Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of drying temperature and exposure times on Aspergillus flavus growth and aflatoxin production on artificially inoculated hazelnuts.

Aspergillus flavus may colonise hazelnuts and produce aflatoxins in field and during storage. The main purpose of this study was to investigate the influence of drying temperature and exposure times on the viability and ability of A. flavus to produce aflatoxins during the drying process and storage. Hazelnuts were inoculated with A. flavus and dried at different temperatures to reach 6% moisture content and a w 0.71, a commercial requirement to avoid fungal development and aflatoxin contamination. Hazelnuts were dried at 30, 35, 40, 45, and 50 °C and subsequently stored at 25 °C for 14 days. After drying at 30, 35 and 40 °C, an increased number of A. flavus was evident, with the highest concentration at 35 °C (6.1 ± 2.4 x10 6 A. flavus CFU/g). At these temperatures, aflatoxins were detected only at 30 °C and 35 °C. Aflatoxins, however, were higher after drying at 30 °C with a concentration of 1.93 ± 0.77 μg/g for aflatoxin B1 (AFB1) and 0.11 ± 0.04 μg/g for aflatoxin B2 (AFB2). After 14 days of storage, the highest A. flavus concentration and the highest level of mycotoxins were detected in samples treated at 35 °C (8.2 ± 2.1 x10 7 A. flavus CFU/g, 9.30 ± 1.58 μg/g and 0.89 ± 0.08 μg/g for AFB1 and AFB2, respectively). In hazelnuts dried at 45 °C or 50 °C no aflatoxins were found both after drying and storage, and a reduction of A. flavus viable conidia was observed, suggesting that a shorter and warmer drying is essential to guarantee the nut safety. The lowest temperature that guarantees the lack of aflatoxins should be selected to maintain the organoleptic quality of hazelnuts. Therefore, 45°C should be the recommended drying temperature to limit A. flavus growth and aflatoxin contamination on hazelnuts.
Immunohistochemical validation study of 15-gene biomarker panel predictive of benefit from adjuvant chemotherapy in resected non-small-cell lung cancer: analysis of JBR.10

Objective There are no validated approaches to predict benefit from adjuvant chemotherapy for resected patients with non-small-cell lung cancer (NSCLC). The aim of this study was to translate a 15-gene mRNA expression profile published by Zhu et al, shown to be prognostic and predictive of benefit, into a readily applicable immunohistochemistry (IHC) panel. Methods For seven of the genes in the gene expression profile (GEP) for which suitable commercial antibodies were available, we semiquantitatively assessed the IHC expression and prognostic significance for 173 patients treated at the Saint John Regional Hospital (SJRH). Cut-offs for high and low expression were defined for each marker and applied to IHC scores from 291 of the 482 patients in JBR.10, including patients on both the adjuvant chemotherapy and observation arms. The prognostic and predictive value of these markers on overall survival (OS) or recurrence-free survival (RFS) was assessed by Cox regression models. Results In the SJRH cohort, in 62 patients with resected stage II–III NSCLC, the prognostic significance of IHC assays for four proteins were concordant with Zhu’s GEP results. Low FOSL2 (OS, HR=0.15; p=0.0001; RFS, HR=0.14; p<0.0001) and high STMN2 (RFS, HR=2.501; p=0.0197) were adverse prognostic factors. Low ATP1B1 and low TRIM14 expression trended toward worse OS and RFS. Validation of these markers with JBR.10 patients failed to show prognostic significance either individually or in combined risk classifications. Additionally, the interaction between these markers and chemotherapy treatment in predicting OS (FOSL2, p=0.52; STMN2 p=0.14; ATP1B1, p=0.33; TRIM14, p=0.81) or RFS (FOSL2, p=0.63; STMN2, p=0.12; ATP1B1, p=0.66; TRIM14, p=0.57) did not reach significance, individually or in combination panels. Conclusions Zhu’s GEP could not be translated into an IHC panel predictive of benefit from adjuvant chemotherapy. Future predictive biomarker analysis in the adjuvant NSCLC setting may need to focus on novel therapies.
Mentalizing stigma: Reflective functioning as a protective factor against depression and anxiety in transgender and gender-nonconforming people.

