Miracle-dz/UniFAR-FTUs huggingface dataset:
Autophagy and Apoptosis Interact to Modulate T-2 Toxin-Induced Toxicity in Liver Cells

T-2 toxin is a mycotoxin generated by Fusarium species which has been shown to be highly toxic to human and animals. T-2 toxin induces apoptosis in various tissues/organs. Apoptosis and autophagy are two closely interconnected processes, which are important for maintaining physiological homeostasis as well as pathogenesis. Here, for the first time, we demonstrated that T-2 toxins induce autophagy in human liver cells (L02). We demonstrated that T-2 toxin induce acidic vesicular organelles formation, concomitant with the alterations in p62/SQSTM1 and LC3-phosphatidylethanolamine conjugate (LC3-II) and the enhancement of the autophagic flux. Using mRFP-GFP-LC3 by lentiviral transduction, we showed T-2 toxin-mediated lysosomal fusion and the formation of autophagosomes in L02 cells. The formation of autophagosomes was further confirmed by transmission electron microcopy. While T-2 toxin induced both autophagy and apoptosis, autophagy appears to be a leading event in the response to T-2 toxin treatment, reflecting its protective role in cells against cellular damage. Activating autophagy by rapamycin (RAPA) inhibited apoptosis, while suppressing autophagy by chloroquine greatly enhanced the T-2 toxin-induced apoptosis, suggesting the crosstalk between autophagy and apoptosis. Taken together, these results indicate that autophagy plays a role in protecting cells from T-2 toxin-induced apoptosis suggesting that autophagy may be manipulated for the alleviation of toxic responses induced by T-2 toxin.
Biophysical Follow-up of Age-Group Swimmers During a Traditional Three-Peak Preparation Program.

Zacca, R, Azevedo, R, Ramos, VR, Abraldes, JA, Vilas-Boas, JP, Castro, FAdS, Pyne, DB, and Fernandes, RJ. Biophysical follow-up of age-group swimmers during a traditional three-peak preparation program. J Strength Cond Res XX(X): 000-000, 2019-The aim of this study was to quantify changes and contributions of bioenergetic, technique, and anthropometric profiles across a traditional 3-peak swimming season. Twenty-four age-group swimmers (11 boys: 15 years 6 months ± 1 year 1 month; 13 girls: 14 years 5 months ± 10 months) of equal maturational stage were monitored through a 400-m test in front crawl (T400). Bioenergetic, technique, and anthropometric characteristics were compared before and after macrocycles I, II and III. Sex interaction was verified only for amplitude of the fast oxygen uptake component and height (moderate). Multiple linear regressions and principal component analysis were used to identify the most influential variables and the relative contribution of each domain (bioenergetics, technique, and anthropometrics) to changes in swimming performance of T400. The relative contributions for the performance of T400 after macrocycles I, II, and III were, respectively, 6, 18, and 27% for bioenergetics, 88, 69, and 54% for technique, and 6, 13, and 20% for anthropometrics. Technique was the biggest contributor (71%) for changes in the performance of T400 over the training season, followed by bioenergetics (17%) and anthropometrics (12%). Technique played the main role during the competitive season, regardless of gradual increase in the contribution of bioenergetics and anthropometrics. Despite that, bioenergetics and technique are closely connected, thus a powerful and endurable metabolic base and cannot be overlooked. Changes and contribution of bioenergetics, technique, and anthropometrics on age-group swimmers' performance over a traditional 3-peak swimming season could be described by the T400 swimming test, providing a comprehensive biophysical overview of the main contributors to swimming performance.
Switchability of Gabapentin Formulations: A Randomized Trial to Assess Bioequivalence Between Neurontin and Gabasandoz on the Individual Subject Level

