Miracle-dz/UniFAR-FTUs huggingface dataset:
Multifaceted Functional Role of Semaphorins in Glioblastoma

Glioblastoma (GBM) is the most malignant tumor type affecting the adult central nervous system. Despite advances in therapy, the prognosis for patients with GBM remains poor, with a median survival of about 15 months. To date, few treatment options are available and recent trials based on the molecular targeting of some of the GBM hallmark pathways (e.g., angiogenesis) have not produced any significant improvement in overall survival. The urgent need to develop more efficacious targeted therapies has led to a better molecular characterization of GBM, revealing an emerging role of semaphorins in GBM progression. Semphorins are a wide group of membrane-bound and secreted proteins, originally identified as axon guidance cues, signaling through their receptors, neuropilins, and plexins. A number of semaphorin signals involved in the control of axonal growth and navigation during development have been found to furthermore participate in crosstalk with different dysfunctional GBM pathways, controlling tumor cell proliferation, migration, and invasion, as well as tumor angiogenesis or immune response. In this review, we summarize the regulatory activities mediated by semaphorins and their receptors on the oncogenic pathways implicated in GBM growth and invasive/metastatic progression.
Synthesis and Antimicrobial Evaluation of Amixicile-Based Inhibitors of the Pyruvate-Ferredoxin Oxidoreductases of Anaerobic Bacteria and Epsilonproteobacteria

ABSTRACT Amixicile is a promising derivative of nitazoxanide (an antiparasitic therapeutic) developed to treat systemic infections caused by anaerobic bacteria, anaerobic parasites, and members of the Epsilonproteobacteria (Campylobacter and Helicobacter). Amixicile selectively inhibits pyruvate-ferredoxin oxidoreductase (PFOR) and related enzymes by inhibiting the function of the vitamin B1 cofactor (thiamine pyrophosphate) by a novel mechanism. Here, we interrogate the amixicile scaffold, guided by docking simulations, direct PFOR inhibition assays, and MIC tests against Clostridium difficile, Campylobacter jejuni, and Helicobacter pylori. Docking simulations revealed that the nitro group present in nitazoxanide interacts with the protonated N4′-aminopyrimidine of thiamine pyrophosphate (TPP). The ortho-propylamine on the benzene ring formed an electrostatic interaction with an aspartic acid moiety (B456) of PFOR that correlated with improved PFOR-inhibitory activity and potency by MIC tests. Aryl substitution with electron-withdrawing groups and substitutions of the propylamine with other alkyl amines or nitrogen-containing heterocycles both improved PFOR inhibition and, in many cases, biological activity against C. difficile. Docking simulation results correlate well with mechanistic enzymology and nuclear magnetic resonance (NMR) studies that show members of this class of antimicrobials to be specific inhibitors of vitamin B1 function by proton abstraction, which is both novel and likely to limit mutation-based drug resistance.
Fluidized Bed Drying of Pumpkin (Cucurbita sp.) Seeds

Pumpkin seeds are a major agricultural waste from the fresh-cut produce industry. The objective of this study was to investigate the drying behavior of untreated, whole pumpkin seeds in a fluidized bed dryer at 50–80 °C (2.87 m/s), with a view to producing a high-quality pumpkin powder from dried seeds. Seeds were dried at 50–80 °C to an average equilibrium moisture value of 0.035 to 0.006 g H2O/g DM (3.4 to 0.6% wb). Drying occurred in the falling rate period only and drying rate constants ranged from 0.0226 to 0.0900 1/min with corresponding diffusivity values for the first falling-rate period ranging from 4.68 to 18.63 × 10−10 m2/s. The activation energy (Ea)—for the first falling rate period was determined to be 43.9 kJ/mol. Of the nineteen thin layer models tested, the Alibas model could be successfully used as a general model to predict the Moisture Ratio (MR) data for all temperatures investigated. After drying, seeds were blended to produce powders, which were found to be high in fat, crude protein and fiber.
Bentonites Modified with Phosphomolybdic Heteropolyacid (HPMo) for Biowaste to Biofuel Production

