Miracle-dz/UniFAR-FTUs huggingface dataset:
Serum APOA4 Pharmacodynamically Represents Administered Recombinant Human Hepatocyte Growth Factor (E3112)

Background: Hepatocyte growth factor (HGF) is an endogenously induced bioactive molecule that has strong anti-apoptotic and tissue repair activities. In this research, we identified APOA4 as a novel pharmacodynamic (PD) marker of the recombinant human HGF (rh-HGF), E3112. Methods: rh-HGF was administered to mice, and their livers were investigated for the PD marker. Candidates were identified from soluble proteins and validated by using human hepatocytes in vitro and an animal disease model in vivo, in which its c-Met dependency was also ensured. Results: Among the genes induced or highly enhanced after rh-HGF exposure in vivo, a soluble apolipoprotein, Apoa4, was found to be induced by rh-HGF in the murine liver. By using primary cultured human hepatocytes, the significant induction of human APOA4 was observed at the mRNA and protein levels, and it was inhibited in the presence of a c-Met inhibitor. Although mice constitutively expressed Apoa4 mRNA in the small intestine and the liver, the liver was the primary organ affected by administered rh-HGF to strongly induce APOA4 in a dose- and c-Met-dependent manner. Serum APOA4 levels were increased after rh-HGF administration, not only in normal mice but also in anti-Fas-induced murine acute liver failure (ALF), which confirmed the pharmacodynamic nature of APOA4. Conclusions: APOA4 was identified as a soluble PD marker of rh-HGF with c-Met dependency. It should be worthwhile to clinically validate its utility through clinical trials with healthy subjects and ALF patients.
Percutaneous CT Fluoroscopy-Guided Core Needle Biopsy of Mediastinal Masses: Technical Outcome and Complications of 155 Procedures during a 10-Year Period

Purpose: To evaluate technical outcome, diagnostic yield and safety of computed tomographic fluoroscopy-guided percutaneous core needle biopsies in patients with mediastinal masses. Methods: Overall, 155 CT fluoroscopy-guided mediastinal core needle biopsies, performed from March 2010 to June 2020 were included. Size of lesion, size of needle, access path, number of success, number of biopsies per session, diagnostic yield, patient’s position, effective dose, rate of complications, tumor localization, size of tumor and histopathological diagnosis were considered. Post-interventional CT was performed, and patients observed for any complications. Complications were classified per the Society of Interventional Radiology (SIR). Results: 148 patients (age, 54.7 ± 18.2) underwent 155 CT-fluoroscopy-guided percutaneous biopsies with tumors in the anterior (114; 73.5%), middle (17; 11%) and posterior (24; 15.5%) mediastinum, of which 152 (98%) were technically successful. For placement of the biopsy needle, in 82 (52.9%) procedures a parasternal trajectory was chosen, in 36 (23.3%) a paravertebral access, in 20 (12.9%) through the lateral intercostal space and in 17 (11%) the thoracic anterior midline, respectively. A total of 136 (89.5%) of the biopsies were considered adequate for a specific histopathologic analysis. Total DLP (dose-length product) was 575.7 ± 488.8 mGy*cm. Mean lesion size was 6.0 ± 3.3 cm. Neoplastic pathology was diagnosed in 115 (75.7%) biopsies and 35 (23%) biopsy samples showed no evidence of malignancy. Minor complications were observed in 18 (11.6%) procedures and major pneumothorax requiring drainage insertion in 3 interventions (1.9%). Conclusion: CT fluoroscopy-guided percutaneous core needle biopsy of mediastinal masses is an effective and safe procedure for the initial assessment of patients with mediastinal tumors.
Comprehensive Analysis of Prognostic and Genetic Signatures for General Transcription Factor III (GTF3) in Clinical Colorectal Cancer Patients Using Bioinformatics Approaches

