Miracle-dz/UniFAR-FTUs huggingface dataset:
Excision Repair Cross-Complementation Group 6 Gene Polymorphism Is Associated with the Response to FOLFIRINOX Chemotherapy in Asian Patients with Pancreatic Cancer

Simple Summary FOLFIRINOX is a platinum-based chemotherapy regimen for patients with pancreatic cancer and is known to be more effective in the presence of the BRCA mutation, one of the DNA damage repair (DDR) gene mutations. However, BRCA mutations are less common in pancreatic cancer patients, accounting for only about 5% of cases worldwide, and are known to be even rarer in Asians. Therefore, this study aimed to uncover new genetic variants of DDR genes related to the response of FOLFIRINOX by analyzing variants of DDR genes using whole exome sequencing. Multivariable Cox regression analysis adjusted for clinical variables showed that a single nucleotide polymorphism (SNP) of the ERCC6 gene is an independent predictor for progression-free survival. If validated, the ERCC6 SNP found in this study could be used as a biomarker to predict responses to FOLFIRINOX. Abstract FOLFIRINOX is currently one of the standard chemotherapy regimens for pancreatic cancer patients, but little is known about the factors that can predict a response to it. We performed a study to discover novel DNA damage repair (DDR) gene variants associated with the response to FOLFIRINOX chemotherapy in patients with pancreatic cancer. We queried a cohort of pancreatic cancer patients who received FOLFIRINOX chemotherapy as the first treatment and who had tissue obtained through an endoscopic ultrasound-guided biopsy that was suitable for DNA sequencing. We explored variants of 148 DDR genes based on whole exome sequencing and performed multivariate Cox regression to find genetic variants associated with progression-free survival (PFS). Overall, 103 patients were included. Among 2384 variants of 141 DDR genes, 612 non-synonymous variants of 123 genes were selected for Cox regression analysis. The multivariate Cox model showed that rs2228528 in ERCC6 was significantly associated with improved PFS (hazard ratio 0.54, p = 0.001). The median PFS was significantly longer in patients with rs2228528 genotype AA vs. genotype GA and GG (23.5 vs. 16.2 and 8.6 months; log-rank p < 0.001). This study suggests that rs2228528 in ERCC6 could be a potential predictor of response to FOLFIRINOX chemotherapy in patients with pancreatic cancer.
Comparison of Environmental Conditions on Summits of Mount Everest and K2 in Climbing and Midwinter Seasons

(1) Background: Today’s elite alpinists target K2 and Everest in midwinter. This study aimed to asses and compare weather at the summits of both peaks in the climbing season (Everest, May; K2, July) and the midwinter season (January and February). (2) Methods: We assessed environmental conditions using the ERA5 dataset (1979–2019). Analyses examined barometric pressure (BP), temperature (Temp), wind speed (Wind), perceived altitude (Alt), maximal oxygen uptake (VO2max), vertical climbing speed (Speed), wind chill equivalent temperature (WCT), and facial frostbite time (FFT). (3) Results: Most climbing-season parameters were found to be more severe (p < 0.05) on Everest than on K2: BP (333 ± 1 vs. 347 ± 1 hPa), Alt (8925 ± 20 vs. 8640 ± 20 m), VO2max (16.2 ± 0.1 vs. 17.8 ± 0.1 ml·kg−1·min−1), Speed (190 ± 2 vs. 223 ± 2 m·h−1), Temp (−26 ± 1 vs. −21 ± 1°C), WCT (−45 ± 2 vs. −37 ± 2 °C), and FFT (6 ± 1 vs. 11 ± 2 min). Wind was found to be similar (16 ± 3 vs. 15 ± 3 m·s−1). Most midwinter parameters were found to be worse (p < 0.05) on Everest vs. K2: BP (324 ± 2 vs. 326 ± 2 hPa), Alt (9134 ± 40 vs. 9095 ± 48 m), VO2max (15.1 ± 0.2 vs. 15.3 ± 0.3 ml·kg−1·min−1), Speed (165 ± 5 vs. 170 ± 6 m·h−1), Wind (41 ± 6 vs. 27 ± 4 m·s−1), and FFT (<1 min vs. 1 min). Everest’s Temp of −36 ± 2 °C and WCT −66 ± 3 °C were found to be less extreme than K2’s Temp of −45 ± 1 °C and WCT −76 ± 2 °C. (4) Conclusions: Everest presents more extreme conditions in the climbing and midwinter seasons than K2. K2’s 8° higher latitude makes its midwinter BP similar and Temp lower than Everest’s. K2’s midwinter conditions are more severe than Everest’s in the climbing season.
Rare Sugars: Recent Advances and Their Potential Role in Sustainable Crop Protection