Two bentonites from Paraíba (Northeastern Brazil) were impregnated with heteropoly phosphomolybdic H3PMo12O40 (HPMo). The materials produced were characterized by various techniques such as N2 adsorption-desorption (specific surface area, SSA), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), Thermogravimetric analysis (TGA/DTG), Scanning Electron Microscopy (SEM) equipped with Dispersive Energy X-ray spectroscopy (EDS), ultraviolet-visible spectroscopy (UV-vis), acid-base titration analysis. The catalytic activity of these materials was tested in the esterification of a waste from palm oil deodorization and the main results obtained (about 93.3% of conversion) indicated that these materials have potential to act as heterogeneous solid acid catalysts. The prepared materials exhibited satisfactory catalytic performance even after a very simple recycling process in three reuse cycles, without significant loss of their activities.
A Comparative Study of Diagnostic Scoring Systems for Autoimmune Pancreatitis

Objective Several diagnostic scoring systems for autoimmune pancreatitis (AIP) have been proposed including the Asian, HISORt (Histology, Imaging, Serology, Other organ involvement and Response to therapy), and International Consensus Diagnostic Criteria (ICDC), which have been compared by a few studies. We evaluated the diagnostic performance of these criteria in patients diagnosed with AIP between May 1992 and August 2011. Methods Scoring systems were applied retrospectively using data obtained in the initial evaluation period, before pancreatic resection was performed. Results One hundred fourteen cases with AIP were included. Eighty-two percent met the diagnostic criteria for AIP according to either the Asian, HISORt, or ICDC criteria. Only 33% met the Asian criteria, probably mainly related to a low rate of diagnostic pancreatography. In 18%, all scoring systems failed to confirm the diagnosis, even though these patients were considered to have a firm diagnosis of AIP. Conclusions In this cohort of AIP patients, the 3 major diagnostic scoring systems for AIP proved to be complementary rather than overlapping. Our data indicate that one-fifth of our AIP patients do not meet any of these scoring systems. The ICDC, Asian, and HISORt criteria should be considered as useful clinical tools but not as criterion standard for the diagnosis.
Giant Viruses—Big Surprises

Viruses are the most prevalent infectious agents, populating almost every ecosystem on earth. Most viruses carry only a handful of genes supporting their replication and the production of capsids. It came as a great surprise in 2003 when the first giant virus was discovered and found to have a >1 Mbp genome encoding almost a thousand proteins. Following this first discovery, dozens of giant virus strains across several viral families have been reported. Here, we provide an updated quantitative and qualitative view on giant viruses and elaborate on their shared and variable features. We review the complexity of giant viral proteomes, which include functions traditionally associated only with cellular organisms. These unprecedented functions include components of the translation machinery, DNA maintenance, and metabolic enzymes. We discuss the possible underlying evolutionary processes and mechanisms that might have shaped the diversity of giant viruses and their genomes, highlighting their remarkable capacity to hijack genes and genomic sequences from their hosts and environments. This leads us to examine prominent theories regarding the origin of giant viruses. Finally, we present the emerging ecological view of giant viruses, found across widespread habitats and ecological systems, with respect to the environment and human health.
Adverse cardiovascular outcomes in women: blame the amygdala?

Emory Women’s Heart Center, 1432 Clifton Rd NE, Suite 505, Atlanta, GA 30322, USA; Division of Cardiology, Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, 1432 Clifton Rd NE, Suite 505, Atlanta, GA 30322, USA; Rollins School of Public Health, 1518 Clifton Rd, Atlanta, GA 30322, USA; University of Texas at Arlington, 701 W Nedderman Dr, Arlington Room 105, TX 76019, USA; and Barbra Streisand Women’s Heart Center, Smidt Heart Institute, Cedars-Sinai Medical Center, 127 S San Vicente Blvd #A3600, Los Angeles, CA 90048, USA
Viral Metagenomics on Cerebrospinal Fluid