Generic substitution of antiepileptic drugs is generally not advised by neurologists. The present study investigated the switchability of gabapentin 800 mg tablets (Neurontin and Gabasandoz) using an individual bioequivalence (IBE) study design with two batches of each product and assessed whether between‐batch and between‐formulation variability in exposure play a significant role in the within‐subject variability. The trial was analyzed according to the US Food and Drug Administration (FDA) framework to establish IBE. The IBE was shown between both products with the 95% upper confidence bound of the IBE criterion being −2.01 and −2.31 for area under the concentration‐time curve from zero to infinity (AUC0–inf) and peak plasma concentration (Cmax), respectively. Subject‐by‐formulation variability (1.35%) was negligible compared with the within‐subject variability of AUC0–inf with Neurontin (19.0%) and Gabasandoz (23.6%). Inclusion of an additional batch did not significantly change this within‐subject variability (20.2% and 23.6%, respectively). This study shows that substitution of gabapentin 800 mg tablets of Neurontin and Gabasandoz should be possible without affecting clinical outcomes.
Triglycerides Paradox Among the Oldest Old: “The Lower the Better?”

Currently, most treatment guidelines suggest lowering hypertriglyceridemia of any severity, even in elderly individuals. However associations of serum triglycerides (TGs) with adverse health and mortality risk decrease with age, it remains unclear among the oldest old (aged 80 years and older). The study was to investigate the relationship of serum TG concentrations with cognitive function, activities of daily living (ADLs), frailty, and mortality among the oldest old in a prospective cohort study.
Smartphone applications validated for joint angle measurement: a systematic review

Mobile health apps are growing constantly in number and popularity. Some mobile apps are used for clinical assessment, and consequently need to be verified and validated appropriately, along with the mobile platform, to ensure their safe and effective operation. We review the current literature on available smartphone goniometric apps validated for joint angle measurement and their main psychometric characteristics. A literature search of Medline and Scopus databases was performed to select papers on smartphone commercial apps validated for joint angle measurement and relevant to Physical Medicine and Rehabilitation. A platform search verified whether the selected apps were still available for download. The literature search identified 126 papers in Medline and 113 in Scopus, 49 of which were selected. They dealt with the validation of 23 apps, eight of which were no longer available and therefore excluded from the review. Psychometric characteristics of the selected apps were robust, but heterogeneity of the studies did not enable comparisons between apps to identify the most valid one. The increase in the number of apps and validation studies highlights the growing interest in this new approach for measuring body angles. Given the precarious commercial availability of some apps, when research is the goal, it is advisable to select apps with the longest durability. A need continues to exist for validation studies on available apps focused on goniometric measurement in gait or during performance of therapeutic exercises in neurological and orthopedic disorders.
Cux2 refines the forelimb field by controlling expression of Raldh2 and Hox genes

ABSTRACT In vertebrates, two pairs of buds that give rise to the fore- and hindlimbs form at discrete positions along the rostral-caudal axis of the body. The mechanism responsible for the positioning of the limb buds is still largely unknown. Here we show a novel function for Cut homeobox transcription factor 2 (Cux2), the ortholog of Drosophila cut, in refining the forelimb field during chick development. Cux2 is expressed in the forelimb field before the emergence of the limb buds. Knocking down the expression of Cux2 using small interfering RNA (siRNA) resulted in a caudal shift of the forelimb bud, whereas misexpression of Cux2 or the constitutively active Cux2-VP16 caused a rostral shift of the forelimb bud or reduction of the forelimb field along the anterior-posterior axis. Further functional analyses revealed that expression of Hoxb genes and retinaldehyde dehydrogenase 2 (Raldh2), which are involved in limb positioning, are directly activated by Cux2 in the lateral plate mesoderm. Our data suggest that Cux2 in the lateral plate mesoderm refines the forelimb field via regulation of Raldh2 and Hoxb genes in chicken embryos. Summary: Cux2 in the lateral plate mesoderm refines the forelimb field via regulation of Raldh2 and Hoxb genes in chicken embryos.
Insight into genetic susceptibility to male breast cancer by multigene panel testing: Results from a multicenter study in Italy