Colorectal cancer (CRC) has the fourth-highest incidence of all cancer types, and its incidence has steadily increased in the last decade. The general transcription factor III (GTF3) family, comprising GTF3A, GTF3B, GTF3C1, and GTFC2, were stated to be linked with the expansion of different types of cancers; however, their messenger (m)RNA expressions and prognostic values in colorectal cancer need to be further investigated. To study the transcriptomic expression levels of GTF3 gene members in colorectal cancer in both cancerous tissues and cell lines, we first performed high-throughput screening using the Oncomine, GEPIA, and CCLE databases. We then applied the Prognoscan database to query correlations of their mRNA expressions with the disease-specific survival (DSS), overall survival (OS), and disease-free survival (DFS) status of the colorectal cancer patient. Furthermore, proteomics expressions of GTF3 family members in clinical colorectal cancer specimens were also examined using the Human Protein Atlas. Finally, genomic alterations of GTF3 family gene expressions in colorectal cancer and their signal transduction pathways were studied using cBioPortal, ClueGO, CluePedia, and MetaCore platform. Our findings revealed that GTF3 family members’ expressions were significantly correlated with the cell cycle, oxidative stress, WNT/β-catenin signaling, Rho GTPases, and G-protein-coupled receptors (GPCRs). Clinically, high GTF3A and GTF3B expressions were significantly correlated with poor prognoses in colorectal cancer patients. Collectively, our study declares that GTF3A was overexpressed in cancer tissues and cell lines, particularly colorectal cancer, and it could possibly step in as a potential prognostic biomarker.
Dietary Starch Concentration Affects Dairy Sheep and Goat Performances Differently during Mid-Lactation

Simple Summary In order to favor milk production, this research suggests that the concentration of starch in the diet of dairy ewes in mid-lactation should be reduced, compared to early lactation, by introducing sources of highly digestible fiber. On the other hand, this type of diet is not adequate for dairy goats, which should maintain the use diets rich in starch, even in mid-lactation, to support milk yield, as well. Abstract Evolution of milk production, body reserves and blood metabolites and their relationships with dietary carbohydrates were compared in 30 Sarda dairy ewes and 26 Saanen dairy goats in mid-lactation. From 92 to 152 ± 11 days in milk (DIM), each species was allocated to two dietary treatments: high-starch (HS: 20.0% starch, on DM basis) and low-starch (LS: 7.8% starch, on DM basis) diets. In mid-lactating goats, the HS diet increased fat-corrected milk yield (FCM (3.5%); 2.65 vs. 2.53 kg/d; p = 0.019) and daily milk net energy (NEL; p = 0.025), compared to the LS diet. The body condition score (BCS) was not affected. In mid-lactating ewes, the LS diet increased FCM (6.5%) (1.47 vs. 1.36 kg/d; p = 0.008), and NEL (p = 0.008), compared to the HS diet. In addition, BCS was greater in HS than in LS ewes (3.53 vs. 3.38; p = 0.008). Goats had a higher growth hormone (GH) and lower insulin concentration than ewes (GH: 2.62 vs. 1.37 ng/mL; p = 0.04; insulin: 0.14 vs. 0.38 µg/L; p < 0.001 in goats and ewes, respectively). In conclusion, in mid-lactation, the two species responded differently to dietary carbohydrates, probably due to differences in the concentration of GH and insulin. The HS diet favored milk yield in goats and body reserve accumulation in ewes. In ewes, the partial replacement of starch with highly digestible fiber increased energy partitioning in favor of milk production.
Compatibility of Beauveria bassiana and a Plant Secondary Metabolite: A Novel Modeling Approach to Invade Host Defense for Effective Control of Oligonychus afrasiaticus (McGregor) on Date Palms

Oligonychus afrasiaticus (McGregor) is an important pest causing substantial economic losses to date palm fruits (dates). The application of mycopathogens with plant secondary metabolites, which may proceed synergistically is thus essential to augment sustainable management strategy for O. afrasiaticus. In this regard, extensive laboratory experimentation involving compatibility, synergism, and host defense was performed to develop stable pest management option. The toxin-pathogen compatibility assay results revealed compatible interaction (biological index = 79–95) of B. bassiana ARSEF 8465 against each tested concentration of commercially available (+)-α-Pinene that provide the opportunity to further explore the time and concentration dependent mortality and defense related enzymatic regulation analysis. The time-mortality response assays that mainly comprised of various proportions of B. bassiana ARSEF 8465 and (+)-α-Pinene revealed that the sole application of B. bassiana ARSEF 8465 (LC50 = 19.16 mg/mL), and (+)-α-Pinene (3.41 mg/mL) found to be least lethal compared with joint applications (LC50 ranged from 1.32–7.06 mg/mL). The treatments complied under Scheme IV (80% (+)-α-Pinene: 20% B. bassiana ARSEF 8465 Conidia) led to strong synergistic interaction (joint toxicity = 755). In addition, synergistic interactions greatly induced enzymatic activities of the studied antioxidants (CAT and SOD), and defense-related enzymes (GST and AchE). We concluded that join application of B. bassiana ARSEF 8465 and (+)-α-Pinene is a promising option for controlling Oligonychus afrasiaticus populations.
Rapid Detection of Escherichia coli Antibiotic Susceptibility Using Live/Dead Spectrometry for Lytic Agents