Identifying the causative pathogen in central nervous system (CNS) infections is crucial for patient management and prognosis. Many viruses can cause CNS infections, yet screening for each individually is costly and time-consuming. Most metagenomic assays can theoretically detect all pathogens, but often fail to detect viruses because of their small genome and low viral load. Viral metagenomics overcomes this by enrichment of the viral genomic content in a sample. VIDISCA-NGS is one of the available workflows for viral metagenomics, which requires only a small input volume and allows multiplexing of multiple samples per run. The performance of VIDISCA-NGS was tested on 45 cerebrospinal fluid (CSF) samples from patients with suspected CNS infections in which a virus was identified and quantified by polymerase chain reaction. Eighteen were positive for an RNA virus, and 34 for a herpesvirus. VIDISCA-NGS detected all RNA viruses with a viral load >2 × 104 RNA copies/mL (n = 6) and 8 of 12 of the remaining low load samples. Only one herpesvirus was identified by VIDISCA-NGS, however, when withholding a DNase treatment, 11 of 18 samples with a herpesvirus load >104 DNA copies/mL were detected. Our results indicate that VIDISCA-NGS has the capacity to detect low load RNA viruses in CSF. Herpesvirus DNA in clinical samples is probably non-encapsidated and therefore difficult to detect by VIDISCA-NGS.
Changes in blood pressure before the development of nosocomial acute kidney injury.

BACKGROUND Blood pressure is an important determinant of renal perfusion and acute kidney injury (AKI) is common in hospital patients. However, there is limited knowledge concerning the incidence of relative hypotension prior to its development in general wards. METHODS We compared blood pressure recordings in a cohort of consecutive patients with no change in renal function to a cohort of patients with acute changes in renal function according to RIFLE classes R, I and F for AKI. We assessed blood pressure over a 3-day period before the development of AKI in index patients and a similar 3-day period in controls. We excluded patients with absolute hypotension [systolic blood pressure (SBP) <90 mmHg]. RESULTS Patients were old (mean age 76.1 +/- 15.1) and mostly female (57.1%). Those who developed AKI had a lower diastolic blood pressure (P = 0.01), a trend towards lower mean arterial pressure (P = 0.077) and a greater decrease in mean systolic (P < 0.0001), mean diastolic (P < 0.0001) and mean arterial pressure (P < 0.0001) compared to controls. On multivariate logistic regression analysis, a decrease in SBP relative to pre-morbid value was a significant independent predictor of the development of AKI and of RIFLE classes I and F (odds ratio 1.084 for every -1 mmHg change in SBP). CONCLUSIONS Relative hypotension is more common in ward patients who develop nosocomial AKI than in controls. In these patients, a decrease in SBP relative to pre-morbid value is a significant independent predictor of the development of severe AKI.
Aberrant interactions of cortical networks in chronic migraine

Objective We investigated resting-state (RS)-fMRI using independent component analysis (ICA) to determine the functional connectivity (FC) between networks in chronic migraine (CM) patients and their correlation with clinical features. Methods Twenty CM patients without preventive therapy or acute medication overuse underwent 3T MRI scans and were compared to a group of 20 healthy controls (HC). We used MRI to collect RS data in 3 selected networks, identified using group ICA: the default mode network (DMN), the executive control network (ECN), and the dorsal attention system (DAS). Results Compared to HC, CM patients had significantly reduced functional connectivity between the DMN and the ECN. Moreover, in patients, the DAS showed significantly stronger FC with the DMN and weaker FC with the ECN. The higher the severity of headache, the increased the strength of DAS connectivity, and the lower the strength of ECN connectivity. Conclusion These results provide evidence for large-scale reorganization of functional cortical networks in chronic migraine. They suggest that the severity of headache is associated with opposite connectivity patterns in frontal executive and dorsal attentional networks.
EFFECTS OF A STRENGTHS-BASED DYADIC PROGRAM ON THE HEALTH OF PERSONS WITH MILD COGNITIVE IMPAIRMENT AND THEIR FAMILY

