Miracle-dz/UniFAR-FTUs huggingface dataset:
Development of EndoScreen Chip, a Microfluidic Pre-Endoscopy Triage Test for Esophageal Adenocarcinoma

Simple Summary Esophageal adenocarcinoma (EAC) is often detected late and has a poor survival rate. Currently, patients are selected for endoscopy-biopsy diagnosis based on clinical risk factors such as the precursor condition Barrett’s esophagus, history heartburn/reflux, age and high body mass index. To enable blood-based screening, we previously discovered and validated novel blood biomarkers for early stage EAC. To support clinical application, here, we report the technology development of the microfluidic EndoScreen chip and validation using the biomarker JAC-C9 (Jacalin-lectin binding complement component C9) in a test cohort of 46 samples. Compared to clinical risk factors alone, we found that use of blood biomarkers JAC-C9 and total C9 in addition to clinical risk factors improved EAC prediction in this cohort, suggesting that a simple blood test can help the physician prioritize patients for endoscopic evaluation. Future work will deploy a panel of markers on a point-of-care version of EndoScreen chip, to enable population screening and early diagnosis of EAC and thereby reduce mortality from this cancer. Abstract The current endoscopy and biopsy diagnosis of esophageal adenocarcinoma (EAC) and its premalignant condition Barrett’s esophagus (BE) is not cost-effective. To enable EAC screening and patient triaging for endoscopy, we developed a microfluidic lectin immunoassay, the EndoScreen Chip, which allows sensitive multiplex serum biomarker measurements. Here, we report the proof-of-concept deployment for the EAC biomarker Jacalin lectin binding complement C9 (JAC-C9), which we previously discovered and validated by mass spectrometry. A monoclonal C9 antibody (m26 3C9) was generated and validated in microplate ELISA, and then deployed for JAC-C9 measurement on EndoScreen Chip. Cohort evaluation (n = 46) confirmed the expected elevation of serum JAC-C9 in EAC, along with elevated total serum C9 level. Next, we asked if the small panel of serum biomarkers improves detection of EAC in this cohort when used in conjunction with patient risk factors (age, body mass index and heartburn history). Using logistic regression modeling, we found that serum C9 and JAC-C9 significantly improved EAC prediction from AUROC of 0.838 to 0.931, with JAC-C9 strongly predictive of EAC (vs. BE OR = 4.6, 95% CI: 1.6–15.6, p = 0.014; vs. Healthy OR = 4.1, 95% CI: 1.2–13.7, p = 0.024). This proof-of-concept study confirms the microfluidic EndoScreen Chip technology and supports the potential utility of blood biomarkers in improving triaging for diagnostic endoscopy. Future work will expand the number of markers on EndoScreen Chip from our list of validated EAC biomarkers.
Methyl jasmonate effects on sugarbeet root responses to postharvest dehydration

Background Sugarbeet (Beta vulgaris L.) roots are stored under conditions that cause roots to dehydrate, which increases postharvest losses. Although exogenous jasmonate applications can reduce drought stress in intact plants, their ability to alleviate the effects of dehydration in postharvest sugarbeet roots or other stored plant products is unknown. Research was conducted to determine whether jasmonate treatment could mitigate physiological responses to dehydration in postharvest sugarbeet roots. Methods Freshly harvested sugarbeet roots were treated with 10 µM methyl jasmonate (MeJA) or water and stored under dehydrating and non-dehydrating storage conditions. Changes in fresh weight, respiration rate, wound healing, leaf regrowth, and proline metabolism of treated roots were investigated throughout eight weeks in storage. Results Dehydrating storage conditions increased root weight loss, respiration rate, and proline accumulation and prevented leaf regrowth from the root crown. Under dehydrating conditions, MeJA treatment reduced root respiration rate, but only in severely dehydrated roots. MeJA treatment also hastened wound-healing, but only in the late stages of barrier formation. MeJA treatment did not impact root weight loss or proline accumulation under dehydrating conditions or leaf regrowth under non-dehydrating conditions. Both dehydration and MeJA treatment affected expression of genes involved in proline metabolism. In dehydrated roots, proline dehydrogenase expression declined 340-fold, suggesting that dehydration-induced proline accumulation was governed by reducing proline degradation. MeJA treatment altered proline biosynthetic and catabolic gene expression, with greatest effect in non-dehydrated roots. Overall, MeJA treatment alleviated physiological manifestations of dehydration stress in stored roots, although the beneficial effects were small. Postharvest jasmonate applications, therefore, are unlikely to significantly reduce dehydration-related storage losses in sugarbeet roots.
Quantitative Muscle MRI in Patients with Neuromuscular Diseases—Association of Muscle Proton Density Fat Fraction with Semi-Quantitative Grading of Fatty Infiltration and Muscle Strength at the Thigh Region