Rare sugars are monosaccharides with a limited availability in the nature and almost unknown biological functions. The use of industrial enzymatic and microbial processes greatly reduced their production costs, making research on these molecules more accessible. Since then, the number of studies on their medical/clinical applications grew and rare sugars emerged as potential candidates to replace conventional sugars in human nutrition thanks to their beneficial health effects. More recently, the potential use of rare sugars in agriculture was also highlighted. However, overviews and critical evaluations on this topic are missing. This review aims to provide the current knowledge about the effects of rare sugars on the organisms of the farming ecosystem, with an emphasis on their mode of action and practical use as an innovative tool for sustainable agriculture. Some rare sugars can impact the plant growth and immune responses by affecting metabolic homeostasis and the hormonal signaling pathways. These properties could be used for the development of new herbicides, plant growth regulators and resistance inducers. Other rare sugars also showed antinutritional properties on some phytopathogens and biocidal activity against some plant pests, highlighting their promising potential for the development of new sustainable pesticides. Their low risk for human health also makes them safe and ecofriendly alternatives to agrochemicals.
Effect of Enamel Matrix Derivatives on Osteoclast Formation from PBMC of Periodontitis Patients and Healthy Individuals after Interaction with Activated Endothelial Cells

Background and objectives: Enamel matrix derivative (EMD) is produced from developing porcine tooth buds and represents a complex of low-molecular-weight hydrophobic enamel proteins. EMD is widely applied in periodontal regeneration. Osteoclasts are multinuclear cells, which are responsible for bone resorption. The precursors of osteoclasts, hematopoietic cells, undergo in vivo the process of transendothelial migration before differentiation. EMD is known to affect the process of osteoclastogenesis, but its effect on human osteoclasts precursors after the interaction with activated endothelium was never studied. Materials and Methods: Human umbilical vein endothelial cells (HUVECs)s were seeded in transwell inserts with a pore size of 8 µm and pre-activated by TNF-α and IL-1β for 18 h. Peripheral blood mononuclear cells (PBMCs), freshly isolated from 16 periodontitis patients and 16 healthy individuals, were added to pre-activated HUVECs. Adherent, non-adherent and transmigrated cells were collected and differentiated to osteoclasts by the standard protocol in the presence or absence of EMD. The number of osteoclasts was determined by tartrate-resistant acid phosphatase staining. Results: PBMCs isolated from periodontitis patients have formed a significantly higher osteoclast number compared to PBMCs isolated from healthy individuals (p < 0.05). EMD induced concentration-dependent inhibition of osteoclast formation from PBMCs. This was true for the different PBMC fractions isolated from both healthy individuals and periodontitis patients. Conclusions: Our data show that EMD inhibits the formation and activity of osteoclasts differentiated from the progenitor cells after the interaction with activated endothelium. This might be associated with bone resorption inhibition and supporting bone regeneration in the frame of periodontal therapy.
Structure and Properties of ZrON Coatings Synthesized by Cathodic Arc Evaporation

The transition metal oxynitrides are a coating material with decorative features due to their adjustable color and good mechanical properties. The purpose of the research was to study the effect of the relative oxygen concentration O2(x) = O2/(N2 + O2) in particular on adhesion, but also on the color, structural and mechanical properties of ZrON coatings synthesized by cathodic arc evaporation on HS6-5-2 steel substrates. The surface morphology, phase and chemical composition and mechanical properties were determined using scanning electron microscopy, X-ray diffraction, wavelength dispersive X-ray spectroscopy, nanoindentation and scratch test. It was found that color of the coatings changed from light yellow for ZrN first to gold and then to graphite for Zr-O phase with increase of oxygen concentration. X-ray diffraction patterns showed that the phase separation of ZrN and ZrO2 occurred for about 35 at. % of oxygen in the coating. Increase in oxygen concentration in the coatings led to decrease in crystallite size from about 20 nm for ZrN to about 5 nm for coatings with about 35 at. % of oxygen and about 25 at. % of nitrogen. An increase in hardness from about 26 GPa for ZrN to about 30 GPa for coating with small concentration of oxygen (about 9 at.%) and then decrease to about 15 GPa was observed. Adhesion of Zr-O-N coatings demonstrated strong dependence on oxygen concentration. Critical load for ZrN is about 80 N and decreases with oxygen concentration increase to about 30 N for ZrO2.
Development and Reliability of the Oxford Meat Frequency Questionnaire