Abstract Mild cognitive impairment (MCI) is characterized by cognitive impairment cognition, neuro-psychiatric symptoms particularly depressed mood, and compromised self-image. This RCT evaluated the effects of a strength-based dyadic program, which supported MCI care dyads for effective symptom and disease management and active social engagement, on the dyadic health outcomes. From Dec 2017-Jan 2019, 103 care dyads were recruited in an elderly community center. By adopting the strength-based and person-centered approach, this 14-week program worked out a dyadic biographies for care dyads to increase identification and recognition of their own strengths. Then, six interactive educative-counseling sessions focusing on cognitive and behavioral symptom management, social interaction and gauge capability were delivered, with four sessions for the MCI clients in small groups and two sessions for the care dyads in their home environment. The control group received usual care. Dyadic health outcomes were measured at baseline, upon program completion and three months thereafter. The results of Generalized Estimating Equations showed that the strength-based dyadic program significantly improved the objective memory (post-test: β=-0.179, p=0.001), and subjective memory (post-test: β=7.542. p=0.007; 3-month: β=7.842. p=0.012), neuro-psychiatric symptoms (post-test: β=2.822, p=0.001; 3-month: β=3.038. p=0.007), and depression (post-test: β=2.665, p=0.017; 3-month: β=3.556. p=0.007). It also improved the caregiver stress in symptom management at post-test (β=2.822. p=0.001) and depression at the 3-month endpoint (β=1.510. p=0.015). Identifying and mobilizing the strengths of the clients with MCI and their family caregivers not only promote a more assertive coping experience and positive self-image for the care dyads, but also improve their health outcomes.
NKT Cell–Driven Enhancement of Antitumor Immunity Induced by Clec9a-Targeted Tailorable Nanoemulsion

Antigen and α-galactosylceramide encapsulated in a nanoemulsion improved the function of iNKT and dendritic cells, which drove cross-priming of antigen-specific CD8+ T cells. Long-term control of solid tumors resulted from a single dose of the emulsion. Invariant natural killer T (iNKT) cells are a subset of lymphocytes with immune regulatory activity. Their ability to bridge the innate and adaptive immune systems has been studied using the glycolipid ligand α-galactosylceramide (αGC). To better harness the immune adjuvant properties of iNKT cells to enhance priming of antigen-specific CD8+ T cells, we encapsulated both αGC and antigen in a Clec9a-targeted nanoemulsion (TNE) to deliver these molecules to cross-presenting CD8+ dendritic cells (DC). We demonstrate that, even in the absence of exogenous glycolipid, iNKT cells supported the maturation of CD8α+ DCs to drive efficient cross-priming of antigen-specific CD8+ T cells upon delivery of Clec9a/OVA-TNE. The addition of αGC to the TNE (Clec9a/OVA/αGC) further enhanced activation of iNKT cells, NK cells, CD8α+ DCs, and polyfunctional CD8+ T cells. When tested therapeutically against HPVE7-expressing TC-1 tumors, long-term tumor suppression was achieved with a single administration of Clec9a/E7 peptide/αGC TNE. Antitumor activity was correlated with the recruitment of mature DCs, NK cells, and tumor-specific effector CD8+ T cells to the tumor-draining lymph node and tumor tissue. Thus, Clec9a-TNE codelivery of CD8+ T-cell epitopes with αGC induces alternative helper signals from activated iNKT cells, elicits innate (iNKT, NK) immunity, and enhances antitumor CD8+ T-cell responses for control of solid tumors.
It’s All in the Genes: The Regulatory Pathways of Sexual Reproduction in Filamentous Ascomycetes

Sexual reproduction in filamentous ascomycete fungi results in the production of highly specialized sexual tissues, which arise from relatively simple, vegetative mycelia. This conversion takes place after the recognition of and response to a variety of exogenous and endogenous cues, and relies on very strictly regulated gene, protein, and metabolite pathways. This makes studying sexual development in fungi an interesting tool in which to study gene–gene, gene–protein, and protein–metabolite interactions. This review provides an overview of some of the most important genes involved in this process; from those involved in the conversion of mycelia into sexually-competent tissue, to those involved in the development of the ascomata, the asci, and ultimately, the ascospores.
Repeated stimulation of the pituitary–adrenal axis alters offspring phenotype of a wild passerine

ABSTRACT Prolonged stress can have long-lasting effects on an individual's physiology and growth. However, the impact of chronically elevated glucocorticoids on the expression of early antipredator responses is still poorly documented. In this study, I simulated the effect of repeated acute stress on offspring phenotype in free-living pied flycatchers (Ficedula hypoleuca) by administering adrenocorticotropic hormone (ACTH) to nestlings for 6 days. The results showed that frequent induction of stress responses by ACTH injections, independent of parental care, adversely affected offspring final body size, wing length and baseline corticosterone levels. Nestling behavioural activity did not differ between ACTH- and saline-treated groups during exposure to control sounds, whereas behavioural activity during exposure to alarm calls was reduced in manipulated offspring only. I conclude that prolonged physiological stress may have short-term benefits to nest-bound offspring, such as more effective antipredator behaviour, but at the expense of negative effects on body size and developmental speed. Summary: Developmental stress has negative effects on pied flycatcher offspring growth and physiology, but may have short-term benefits on performance by enhancing antipredator behaviour.
Regulation of Schizosaccharomyces pombe Wee1 Tyrosine Kinase*