(1) Background and Purpose: The skeletal muscles of patients suffering from neuromuscular diseases (NMD) are affected by atrophy, hypertrophy, fatty infiltration, and edematous changes. Magnetic resonance imaging (MRI) is an important tool for diagnosis and monitoring. Concerning fatty infiltration, T1-weighted or T2-weighted DIXON turbo spin echo (TSE) sequences enable a qualitative assessment of muscle involvement. To achieve higher comparability, semi-quantitative grading scales, such as the four-point Mercuri scale, are commonly applied. However, the evaluation remains investigator-dependent. Therefore, effort is being invested to develop quantitative MRI techniques for determination of imaging markers such as the proton density fat fraction (PDFF). The present work aims to assess the diagnostic value of PDFF in correlation to Mercuri grading and clinically determined muscle strength in patients with myotonic dystrophy type 2 (DM2), limb girdle muscular dystrophy type 2A (LGMD2A), and adult Pompe disease. (2) Methods: T2-weighted two-dimensional (2D) DIXON TSE and chemical shift encoding-based water-fat MRI were acquired in 13 patients (DM2: n = 5; LGMD2A: n = 5; Pompe disease: n = 3). Nine different thigh muscles were rated in all patients according to the Mercuri grading and segmented to extract PDFF values. Muscle strength was assessed according to the British Medical Research Council (BMRC) scale. For correlation analyses between Mercuri grading, muscle strength, and PDFF, the Spearman correlation coefficient (rs) was computed. (3) Results: Mean PDFF values ranged from 7% to 37% in adults with Pompe disease and DM2 and up to 79% in LGMD2A patients. In all three groups, a strong correlation of the Mercuri grading and PDFF values was observed for almost all muscles (rs > 0.70, p < 0.05). PDFF values correlated significantly to muscle strength for muscle groups responsible for knee flexion (rs = −0.80, p < 0.01). (4) Conclusion: In the small, investigated patient cohort, PDFF offers similar diagnostic precision as the clinically established Mercuri grading. Based on these preliminary data, PDFF could be further considered as an MRI-based biomarker in the assessment of fatty infiltration of muscle tissue in NMD. Further studies with larger patient cohorts are needed to advance PDFF as an MRI-based biomarker in NMD, with advantages such as its greater dynamic range, enabling the assessment of subtler changes, the amplified objectivity, and the potential of direct correlation to muscle function for selected muscles.
The Probiotic Strain H. alvei HA4597® Improves Weight Loss in Overweight Subjects under Moderate Hypocaloric Diet: A Proof-of-Concept, Multicenter Randomized, Double-Blind Placebo-Controlled Study

Background: Increasing evidence supports the role of the gut microbiota in the control of body weight and feeding behavior. Moreover, recent studies have reported that the probiotic strain Hafnia alvei HA4597® (HA), which produces the satietogenic peptide ClpB mimicking the effect of alpha-MSH, reduced weight gain and adiposity in rodent models of obesity. Methods: To investigate the clinical efficacy of HA, 236 overweight subjects were included, after written informed consent, in a 12-week prospective, double-blind, randomized study. All subjects received standardized counselling for a −20% hypocaloric diet and were asked to maintain their usual physical activity. Subjects of the HA group received two capsules per day providing 100 billion bacteria per day and subjects in the Placebo (P) group received two placebo capsules. The primary endpoint was the percentage of subjects achieving a weight loss of at least 3% after 12 weeks. Intention-to-treat statistical analysis was performed using exact-Fischer, Mann-Whitney and paired-Wilcoxon tests as appropriate. Results: In the HA group, significantly more subjects (+33%) met the primary endpoint than in the P group (54.9 vs. 41.4%, p = 0.048). In the HA group, an increased feeling of fullness (p = 0.009) and a greater loss of hip circumference (p < 0.001) at 12 weeks were also observed. Fasting glycemia at 12 weeks was significantly lower (p < 0.05) in the HA compared to P group. Clinical and biological tolerance was good in both groups. Conclusions: A 12-week treatment with the probiotic strain H. alvei HA4597® significantly improves weight loss, feeling of fullness and reduction of hip circumference in overweight subjects following moderate hypocaloric diet. These data support the use of H. alvei HA4597® in the global management of excess weight.
Effect of Immersion in Water or Alkali Solution on the Structures and Properties of Epoxy Resin

