Miracle-dz/UniFAR-FTUs huggingface dataset:
Cluster adaptive training for deep neural network

Although context-dependent DNN-HMM systems have achieved significant improvements over GMM-HMM systems, there still exists big performance degradation if the acoustic condition of the test data mismatches that of the training data. Hence, adaptation and adaptive training of DNN are of great research interest. Previous works mainly focus on adapting the parameters of a single DNN by regularized or selective fine-tuning, applying linear transforms to feature or hidden-layer output, or introducing vector representation of non-speech variability into the input. These methods all require relatively large number of parameters to be estimated during adaptation. In contrast, this paper employs the cluster adaptive training (CAT) framework for DNN adaptation. Here, multiple DNNs are constructed to form the bases of a canonical parametric space. During adaptation, an interpolation vector, specific to a particular acoustic condition, is used to combine the multiple DNN bases into a single adapted DNN. The DNN bases can also be constructed at layer level for more flexibility. The CAT-DNN approach was evaluated on an English switchboard task in unsupervised adaptation mode. It achieved significant WER reductions over the unadapted DNN-HMM, relative 6% to 8.5%, with only 10 parameters.
Adherence to a Mediterranean-Style Diet and Appendicular Lean Mass in Community-Dwelling Older People: Results From the Berlin Aging Study II.

BACKGROUND Selected nutrients or food groups have often been studied with regard to long-term mortality and cardiovascular disease, whereas the relation between diet quality and appendicular lean mass (ALM) has rarely been researched. OBJECTIVE The aim of this study was to explore the association between a Mediterranean-style diet and ALM in community-dwelling older people. METHODS Cross-sectional data from the Berlin Aging Study II were available for 1,509 participants (51% women, 68.2±3.7 years). Nutrient intake was assessed using the European Prospective Investigation into Cancer and Nutrition Food Frequency Questionnaire. Adherence to a Mediterranean-style diet was evaluated with the modified Mediterranean-type diet score (mMedTypeDiet). ALM was determined by dual-energy X-ray absorptiometry and related to body mass index (ALM/BMI). A general linear regression model was carried out to assess the association between mMedTypeDiet score groups and ALM/BMI. RESULTS ALM/BMI was higher in women with a higher adherence to the mMedTypeDiet (0.64±0.1 vs 0.62±0.1 and 0.61±0.1 in low and medium adherence, retrospectively, p = .004). In the risk factor-adjusted general linear regression analysis, a higher adherence to the mMedTypeDiet was associated with higher ALM/BMI in women and better ALM/fat mass ratio when compared to a medium and a low diet quality. No significant associations were seen in men. CONCLUSIONS Higher adherence to a Mediterranean-style diet was associated with a positive effect on ALM/BMI in women.
Endothelin Confers Protection against High Glucose-Induced Neurotoxicity via Alleviation of Oxidative Stress

Recent findings linked the inhibition in the neuromodulator peptide endothelin-1 (ET-1) level to the high glucose-evoked neurotoxicity. However, definitive neuroprotective role for ET-1 and the major neuronal ET (ET-3) against high glucose-evoked toxicity and the implicated neurochemical responses triggered by their ET-A and ET-B receptors remain unknown. Here, we tested the hypothesis that ET-B activation alleviates high glucose-evoked oxidative stress and cell death. High glucose (100 mM for 48 hours)-evoked cell death was associated with elevation in reactive oxygen species, inhibition of catalase activity, and a paradoxical upregulation of hemeoxygenase-1 expression along with ET-A and ET-B receptors were downregulated and upregulated, respectively. ET-1 or ET-3, in concentrations that had no effect on PC12 cell viability in normal glucose medium, alleviated all high glucose-evoked neurochemical responses, except for the reduction in ET-A receptor expression. Prior (4 hours) incubation with a selective ET-A (BQ123) or ET-B (BQ788) receptor blocker abrogated the neuroprotection conferred by ET-1 or ET-3. However, the ET-B receptor played a greater role because BQ788 abrogated the favorable ET-1- or ET-3-mediated reversal of the ERK1/2 phosphorylation and the inhibition in catalase activity caused by high glucose. These findings suggest that endothelin exerts ET-B receptor-dependent favorable redox and neuroprotective effects against high glucose-evoked oxidative damage and neurotoxicity.
A Quasi‐3D compartmental multi‐scale approach to detect and quantify diseased regional lung constriction using spirometry data