Wee1 tyrosine kinase regulates mitosis by carrying out the inhibitory tyrosine 15 phosphorylation of Cdc2 M-phase inducing kinase. Schizosaccharomyces pombe Wee1 is a large protein, consisting of a C-terminal catalytic domain of ∼350 amino acids preceded by a N-terminal domain of ∼550 residues. The functional properties of the Wee1 N-terminal domain were investigated by expressing truncated forms of Wee1 in S. pombe. Both positive and negative regulatory domains were identified. Sequences important for Wee1 function were mapped to a central region (residues 363–408). This region is not required for kinase activity or nuclear localization, suggesting it may be involved in substrate recognition. The negative regulatory domain resides in the N-terminal third of Wee1, Wee1 constructs lacking this domain are more effective at delaying mitosis than wild-type Wee1. The negative regulatory domain contains clusters of potential Cdc2 phosphorylation sites. Investigations to monitor the abundance of Wee1 mRNA and protein during the cell cycle were also carried out.
The association between daytime sleepiness and sleep-disordered breathing in NREM and REM sleep.

BACKGROUND Daytime sleepiness is common in patients with sleep-disordered breathing. Although respiratory events during sleep are associated with the occurrence of daytime sleepiness, the differential impact of these events during non-rapid eye movement (NREM) and rapid eye movement (REM) sleep on daytime sleepiness has not been well characterized. STUDY OBJECTIVES To determine the effect of respiratory events during REM sleep and NREM sleep on daytime sleepiness, as assessed by the multiple sleep latency test (MSLT). DESIGN Cross-sectional study. SETTING University-based sleep disorders laboratory. PARTICIPANTS Patients referred for polysomnography and daytime MSLT (n=1,821). INTERVENTIONS N/A. MEASUREMENTS AND RESULTS The study sample was initially divided into quartiles based on the level of the apnea-hypopnea index (AHI) during NREM sleep. Within the first NREM-AHI quartile (NREM-AHI < 8.3 events/hr), the association between REM-related respiratory events and daytime sleepiness was examined using the method of Kaplan-Meier analysis and Cox proportional hazards regression. After adjusting for age, gender, body mass index, and the duration of NREM and REM sleep, REM-AHI was not associated with daytime sleepiness (Relative Risk: 1.01; 95%CI: 0.94-1.10). Similarly, no significant association was observed between REM-AHI and the MSLT in patients within the second through fourth NREM-AHI quartiles. In contrast, increasing severity of disordered breathing during NREM sleep was associated with daytime sleepiness. For a 10-point increase in NREM-AHI, the adjusted relative risks for daytime sleepiness in the second through fourth NREM-AHI quartile were 1.21 (95%CI: 1.01-1.46), 1.20 (95%CI: 1.05-1.37), and 1.10 (95%CI: 1.04-1.16), respectively. CONCLUSION Sleep-disordered breathing during NREM sleep, but not REM sleep, is associated with increased risk of daytime sleepiness.
Gender, stage of transition and situational avoidance: a UK study of trans people's experiences

Most societies are heavily organised around a dichotomous model of gender, and individuals are heavily policed on their conformity (or otherwise) to gender norms. This scrutinisation of gender has a profound impact on the identities and lived experiences of trans people, especially for those whose gender identity (or presentation) does not appear to match social expectations for that gender; or where someone's physical body in some way does not match the body conventionally associated with that gender. This might result in trans people avoiding certain situations to reduce the risk of being exposed. Based on a sample of 889 UK-based participants who self-defined as trans, the current paper explores situational avoidance with particular reference to gender identity and stage of transition. A key finding of this study concerned statistically significant associations between group (gender identity and stage of transition) and avoidance (or not) of certain situations, namely clothing shops, gyms, and public toilets. The implications of these findings for supporting trans people through transition – in particular, the real life experience – are also discussed.