Breast cancer (BC) in men is rare and genetic predisposition is likely to play a relevant role in its etiology. Inherited mutations in BRCA1/2 account for about 13% of all cases and additional genes that may contribute to the missing heritability need to be investigated. In our study, a well‐characterized series of 523 male BC (MBC) patients from the Italian multicenter study on MBC, enriched for non‐BRCA1/2 MBC cases, was screened by a multigene custom panel of 50 cancer‐associated genes. The main clinical‐pathologic characteristics of MBC in pathogenic variant carriers and non‐carriers were also compared. BRCA1/2 pathogenic variants were detected in twenty patients, thus, a total of 503 non‐BRCA1/2 MBC patients were examined in our study. Twenty‐seven of the non‐BRCA1/2 MBC patients were carriers of germline pathogenic variants in other genes, including two APC p.Ile1307Lys variant carriers and one MUTYH biallelic variant carrier. PALB2 was the most frequently altered gene (1.2%) and PALB2 pathogenic variants were significantly associated with high risk of MBC. Non‐BRCA1/2 pathogenic variant carriers were more likely to have personal (p = 0.0005) and family (p = 0.007) history of cancer. Results of our study support a central role of PALB2 in MBC susceptibility and show a low impact of CHEK2 on MBC predisposition in the Italian population. Overall, our data indicate that a multigene testing approach may benefit from appropriately selected patients with implications for clinical management and counseling of MBC patients and their family members.
A critical review on grape polyphenols for neuroprotection: Strategies to enhance bioefficacy

Abstract The aging of populations worldwide is driving greater demands for dietary polyphenols which have been recognized as promising prophylactic and/or therapeutic agents in the context of neurodegeneration, and are ubiquitously present in plant-based diets. In particular, grape-derived products encompass a wide array of phenolic compounds purported with multiple health benefits including neuroprotective efficacy. Despite the increasing preclinical and clinical evidence demonstrating high potential of grape polyphenol (GPP)-rich botanicals in preventing and attenuating diverse neurodegenerative disorders, the limited bioavailability of GPPs, especially in the brain, generates questions as to their applications and effectiveness in neuroprotection. To address this issue, significant research efforts have been made to enhance oral bioavailability of GPPs via application of novel strategies. This review highlights some critical issues related to the bioavailability and neuroprotective efficacy of GPPs and GPP-rich botanicals. The representative bioavailability-enhancing strategies are critically reviewed to provide practical solutions for augmenting the bioefficacy of GPP-rich botanicals. Synergistic applications of encapsulation techniques (for physiochemical protection and bypassing xenobiotic metabolism) and dietary intervention strategies involving modulation of gut microbiota (for generating more bioavailable phenolic metabolites) appear promising, and may substantially enhance the bioefficacy, especially the neuroprotective efficacy, of orally consumed GPPs.
Risk of Parkinson's disease dementia related to level I MDS PD‐MCI

The International Parkinson and Movement Disorders Society criteria for mild cognitive impairment in PD need validation. The objectives of this present study were to evaluate prognostic validity of level I (abbreviated) International Parkinson and Movement Disorders Society mild cognitive impairment in PD criteria for development of PD dementia and compared them with level II (comprehensive) criteria.
LA COMUNICACIÓN Y LA SEGURIDAD DEL PACIENTE EN EL CAMBIO DE TURNO EN LAS UNIDADES DE CUIDADOS INTENSIVOS NEONATALES

Estudio cuantitativo, descriptivo/exploratorio, para identificar factores asociados con la seguridad del paciente en la comunicacion del cambio de turno de grupos de enfermeria. Realizado entre abril/mayo de 2012, con 70 profesionales del equipo de enfermeria de tres unidades de cuidados intensivos neonatales, con formulario validado con informaciones del cambio de turno. Los datos se analizaron con pruebas chi-cuadrado y t de Student. Los resultados demostraron que los factores que pueden comprometer la seguridad del paciente durante el cambio de turno produjeron retrasos, salidas anticipadas, realizacion de cuidados y conversaciones paralelas. Los enfermeros tenian una mejor percepcion de estos factores en comparacion con los tecnicos. Profesionales con formacion inicial mencionaron mas informaciones: "la condicion clinica del paciente", "drogas", "cuidados generales/procedimientos. " Se puede concluir que hay indicios para la comunicacion segura, incluso con el conocimiento limitado de la seguridad del paciente y la comunicacion en el cambio de turno, por lo que es necesaria formacion y protocolos especificos.
Elective cesarean delivery at term and the long-term risk for endocrine and metabolic morbidity of the offspring