Antibiotic resistance is a serious threat to public health. The empiric use of the wrong antibiotic occurs due to urgency in treatment combined with slow, culture-based diagnostic techniques. Inappropriate antibiotic choice can promote the development of antibiotic resistance. We investigated live/dead spectrometry using a fluorimeter (Optrode) as a rapid alternative to culture-based techniques through application of the LIVE/DEAD® BacLightTM Bacterial Viability Kit. Killing was detected by the Optrode in near real-time when Escherichia coli was treated with lytic antibiotics—ampicillin and polymyxin B—and stained with SYTO 9 and/or propidium iodide. Antibiotic concentration, bacterial growth phase, and treatment time used affected the efficacy of this detection method. Quantification methods of the lethal action and inhibitory action of the non-lytic antibiotics, ciprofloxacin and chloramphenicol, respectively, remain to be elucidated.
Autoimmune Diseases and COVID-19 as Risk Factors for Poor Outcomes: Data on 13,940 Hospitalized Patients from the Spanish Nationwide SEMI-COVID-19 Registry

(1) Objectives: To describe the clinical characteristics and clinical course of hospitalized patients with COVID-19 and autoimmune diseases (ADs) compared to the general population. (2) Methods: We used information available in the nationwide Spanish SEMI-COVID-19 Registry, which retrospectively compiles data from the first admission of adult patients with COVID-19. We selected all patients with ADs included in the registry and compared them to the remaining patients. The primary outcome was all-cause mortality during admission, readmission, and subsequent admissions, and secondary outcomes were a composite outcome including the need for intensive care unit (ICU) admission, invasive and non-invasive mechanical ventilation (MV), or death, as well as in-hospital complications. (3) Results: A total of 13,940 patients diagnosed with COVID-19 were included, of which 362 (2.6%) had an AD. Patients with ADs were older, more likely to be female, and had greater comorbidity. On the multivariate logistic regression analysis, which involved the inverse propensity score weighting method, AD as a whole was not associated with an increased risk of any of the outcome variables. Habitual treatment with corticosteroids (CSs), age, Barthel Index score, and comorbidity were associated with poor outcomes. Biological disease-modifying anti-rheumatic drugs (bDMARDs) were associated with a decrease in mortality in patients with AD. (4) Conclusions: The analysis of the SEMI-COVID-19 Registry shows that ADs do not lead to a different prognosis, measured by mortality, complications, or the composite outcome. Considered individually, it seems that some diseases entail a different prognosis than that of the general population. Immunosuppressive/immunoregulatory treatments (IST) prior to admission had variable effects.
MiR-182-5p and miR-375-3p Have Higher Performance Than PSA in Discriminating Prostate Cancer from Benign Prostate Hyperplasia

