Miracle-dz/UniFAR-FTUs huggingface dataset:
The Effect of Stimulus Choice on an EEG-Based Objective Measure of Speech Intelligibility.

OBJECTIVES Recently, an objective measure of speech intelligibility (SI), based on brain responses derived from the electroencephalogram (EEG), has been developed using isolated Matrix sentences as a stimulus. We investigated whether this objective measure of SI can also be used with natural speech as a stimulus, as this would be beneficial for clinical applications. DESIGN We recorded the EEG in 19 normal-hearing participants while they listened to two types of stimuli: Matrix sentences and a natural story. Each stimulus was presented at different levels of SI by adding speech weighted noise. SI was assessed in two ways for both stimuli: (1) behaviorally and (2) objectively by reconstructing the speech envelope from the EEG using a linear decoder and correlating it with the acoustic envelope. We also calculated temporal response functions (TRFs) to investigate the temporal characteristics of the brain responses in the EEG channels covering different brain areas. RESULTS For both stimulus types, the correlation between the speech envelope and the reconstructed envelope increased with increasing SI. In addition, correlations were higher for the natural story than for the Matrix sentences. Similar to the linear decoder analysis, TRF amplitudes increased with increasing SI for both stimuli. Remarkable is that although SI remained unchanged under the no-noise and +2.5 dB SNR conditions, neural speech processing was affected by the addition of this small amount of noise: TRF amplitudes across the entire scalp decreased between 0 and 150 ms, while amplitudes between 150 and 200 ms increased in the presence of noise. TRF latency changes in function of SI appeared to be stimulus specific: the latency of the prominent negative peak in the early responses (50 to 300 ms) increased with increasing SI for the Matrix sentences, but remained unchanged for the natural story. CONCLUSIONS These results show (1) the feasibility of natural speech as a stimulus for the objective measure of SI; (2) that neural tracking of speech is enhanced using a natural story compared to Matrix sentences; and (3) that noise and the stimulus type can change the temporal characteristics of the brain responses. These results might reflect the integration of incoming acoustic features and top-down information, suggesting that the choice of the stimulus has to be considered based on the intended purpose of the measurement.
Likeness, Familiarity, and the Ambient Portrait Average

This artist-led research project involved 10 visual artists producing 10 ambient portraits and a portrait average of a locally familiar Sitter, and 10 ambient portraits and a portrait average of a less locally familiar Sitter. All were then assessed for likeness by more than 150 members of the general public attending an exhibition during Australia’s 2018 National Science Week. The results of this study are that portrait averages can be highly shape accurate and tend to be seen as a good likeness by all viewers. However, the portrait average is not necessarily the best likeness. Extending and validating our previous findings regarding the relationship of likeness, familiarity, and shape accuracy (as measured using geometric morphometrics) in portraiture, unfamiliar viewers favouring shape accurate depictions of a Sitter attained statistical significance. Familiar viewers, however, although also tending to view shape accurate depictions a good to very good likeness, were shown to have a stronger preference for portraits that exaggerate a Sitter’s facial distinctiveness, including an exaggeration of their head pose, providing such exaggerations are in approximate proportional agreement.
Scrophularia Tenuipes Coss and Durieu: Phytochemical Composition and Biological Activities

Scrophularia tenuipes is an Algerian-Tunisian endemic species, which has not been studied yet. Ethyl acetate (EA) and n-butanol (Bu) fractions obtained from Scrophularia tenuipes were investigated for their health benefit properties, in particular with respect to in vivo/in vitro anti-inflammatory and antioxidant activities, as well as their potential to inhibit key enzymes with impact in diabetes (α-glucosidase and α-amylase). The fractions had a distinct phytochemical composition, of which EA was richer in total phenolic compounds (225 mg GAE/g) and mostly composed of the phenylethanoid acetyl martynoside. Compared to EA, Bu had higher amounts of total flavonoids, and according to the result obtained from UHPLC-DAD-ESI-MSn analysis, harpagoside (iridoid) was its major phytochemical. EA fraction was quite promising with regard to the in vivo (at 200 mg/kg, po) anti-inflammatory effect (62% and 52% for carrageenan-induced rat paw edema and xylene-induced ear edema tests, respectively), while Bu fraction exhibited a stronger antioxidant capacity in all tests (IC50 = 68 µg/mL, IC50 = 18 µg/mL, IC50 = 18 µg/mL and A0.50 = 43 µg/mL for DPPH●, ABTS•+, O2•− scavenging assays and cupric-reducing antioxidant capacity method, respectively). Both fractions also showed a strong effect against α-amylase enzyme (IC50 = 8 µg/mL and 10 µg/mL for EA and Bu fraction, respectively).
Effect of ethylene oxide sterilization on polyvinyl alcohol hydrogel compared to gamma radiation.