Abstract Other than obesity, no definitive insights have been gained regarding the apparent association between mode of delivery and long-term endocrine and metabolic outcomes in the offspring. We aimed to determine whether elective cesarean delivery (CD) impacts on long-term endocrine and metabolic morbidity of the offspring. A population-based cohort analysis was performed including all singleton-term deliveries occurring between 1991 and 2014 at a single tertiary medical center. A comparison was performed between children delivered via a non-emergent CD and those delivered vaginally (VD). Hospitalizations of the offspring up to the age of 18 years involving endocrine morbidity were evaluated. A Kaplan–Meier survival curve was used to compare cumulative morbidity incidence. Cox and a Weibull regression models were used to control for confounders. During the study period 131,880 term deliveries met the inclusion criteria; 8.9% were elective non-urgent CDs (n=11,768) and 91.1% (n=120,112) were VDs. The survival curve demonstrated a significantly higher cumulative incidence of endo-metabolic morbidity in offspring born via CD (P=0.010). In the regression models, adjusted for maternal obesity, CD was not noted as an independent risk factor for long-term pediatric endocrine and metabolic morbidity of the offspring while maternal obesity emerged as a strong predictor. We therefore conclude that CD per-se does not appear to increase the risk for long-term pediatric endo-metabolic morbidity of the offspring.
GFP-Forked, a genetic reporter for studying Drosophila oocyte polarity

ABSTRACT The polarized organization of the Drosophila oocyte can be visualized by examining the asymmetric localization of mRNAs, which is supported by networks of polarized microtubules (MTs). In this study, we used the gene forked, the putative Drosophila homologue of espin, to develop a unique genetic reporter for asymmetric oocyte organization. We generated a null allele of the forked gene using the CRISPR-Cas9 system and found that forked is not required for determining the axes of the Drosophila embryo. However, ectopic expression of a truncated form of GFP-Forked generated a distinct network of asymmetric Forked, which first accumulated at the oocyte posterior and was then restricted to the anterolateral region of the oocyte cortex in mid-oogenesis. This localization pattern resembled that reported for the polarized MTs network. Indeed, pharmacological and genetic manipulation of the polarized organization of the oocyte showed that the filamentous Forked network diffused throughout the entire cortical surface of the oocyte, as would be expected upon perturbation of oocyte polarization. Finally, we demonstrated that Forked associated with Short-stop and Patronin foci, which assemble non-centrosomal MT-organizing centers. Our results thus show that clear visualization of asymmetric GFP-Forked network localization can be used as a novel tool for studying oocyte polarity. Summary: The novel asymmetric Forked network could be used as a genetic reporter for visualizing and studying oocyte polarity.
PATTERNS OF SWITCHING IN INDONESIAN - ENGLISH BILINGUAL POP SONGS

Recently many studies are conducted to explore the use of code switching in everyday conversation, which is spontaneous. However, there has been little concern on how code switching is used in written data or prepared discourse. Thus, the recent phenomenon of using code switching in the lyrics of Indonesian – English bilingual pop songs, which are well-prepared, is illustrated in this paper. This paper focuses on the examination of the patterns of code switching between Indonesian and English in pop music genre, and whether these patterns are similar to the ones in everyday informal conversation, which is spontaneous. The data analysed in this paper were gained from a corpus consisting of the lyrics of 25 popular songs. Different patterns of switching are identified. It is suggested that the language mixture in the lyrics of Indonesian – English bilingual pop songs shows four different patterns of switching; they are conversational-style code switching, lexically motivated code switching, organizational code switching, and switching in English-dominant lyrics. Moreover, most of those patterns have similarity to those in everyday spontaneous conversation.
Effect of manganese preconditioning and replacing inorganic manganese with organic manganese on performance of male broiler chicks

