as the predominant type (70.2%), followed by ERIC I (29.8%). In the second part of the study, we typed 59 outbreak-related ERIC I isolates using whole-genome sequencing, which revealed seven ERIC I-ST2 outbreak clusters (≤35 allele differences). The transmission of the outbreak clone within a 3-km radius was observed in all seven clusters and could be explained by the activity of honeybees. The transmission of the outbreak clone between geographically distant apiaries was observed in three clusters and could be explained by migratory beekeeping and trading of bee colonies. The present findings highlight the importance of beekeeping activities in the transmission of P. larvae over large geographic distances. Abstract Paenibacillus larvae is the causative agent of American foulbrood (AFB), a fatal disease of honeybee brood. Here, we obtained 506 P. larvae isolates originating from honey or brood samples and from different geographic regions of Slovenia in the period 2017–2019. In the first part of the study, we conducted ERIC-PCR typing to assess the frequency of ERIC types in Slovenia. Capillary electrophoresis was used for the analysis of ERIC patterns, revealing good separation efficiency and enabling easy lane-to-lane comparisons. ERIC II was the predominant type (70.2%), followed by ERIC I (29.8%); two slightly altered ERIC I banding patterns were observed but were not considered relevant for the discrimination of ERIC types. No evident spatiotemporal clustering of ERIC types was observed. To assess the clonality of the outbreak-related P. larvae ERIC I isolates, 59 isolates of this type underwent whole-genome sequencing (WGS). Whole-genome multilocus sequence typing (wgMLST) revealed seven ERIC I-ST2 outbreak clusters (≤35 allele differences) with the median intra-outbreak diversity ranging from 7 to 27 allele differences. In all seven clusters, the transmission of P. larvae outbreak clone within a 3-km radius (AFB zone) was observed, which could be explained by the activity of honeybees. In three clusters, the transmission of the outbreak clone between geographically distant apiaries was revealed, which could be explained by the activities of beekeepers such as migratory beekeeping and trading of bee colonies. The present findings reinforce the importance of beekeeping activities in the transmission of P. larvae. WGS should be used as a reference typing method for the detection of P. larvae transmission clusters.
Rituximab Therapy for Treatment of Pemphigus in Southeast Asians

Background Rituximab provides more effective and less adverse effects than the standard dose of corticosteroids, but evidence on its efficacy and safety in the Thai population is lacking. Objective To evaluate the efficacy and safety of rituximab in the treatment of pemphigus and also to determine prognostic factors linked to the treatment outcomes. Methods Pemphigus patients who received rituximab from November 2017 to December 2020 were retrospectively reviewed. The outcome was evaluated by using early (end of consolidation phase [ECP]) and late endpoints (complete remission [CR] on/off therapy, immunological remission [IR], and relapse). Adverse events were noted. Prognostic factors associated with remission and relapse were analyzed. Results Of 53 pemphigus patients, all attained ECP within 1.61 months. Almost 80% achieved CR on therapy within a median time of 6.36 months, while 33.9% reached CR off therapy in 19.74 months. Nearly half had IR within a median time of 6.88 months. Relapse occurred in 33.3% with a median time of 14 months. In multivariate analysis, receiving rituximab within 12 months of disease duration was more likely to achieve CR off therapy and IR (hazard ratio [HR] 3.79; 95% confidence interval [CI] 1.38, 10.42; P = 0.01 and HR 2.74; 95% CI 1.12, 6.69; P = 0.027, respectively), whereas older patients and positive anti-desmoglein 1 levels at the time of CR were predictive indicators for relapse (HR 1.07; 95% CI 1.01, 1.13; P = 0.036 and HR 4.38; 95% CI 1.24, 15.46; P = 0.022, respectively). The treatment-related adverse effects occurred in 33.9%. Conclusion Rituximab is effective and safe in Thai pemphigus patients. Early administration of rituximab was a predictor of clinical and immunological remission. Older age and persistently positive anti-Dsg1 were correlated with disease relapse.