This study investigated the effects of terminal sterilization of polyvinyl alcohol (PVA) biomaterials using clinically translatable techniques, specifically ethylene oxide and gamma (γ) irradiation. While a few studies have reported the possibility of sterilizing PVA with γ-radiation, the use of ethylene oxide (EtO) sterilization of PVA requires additional study. PVA solutions were chemically crosslinked with trisodium trimetaphosphate and sodium hydroxide. The three experimental groups included untreated control, EtO, and γ-irradiation, which were tested for the degree of swelling and water content, and mechanical properties such as radial compliance, longitudinal tensile, minimum bend radius, burst pressure, and suture retention strength. Additionally, samples were characterized with scanning electron microscopy, differential scanning calorimeter, X-ray photoelectron spectroscopy, and water contact angle measurements. Cell attachment was assessed using the endothelial cell line EA.hy926 and the sterilized PVA cytotoxicity was studied with a live/dead stain. Platelet and fibrin accumulation were measured using an ex vivo shunt baboon model. Lastly, the immune responses of PVA implants were analyzed after a 21-day subcutaneous implantation in rats and a 30-day implantation in baboon. EtO sterilization reduced the PVA graft wall thickness, its degree of swelling and water content compared to both γ-irradiated and untreated PVA. Moreover, EtO sterilization significantly reduced the radial compliance and increased Young's modulus. EtO did not change PVA hydrophilicity, while γ-irradiation increased the water contact angle of the PVA. Consequently, endothelial cell attachment on the EtO sterilized PVA showed similar results to the untreated PVA, while cell attachment significantly improved on the γ-irradiated PVA. When exposing the PVA grafts to circulating whole blood, fibrin accumulation of EtO sterilized PVA was found to be significantly lower than γ-irradiated PVA. The immune response of γ-irradiated PVA, EtO treated PVA, and untreated PVA were compared. Implanted EtO treated PVA showed the least MAC387 reaction. The terminal sterilization methods in this study changed PVA hydrogel properties; nevertheless, based on the characterizations performed, both sterilization methods were suitable for sterilizing PVA. We concluded that EtO can be used as an alternative method to sterilize PVA hydrogel material.
A Collection of Pre-mRNA Splicing Mutants in Arabidopsis thaliana

To investigate factors influencing pre-mRNA splicing in plants, we conducted a forward genetic screen using an alternatively-spliced GFP reporter gene in Arabidopsis thaliana. This effort generated a collection of sixteen mutants impaired in various splicing-related proteins, many of which had not been recovered in any prior genetic screen or implicated in splicing in plants. The factors are predicted to act at different steps of the spliceosomal cycle, snRNP biogenesis pathway, transcription, and mRNA transport. We have described eleven of the mutants in recent publications. Here we present the final five mutants, which are defective, respectively, in RNA-BINDING PROTEIN 45D (rbp45d), DIGEORGE SYNDROME CRITICAL REGION 14 (dgcr14), CYCLIN-DEPENDENT KINASE G2 (cdkg2), INTERACTS WITH SPT6 (iws1) and CAP BINDING PROTEIN 80 (cbp80). We provide RNA-sequencing data and analyses of differential gene expression and alternative splicing patterns for the cbp80 mutant and for several previously published mutants, including smfa and new alleles of cwc16a, for which such information was not yet available. Sequencing of small RNAs from the cbp80 mutant highlighted the necessity of wild-type CBP80 for processing of microRNA (miRNA) precursors into mature miRNAs. Redundancy tests of paralogs encoding several of the splicing factors revealed their functional non-equivalence in the GFP reporter gene system. We discuss the cumulative findings and their implications for the regulation of pre-mRNA splicing efficiency and alternative splicing in plants. The mutant collection provides a unique resource for further studies on a coherent set of splicing factors and their roles in gene expression, alternative splicing and plant development.
PLK1 is required for chromosome compaction and microtubule organization in mouse oocytes

