Miracle-dz/UniFAR-FTUs huggingface dataset:
Oral Administration of Microencapsulated B. Longum BAA-999 and Lycopene Modulates IGF-1/IGF-1R/IGFBP3 Protein Expressions in a Colorectal Murine Model

The Insulin-like growth factor-I/Insulin-like growth factor-I receptor (IGF-1/IGF-1R) system is a major determinant in colorectal cancer (CRC) pathogenesis. Probiotics (Bifidobacterium longum, BF) and lycopene (LYC) have been individually researched for their beneficial effects in the prevention of CRC. However, the effect of a combined treatment of microencapsulated BF and LYC on IGF-1/IGF-1R/IGFBPs (Insulin-like growth factor-binding proteins) expression in an azoxymethane (AOM)-dextran sulfate sodium (DSS)-induced CRC model have not been demonstrated. BF was microencapsulated by the spray drying technique, with high viability, and daily gavaged with LYC for 16 weeks to CD-1 mice in an AOM-DSS model. The results indicated that BF- and BF + LYC-treated groups had significantly lower inflammation grade, tumor incidence (13–38%) and adenocarcinoma (13–14%) incidence compared to the AOM + DSS group (80%), whereas LYC treatment only protected against inflammation grade and incidence. Caecal, colonic and fecal pH and β-glucuronidase (β-GA) values were significantly normalized by BF and LYC. Similarly, BF and BF + LYC treatments significantly reduced both the positive rate and expression grade of IGF-1 and IGF-1R proteins and normalized Insulin-like growth factor-binding protein-3 (IGFBP3) expression. Based on intestinal parameters related to the specific colon carcinogenesis in an AOM-DSS-induced model, LYC and microencapsulated BF supplementation resulted in a significant chemopreventive potential through the modulation of IGF-1/IGF-1R system.
Twenty-year follow-up of functional treatment with a bionator appliance: A retrospective dental cast analysis.

OBJECTIVE To investigate changes in dental arch configuration, relationship, and malocclusion directly after Class II malocclusion treatment with a Balters bionator modified by Ascher as well as 20 years after treatment. MATERIALS AND METHODS Orthodontic dental cast analysis of 18 patients with skeletal Class II treated with a bionator without any additional fixed therapy was performed with a digital caliper at three stages: before (T0), after (T1) and 20 years after (T2) treatment. Arch perimeter and depth, intermolar and intercanine distance, overjet, overbite, sagittal molar and canine relationship, mandibular incisor irregularity (Little's index), and malocclusion (PAR index) were assessed. RESULTS During treatment (T0-T1), upper arch perimeter significantly increased with a significant decrease in the upper and lower arch perimeter long-term (T1-T2), whereas corresponding arch depths changed only slightly in both periods. Transverse intermolar width increased significantly during treatment, remaining almost constant from T1 to T2. Lower intercanine distance remained fairly unchanged during treatment, but decreased significantly during follow-up. Lower incisor irregularity improved slightly during treatment but increased significantly long-term. After treatment, sagittal molar relationships on both sides were improved, overjet and overbite reduced; these significant changes remained stable long-term. The peer assessment rating (PAR) index was significantly lower after treatment and increased insignificantly during follow-up. CONCLUSIONS 20 years after bionator treatment without additional fixed appliances, the improved sagittal relationship and the reduced overjet and PAR index remained fairly stable. Long-term changes are most likely due to physiological aging processes and are not associated with bionator treatment.
Assessment of Deep Learning Using Nonimaging Information and Sequential Medical Records to Develop a Prediction Model for Nonmelanoma Skin Cancer.

