Miracle-dz/UniFAR-FTUs huggingface dataset:
Developmental Shifts in Detection and Attention for Auditory, Visual, and Audiovisual Speech.

Purpose Successful speech processing depends on our ability to detect and integrate multisensory cues, yet there is minimal research on multisensory speech detection and integration by children. To address this need, we studied the development of speech detection for auditory (A), visual (V), and audiovisual (AV) input. Method Participants were 115 typically developing children clustered into age groups between 4 and 14 years. Speech detection (quantified by response times [RTs]) was determined for 1 stimulus, /buh/, presented in A, V, and AV modes (articulating vs. static facial conditions). Performance was analyzed not only in terms of traditional mean RTs but also in terms of the faster versus slower RTs (defined by the 1st vs. 3rd quartiles of RT distributions). These time regions were conceptualized respectively as reflecting optimal detection with efficient focused attention versus less optimal detection with inefficient focused attention due to attentional lapses. Results Mean RTs indicated better detection (a) of multisensory AV speech than A speech only in 4- to 5-year-olds and (b) of A and AV inputs than V input in all age groups. The faster RTs revealed that AV input did not improve detection in any group. The slower RTs indicated that (a) the processing of silent V input was significantly faster for the articulating than static face and (b) AV speech or facial input significantly minimized attentional lapses in all groups except 6- to 7-year-olds (a peaked U-shaped curve). Apparently, the AV benefit observed for mean performance in 4- to 5-year-olds arose from effects of attention. Conclusions The faster RTs indicated that AV input did not enhance detection in any group, but the slower RTs indicated that AV speech and dynamic V speech (mouthing) significantly minimized attentional lapses and thus did influence performance. Overall, A and AV inputs were detected consistently faster than V input; this result endorsed stimulus-bound auditory processing by these children.
Glutamine Deprivation Enhances Acetyl-CoA Carboxylase Inhibitor-induced Death of Human Pancreatic Cancer Cells

Background/Aim: Acetyl-CoA carboxylase (ACC) is a rate-limiting enzyme in fatty acid synthesis. In this study, we investigated the effect of ACC inhibition on survival of pancreatic cancer cells. Material and Methods: AsPC-1, BxPC-3 and PANC-1 were used as human pancreatic cancer cell lines. 5-(etradecyloxy)-2-furoic acid (TOFA) and bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl) ethyl sulfide (BPTES) were used as inhibitors of ACC and glutaminase (GLS) respectively. Apoptotic and live cells were distinguished by annexin-V staining. The activity of caspase-3 was evaluated by measuring the fluorescence intensity of the degradation product of the substrate, N-acetyl-Asp-Glu-Val-Asp-7-amido-4-trifluoromethylcoumarin. Results: TOFA increased the number of annexin V-positive cells and enhanced caspase-3 activity in AsPC-1 and BxPC-3, but not in PANC-1 cells. The number of PANC-1 cells increased after 48 h in Earle's balanced salt solution. Interestingly, proliferation of PANC-1 cells was drastically suppressed by glutamine deprivation, but not by inhibition of glycolysis. BPTES also induced cell death to the same extent as glutamine deprivation. In addition, TOFA induced cell death of PANC-1 cells, both in the presence of BPTES and with glutamine deprivation, suggesting that inhibition of glutaminolysis causes cell death and enhances the effect of TOFA in PANC-1 cells. Conclusion: These findings suggest that glutaminolysis is important for the survival of pancreatic cancer cells showing tolerance to nutrient starvation such as PANC-1 cells, and use of a combination of inhibitors of ACC and GLS may be a new strategy for treatment of pancreatic cancer.
RGD‐functionalized polyurethane scaffolds promote umbilical cord blood mesenchymal stem cell expansion and osteogenic differentiation