Errors during meiotic resumption in oocytes can result in chromosome missegregation and infertility. Several cell cycle kinases have been linked with roles in coordinating events during meiotic resumption, including polo-like kinases (PLKs). Mammals express four kinase-proficient PLKs (PLK1–4). Previous studies assessing the role of PLK1 have relied on RNA knockdown and kinase inhibition approaches, as Plk1 null mutations are embryonically lethal. To further assess the roles of PLK1 during meiotic resumption, we developed a Plk1 conditional knockout (cKO) mouse to specifically mutate Plk1 in oocytes. Despite normal oocyte numbers and follicle maturation, Plk1 cKO mice were infertile. From analysis of meiotic resumption, Plk1 cKO oocytes underwent nuclear envelope breakdown with the same timing as control oocytes. However, Plk1 cKO oocytes failed to form compact bivalent chromosomes, and localization of cohesin and condensin were defective. Furthermore, Plk1 cKO oocytes either failed to organize α-tubulin or developed an abnormally small bipolar spindle. These abnormalities were attributed to aberrant release of the microtubule organizing center (MTOC) linker protein, C-NAP1, and the failure to recruit MTOC components and liquid-like spindle domain (LISD) factors. Ultimately, these defects result in meiosis I arrest before homologous chromosome segregation.
Key Potentially Inappropriate Drugs in Pediatrics: The KIDs List.

OBJECTIVES The safe use of medications in pediatric patients requires practitioners to consider the unique pharmacokinetics and pharmacodynamics of drugs prescribed in this age group. In an effort to create a standard of care for the safe use of medications in this population, a list of drugs that are potentially inappropriate for use in pediatric patients has been developed and titled the "KIDs List. " METHODS A panel of 7 pediatric pharmacists from the Pediatric Pharmacy Association were recruited to evaluate primary, secondary, and tertiary literature; FDA Pediatric Safety Communications; the Lexicomp electronic database; and product information for drugs that should be considered potentially inappropriate for use in pediatric patients. Information was rated using predefined criteria. A PubMed search was conducted using the following terms: adverse drug events OR adverse drug reactions. The search was limited to humans; age <18 years; case reports, observational studies, or clinical trials; and English language. No date range was used. Results were used to create an evidence-based list of candidate drugs that was then peer-reviewed and subjected to a 30-day public comment period prior to being finalized. RESULTS A PubMed search yielded 4049 unique titles, of which 210 were deemed relevant for full review. Practitioner recommendations highlighted an additional 77 drugs. FDA Pediatric Safety Communications and the Lexicomp database yielded 22 and 619 drugs, respectively. After critical analysis, peer review, and public review the final KIDs List contains 67 drugs and/or drug classes and 10 excipients. CONCLUSIONS This extensive effort led to compilation of the first list of drugs that are potentially inappropriate for prescribing in all or in a select subgroup of pediatric patients. If avoidance is not clinically possible, the drug should be used with caution and accompanied by appropriate monitoring.
Randomized Trial of Intraarterial Infusion of Urokinase Within 6 Hours of Middle Cerebral Artery Stroke

Background and Purpose— The Middle Cerebral Artery Embolism Local Fibrinolytic Intervention Trial (MELT) Japan was organized to determine the safety and clinical efficacy of intraarterial infusion of urokinase (UK) in patients with stroke within 6 hours of onset. Methods— Patients with ischemic stroke presenting within 6 hours of onset and displaying occlusions of the M1 or M2 portion of the middle cerebral artery on carotid angiography were randomized to the UK or control groups. Clinical outcome was assessed by the modified Rankin Scale, National Institutes of Health Stroke Scale, and Barthel Index. Results— The Independent Monitoring Committee recommended stopping the trial after approval of intravenous infusion of recombinant tissue plasminogen activator in Japan. A total of 114 patients underwent randomization, 57 patients in each group. Background characteristics were comparable between the 2 groups. The primary end point of favorable outcome (modified Rankin Scale 0 to 2) at 90 days was somewhat mo.
Knockdown of N-Acetylglucosaminyltransferase-II Reduces Matrix Metalloproteinase 2 Activity and Suppresses Tumorigenicity in Neuroblastoma Cell Line