Importance A prediction model for new-onset nonmelanoma skin cancer could enhance prevention measures, but few patient data-driven tools exist for more accurate prediction. Objective To use machine learning to develop a prediction model for incident nonmelanoma skin cancer based on large-scale, multidimensional, nonimaging medical information. Design, Setting, and Participants This study used a database comprising 2 million randomly sampled patients from the Taiwan National Health Insurance Research Database from January 1, 1999, to December 31, 2013. A total of 1829 patients with nonmelanoma skin cancer as their first diagnosed cancer and 7665 random controls without cancer were included in the analysis. A convolutional neural network, a deep learning approach, was used to develop a risk prediction model. This risk prediction model used 3-year clinical diagnostic information, medical records, and temporal-sequential information to predict the skin cancer risk of a given patient within the next year. Stepwise feature selection was also performed to investigate important and determining factors of the model. Statistical analysis was performed from November 1, 2016, to October 31, 2018. Main Outcomes and Measures Sensitivity, specificity, and area under the receiver operating characteristic (AUROC) curve were used to evaluate the performance of the models. Results A total of 1829 patients (923 women [50.5%] and 906 men [49.5%]; mean [SD] age, 65.3 [15.7] years) with nonmelanoma skin cancer and 7665 random controls without cancer (3951 women [51.5%] and 3714 men [48.4%]; mean [SD] age, 47.5 [17.3] years) were included in the analysis. The 1-year incident nonmelanoma skin cancer risk prediction model using sequential diagnostic information and drug prescription information as a time-incorporated feature matrix could attain an AUROC of 0.89 (95% CI, 0.87-0.91), with a mean (SD) sensitivity of 83.1% (3.5%) and mean (SD) specificity of 82.3% (4.1%). Carcinoma in situ of skin (AUROC, 0.867; -2.80% loss) and other chronic comorbidities (eg, degenerative osteopathy [AUROC, 0.872; -2.32% loss], hypertension [AUROC, 0.879; -1.53% loss], and chronic kidney insufficiency [AUROC, 0.879; -1.52% loss]) served as more discriminative factors for the prediction. Medications such as trazodone, acarbose, systemic antifungal agents, statins, nonsteroidal anti-inflammatory drugs, and thiazide diuretics were the top-ranking discriminative features in the model; each led to more than a 1% decrease of the AUROC when eliminated individually (eg, trazodone AUROC, 0.868; -2.67% reduction; acarbose AUROC, 0.870; -2.50 reduction; and systemic antifungal agents AUROC, 0.875; -1.99 reduction). Conclusions and Relevance The findings of this study suggest that a risk prediction model may have potential predictive factors for nonmelanoma skin cancer. This model may help health care professionals target high-risk populations for more intensive skin cancer preventive methods.
Co-ensiling garlic stalk with citrus pulp improves the fermentation quality and feed-nutritional value

Objective Ensiling is a simple and effective method for long-term preservation; however, less information exists about the ensilability characteristics of garlic stalk (GS). Therefore, the objectives were to examine the ensiling feasibility of GS. Methods The GS was ensiled alone or inoculated with Lactobacillus plantarum KU5 in the presence or absence of 5% molasses and ensiled for 7, 14, and 28 d. As an alternative storage method, GS was co-ensiled with wet citrus pulp (CP) at different proportions (GS:CP: 70:30, 60:40, 50:50, and 40:60). Analysis was made on physicochemical, fermentative, and nutritional parameters. Results The GS was found to be a biomass which is difficult to ensile. A combination of microbial inoculant and molasses was successful in the improvement of the silage fermentation quality of GS. Co-ensiling of GS with wet CP at the mixing ratio of 50:50 provided the most desirable silage fermentation parameters, including the substantial lactic acid formation, low final pH, minor effluent loss, and the more favorable organoleptic properties. Conclusion Co-ensiling GS with CP appears to be a simple and viable method of conservation, enabling the more efficient utilization of these by-product resources over a prolonged period.
Severity of Desaturations Reflects OSA-Related Daytime Sleepiness Better Than AHI.

STUDY OBJECTIVES The aim was to investigate how the severity of apneas, hypopneas, and related desaturations is associated with obstructive sleep apnea (OSA)-related daytime sleepiness. METHODS Multiple Sleep Latency Tests and polysomnographic recordings of 362 patients with OSA were retrospectively analyzed and novel diagnostic parameters (eg, obstruction severity and desaturation severity), incorporating severity of apneas, hypopneas, and desaturations, were computed. Conventional statistical analysis and multivariate analyses were utilized to investigate connection of apnea-hypopnea index (AHI), oxygen desaturation index (ODI), conventional hypoxemia parameters, and novel diagnostic parameters with mean daytime sleep latency (MSL). RESULTS In the whole population, 10% increase in values of desaturation severity (risk ratio = 2.01, P < .001), obstruction severity (risk ratio = 2.18, P < .001) and time below 90% saturation (t90%) (risk ratio = 2.05, P < .001) induced significantly higher risk of having mean daytime sleep latency ≤ 5 minutes compared to 10% increase in AHI (risk ratio = 1.63, P < .05). In severe OSA, desaturation severity had significantly (P < .02) stronger negative correlation (ρ = -.489, P < .001) with mean daytime sleep latency compared to AHI (ρ = -.402, P < 0.001) and ODI (ρ = -.393, P < .001). Based on general regression model, desaturation severity and male sex were the most significant factors predicting daytime sleep latency. CONCLUSIONS Severity of sleep-related breathing cessations and desaturations is a stronger contributor to daytime sleepiness than AHI or ODI and therefore should be included in the diagnostics and severity assessment of OSA. CITATION Kainulainen S, Töyräs J, Oksenberg A, Korkalainen H, Sefa S, Kulkas A, Leppänen T. Severity of desaturations reflects OSA-related daytime sleepiness better than AHI. J Clin Sleep Med. 2019;15(8):1135-1142.
Lifestyle factors, diet and attention-deficit/hyperactivity disorder in Spanish children – an observational study