Biomimetic materials are essential for the production of clinically relevant bone grafts for bone tissue engineering applications. Their ability to modulate stem cell proliferation and differentiation can be used to harness the regenerative potential of those cells and optimize the efficiency of engineered bone grafts. The arginyl‐glycyl‐aspartic acid (RGD) peptide has been recognized as the adhesion motif of various extracellular matrix proteins and can affect stem cell behaviour in biomaterials. Attempts to functionalize biomaterials with RGD have been limited to a maximum of 1‐ to 3‐mm thickness scaffolds, overlooking the issue of core infiltration that represents a major hurdle in developing real thickness scaffolds. Herein, we present the cross‐linking of RGD on the surface of “real thickness” (5 × 5 × 5 mm) porous polyurethane scaffolds (PU‐RGD), to be used for the expansion and osteogenic differentiation of umbilical cord blood mesenchymal stem cells (UCB MSCs). RGD‐functionalized scaffolds increased initial cell adhesion (1.5‐fold to twofold) and achieved a 3.4‐fold increase in cell numbers at the end of culture compared with a 1.5‐fold increase in non‐functionalized controls. Homogenous cell infiltration to the scaffold core was observed in the PU‐RGD scaffolds. Importantly, PU‐RGD scaffolds were able to enhance the osteogenic differentiation of UCB MSCs. Osteogenic gene and protein expression increased in scaffolds functionalized with 100 μg/ml RGD. Higher RGD concentrations (200 μg/ml) were less efficient in stimulating osteogenic differentiation. We conclude that robust RGD tethering to 3D PU “real thickness” scaffolds is possible and that it promotes core infiltration, expansion, and osteogenic differentiation of UCB MSCs for the purposes of bone regeneration.
The pKa values of the catalytic residues in the retaining glycoside hydrolase T26H mutant of T4 lysozyme

T4 phage lysozyme (T4L) is an enzyme that cleaves bacterial cell wall peptidoglycan. Remarkably, the single substitution of the active site Thr26 to a His (T26H) converts T4L from an inverting to a retaining glycoside hydrolase with transglycosylase activity. It has been proposed that T26H–T4L follows a double displacement mechanism with His26 serving as a nucleophile to form a covalent glycosyl‐enzyme intermediate (Kuroki et al., PNAS 1999; 96:8949–8954). To gain further insights into this or alternative mechanisms, we used NMR spectroscopy to measure the acid dissociation constants (pKa values) and/or define the ionization states of the Asp, Glu, His, and Arg residues in the T4L mutant. Most notably, the pKa value of the putative nucleophile His26 is 6.8 ± 0.1, whereas that of the general acid Glu11 is 4.7 ± 0.1. If the proposed mechanism holds true, then T26H–T4L follows a reverse protonation pathway in which only a minor population of the free enzyme is in its catalytically competent ionization state with His26 deprotonated and Glu11 protonated. Our studies also confirm that all arginines in T26H–T4L, including the active site Arg145, are positively charged under neutral pH conditions.
Evidence for regional aeolian transport of freshwater micrometazoans in arid regions

While separated by large expanses of dry terrain unsuitable for aquatic biota, aridland waters possess high biodiversity. How aquatic micrometazoans disperse to, and colonize, these isolated ephemeral habitats are not well understood. We used a multi‐faceted approach including wind tunnel and rehydration experiments, and next‐generation sequencing to assess potential movement of diapausing propagules of aquatic invertebrates by anemochory across regional scales (102–105 km). Wind tunnel experiments using dry playa sediments with added micrometazoan propagules demonstrated that after entrainment by saltation and downwind transport, propagules could be subsequently rehydrated and were viable. Further, rehydration of fallen natural dust yielded micrometazoans, including rotifers, gastrotrichs, microcrustaceans, and nematodes. Using conserved DNA primers, we identified > 3300 eukaryotic Operational Taxonomic Units (excluding fungi) in the dust including some taxa found in rehydration experiments. Thus, we provide strong evidence that anemochory can disperse micrometazoans among isolated, ephemeral ecosystems in North American deserts and likely elsewhere.
Medication adherence among patients with Type 2 diabetes: A mixed methods study

Objective Oral hypoglycemic agents (OHAs) are highly effective in managing Type 2 diabetes if taken appropriately. This study assessed adherence to OHAs among patients with Type 2 diabetes and explored factors associated with adherence behaviour. Research design and methods Mixed methods were used comprising a cross-sectional study using the Arabic version of the Morisky Medication Adherence Scale followed by semi-structured interviews using the Theoretical Domain Framework to explore key determinants of adherence. Results The cross-sectional study included 395 patients of whom 40% achieved a high level of OHA adherence. Lower adherence was associated with younger age (Odds Ratio (OR) 1.084; 95% CI 1.056 to 1.112), higher numbers of non-OHAs (OR 0.848; 95% CI 0.728 to 0.986) and higher HbA1c levels (OR 0.808; 95% CI 0.691 to 0.943). Semi structured interviews based on the Theoretical Domain Framework were completed with 20 patients and identified a wide range of factors potentially associated with OHA adherence, particularly behavioural related factors (e.g. scheduling medication intake, ability to develop a habitual behaviour), social influences (e.g. acting as a role model, the effect of family support), and gaps in knowledge about diabetes and its management with OHAs. Conclusions This unique mixed-methods study has highlighted possible reasons for the low levels of OHA adherence in this patient population. Whilst the theoretically-derived determinants of behaviour illustrate the complexities associated with OHA adherence, they also provide a robust underpinning for future intervention(s) development to improve adherence and maximise patient health outcomes.
A 10-point plan for avoiding hyaluronic acid dermal filler-related complications during facial aesthetic procedures and algorithms for management