The durability of fiber-reinforced polymer (FRP) composites is significantly dependent on the structures and properties of the resin matrix. In the present paper, the effects of physical or chemical interactions between the molecular chain of the epoxy resin matrix and water molecules or alkaline groups on the water absorption, mechanical structures, and microstructures of epoxy resin samples were studied experimentally. The results showed that the water uptake curves of the epoxy resin immersed in water and an alkali solution over time presented a three-stage variation. At different immersion stages, the water uptake behavior of the resin showed unique characteristics owing to the coupling effects of the solution concentration gradient diffusion, molecular hydrolysis reaction, and molecular segment movement. In comparison with the water immersion, the alkali solution environment promoted the hydrolysis reaction of the epoxy resin molecular chain. After the immersion in water or the alkali solution for one month, the water uptake of the resin was close to saturate, and the viscoelasticity was observed to decrease significantly. The micropore and free volume space on the surface and in the interior of the resin gradually increased, while the original large-scale free volume space decreased. The tensile strength decreased to the lowest point after the immersion in water and the alkali solution for one month, and the decrease percentages at 20 °C and 60 °C water or 60 °C alkali solution were 24%, 28%, and 22%, respectively. Afterward, the tensile strength recovered with the further extension of immersion time. In addition, it can be found that the effect of the alkali solution and water on the tensile strength of the epoxy resin was basically the same.
Ameliorative Effects of Aspergillus awamori against the Initiation of Hepatocarcinogenesis Induced by Diethylnitrosamine in a Rat Model: Regulation of Cyp19 and p53 Gene Expression

Hepatocellular carcinoma (HCC) is the most common cancer in humans. Despite advances in its treatment, liver cancer remains one of the most difficult cancers to treat. This study aimed to investigate the ameliorative action and potential mechanism of Aspergillus awamori (ASP) administration against the initiation process of liver carcinogenesis induced by diethylnitrosamine (DEN) in male Wistar rats. Seventy-two male rats were divided equally into eight groups as follows, Group 1: untreated control; Group 2: DEN (200 mg/kg bw) intra-peritoneally for the initiation of HCC; Groups 3–5: DEN + ASP at a dose of 1, 0.5, and 0.25 mg/kg bw and groups 6–8: ASP at a dose of 1, 0.5, and 0.25 mg/kg bw. Supplementation of A. awamori significantly lightened the adverse impacts induced by DEN via restoring the leukogram to normal, lowering the elevated serum aspartate aminotransferase (AST), alanine transaminase (ALT), and γ-glutamyl transferase (GGT), and alkaline phosphatase (ALP). Furthermore, it enhanced the hepatic antioxidant capacity through increasing the reduced glutathione (GSH) level and catalase (CAT) activity with a marked reduction in malondialdehyde (MDA) level. In addition, it decreased the positive GST-P foci. Likewise, a significant alteration of DEN-associated hepatocarcinogenesis occurred through inhibiting cytochrome P450 (Cyp19) and activating p53 gene expression. In conclusion, supplementation of A. awamori counteracts the negative effects of DEN, inhibits the early development of GST-P-positive foci and could be used as a new alternative strategy for its chemo-preventive effect in liver cancer. To the best of our knowledge, the present study is the first to report the hepato-protective effect of A. awamori in induced hepatocarcinogenesis.
Modeling Stratum Corneum Swelling for the Optimization of Electrode-Based Skin Hydration Sensors