Simple Summary Prostate cancer (PCa) is the most prevalent neoplasia among men worldwide but is commonly “mimicked” by benign prostate hyperplasia (BPH). Their discrimination by the prostate-specific antigen (PSA) is often uncertain, resulting in lengthy diagnostic protocols and recurrent tissue biopsies. The development of more appropriate biomarkers, possibly present in liquid biopsy, would significantly improve PCa and BPH patient management. To address this challenge, in this study miR-375-3p, miR-182-5p, miR-21-5p, and miR-148a-3p were analyzed by ddPCR in blood plasma and seminal plasma of patients with PCa and BPH prior to tissue biopsy. Among other findings, miR-182-5p and miR-375-3p were found to have statistically significantly higher expression in PCa patients compared to BPH in blood, with a combined specificity of 90.2% to predict positive or negative biopsy results. The data presented emphasize the great potential of miRNAs as liquid biopsy biomarkers for PCa. Abstract Prostate cancer (PCa) is the most commonly diagnosed neoplasm among men. Since it often resembles benign prostate hyperplasia (BPH), biomarkers with a higher differential value than PSA are required. Epigenetic biomarkers in liquid biopsies, especially miRNA, could address this challenge. The absolute expression of miR-375-3p, miR-182-5p, miR-21-5p, and miR-148a-3p were quantified in blood plasma and seminal plasma of 65 PCa and 58 BPH patients by digital droplet PCR. The sensitivity and specificity of these microRNAs were determined using ROC curve analysis. The higher expression of miR-182-5p and miR-375-3p in the blood plasma of PCa patients was statistically significant as compared to BPH (p = 0.0363 and 0.0226, respectively). Their combination achieved a specificity of 90.2% for predicting positive or negative biopsy results, while PSA cut-off of 4 µg/L performed with only 1.7% specificity. In seminal plasma, miR-375-3p, miR-182-5p, and miR-21-5p showed a statistically significantly higher expression in PCa patients with PSA >10 µg/L compared to ones with PSA ≤10 µg/L. MiR-182-5p and miR-375-3p in blood plasma show higher performance than PSA in discriminating PCa from BPH. Seminal plasma requires further investigation as it represents an obvious source for PCa biomarker identification.
IDH1 and IDH2 Mutations in Colorectal Cancers.

OBJECTIVES To elucidate clinicopathologic and molecular characteristics of IDH1 and IDH2 (IDH1/2) mutations in colorectal cancers (CRCs). METHODS We evaluated IDH1/2 mutations in 1,623 CRCs using a next-generation sequencing assay. RESULTS IDH1/2 mutations, predominantly IDH1 p.R132C, were detected in 15 (0.9%) CRCs and in 5 (3.0%) of 167 BRAF p.V600E-mutated CRCs. Three IDH1/2-mutated CRCs were associated with inflammatory bowel disease. They were significantly associated with old age, mucinous or signet ring cell adenocarcinoma, and high-grade histomorphology. Concordance of variant allele frequency between IDH1/2 mutants and other trunk drivers in CRCs and presence of IDH1/2 mutation in the adenoma and early adenocarcinoma indicated IDH1/2 mutations could be trunk drivers suitable for targeted therapy. CONCLUSIONS IDH1/2 mutations in CRCs were uncommon but enriched in BRAF p.V600E-mutated CRCs and perhaps colitis-associated CRCs. Further studies on IDH1/2-mutated CRCs are needed to clarify their clinicopathologic features and implications for targeted therapy.
Effects of Overexpression of Neurosecretory Protein GL-Precursor Gene on Glucose Homeostasis and Insulin Sensitivity in Mice

A high-fat diet (HFD) quickly induces obesity with insulin resistance and hyperglycemia. We previously reported that a novel hypothalamic small protein, named neurosecretory protein GL (NPGL), stimulates feeding and fat accumulation in mice. However, the effects of NPGL on insulin sensitivity and glucose homeostasis remain unknown. Hence, we subjected NPGL-precursor gene (Npgl)-overexpressing mice to the oral glucose tolerance test (OGTT) and intraperitoneal insulin tolerance test (IPITT) under normal chow (NC) and HFD conditions. Npgl overexpression promoted body mass gain and tended to increase food intake of NC-fed mice, whereas it had little effect on HFD-fed mice. The OGTT showed elevated blood glucose and insulin levels in Npgl-overexpressing NC-fed mice 15 min after glucose administration. Both the OGTT and IPITT demonstrated that Npgl overexpression decreased blood glucose levels in HFD-fed mice 60 min after glucose and insulin treatments. Notably, Npgl overexpression increased adipose tissue masses only in NC-fed mice, and it decreased blood glucose and insulin levels in HFD-fed mice at the experimental end point. It also increased the mRNA expression of galanin, one of the feeding and metabolic regulatory neuropeptides, in the hypothalamus of HFD-fed mice. Therefore, NPGL may alleviate HFD-induced hyperglycemia and insulin resistance in mice.
CANreduce 2.0 Adherence-Focused Guidance for Internet Self-Help Among Cannabis Users: Three-Arm Randomized Controlled Trial