The recent rapid growth in dermal filler use, in conjunction with inadequate product and injector control, has heralded a concerning increase in filler complications. The 10-point plan has been developed to minimize complications through careful preconsideration of causative factors, categorized as patient, product, and procedure related. Patient-related factors include history, which involves a preprocedural consultation with careful elucidation of skin conditions, systemic disease, medications, and previous cosmetic procedures. Other exclusion criteria include autoimmune diseases and multiple allergies. The temporal proximity of dental or routine medical procedures is discouraged. Insightful patient assessment, with the consideration of ethnicity, gender, and generational needs, is of paramount importance. Specified informed consent is vital due to the concerning increase in vascular complications, which carry the risk for skin compromise and loss of vision. Informed consent should be signed for both adverse events and their treatment. Product-related factors include reversibility, which is a powerful advantage when using hyaluronic acid (HA) products. Complications from nonreversible or minimally degradable products, especially when layered over vital structures, are more difficult to control. Product characteristics such as HA concentration and proprietary cross-linking should be understood in the context of ideal depth, placement, and expected duration. Product layering over late or minimally degradable fillers is discouraged, while layering of HA of over the same brand, or even across brands, seems to be feasible. Procedural factors such as photographic documentation, procedural planning, aseptic technique, and anatomical and technical knowledge are of pivotal importance. A final section is dedicated to algorithms and protocols for the management and treatment of complications such as hypersensitivity, vascular events, infection, and late-onset nodules. The 10-point plan is a systematic, effective strategy aimed at reducing the risk of dermal filler complications.
The importance of pancreatic inflammation in endosonographic diagnostics of solid pancreatic masses.

AIMS Endosonography (EUS) is one of the main diagnostic tools for the differential diagnosis of pancreatic masses. The aim of our study was to describe the value of this technique in the work-up of solid pancreatic lesions, considering the influence of the morphological evidence of pancreatic inflammation in the diagnostic process. MATERIAL AND METHODS Retrospective analysis of prospectively collected data in our tertiary University center. From March 2007 to October 2015, 218 patients underwent EUS for a suspected solid pancreatic neoplasm (based on previous cross-sectional imaging results, idiopatic acute pancreatitis, weight loss, pancreatic hyperenzymemia, painless jaundice or elevated Ca 19-9 values). RESULTS Malignant lesions were diagnosed in 98 (45%) patients. Sensitivity of EUS for malignancy was 91% and specificity 89.2%. Signs of pancreatic inflammation in the surrounding pancreatic parenchyma around the focal lesion were present in 97 patients (44.4%)(more often in men, smokers and drinkers, and the most common etiology was focal chronic pancreatitis) and in these patients the sensitivity and sensibility dropped to 44% and 87.1%, respectively. In patients without signs of pancreatic inflammation, the pancreatic focal lesions were adenocarcinoma, neuroendocrine tumor, ventral/dorsal split, non-pancreatic pathology, pancreatic lipomatosis and autoimmune pancreatitis. CONCLUSION Pancreatic inflammation (either focal or involving the whole gland) lowers the diagnostic sensibility of EUS in the work- up of pancreatic masses suspected for cancer, requiring further invasive diagnostic methods. Focal autoimmune pancreatitis and paraduodenal pancreatitis are still confused with pancreatic cancer, even in the absence of pancreatic inflammation.
Senotherapeutics: emerging strategy for healthy aging and age-related disease