Neuroblastoma (NB) development and progression are accompanied by changes in N-glycans attached to proteins. Here, we investigated the role of N-acetylglucosaminyltransferase-II (GnTII, MGAT2) protein substrates in neuroblastoma (NB) cells. MGAT2 was silenced in human BE(2)-C NB (HuNB) cells to generate a novel cell line, HuNB(-MGAT2), lacking complex type N-glycans, as in rat B35 NB cells. Changes in N-glycan types were confirmed by lectin binding assays in both cell lines, and the rescued cell line, HuNB(-/+MGAT2). Western blotting of cells heterologously expressing a voltage-gated K+ channel (Kv3.1b) showed that some hybrid N-glycans of Kv3.1b could be processed to complex type in HuNB(-/+MGAT2) cells. In comparing HuNB and HuNB(-MGAT2) cells, decreased complex N-glycans reduced anchorage-independent cell growth, cell proliferation, and cell invasiveness, while they enhanced cell-cell interactions. Cell proliferation, invasiveness and adhesion of the HuNB(-/+MGAT2) cells were more like the HuNB than HuNB(-MGAT2). Western blotting revealed lower protein levels of MMP-2, EGFR and Gab2 in glycosylation mutant cells relative to parental cells. Gelatin zymography demonstrated that decreased MMP-2 protein activity was related to lowered MMP-2 protein levels. Thus, our results support that decreased complex type N-glycans suppress cell proliferation and cell invasiveness in both NB cell lines via remodeling ECM.
Pharmacokinetics-Pharmacodynamics of Enmetazobactam Combined with Cefepime in a Neutropenic Murine Thigh Infection Model

Third-generation cephalosporin (3GC)-resistant Enterobacteriaceae are classified as critical priority pathogens, with extended-spectrum β-lactamases (ESBLs) as principal resistance determinants. Enmetazobactam (formerly AAI101) is a novel ESBL inhibitor developed in combination with cefepime for empirical treatment of serious Gram-negative infections in settings where ESBLs are prevalent. Cefepime-enmetazobactam has been investigated in a phase 3 trial in patients with complicated urinary tract infections or acute pyelonephritis. ABSTRACT Third-generation cephalosporin (3GC)-resistant Enterobacteriaceae are classified as critical priority pathogens, with extended-spectrum β-lactamases (ESBLs) as principal resistance determinants. Enmetazobactam (formerly AAI101) is a novel ESBL inhibitor developed in combination with cefepime for empirical treatment of serious Gram-negative infections in settings where ESBLs are prevalent. Cefepime-enmetazobactam has been investigated in a phase 3 trial in patients with complicated urinary tract infections or acute pyelonephritis. This study examined pharmacokinetic-pharmacodynamic (PK-PD) relationships of enmetazobactam, in combination with cefepime, for ESBL-producing isolates of Klebsiella pneumoniae in 26-h murine neutropenic thigh infection models. Enmetazobactam dose fractionation identified the time above a free threshold concentration (fT > CT) as the PK-PD index predictive of efficacy. Nine ESBL-producing isolates of K. pneumoniae, resistant to cefepime and piperacillin-tazobactam, were included in enmetazobactam dose-ranging studies. The isolates encoded CTX-M-type, SHV-12, DHA-1, and OXA-48 β-lactamases and covered a cefepime-enmetazobactam MIC range from 0.06 to 2 μg/ml. Enmetazobactam restored the efficacy of cefepime against all isolates tested. Sigmoid curve fitting across the combined set of isolates identified enmetazobactam PK-PD targets for stasis and for a 1-log10 bioburden reduction of 8% and 44% fT > 2 μg/ml, respectively, with a concomitant cefepime PK-PD target of 40 to 60% fT > cefepime-enmetazobactam MIC. These findings support clinical dose selection and breakpoint setting for cefepime-enmetazobactam.
Hyaluronic acid as a bioink for extrusion-based 3D printing