OBJECTIVE The current study examined the role of internalized transphobia (IT) as a mediator between gender-related rejection and mental health, and reflective functioning (or mentalization) as a resilience factor moderating the relationship between both rejection and IT with mental health. METHOD This online study included 203 Italian transgender and gender-nonconforming (TGNC) individuals ranged in age from 18 to 66 years old (M = 30.70; standard deviation = 10.79). Moderated-mediation analysis was performed using a structural equation modeling approach. RESULTS Both rejection and IT were positively associated with mental health, and IT mediated the relationship between rejection and mental health. Mentalization moderated the relationship between rejection and IT with mental health. The indirect effect of rejection on mental health through IT was moderated by mentalization. CONCLUSIONS Findings highlight psychological paths that may inform individual- and group-level mentalization-based interventions to reduce minority stress in TGNC individuals.
Chemodiversity of Essential Oils from Nine Species of Celastraceae

Extracts and compounds obtained from several species of Celastraceae family are reported as potential sources of drugs due to their diverse pharmacological properties. Nevertheless, essential oil composition from these species is still little known. This work aimed at the analysis of essential oils obtained from different Brazilian Celastraceae species. A total of seventeen oils were obtained using hydrodistillation process and analyzed by gas chromatography/mass spectrometry (GC/MS). Principal component analysis (PCA) allowed the identification of a chemical composition pattern among the analyzed essential oils. Some compounds were more frequent among Celastraceae species, such as cis‐ and trans‐linalool oxide (14/17 oil samples), nerylacetone (13/17), linalool (11/17), β‐ionone (10/17), α‐ionone (9/17), nerolidol (10/17), decanal (10/17), and dodecanoic acid (10/17). These results contribute to the chemophenetics of Celastraceae species.
Improved detection of hepatocellular carcinoma by dynamic computed tomography in cirrhotic patients with chronic hepatitis B: A multicenter study

Current guidelines for chronic hepatitis B (CHB) patients are to undergo surveillance for hepatocellular carcinoma (HCC) with 6‐monthly ultrasonography (US). However, sensitivities of US to detect early‐stage HCC in cirrhotic patients are suboptimal. We aimed to compare overall survival and detection rates of very‐early‐stage HCC in two groups: group A, undergoing 6‐monthly US versus group B, undergoing 6‐monthly US alternating with dynamic computed tomography (CT).
Transforming growth factor‐β promotes the function of HIV‐specific CXCR5+CD8 T cells

HIV replication can be inhibited by CXCR5+CD8 T cells (follicular cytotoxic T cell [TFC]) which transfer into B‐cell follicles where latent HIV infection persists. However, how cytokines affect TFC remain unclear. Understanding which cytokines show the ability to affect TFC could be a key strategy toward curing HIV. Similar mechanisms could be used for the growth and transfer of TFCs and follicular helper T (TFH) cells; as a result, we hypothesized that cytokines IL‐6, IL‐21, and transforming growth factor‐β (TGF‐β), which are necessary for the differentiation of TFH cells, could also dictate the development of TFCs. In this work, lymph node mononuclear cells and peripheral blood mononuclear cells from HIV‐infected individuals were cocultured with IL‐6, IL‐21, and TGF‐β. We then carried out T‐cell receptor (TCR) repertoire analysis to compare the differences between CXCR5– and CXCR5+CD8 T cells. Our results showed that the percentage and function of TFC can be enhanced by stimulation with TGF‐β. Besides, TGF‐β stimulation enhanced the diversity of TCR and complementarity‐determining region 3 sequences. HIV DNA showed a negative correlation with TFC. The use of TGF‐β to promote the expression of CXCR5+CD8 T cells could become a new treatment approach for curing HIV.
A putative placebo analysis of the effects of sacubitril/valsartan in heart failure across the full range of ejection fraction