We present a novel computational model of the human skin designed to investigate dielectric spectroscopy electrodes for stratum corneum hydration monitoring. The multilayer skin model allows for the swelling of the stratum corneum, as well as the variations of the dielectric properties under several hydration levels. According to the results, the stratum corneum thickness variations should not be neglected. For high hydration levels, swelling reduces the skin capacitance in comparison to a fixed stratum corneum thickness model. In addition, different fringing-field electrodes are evaluated in terms of sensitivity to the stratum corneum hydration level. As expected, both conductance and capacitance types of electrodes are influenced by the electrode geometry and dimension. However, the sensitivity of the conductance electrodes is more affected by dimension changes than the capacitance electrode leading to potential design optimization.
Non-Toxic Crosslinking of Electrospun Gelatin Nanofibers for Tissue Engineering and Biomedicine—A Review

Electrospinning can be used to prepare nanofiber mats from diverse polymers, polymer blends, or polymers doped with other materials. Amongst this broad range of usable materials, biopolymers play an important role in biotechnological, biomedical, and other applications. However, several of them are water-soluble, necessitating a crosslinking step after electrospinning. While crosslinking with glutaraldehyde or other toxic chemicals is regularly reported in the literature, here, we concentrate on methods applying non-toxic or low-toxic chemicals, and enzymatic as well as physical methods. Making gelatin nanofibers non-water soluble by electrospinning them from a blend with non-water soluble polymers is another method described here. These possibilities are described together with the resulting physical properties, such as swelling behavior, mechanical strength, nanofiber morphology, or cell growth and proliferation on the crosslinked nanofiber mats. For most of these non-toxic crosslinking methods, the degree of crosslinking was found to be lower than for crosslinking with glutaraldehyde and other common toxic chemicals.
Preharvest Treatment with Oxalic Acid Improves Postharvest Storage of Lemon Fruit by Stimulation of the Antioxidant System and Phenolic Content

Lemon trees (Citrus limon (L.) Burm. F) were treated monthly with oxalic acid (OA) at 0.1, 0.5, and 1 mM from initial fruit growth on the tree until harvest in2019. The experiment was repeated in 2020, with the application of OA 1 mM (according to the best results of 2019). In both years, fruit from OA-treated trees and the controls were stored for 35 days at 10 °C. Results showed that all treatments reduced weight loss (WL) and maintained higher firmness, total soluble solids (TSS), and total acidity (TA) than in the controls. Meanwhile, colour (hue angle) did not show significant differences. The activity of antioxidant enzymes, catalase (CAT), ascorbate peroxidase (APX), and peroxidase (POD) in the flavedo of the fruit from the OA-treated trees was higher than in the controls at harvest and after 35 days of storage. Similarly, the total phenolic content (TPC) in the flavedo and juice of the fruit from the OA-treated trees were higher than in the controls. The increase in the activity of the antioxidant enzymes and TPC started with the first preharvest OA treatment and were maintained during fruit development on the tree until harvest. Preharvest OA treatments enhanced the antioxidant system of the lemon fruits, reducing the postharvest incidence of decay. Thus, OA could be a useful tool to increase the quality and functional properties of lemon fruits.
Production of Siderophores by an Apple Root-Associated Streptomyces ciscaucasicus Strain GS2 Using Chemical and Biological OSMAC Approaches

Apple Replant Disease (ARD) is a significant problem in apple orchards that causes root tissue damage, stunted plant growth, and decline in fruit quality, size, and overall yield. Dysbiosis of apple root-associated microbiome and selective richness of Streptomyces species in the rhizosphere typically concurs root impairment associated with ARD. However, possible roles of Streptomyces secondary metabolites within these observations remain unstudied. Therefore, we employed the One Strain Many Compounds (OSMAC) approach coupled to high-performance liquid chromatography-high-resolution tandem mass spectrometry (HPLC-HRMSn) to evaluate the chemical ecology of an apple root-associated Streptomyces ciscaucasicus strain GS2, temporally over 14 days. The chemical OSMAC approach comprised cultivation media alterations using six different media compositions, which led to the biosynthesis of the iron-chelated siderophores, ferrioxamines. The biological OSMAC approach was concomitantly applied by dual-culture cultivation for microorganismal interactions with an endophytic Streptomyces pulveraceus strain ES16 and the pathogen Cylindrocarpon olidum. This led to the modulation of ferrioxamines produced and further triggered biosynthesis of the unchelated siderophores, desferrioxamines. The structures of the compounds were elucidated using HRMSn and by comparison with the literature. We evaluated the dynamics of siderophore production under the combined influence of chemical and biological OSMAC triggers, temporally over 3, 7, and 14 days, to discern the strain’s siderophore-mediated chemical ecology. We discuss our results based on the plausible chemical implications of S. ciscaucasicus strain GS2 in the rhizosphere.
Molecular Characterization of KPC-2-Producing Enterobacter cloacae Complex Isolates from Cali, Colombia