Cellular senescence (CS) is one of hallmarks of aging and accumulation of senescent cells (SCs) with age contributes to tissue or organismal aging, as well as the pathophysiologies of diverse age-related diseases (ARDs). Genetic ablation of SCs in tissues lengthened health span and reduced the risk of age-related pathologies in a mouse model, suggesting a direct link between SCs, longevity, and ARDs. Therefore, senotherapeutics, medicines targeting SCs, might be an emerging strategy for the extension of health span, and prevention or treatment of ARDs. Senotherapeutics are classified as senolytics which kills SCs selectively; senomorphics which modulate functions and morphology of SCs to those of young cells, or delays the progression of young cells to SCs in tissues; and immune-system mediators of the clearance of SCs. Some senolytics and senomorphics have been proven to markedly prevent or treat ARDs in animal models. This review will present the current status of the development of senotherapeutics, in relation to aging itself and ARDs. Finally, future directions and opportunities for senotherapeutics use will discussed. This knowledge will provide information that can be used to develop novel senotherapeutics for health span and ARDs.
Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women

AIMS Carnitine and choline are major nutrient precursors for gut microbiota-dependent generation of the atherogenic metabolite, trimethylamine N-oxide (TMAO). We performed randomized-controlled dietary intervention studies to explore the impact of chronic dietary patterns on TMAO levels, metabolism and renal excretion. METHODS AND RESULTS Volunteers (N = 113) were enrolled in a randomized 2-arm (high- or low-saturated fat) crossover design study. Within each arm, three 4-week isocaloric diets (with washout period between each) were evaluated (all meals prepared in metabolic kitchen with 25% calories from protein) to examine the effects of red meat, white meat, or non-meat protein on TMAO metabolism. Trimethylamine N-oxide and other trimethylamine (TMA) related metabolites were quantified at the end of each diet period. A random subset (N = 13) of subjects also participated in heavy isotope tracer studies. Chronic red meat, but not white meat or non-meat ingestion, increased plasma and urine TMAO (each >two-fold; P < 0.0001). Red meat ingestion also significantly reduced fractional renal excretion of TMAO (P < 0.05), but conversely, increased fractional renal excretion of carnitine, and two alternative gut microbiota-generated metabolites of carnitine, γ-butyrobetaine, and crotonobetaine (P < 0.05). Oral isotope challenge revealed red meat or white meat (vs. non-meat) increased TMA and TMAO production from carnitine (P < 0.05 each) but not choline. Dietary-saturated fat failed to impact TMAO or its metabolites. CONCLUSION Chronic dietary red meat increases systemic TMAO levels through: (i) enhanced dietary precursors; (ii) increased microbial TMA/TMAO production from carnitine, but not choline; and (iii) reduced renal TMAO excretion. Discontinuation of dietary red meat reduces plasma TMAO within 4 weeks.
Phytotoxic Potential of Zanthoxylum affine and Its Major Compound Linarin as a Possible Natural Herbicide

Four compounds, the flavone linarin (1), the triterpene lupenone (2), the tocopherol (vitamin E, 3), and the new natural alkaloid 1,2,3,4-tetrahydro-1,1-dimethyl-6,7-isoquinolindiol (affineine, 4), were the major natural products isolated from Zanthoxylum affine (syn. Zanthoxylum fagara, Rutaceae). Compound 1 is highly abundant in this plant and was isolated as a white precipitate obtained from the acetone and methanol extracts. The structure of these four compounds was established by 1D and 2D NMR spectroscopy including 1H, 13C, DEPT, COSY, HSQC, and HMBC experiments. The hexane, acetone, and methanol extracts, as well as 1, were evaluated for their potential phytotoxic effects in pre- and post-emergent assays, as well as to identify their mechanisms of action. As pre-emergent phytotoxic agents, the hexane, acetone, and methanol extracts inhibited germination and residual growth (root and stem elongation) of Lactuca sativa (lettuce) and Lolium perenne (perennial ryegrass). As post-emergent agents, they inhibited dry biomass. Compound 1 acts as a pre-emergent herbicide, by inhibiting germination, seed respiration, residual seedling growth and, notably, root hair development. Furthermore, 1 inhibited the synthesis of ATP and the electron transport chain of isolated spinach chloroplasts; in this way, it behaves as a Hill reaction inhibitor. The site of inhibition was located at the donor site of PSII from the oxygen evolving complex to QA, thus acting as a multisite compound. These results suggest that compound 1 can be used as a lead for a potential green herbicide with different targets.
Comparing Cephalic Index and Midsagittal Vector Analysis in Assessing Morphology in Sagittal Synostosis: A CT-Based Morphometric Analysis