Abstract Aims The PARADIGM-HF and PARAGON-HF trials tested sacubitril/valsartan against active controls given renin–angiotensin system inhibitors (RASi) are ethically mandated in heart failure (HF) with reduced ejection fraction and are used in the vast majority of patients with HF with preserved ejection fraction. To estimate the effects of sacubitril/valsartan had it been tested against a placebo control, we made indirect comparisons of the effects of sacubitril/valsartan with putative placebos in HF across the full range of left ventricular ejection fraction (LVEF). Methods and results We analysed patient-level data from the PARADIGM-HF and PARAGON-HF trials (n = 13 194) and the CHARM-Alternative and CHARM-Preserved trials (n = 5050, candesartan vs. placebo). The rate ratio (RR) of sacubitril/valsartan vs. putative placebo was estimated by the product of the RR for sacubitril/valsartan vs. RASi and the RR for RASi vs. placebo. Total HF hospitalizations and cardiovascular death were analysed using the negative binomial method. Treatment effects were estimated using cubic spline methods by ejection fraction as a continuous measure. Across the range of LVEF, sacubitril/valsartan was associated with a RR 0.54 [95% confidence interval (CI) 0.45–0.65] for the recurrent primary endpoint compared with putative placebo (P < 0.001). Treatment benefits of sacubitril/valsartan vs. putative placebo varied non-linearly with LVEF with attenuation of effects observed at LVEF above 60%. When analyzing data from PARADIGM-HF and CHARM-Alternative, the estimated risk reduction of sacubitril/valsartan vs. putative placebo was 48% (95% CI 35–58%); P < 0.001. When analyzing data from PARAGON-HF and CHARM-Preserved (with LVEF ≥ 45%), the estimated risk reduction of sacubitril/valsartan vs. putative placebo was 29% (95% CI 7–46%); P = 0.013. Across the full range of LVEF, consistent effects were observed for time-to-first endpoints: first primary endpoint (RR 0.72, 95% CI 0.64–0.82), first HF hospitalization (RR 0.67, 95% CI 0.58–0.78), cardiovascular death (RR 0.76, 95% CI 0.64–0.89), and all-cause death (RR 0.83, 95% CI 0.71–0.96); all P < 0.02. Conclusion This putative placebo analysis reinforces the treatment benefits of sacubitril/valsartan on risk of adverse cardiovascular events across the full range of LVEF, with most pronounced effects observed at a LVEF up to 60%.
Probiotics, prebiotics, and synbiotics supplementation in prediabetes: protocol for a systematic review and meta-analysis

Abstract Background: The prevalence of prediabetes and diabetes is increasing rapidly, and 5% to 10% of prediabetic patients will develop diabetes every year. Diabetes causes major health problems as well as a large economic burden. Human studies have demonstrated the beneficial effects of probiotics, prebiotics, and synbiotics supplementation in prediabetes. However, there are no systematic reviews that explore the therapeutic efficacy of probiotics, prebiotics, and synbiotics supplementation in patients with prediabetes. Therefore, we aim to synthesize the existing evidence evaluating the effectiveness and safety of probiotics, prebiotics, and synbiotics supplementation in prediabetic patients. Methods: We will search PubMed, EMBASE, Cochrane Library, Web of Science, the Clinical Trials.gov website, China National Knowledge Infrastructure, China Science and Technology Journal Database, and Wanfang Data Knowledge Service Platform from inception to August 2020. Additionally, the search will be conducted in multiple languages. Search terms are keywords and medical subject headings related to prediabetes, probiotics, prebiotics, and synbiotics. The primary outcomes are differences in glycated hemoglobin and fasting blood glucose. The secondary outcomes are differences in fasting insulin, homeostasis model assessment of insulin resistance, quantitative insulin sensitivity check index, and adverse events. The meta-analysis will be performed using the Revman5.3. 0 software provided by the Cochrane Collaboration. Results: Our study will systematically evaluate the effectiveness and safety of probiotics, prebiotics, and synbiotics supplementation in prediabetes. Conclusion: The findings of this study will provide the best available evidence for probiotics, prebiotics, and synbiotics in the treatment of prediabetes, and provide a strong basis for clinical treatment.
Circular RNA circFBXO11 modulates hepatocellular carcinoma progress and oxaliplatin resistance through miR‐605/FOXO3/ABCB1 axis

Increasing findings suggest the critical role of circular RNA (circRNA) in human cancer, and chemotherapy resistance is a poor prognostic factor for hepatocellular carcinoma (HCC). The function of circRNA in the HCC oxaliplatin (OXA) resistance remains largely unknown. In this study, we found that circRNA circFBXO11 was significantly up‐regulated in HCC tissues, and the circFBXO11 overexpression was associated with poor prognosis. CircFBXO11 was found to promote the HCC proliferation, cycle progress and OXA resistance. Mechanistically, circFBXO11 was predominantly localized in the cytoplasm and harboured the miR‐605, thereby targeting FOXO3 protein. Furthermore, FOXO3 targeted the promoter region of ABCB1 to accelerate its expression. In conclusion, this research reveals the role of circFBXO11/miR‐605/FOXO3/ABCB1 axis in the HCC OXA resistance, providing new insight for circRNA‐based diagnostic and therapeutic strategies.
Survival of Salmonella in Various Wild Animal Feces That May Contaminate Produce.