ABSTRACT The effects of manganese (Mn) preconditioning, 96 h post‐hatch followed by the replacement of inorganic Mn with different levels of organic Mn (5 to 21 D), on growth, tissue excreta Mn content, gene expression, and enzyme activity were evaluated. A total of 420 day‐old male Cobb 500 broilers were divided into 2 groups. One group was fed a corn‐soybean meal basal diet containing 17 mg of Mn/kg (preconditioning diet, MnPD); the second group was fed the non‐preconditioning diet (NPCD), which was the MnPD supplemented with 60 mg of Mn/kg from manganese sulfate (MnSO4). On day 5, each group was divided into 5 subgroups and were randomly assigned to dietary treatments consisting of MnPD alone or MnPD supplemented with 12 or 60 mg Mn/kg Mn as MnSO4 or Mn proteinate (6 replicate cages of 6 birds). Broiler chicks that were fed the MnPD had lower (P ≤ 0.05) body weight gain (BWG) and G:F ratio when compared to those that were fed the NPCD for 4 D. Birds that were fed MnPD (1 to 4 D) and switched to MnPD supplemented with 60 mg/kg Mn (5 to 21 D) had lower (P ≤ 0.05) BWG compared to those that were fed NPCD (1 to 4 D) and switched to MnPD supplemented with 60 mg/kg Mn for 21 D. Excreta, tibia ash, liver, and heart Mn levels were increased (P ≤ 0.05) by supplemental Mn. The expression of jejunum divalent metal transporter‐1 mRNA levels, as well as activities of plasma total super oxide dismutase and liver alanine transaminase, was not affected by MnPD or Mn source and levels. These results confirmed that feeding marginally deficient Mn diets to broiler chicks post‐hatch does affect growth rate and tissue Mn concentration.
Doxorubicin Is Key for the Cardiotoxicity of FAC (5-Fluorouracil + Adriamycin + Cyclophosphamide) Combination in Differentiated H9c2 Cells

Currently, a common therapeutic approach in cancer treatment encompasses a drug combination to attain an overall better efficacy. Unfortunately, it leads to a higher incidence of severe side effects, namely cardiotoxicity. This work aimed to assess the cytotoxicity of doxorubicin (DOX, also known as Adriamycin), 5-fluorouracil (5-FU), cyclophosphamide (CYA), and their combination (5-Fluorouracil + Adriamycin + Cyclophosphamide, FAC) in H9c2 cardiac cells, for a better understanding of the contribution of each drug to FAC-induced cardiotoxicity. Differentiated H9c2 cells were exposed to pharmacological relevant concentrations of DOX (0.13–5 μM), 5-FU (0.13–5 μM), CYA (0.13–5 μM) for 24 or 48 h. Cells were also exposed to FAC mixtures (0.2, 1 or 5 μM of each drug and 50 μM 5-FU + 1 μM DOX + 50 μM CYA). DOX was the most cytotoxic drug, followed by 5-FU and lastly CYA in both cytotoxicity assays (reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and neutral red (NR) uptake). Concerning the equimolar combination with 1 or 5 μM, FAC caused similar cytotoxicity to DOX alone. Even in the presence of higher concentrations of 5-FU and CYA (50 μM 5-FU + 1 μM DOX + 50 μM CYA), 1 μM DOX was still a determinant for the cardiotoxicity observed in the cytotoxicity assays, phase contrast morphological evaluation, and mitochondrial potential depolarization evaluation. To the best of our knowledge, this was the first in vitro work with this combination regimen, DOX being the most toxic drug and key to the toxicity of FAC.
Emergence of Topological Hall Effect in a SrRuO3 Single Layer

Topological Hall effect (THE), appearing as bumps and/or dips in the Hall resistance curves, is considered as a hallmark of the skyrmion spin texture originated from the inversion symmetry breaking and spin–orbit interaction. Recently, Néel‐type skyrmion is proposed based on the observed THE in 5d transition metal oxides heterostructures such as SrRuO3/SrIrO3 bilayers, where the interfacial Dzyaloshinskii–Moriya interaction (DMI), due to the strong spin–orbit coupling (SOC) in SrIrO3 and the broken inversion symmetry at the interface, is believed to play a significant role. Here the emergence of THE in SrRuO3 single layers with thickness ranging from 3 to 6 nm is experimentally demonstrated. It is found that the oxygen octahedron rotation in SrRuO3 also has a significant effect on the observed THE. Furthermore, the THE may be continuously tuned by an applied electrical field. It is proposed that the large SOC of Ru ions together with the broken inversion symmetry, mainly from the interface, produce the DMI that is responsible for the observed THE. The emergence of the gate‐tunable DMI in SrRuO3 single layer may stimulate further investigations of new spin–orbit physics in strong SOC oxides.