Spirometry is a widely used pulmonary function test to detect the airflow limitations associated with various obstructive lung diseases, such as asthma, chronic obstructive pulmonary disease, and even obesity‐related complications. These conditions arise due to the change in the airway resistance, alveolar compliance, and inductance values. Currently, zero‐dimensional compartmental models are commonly used for calibrating these resistance, compliance, and inductance values, ie, solving the inverse spirometry problem. However, zero‐dimensional compartments cannot capture the flow physics or the spatial geometry effects, thereby generating a low fidelity prediction of the diseased lung. Computational fluid dynamics (CFD) models offer higher fidelity solutions but may be impractical for certain applications due to the duration of these simulations. Recently, a novel, fast‐running, and robust Quasi‐3D (Q3D) wire model for simulating the airflow in the human lung airway was developed by CFD Research Corporation. This Q3D method preserved the 3D spatial nature of the airways and was favorably validated against CFD solutions. In the present study, the Q3D compartmental multi‐scale combination is further improved to predict regional lung constriction of diseased lungs using spirometry data. The Q3D mesh is resolved up to the eighth lung airway generation. The remainder of the airways and the alveoli sections are modeled using a compartmental approach. The Q3D geometry is then split into different spatial sections, and the resistance values in these regions are obtained using parameter inversion. Finally, the airway diameter values are then reduced to create the actual diseased lung model, corresponding to these resistance values. This diseased lung model can be used for patient‐specific drug deposition predictions and the subsequent optimization of the orally inhaled drug products.
A comprehensive approach to identifying repurposed drugs to treat SCN8A epilepsy

Many previous studies of drug repurposing have relied on literature review followed by evaluation of a limited number of candidate compounds. Here, we demonstrate the feasibility of a more comprehensive approach using high‐throughput screening to identify inhibitors of a gain‐of‐function mutation in the SCN8A gene associated with severe pediatric epilepsy.
Use and effectiveness of dapagliflozin in routine clinical practice: An Italian multicentre retrospective study

In randomized controlled trials (RCTs), sodium‐glucose co‐transporter‐2 (SGLT2) inhibitors have been shown to confer glycaemic and extra‐glycaemic benefits. The DARWIN‐T2D (DApagliflozin Real World evIdeNce in Type 2 Diabetes) study was a multicentre retrospective study designed to evaluate the baseline characteristics of patients receiving dapagliflozin vs those receiving selected comparators (dipeptidyl peptidase‐4 inhibitors, gliclazide, or glucagon‐like peptide‐1 receptor agonists), and drug effectiveness in routine clinical practice. From a population of 281 217, the analysis included 17 285 patients initiating dapagliflozin or comparator glucose‐lowering medications (GLMs), 6751 of whom had a follow‐up examination. At baseline, participants starting dapagliflozin were younger, had a longer disease duration, higher glycated haemoglobin (HbA1c) concentration, and a more complex history of previous GLM use, but the clinical profile of patients receiving dapagliflozin changed during the study period. Dapagliflozin reduced HbA1c by 0.7%, body weight by 2.7 kg, and systolic blood pressure by 3.0 mm Hg. Effects of comparator GLMs were also within the expected range, based on RCTs. This real‐world study shows an initial channelling of dapagliflozin to difficult‐to‐treat patients. Nonetheless, dapagliflozin provided significant benefits with regard to glucose control, body weight and blood pressure that were in line with findings from RCTs.
Agronomic performance of insect-protected and herbicide-tolerant MON 89034 × TC1507 × NK603 × DAS-40278–9 corn is equivalent to that of conventional corn