Reliable and valid measurements of meat intake are needed to advance understanding of its health effects and to evaluate interventions to reduce meat consumption. Here, we describe the development and reliability of the Oxford Meat Frequency Questionnaire (MFQ). It asks individuals to report the number of servings of meat and seafood products they consumed in the last 24 h and is administered daily over 7 days. The MFQ combines food portion size data from the UK Food Standards Agency with estimates of meat content in composite dishes from the UK’s National Diet and Nutrition Survey. Adults who self-reported to eat meat (n = 129) completed a 3-week web-based test–retest reliability study assessing the MFQ twice, with a wash-out week in the middle. Two-way random intraclass correlation coefficients (ICC) revealed moderate to good agreement on all meat outcomes (total meat ICC = 0.716; minimum–maximum individual components = 0.531–0.680), except for fish and seafood (ICC = 0.257). Participants reported finding the questionnaire easy to use and, on average, completed it in less than 2 min. This new MFQ offers a quick, acceptable, and reliable method to measure changes in an individual’s meat intake in a UK population.
Factors Affecting Attitudes towards COVID-19 Vaccination: An Online Survey in Slovenia

While the problem of vaccine hesitancy is not new, it has become more pronounced with the new COVID-19 vaccines and represents an obstacle to resolving the crisis. Even people who would usually trust vaccines and experts now prefer to wait for more information. A cross-sectional online survey was conducted in Slovenia in December 2020 to find out the attitudes of the population regarding COVID-19 vaccination and the factors that affect these attitudes. Based on 12,042 fully completed questionnaires, we find that higher intention to get vaccinated is associated with men, older respondents, physicians and medical students, respondents who got the influenza vaccination, those who knew someone who had gotten hospitalised or died from COVID-19 and those who have more trust in experts, institutions and vaccines. Nurses and technicians were less likely to get vaccinated. In answers to an open question, sceptics were split into those doubting the quality due to the rapid development of the vaccine and those that reported personal experiences with side effects of prior vaccinations. Although the Slovenian population is diverse in its attitudes towards vaccination, the results are comparable to those found in other countries. However, there are potential limitations to the generalizability of the findings that should be addressed in future studies.
Silymarin-Enriched Biostimulant Foliar Application Minimizes the Toxicity of Cadmium in Maize by Suppressing Oxidative Stress and Elevating Antioxidant Gene Expression

For maize, the potential preventive role of foliar spraying with an extract derived from maize grain (MEg, 2%), silymarin (Sm, 0.5 mM), or silymarin-enriched MEg (MEg-Sm) in attenuating the stress effects of cadmium (Cd, 0.5 mM) was examined using a completely randomized design layout. Under normal conditions, foliar spraying with MEg, Sm, or MEg-Sm was beneficial (with MEg-Sm preferred) for maize plants, whereas the benefit was more pronounced under Cd stress. The use of Cd through irrigation water decreased plant growth traits, photosynthetic efficiency, including instantaneous carboxylation efficiency, Fv/Fm, and pigment contents, and hormonal contents (e.g., auxin, gibberellins, cytokinins including trans-zeatin, and salicylic acid). These undesired findings were due to an increase in Cd content, leading to increased levels of oxidative stress (O2•− and H2O2), ionic leakage, and lipid peroxidation. Therefore, this damage resulted in an increase in the activities of nonenzymatic antioxidants, Sm, antioxidative enzymes, and enzyme gene expression. However, under Cd stress, although foliar spray with MEg or Sm had better findings than control, MEg-Sm had better findings than MEg or Sm. Application of MEg-Sm greatly increased photosynthesis efficiency, restored hormonal homeostasis, and further increased the activities of various antioxidants, Sm, antioxidative enzymes, and enzyme gene expression. These desired findings were due to the suppression of the Cd content, and thus the levels of O2•−, H2O2, ionic leakage, and lipid peroxidation, which were positively reflected in the growth and accumulation of dry matter in maize plants. The data obtained in this study recommend applying silymarin-enriched maize grain extract (MEg-Sm at 0.24 g Sm L−1 of MEg) as a spray solution to maize plants when exposed to excess Cd in soil or irrigation water.
The Composition, Physicochemical Properties, Antioxidant Activity, and Sensory Properties of Estonian Honeys