ABSTRACT Heightened concerns about wildlife on produce farms and possible introduction of pathogens to the food supply have resulted in required actions following intrusion events. The purpose of this study was to evaluate the survival of Salmonella in feces from cattle and various wild animals (feral pigs, waterfowl, deer, and raccoons) in California, Delaware, Florida, and Ohio. Feces were inoculated with rifampin-resistant Salmonella enterica cocktails that included six serotypes: Typhimurium, Montevideo, Anatum, Javiana, Braenderup, and Newport (104 to 106 CFU/g). Fecal samples were stored at ambient temperature. Populations were enumerated for up to 1 year (364 days) by spread plating onto tryptic soy agar supplemented with rifampin. When no colonies were detected, samples were enriched. Colonies were banked on various sampling days based on availability of serotyping in each state. During the 364-day storage period, Salmonella populations decreased to ≤2.0 log CFU/g by day 84 in pig, waterfowl, and raccoon feces from all states. Salmonella populations in cattle and deer feces were 3.3 to 6.1 log CFU/g on day 336 or 364; however, in Ohio Salmonella was not detected after 120 days. Salmonella serotypes Anatum, Braenderup, and Javiana were the predominant serotypes throughout the storage period in all animal feces and states. Determination of appropriate risk mitigation strategies following animal intrusions can improve our understanding of pathogen survival in animal feces. HIGHLIGHTS
Gene therapy strategies for X-linked myotubular myopathy

ABSTRACT Introduction: X-linked myotubular myopathy (XLMTM) is a severe, frequently fatal, type of congenital myopathy for which only supportive care is currently available. XLMTM is due to MTM1 mutations that lead to a deficiency in myotubularin, a lipid phosphatase. Restoring functional myotubularin expression in skeletal muscle would be the most direct approach to treat XLMTM. Recent work in gene therapy using animal models has revealed exciting, clinically meaningful results. Areas covered: Gene therapy using skeletal muscle trophic adenoassociated virus 8 (AAV8) as a vector has shown promise to safely deliver MTM1 and restore myotubularin expression, which improves muscle function, ameliorates pathology and considerably lengthens survival over time. The XLMTM dog has provided a large animal model for these experiments, which has enhanced their value and our ability to move toward implementing gene therapy into XLMTM clinical care. An overview the progress that has been made will be provided here. Expert opinion: A variety of approaches have been applied to treat XLMTM, but gene therapy appears to be the most efficient and direct means to safely restore myotubularin expression in XLMTM skeletal muscle. Future efforts will focus on ensuring the safety of gene therapy vectors while developing clinically relevant dosing regimens.
Upper Extremity Phlegmasia Cerula Dolens: Presentation by Color Duplex Ultrasound

Introduction Phlegmasia cerula dolens (PCD) is an uncommon complication of deep vein thrombosis (DVT), and involvement in the upper extremities is rare. We report a case in which color duplex ultrasound (CDU) was used to diagnose PCD in a patient with extensive upper extremity DVT. Patient A 57-year-old woman underwent an open lung biopsy. On the first postoperative day, she had right hand and forearm pain, edema, and cyanosis. Findings CDU revealedacute DVT in the right radial, ulnar, and brachial veins and extensive thrombosis of the right cephalic and basilic veins. Arterial signals recorded from the ipsilateral arteries were remarkable for pandiastolic flow reversal (PDFR). In contrast, arterial signals from the contralateral arm had a normal, triphasic pattern. Arteriography revealed patent arteries to the wrist and no flow present in the right hand. Conclusions This report demonstrates the sensitivity of CDU to arterial compromise associated with PCD in a case of upper extremity DVT. Vascular technologists should consider including arterial Doppler signals in their venous duplex protocols in cases of extensive deep and superficial vein thrombosis.
A-l and Coronary Artery Disease in Humans