Background Despite increasing demand for treatment among cannabis users in many countries, most users are not in treatment. Internet-based self-help offers an alternative for those hesitant to seek face-to-face therapy, though low effectiveness and adherence issues often arise. Objective Through adherence-focused guidance enhancement, we aimed to increase adherence to and the effectiveness of internet-based self-help among cannabis users. Methods From July 2016 to May 2019, cannabis users (n=775; male: 406/575, 70.6%, female: 169/575, 29.4%; age: mean 28.3 years) not in treatment were recruited from the general population and were randomly assigned to (1) an adherence-focused guidance enhancement internet-based self-help intervention with social presence, (2) a similar intervention with an impersonal service team, and (3) access to internet as usual. Controls who were placed on a waiting list for the full intervention after 3 months underwent an assessment and had access to internet as usual. The primary outcome measurement was cannabis-use days over the preceding 30 days. Secondary outcomes included cannabis-dependence severity, changes in common mental disorder symptoms, and intervention adherence. Differences between the study arms in primary and secondary continuous outcome variables at baseline, posttreatment, and follow-up were tested using pooled linear models. Results All groups exhibited reduced cannabis-use days after 3 months (social presence: –8.2 days; service team: –9.8 days; internet as usual: –4.2 days). The participants in the service team group (P=.01, d=.60) reported significantly fewer cannabis-use days than those in the internet as usual group; the reduction of cannabis use in the social presence group was not significant (P=.07, d=.40). There was no significant difference between the 2 intervention groups regarding cannabis-use reduction. The service team group also exhibited superior improvements in cannabis-use disorder, cannabis-dependence severity, and general anxiety symptoms after 3 months to those in the internet as usual group. Conclusions The adherence-focused guidance enhancement internet-based self-help intervention with an impersonal service team significantly reduced cannabis use, cannabis-use disorder, dependence severity, and general anxiety symptoms. Trial Registration ISRCTN Registry ISRCTN11086185; http://www.isrctn. com/ISRCTN11086185
Glucose Level Sensing Using Single Asymmetric Split Ring Resonator

In this article, a biosensor composed of a single metamaterial asymmetric resonator is specifically designed for sensing the glucose level of 1 µL of solution. The resonator has two gaps, and one of them ends with a semicircle shape on which the glucose solution is placed. This design helps in confining the drops of glucose solutions in a specific area where the field is maximally confined in order to enhance the electromagnetic wave-matter interaction. Six samples of glucose solutions with concentrations that cover hypoglycemia, normal and hyperglycemia conditions that vary from around 41 to 312 mg/dL were prepared and examined by this biosensor. The resonance frequency redshift was used as a measure of the changes in the glucose level of the solutions. Without glucose solution, an excellent agreement between the measured and simulated transmission amplitude was observed. The increase in glucose concentrations exhibited clear and noticeable redshifts in the resonance frequency. This biosensor revealed a 0.9997 coefficient of determination, which implies an excellent prediction fitting model. More importantly, a sensitivity of 438 kHz/(mg/dL) was observed over the range of concentrations of the aqueous solution.
The Bacterial Genomic Context of Highly Trimethoprim-Resistant DfrB Dihydrofolate Reductases Highlights an Emerging Threat to Public Health

Type B dihydrofolate reductase (dfrb) genes were identified following the introduction of trimethoprim in the 1960s. Although they intrinsically confer resistance to trimethoprim (TMP) that is orders of magnitude greater than through other mechanisms, the distribution and prevalence of these short (237 bp) genes is unknown. Indeed, this knowledge has been hampered by systematic biases in search methodologies. Here, we investigate the genomic context of dfrbs to gain information on their current distribution in bacterial genomes. Upon searching publicly available databases, we identified 61 sequences containing dfrbs within an analyzable genomic context. The majority (70%) of those sequences also harbor virulence genes and 97% of the dfrbs are found near a mobile genetic element, representing a potential risk for antibiotic resistance genes. We further identified and confirmed the TMP-resistant phenotype of two new members of the family, dfrb10 and dfrb11. Dfrbs are found both in Betaproteobacteria and Gammaproteobacteria, a majority (59%) being in Pseudomonas aeruginosa. Previously labelled as strictly plasmid-borne, we found 69% of dfrbs in the chromosome of pathogenic bacteria. Our results demonstrate that the intrinsically TMP-resistant dfrbs are a potential emerging threat to public health and justify closer surveillance of these genes.