ABSTRACT Background: The aetiology of Attention Deficit Hyperactivity Disorder (ADHD) continues to be debated, although several contributing factors have been acknowledged. Objective: Assess the association between weight, birth attributes, exercise and sleep habits, dietary intake and adherence to a Mediterranean diet, and impulsive behaviour on Spanish ADHD children. Establish whether specific food groups (not just adherence to the Mediterranean diet) associate with impulsive behaviour. Methods: This observational cross-sectional study included 57 ADHD children from Madrid (Spain). Demographic, clinical data, sleep, exercise and technology-use habits were obtained. Anthropometric measurements included height and weight. Adherence to the Mediterranean diet was assessed using the KIDMED test. Barratt Impulsivity Scale version-11c was used to assess impulsivity. Subjects were divided into three groups for analysis, according to their age (6–10 years, children; 11–13 years, pre-adolescents; 14–16 years, adolescents). Results: There were clear associations between those who had higher BIS scores and who slept less at weekends (49.4 ± 10.16 vs. 43.8 ± 12.51), who adhered poorly to the Mediterranean diet (49.9 ± 11.72 vs. 41.6 ± 16.52), who used internet and technological devices for >3 h/day (45.5 ± 13.6 vs. 44.7 ± 12.11), who were born with >2.5 kg (46.1 ± 11.61 vs. 42.9 ± 15.29), who were delivered by caesarean (45.1 ± 12.78 vs. 44.7 ± 12.5) and who were not breastfed (45.0 ± 13.38 vs. 44.8 ± 12.39). Subjects exercising more than 3 days a week also scored slightly higher (45.4±14.02 vs. 44.6±11.85) in the BIS. Conclusion: There is a need to follow up the link between ADHD and sleep onset difficulties, dietary patterns, technological habits, perinatal factors, breastfeeding and birth delivery mode.
Early Wound Healing Score (EHS): An Intra- and Inter-Examiner Reliability Study

The early wound healing score (EHS) was introduced to assess early wound healing of periodontal soft tissues after surgical incision. The purpose of this study is to evaluate the intra- and inter-examiner reliability of the EHS. Six examiners with different levels of training and clinical focus were enrolled. Each examiner was trained on the use of the EHS before starting the study. Thereafter, 63 photographs of three different types of surgical incisions taken at day 1, 3 or 7 post-operatively were independently evaluated according to the proposed assessment method. A two-way random intra-class correlation coefficient (ICC) and 95% confidence interval (CI) were used to analyze the intra- and inter-examiner reliability for the EHS. The inter-examiner reliability for the EHS was 0.828 (95% CI: 0.767–0.881). The intra-examiner reliability ranged between 0.826 (95% CI: 0.728–0.891) and 0.915 (95% CI: 0.856–0.950). The results therefore show an “almost perfect agreement” for intra- and inter-examiner reliability. The EHS provides a system for reproducible repeated ratings for the early healing assessment of incisions of periodontal soft tissues. Even when used by examiners with different clinical experience and specialty, it shows a high correlation coefficient.
Streptozotocin-Induced Diabetic Neuropathic Pain Is Associated with Potentiated Calcium-Permeable AMPA Receptor Activity in the Spinal Cord