Biofabrication is enriching the tissue engineering field with new ways of producing structurally organized complex tissues. Among the numerous bioinks under investigation, hyaluronic acid (HA) and its derivatives stand out for their biological relevance, cytocompatibility, shear-thinning properties, and potential to fine-tune the desired properties with chemical modification. In this paper, we review the recent advances on bioinks containing HA. The available literature is presented based on subjects including the rheological properties in connection with printability, the chemical strategies for endowing HA with the desired properties, the clinical application, the most advanced preclinical studies, the advantages and limitations in comparison with similar biopolymer-based bioinks, and future perspectives.
Evaluation of ischemia-modified albumin levels and parametersof arterial stiffness in patients with hypothyroidism -

Aim: The cardiovascular system is susceptible to thyroid hormones. Many studies show that hypothyroidism is associated with increased cardiovascular risk, functional abnormalities, atherosclerosis, and increased arterial stiffness. Pulse wave velocity (PWV) and augmentation index (AI) are regarded as indexes of arterial stiffness. Oxidative free radicals that occur during ischemic events cause certain chemical changes in the albumin molecules. The ischemia-modified albumin (IMA) has been suggested as an indicator of oxidative stress. Evaluation of oxidative stress markers and parameters of arterial stiffness can shed light on the mechanism of increased cardiovascular risk in patients with hypothyroidism. Material and Methods: For this study, PWV, AI measurements, and IMA levels of 20 untreated patients with overt hypothyroidism (OH), 21 untreated patients with subclinical hypothyroidism (SH), and 30 healthy controls (control-CNT) were evaluated. Patients and the healthy controls’ gender, age, weight, height, body mass index, waist circumference, smoking habit and blood biochemical results were recorded. Results: PWV was found to be increased in patients with overt hypothyroidism; however, there was no difference in between subclinical hypothyroidism and control group(p=0,881). Also, PWV had a significant positive correlation with; age, BMI, waist circumference, blood glucose, uric acid, pulse pressure and systolic and diastolic blood pressures. IMA levels were not different in between the groups. Conclusion: Hence the increased CV risk in patients withhypothyroidism is a multifactorial state; the interplay of many factors determines it.Future studies with larger sample sizes are needed to evaluate the possible relationship among IMA levels, arterial stiffness parameters and cardiovascular risk factors in patients with hypothyroidism.
Phylotranscriptomics of the Pentapetalae Reveals Frequent Regulatory Variation in Plant Local Responses to the Fungal Pathogen Sclerotinia sclerotiorum[OPEN]

Comparative transcriptome analyses reveal a major contribution of regulatory divergence in conserved genes during the response of Pentapetalae plants to the fungal pathogen Sclerotinia sclerotiorum. Quantitative disease resistance (QDR) is a conserved form of plant immunity that limits infections caused by a broad range of pathogens. QDR has a complex genetic determinism. The extent to which molecular components of the QDR response vary across plant species remains elusive. The fungal pathogen Sclerotinia sclerotiorum, causal agent of white mold diseases on hundreds of plant species, triggers QDR in host populations. To document the diversity of local responses to S. sclerotiorum at the molecular level, we analyzed the complete transcriptomes of six species spanning the Pentapetalae (Phaseolus vulgaris, Ricinus communis, Arabidopsis [Arabidopsis thaliana], Helianthus annuus, Solanum lycopersicum, and Beta vulgaris) inoculated with the same strain of S. sclerotiorum. About one-third of plant transcriptomes responded locally to S. sclerotiorum, including a high proportion of broadly conserved genes showing frequent regulatory divergence at the interspecific level. Evolutionary inferences suggested a trend toward the acquisition of gene induction relatively recently in several lineages. Focusing on a group of ABCG transporters, we propose that exaptation by regulatory divergence contributed to the evolution of QDR. This evolutionary scenario has implications for understanding the QDR spectrum and durability. Our work provides resources for functional studies of gene regulation and QDR molecular mechanisms across the Pentapetalae.