The Enterobacter cloacae complex is an emerging opportunistic pathogen whose increased resistance to carbapenems is considered a public health problem. This is due to the loss of efficacy of beta-lactam antibiotics, which are used as the first treatment option in the management of infections caused by Gram-negative bacteria. The objective of this study was to perform the molecular characterization of 28 isolates of the E. cloacae complex resistant to cephalosporins and carbapenems isolated between 2011 and 2018 from five hospitals located in the municipality of Santiago de Cali, Colombia. Molecular detection of blaKPC, blaVIM, blaNDM and blaOXA-48-like genes was performed on these isolates and the genetic relationship between the isolates was assessed using multilocus sequence typing (MLST). Forty-three percent of the isolates carried the blaKPC-2 gene variant. MLST showed high genetic diversity among isolates, the most frequent being the sequence type ST510 with a frequency of 50%. The identification of the genes involved in carbapenem resistance and dispersing genotypes is an important step toward the development of effective prevention and epidemiological surveillance strategies in Colombian hospitals.
Prevalence and Factors Associated with the Triple Burden of Malnutrition among Mother-Child Pairs in Sub-Saharan Africa

Despite concerns about the coexistence of overnutrition, undernutrition and micronutrient deficiencies, which is compositely referred to as the triple burden of malnutrition (TBM), little is known about the phenomenon in sub-Saharan Africa (SSA). We, therefore, aimed to examine the prevalence and investigate the factors associated with TBM in SSA. This study uses cross-sectional survey data collected through the Demographic and Health Surveys (DHS) Program from 2010 to 2019. Data from 32 countries in SSA were used for the analysis. The prevalence of TBM were presented in tables and maps using percentages. The predictors of TBM were examined by fitting a negative log-log regression to the data. The results were then presented using adjusted odds ratios (aORs) at 95% Confidence Intervals (CIs). Out of the 169,394 children, 734 (1%) suffered from TBM. The highest proportion of children with TBM in the four geographic regions in SSA was found in western Africa (0.75%) and the lowest in central Africa (0.21%). Children aged 1 [aOR = 1.283; 95% CI = 1.215–1.355] and those aged 2 [aOR = 1.133; 95% CI = 1.067–1.204] were more likely to experience TBM compared to those aged 0. TBM was less likely to occur among female children compared to males [aOR = 0.859; 95% CI = 0.824–0.896]. Children whose perceived size at birth was average [aOR = 1.133; 95% CI = 1.076–1.193] and smaller than average [aOR = 1.278; 95% CI = 1.204–1.356] were more likely to suffer from TBM compared to those who were larger than average at birth. Children born to mothers with primary [aOR = 0.922; 95% CI = 0.865–0.984] and secondary [aOR = 0.829; 95% CI = 0.777–0.885] education were less likely to suffer from TBM compared to those born to mothers with no formal education. Children born to mothers who attended antenatal care (ANC) had lower odds of experiencing TBM compared to those born to mothers who did not attend ANC [aOR = 0.969; 95% CI = 0.887–0.998]. Children born to mothers who use clean household cooking fuel were less likely to experience TBM compared to children born to mothers who use unclean household cooking fuel [aOR = 0.724; 95% CI = 0.612–0.857]. Essentially, higher maternal education, ANC attendance and use of clean cooking fuel were protective factors against TBM, whereas higher child age, low size at birth and being a male child increased the risk of TBM. Given the regional variations in the prevalence and risk of TBM, region-specific interventions must be initiated to ensure the likelihood of those interventions being successful at reducing the risk of TBM. Countries in Western Africa in particular would have to strengthen their current policies and programmes on malnutrition to enhance their attainment of the SDGs.