Thirty honey samples from different regions of Estonia were investigated to determine the chemical compositions, physicochemical properties, bioactive compounds, and sensory characteristics of typical honeys from a northern climate. The physicochemical parameters, such as electrical conductivity, moisture content, free acidity, hydroxymethylfurfural, diastase, and invertase activity were measured. The color was measured and expressed by L*-, a*-, and b*-coordinates. Sensory parameters were determined by using “fruity”, “floral”, “berry-like”, “herbal”, “woody”, “spicy”, “sweet”, and “animal-like” as the main odor and flavor attributes. The total polyphenol and flavonoid contents were in the range of 26.2–88.7 mg gallic acid equivalents (GAE) per 100 g and 1.9–6.4 mg quercetin equivalents (QE) per 100 g, respectively. The identified polyphenols showed the highest intensities of caffeic acid, coumaric acid, and abscisic acid and its derivatives. The protocatechuic acid intensity was highest in honeys containing traces of honeydew elements and of cinnamic acid and myricetin in heather honey. The water-soluble antioxidant values were 37.8–311.2 mg ascorbic acid equivalents (AAE) per 100 g and the lipid soluble antioxidant values were 14.4–60.7 mg Trolox equivalents (TE) per 100 g. The major amino acid in the analyzed honeys was proline, with variable values depending on the honey’s botanical source. Correlations were calculated based on the results obtained. It was revealed that the typical Estonian honey has floral, berry-like, sweet, and rather mild sensory characteristics. Most of the honeys lacked stronger spicy, woody, and animal-like attributes. The typical color of Estonian honey is quite light.
Testosterone in Female Depression: A Meta-Analysis and Mendelian Randomization Study

Testosterone’s role in female depression is not well understood, with studies reporting conflicting results. Here, we use meta-analytical and Mendelian randomization techniques to determine whether serum testosterone levels differ between depressed and healthy women and whether such a relationship is casual. Our meta-analysis shows a significant association between absolute serum testosterone levels and female depression, which remains true for the premenopausal group while achieving borderline significance in the postmenopausal group. The results from our Mendelian randomization analysis failed to show any causal relationship between testosterone and depression. Our results show that women with depression do indeed display significantly different serum levels of testosterone. However, the directions of the effect of this relationship are conflicting and may be due to menopausal status. Since our Mendelian randomization analysis was insignificant, the difference in testosterone levels between healthy and depressed women is most likely a manifestation of the disease itself. Further studies could be carried out to leverage this newfound insight into better diagnostic capabilities culminating in early intervention in female depression.
A Food Insecurity Systematic Review: Experience from Malaysia

Living free from hunger is a basic human right. However, some communities still experience household food insecurity. This systematic literature review explored different aspects of household food insecurity in Malaysia including vulnerable groups, prevalence, risk factors, coping strategies, and the consequences of food insecurity. The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Thirty-three relevant articles were selected from scientific databases such as CINAHL, Pubmed and Google Scholar, scrutiny of reference lists, and personal communication with experts in the field. The prevalence of household food insecurity in Malaysia was unexpectedly reported as high, with affected groups including Orang Asli, low-income household/welfare-recipient households, university students, and the elderly. Demographic risk factors and socioeconomic characteristics included larger household, living in poverty, and low education. Coping strategies were practices to increase the accessibility of food in their households. Consequences of household food insecurity included psychological, dietary (macro- and micronutrient intakes), nutritional status, and health impacts. In conclusion, this review confirmed that household food insecurity in Malaysia continues to exist. Nevertheless, extensive and active investigations are encouraged to obtain a more holistic and comprehensive picture pertaining to household food security in Malaysia.
Exosomes from COVID-19 Patients Carry Tenascin-C and Fibrinogen-β in Triggering Inflammatory Signals in Cells of Distant Organ