T review initially will consider the association between premature coronary artery disease and abnormal lipoprotein cholesterol levels, but then focus on recent evidence linking the apoproteins of lipoproteins to atherosclerosis. This evidence suggests that although cholesterol is the major component common to the plasma and the arterial wall, plasma apoproteins may serve as a better marker of risk for atherosclerosis.
History of Discovery How We Learned to Say NO

What seest thou else In the dark backward and abysm of time —William Shakespeare First, there was Robert Furchgott.1 He simply and brilliantly demonstrated that endothelial cells play a pivotal role in relaxations evoked by acetylcholine in isolated arteries, and do so by activating muscarinic receptors of these cells. Actually, the quest for the understanding of the mechanism(s) underlying the vasodilator effect of acetylcholine in vivo (in contrast with the vasoconstrictor effect that the cholinergic transmitter almost always had in vitro) had started many years before that and led to the earlier interpretation that this could be explained best by a prejunctional (presynaptic) muscarinic effect resulting in the local inhibition of adrenergic neurotransmission in the blood vessel wall.2 To be honest, I am still convinced that if acetylcholine released from cholinergic nerves (the most likely, if not the only, source of acetylcholine in our body) contributes to the control of vasomotor tone, it does so by inhibiting the release of norepinephrine in the adventitia rather than by diffusing through the media to the endothelial cells. When asked the role is of muscarinic receptors on endothelial cells, I usually respond by saying that they have been placed there to make sure that Robert Furchgott, who already had contributed immensely to pharmacology before discovering endothelium-dependent relaxations, would make the trip to Stockholm! Yet his simple pharmacological experiments had opened a totally new avenue not only in vascular pharmacology and physiology but in science in general as they set the stage for the discovery of the role of nitric oxide (NO) in biology.
Inflammatory Mediators and Cell Adhesion Molecules as Indicators of Severity of Atherosclerosis

Inflammatory mediators and soluble cell adhesion molecules predict cardiovascular events. It is not clear whether they reflect the severity of underlying atherosclerotic disease. Within the Rotterdam Study, we investigated the associations of C-reactive protein (CRP), interleukin-6 (IL-6), soluble intercellular adhesion molecule-1, and soluble vascular cell adhesion molecule-1 with noninvasive measures of atherosclerosis. Levels of CRP were assessed in a random sample of 1317 participants, and levels of IL-6 and soluble cell adhesion molecules were assessed in a subsample of 714 participants. In multivariate analyses, logarithmically transformed CRP (regression coefficient [ ] 0.023, 95% CI 0.033 to 0.012) and IL-6 ( 0.025, 95% CI 0.049 to 0.001) were inversely associated with the ankle-arm index. Only CRP was associated with carotid intima-media thickness ( 0.018, 95% CI 0.010 to 0.027). Compared with the lowest tertile, the odds ratio for moderate to severe carotid plaques associated with levels of CRP in the highest tertile was 2.0 (95% CI 1.3 to 3.0). Soluble intercellular adhesion molecule-1 levels were strongly associated with carotid plaques (odds ratio 2.5, 95% CI 1.5 to 4.4 [highest versus lowest tertile]). Soluble vascular cell adhesion molecule-1 was not significantly associated with any of the measures of atherosclerosis. This study indicates that CRP is associated with the severity of atherosclerosis measured at various sites. Associations of the other markers with atherosclerosis were less consistent. (Arterioscler Thromb Vasc Biol. 2002;22:838-842.)
Moving Marksmen of Redox Signaling?

Despite tremendous advances in our knowledge of the role of oxidative species in vascular disease, much debate remains regarding the mechanism by which NADPH oxidases (Nox) impart specific effects in cells. Over the past 2 decades, the term oxidative stress has often been used to describe the effects of Nox-derived reactive oxygen species (ROS). Much credence was initially given to relatively large quantities of ROS as mediators of myriad and varied cellular responses, ranging from connective tissue expression to differentiation, hypertrophy, proliferation, and apoptosis.1 With the discovery of multiple Nox isoforms and emergence of loss-of-function and gain-of-function technologies manipulating the levels of individual isoforms, a large body of literature emerged suggesting that small, localized ROS derived from individual Nox proteins can impart unique cellular responses. The lack of sophisticated detection methods for localizing perhaps subtle changes in ROS continues to stymie our understanding of how one Nox may confer activation of a specific signaling cascade and render distinct cell changes. The conundrum of why similar whole cell or tissue increases or decreases in ROS confer disparate phenotypes continues to confound leaders in the field.