Neuronal hyperactivity in the spinal dorsal horn can amplify nociceptive input in diabetic neuropathic pain. The glutamate N‐methyl‐d‐aspartate and α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (NMDA receptors and AMPA receptors, respectively) are involved in spinal nociceptive transmission. It is unclear, however, whether painful diabetic neuropathy is associated with changes in the activity of synaptic NMDA receptors and AMPA receptors in spinal dorsal horn neurons. AMPA receptors lacking GluA2 are Ca2+-permeable (CP-AMPA receptors), and their currents display characteristic inward rectification. In this study, we showed that evoked excitatory postsynaptic currents (EPSCs), induced by streptozotocin, exhibited inward rectification in spinal dorsal neurons in diabetic rats. Presynaptic and postsynaptic NMDA receptor activity in the spinal dorsal horn was similar in diabetic and control rats. In the dorsal spinal cord, the membrane GluA2 protein level was significantly lower in diabetic than in control rats, whereas the cytosolic GluA2 level was greater in diabetic than in control rats. In contrast, the GluA1 subunit levels in the plasma membrane and cytosol did not differ between the two groups. Blocking CP-AMPA receptors significantly reduced the amplitude of EPSCs of dorsal horn neurons in diabetic but not in control rats. Furthermore, blocking spinal CP-AMPA receptors reduced pain hypersensitivity in diabetic rats but had no effect on nociception in control rats. Our study suggests that diabetic neuropathy augments CP-AMPA receptor activity in the spinal dorsal horn by causing intracellular retention of GluA2 and impairing GluA2 membrane trafficking. Increased prevalence of spinal CP-AMPA receptors sustains diabetic neuropathic pain. SIGNIFICANCE STATEMENT This study demonstrates that the prevalence of synaptic calcium-permeable AMPA receptors is increased in the spinal dorsal horn, which mediates pain hypersensitivity in diabetic neuropathy. Thus, calcium-permeable AMPA receptors play an important role in glutamatergic synaptic plasticity in the spinal cord in painful diabetic neuropathy. This new knowledge improves our understanding of the mechanisms involved in central sensitization associated with diabetic neuropathic pain and suggests that calcium-permeable AMPA receptors are an alternative therapeutic target for treating this chronic pain condition.
Computational Drug Repurposing Algorithm Targeting TRPA1 Calcium Channel as a Potential Therapeutic Solution for Multiple Sclerosis

Multiple sclerosis (MS) is a chronic autoimmune disease affecting the central nervous system (CNS) through neurodegeneration and demyelination, leading to physical/cognitive disability and neurological defects. A viable target for treating MS appears to be the Transient Receptor Potential Ankyrin 1 (TRPA1) calcium channel, whose inhibition has been shown to have beneficial effects on neuroglial cells and protect against demyelination. Using computational drug discovery and data mining methods, we performed an in silico screening study combining chemical graph mining, quantitative structure–activity relationship (QSAR) modeling, and molecular docking techniques in a global prediction model in order to identify repurposable drugs as potent TRPA1 antagonists that may serve as potential treatments for MS patients. After screening the DrugBank database with the combined generated algorithm, 903 repurposable structures were selected, with 97 displaying satisfactory inhibition probabilities and pharmacokinetics. Among the top 10 most probable inhibitors of TRPA1 with good blood brain barrier (BBB) permeability, desvenlafaxine, paliperidone, and febuxostat emerged as the most promising repurposable agents for treating MS. Molecular docking studies indicated that desvenlafaxine, paliperidone, and febuxostat are likely to induce allosteric TRPA1 channel inhibition. Future in vitro and in vivo studies are needed to confirm the biological activity of the selected hit molecules.
First Isolation and Rapid Identification of Newcastle Disease Virus from Aborted Fetus of Dromedary Camel Using Next-Generation Sequencing

Newcastle disease virus (NDV) causes morbidities and mortalities in wild and domestic birds globally. For humans, exposure to infected birds can cause conjunctivitis and influenza-like symptoms. NDV infections in mammals are rarely reported. In this study, using next-generation sequencing, an NDV was identified and isolated from Vero cells inoculated with the nasal swab of an aborted dromedary fetus in Dubai, during the time when an NDV outbreak occurred in a pigeon farm located in close proximity to the dairy camel farm where the mother of the aborted dromedary fetus resided, and there were a lot of pigeons in the camel farm. Genome analysis revealed that the structurally and functionally important features of other NDVs were also present in this dromedary NDV genome. Phylogenetic analysis based on the nucleotide sequences of fusion protein (F), hemagglutinin-neuraminidase protein (HN) and complete polyprotein showed that the virus belonged to sub-genotype VIg of class II NDV and is most closely related to pigeon NDVs in Egypt in the same year. The present study is the first that demonstrated isolation of NDV in dromedaries. Further study is warranted to investigate the relationship between NDV infection and abortion.
Evaluation of Bipolar, Tripolar, and Quadripolar Laplacian Estimates of Electrocardiogram via Concentric Ring Electrodes