Introduction: Assessment of cranial dysmorphism in sagittal synostosis is often subjective but objective measures can be applied. These include cephalic index (CI) and midsagittal vector analysis (MSVA). Objective: To assess discriminant validity, construct validity, and responsiveness of CI and MSVA measured from computed tomography (CT) in patients with sagittal synostosis. Methods: Patients with nonsyndromic isolated sagittal synostosis with complete preoperative (n = 30) and postoperative (n = 13) CT data were included. Age-matched control group (n = 24) comprised of normocephalic patients who underwent CT for reasons related to trauma. Outcome Measures: Retrospective CT evaluation of CI and MSVA was conducted and correlated with a dysmorphism numeric rating scale (D-NRS) that measured surgeon-rated severity of sagittal synostosis. Responsiveness of CI and MSVA was evaluated using dysmorphism global rating of change (D-GRC). Results: Thirty patients with sagittal synostosis were demographically similar to 24 normocephalic patients. The difference in CI and MSVA was statistically significant between normocephalic and scaphocephalic patients. Cephalic index had a good correlation with D-NRS (r = −0.665, ρ = −0.667), but not with MSVA (r = 0.250, ρ = 0.203). Change in CI (r = 0.738, ρ = 0.657) was well correlated with D-GRC, but not with MSVA (r = −0.409, ρ = −0.301). Conclusion: Cephalic index appears to quantify the severity of sagittal synostosis better than MSVA. Cephalic index also has better responsiveness than MSVA to measure a reduction in severity of disease; however, MSVA is a better descriptive craniometric measurement. Midsagittal vector analysis was able to quantify the shift in morphology in sagittal synostosis following surgical treatment.
Voltage-dependent dynamics of the BK channel cytosolic gating ring are coupled to the membrane-embedded voltage sensor

In humans, large conductance voltage- and calcium-dependent potassium (BK) channels are regulated allosterically by transmembrane voltage and intracellular Ca2+. Divalent cation binding sites reside within the gating ring formed by two Regulator of Conductance of Potassium (RCK) domains per subunit. Using patch-clamp fluorometry, we show that Ca2+ binding to the RCK1 domain triggers gating ring rearrangements that depend on transmembrane voltage. Because the gating ring is outside the electric field, this voltage sensitivity must originate from coupling to the voltage-dependent channel opening, the voltage sensor or both. Here we demonstrate that alterations of the voltage sensor, either by mutagenesis or regulation by auxiliary subunits, are paralleled by changes in the voltage dependence of the gating ring movements, whereas modifications of the relative open probability are not. These results strongly suggest that conformational changes of RCK1 domains are specifically coupled to the voltage sensor function during allosteric modulation of BK channels.
Comparison of trauma outcomes between Japan and the USA using national trauma registries

Background The National Trauma Data Bank (NTDB) has served as a global benchmark for trauma care quality and outcomes. Herein, we compared patient characteristics, trauma management, and outcomes between Japanese emergency and critical care centers and US level 1 trauma centers using the Japanese Trauma Data Bank (JTDB) and NTDB. Methods A retrospective cohort matching (1:1) study was performed. Patients treated in 2013 with an Injury Severity Score ≥9 were included. The primary outcome measure was in-hospital mortality. The secondary outcome measures included the hospital length of stay and the rate of use of radiological diagnostic modalities. Results A total of 14 960 pairs with well-balanced characteristics were generated from 22 535 and 112 060 eligible patients in the JTDB and NTDB, respectively. Before matching, the in-hospital mortality was higher in the JTDB than in the NTDB (7.6% vs. 6.1%; OR, 1.28; 95% CI 1.21 to 1.35). However, after matching, the in-hospital mortality was lower in the JTDB cohort (4.2% vs. 5.8%; OR, 0.72; 95% CI 0.65 to 0.80). CT scans were used in >80% of JTDB patients, which was more than 1.5 times as often as the use in the NTDB cohort. In subgroup analyses, only patients who received a blood transfusion had a poorer survival outcome in the JTDB compared with the NTDB (OR, 1.32; 95% CI 1.07 to 1.64). Discussion We observed marked differences in trauma care between Japan and the USA. Although the quality of the recent Japanese trauma care appears to be approaching that of the USA, it may be further improved, such as by the establishment of transfusion protocols. Level of evidence Level IV.