SARS-CoV-2 infection can cause cytokine storm and may overshoot immunity in humans; however, it remains to be determined whether virus-induced soluble mediators from infected cells are carried by exosomes as vehicles to distant organs and cause tissue damage in COVID-19 patients. We took an unbiased proteomic approach for analyses of exosomes isolated from plasma of healthy volunteers and COVID-19 patients. Our results revealed that tenascin-C (TNC) and fibrinogen-β (FGB) are highly abundant in exosomes from COVID-19 patients’ plasma compared with that of healthy normal controls. Since TNC and FGB stimulate pro-inflammatory cytokines via the Nuclear factor-κB (NF-κB) pathway, we examined the status of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and C–C motif chemokine ligand 5 (CCL5) expression upon exposure of hepatocytes to exosomes from COVID-19 patients and observed significant increase compared with that from healthy subjects. Together, our results demonstrate that TNC and FGB are transported through plasma exosomes and potentially trigger pro-inflammatory cytokine signaling in cells of distant organ.
Usability of a Psychotherapeutic Interactive Gaming Tool Used in Facial Emotion Recognition for People with Schizophrenia

The objective of the study was to test the usability of ‘Feeling Master’ as a psychotherapeutic interactive gaming tool with LEGO cartoon faces showing the five basic emotions, for the assessment of emotional recognition in people with schizophrenia in comparison with healthy controls, and the relationship between face affect recognition (FER), attributional style, and theory of mind (ToM), which is the ability to understand the potential mental states and intentions of others. Nineteen individuals with schizophrenia (SZ) and 17 healthy control (HC) subjects completed the ‘Feeling Master’ that includes five basic emotions. To assess social cognition, the group with schizophrenia was evaluated with the Personal and Situational Attribution Questionnaire (IPSAQ) for the assessment of attributional style and the Hinting Task (ToM). Patients with SZ showed significant impairments in emotion recognition and their response time appeared to be slower than the HC in the recognition of each emotion. Taking into account the impairment in the recognition of each emotion, we only found a trend toward significance in error rates on fear recognition. The correlations between correct response on the ‘Feeling Master’ and the hinting task appeared to be significant in the correlation of surprise and theory of mind. In conclusion, this study demonstrated that the ‘Feeling Master’ could be useful for the evaluation of FER in people with schizophrenia. These results sustain the notion that impairments in emotion recognition are more prevalent in people with schizophrenia and that these are related with impairment in ToM.
Effects of Regular Taekwondo Intervention on Health-Related Physical Fitness, Cardiovascular Disease Risk Factors and Epicardial Adipose Tissue in Elderly Women with Hypertension

Regular exercise has been proven to prevent hypertension and to help in the management of hypertension. There is a lack of studies examining changes in these issues as a result of Taekwondo training intervention. The aim of the current trial is to identify the effects of a regular Taekwondo (TKD) training program on health-related physical fitness (HRPF), cardiovascular disease (CVD) risk factors, inflammatory factors, and epicardial adipose tissue (EAT) in elderly women with hypertension. To accomplish this, 20 participants, who were older women with hypertension, were divided into a TKD group (n = 10) and a control group (n = 10). The TKD program was conducted in program for 90 min, three times a week, for 12 weeks. Outcomes, including body composition, blood pressure (BP), HRPF, cardiovascular risk factor and EAT, were measured before and after the Taekwondo program. The 12-week TKD program improved body composition, BP, HRPF, CVD risk factor, and EAT in elderly women with hypertension relative to controls. Meanwhile, EAT and interukin-1β (r = 0.530, p < 0.05), monocyte chemotactic protein-1 (r = 0.524, p < 0.05), triglyceride (r = 0.493, p < 0.05) and sedentary behavior (r = 0.459, p < 0.05) presented a positive correlation, while EAT and lean body mass (r = −0.453, p < 0.05) showed a negative correlation. The 12-week regular TKD training intervention was found to be effective in reducing the thickness of EAT measured by multi-detector computed tomography and can also enhance health-related physical fitness and risk factors of CVD in older individuals with hypertension.
Synthesis and Evaluation of Novel α-Aminoamides Containing Benzoheterocyclic Moiety for the Treatment of Pain

Novel α-aminoamide derivatives containing different benzoheterocyclics moiety were synthesized and evaluated as voltage-gated sodium ion channels blocks the treatment of pain. Compounds 6a, 6e, and 6f containing the benzofuran group displayed more potent in vivo analgesic activity than ralfinamide in both the formalin test and the writhing assay. Interestingly, they also exhibited potent in vitro anti-Nav1.7 and anti-Nav1.8 activity in the patch-clamp electrophysiology assay. Therefore, compounds 6a, 6e, and 6f, which have inhibitory potency for two pain-related Nav targets, could serve as new leads for the development of analgesic medicines.