Surface Laplacian estimates via concentric ring electrodes (CREs) have proven to enhance spatial resolution compared to conventional disc electrodes, which is of great importance for P-wave analysis. In this study, Laplacian estimates for traditional bipolar configuration (BC), two tripolar configurations with linearly decreasing and increasing inter-ring distances (TCLDIRD and TCLIIRD, respectively), and quadripolar configuration (QC) were obtained from cardiac recordings with pentapolar CREs placed at CMV1 and CMV2 positions. Normalized P-wave amplitude (NAP) was computed to assess the contrast to study atrial activity. Signals were of good quality (20–30 dB). Atrial activity was more emphasized at CMV1 (NAP ≃ 0.19–0.24) compared to CMV2 (NAP ≃ 0.08–0.10). Enhanced spatial resolution of TCLIIRD and QC resulted in higher NAP values than BC and TCLDIRD. Comparison with simultaneous standard 12-lead ECG proved that Laplacian estimates at CMV1 outperformed all the limb and chest standard leads in the contrast to study P-waves. Clinical recordings with CRE at this position could allow more detailed observation of atrial activity and facilitate the diagnosis of associated pathologies. Furthermore, such recordings would not require additional electrodes on limbs and could be performed wirelessly, so it should also be suitable for ambulatory monitoring, for example, using cardiac Holter monitors.
Clinicopathologic Characteristics of Epstein–Barr Virus-Associated Gastric Cancer Over the Past Decade in Japan

Epstein–Barr virus (EBV) is a ubiquitous human herpes virus, but related with several types of malignancies. Among EBV-related malignancies, EBV-associated gastric carcinoma (EBVaGC) has the largest patient’s number. We screened for EBV infection in 1067 GC lesions of 1132 patients who underwent surgical resection from 2007 to 2017 in Japan and examined clinicopathological features of EBVaGC. EBV infection was detected by in situ hybridization with EBV-encoded small RNA 1(EBER-1 ISH). EBV was infected in 80 GC lesions (7.1%). Mean age was significantly lower in patients with EBVaGC than with EBV-negative GC. EBVaGC was more frequent in men than in women. EBVaGC was found twice as frequent in the upper or middle stomach as in the lower stomach. Early EBVaGC was more frequent, and submucosally invaded cases were dominant. The presence of lymphatic vessel invasion was less in EBVaGC, but frequency of lymph node metastasis was similar. Carcinoma with lymphoid stroma (CLS) was found in 3.8% (43/1132) of all lesions with 60.5% of EBV positivity. The synchronous or metachronous multiple GC was frequent in EBVaGC. We clarified clinicopathologic characteristics of EBVaGC over the past decade in Japan. EBV infection should be examined in gastric cancer cases showing these characteristics.
Sparassis crispa Intake Improves the Reduced Lipopolysaccharide-Induced TNF-α Production That Occurs upon Exhaustive Exercise in Mice

Our previous study showed that lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-α production is inhibited by acute exhaustive exercise in mice, leading to transient immunodepression after exercise. Sparassis crispa (SC), an edible mushroom, has immunopotentiative properties. This study aimed to clarify the effects of SC intake on reduced LPS-induced TNF-α production upon exhaustive exercise in mice. Male C3H/HeN mice were randomly divided into three groups: normal chow intake + resting sedentary, normal chow intake + acute exhaustive treadmill running exercise, and SC intake (chow containing 5% SC powder for 8 weeks) + the exhaustive exercise groups. Each group was injected with LPS immediately after the exhaustive exercise or rest. Plasma and tissue TNF-α levels were significantly decreased by exhaustive exercise. However, this reduction of the TNF-α level was partially attenuated in the plasma and small intestine by SC intake. Although levels of TLR4 and MyD88 protein expression were significantly decreased in tissues by exhaustive exercise, the reduction of TLR4 and MyD88 levels in the small intestine was partially attenuated by SC intake. These results suggest that SC intake attenuates exhaustive exercise-induced reduction of TNF-α production via the retention of TLR4 and MyD88 expression in the small intestine.