ABSTRACT Agronomic characteristics of genetically modified (GM) MON 89034 × TC1507 × NK603 × DAS-40278–9 (PowerCore™ Enlist™), MON 89034 × TC1507 × NK603 (PowerCore™), and DAS-40278–9 (Enlist™) corn, a non-GM near-isogenic hybrid, and 2 commercial non-GM hybrids were assessed in a field study to determine if the agronomic performance of the GM corn hybrids is equivalent to that of non-transgenic hybrid corn. The MON 89034 × TC1507 × NK603 × DAS-40278–9 hybrid corn was developed through stacking of 4 individual transgenic events, MON 89034, TC1507, NK603, and DAS-40278–9 by traditional breeding and contains the cry1A.105 and cry2Ab2 (MON 89034), cry1F and pat (TC1507), cp4 epsps (NK603) and aad-1 (DAS-40278–9) transgenes. These transgenes encode the proteins Cry1A.105, Cry2Ab2, and Cry1F, which confer insect resistance, PAT, CP4 EPSPS, and AAD-1, which confer herbicide tolerance. The following agronomic characteristics were assessed in the study: initial and final stand count, seedling vigor, time to silk, time to pollen shed, pollen viability, plant height, ear height, stalk lodging, root lodging, days to maturity, stay green, disease incidence, insect damage, herbicide injury, and yield. The agronomic assessment was conducted in 2 regions of Brazil (Indianopolis-MG; Cravinhos-SP). The agronomic attributes for all GM entries were statistically indistinguishable from the non-GM near-isogenic hybrid. In addition, most of the agronomic assessments fell within the range of the commercial varieties included in the study. Taken together, MON 89034 × TC1507 × NK603 × DAS-40278, MON 89034 × TC1507 × NK603, and DAS-40278–9 were found to be agronomically equivalent to non-GM corn.
Fabrication of Tip-Dissolving Microneedles for Transdermal Drug Delivery of Meloxicam

Dissolving microneedles (MNs) offered a simple, minimally invasive method for meloxicam (MX) delivery to the skin. However, the fabrication of dissolving MNs still faced some challenges, such as significant time consumption, loss of drug activity, and difficulty in regulating MN drug loading. To address these issues, we developed the tip-dissolving (TD) MNs. Several kinds of drugs were encapsulated successfully, and the quantity of MX ranged from 37.23 ± 8.40 to 332.53 ± 13.37 μg was precisely controlled. The effects of fabrication process on biomacromolecules stability were studied, and it was found that tyrosinase kept 90.4% activity during the fabrication process. The whole process for the fabrication of MNs only takes approximately 1 h. In order to further evaluate the potential of the TD MNs, MX TD MNs were prepared for in vitro release experiments, in vivo release experiments, safety evaluation, pharmacokinetic studies, and pharmacodynamic studies. The results demonstrated that MX TD MNs offered several advantages, including rapid release of the encapsulated drug (91.72% within 30 min), efficient drug delivery to skin (79.18%), no obvious skin irritation, decent relative bioavailability (122.3%), and strong anti-inflammatory and analgesic effects. Based on these results, we envisage that the TD MNs have promising potential for transdermal drug delivery of MX.
Elucidation of porcine corneal ultrastructure to inform development of corneal xenographs or biomimetic replacements

The transparent, anterior-most tissue of the eye globe, which allows light into the eye for sight, is the cornea. The main thickness of the cornea, known as the stroma, is a collagenous extra cellular matrix (ECM) that is comprised of fibrous collagen types I, V and VI along with keratan sulphate (KS) and chondroitin/dermatan sulphate (CS/DS) proteoglycans. These components maintain the collagen fibrils in a quasi-crystalline arrangement, which enables the tissue to be transparent.
Invasive and Non-Invasive Congeners Show Similar Trait Shifts between Their Same Native and Non-Native Ranges

Differences in morphological or ecological traits expressed by exotic species between their native and non-native ranges are often interpreted as evidence for adaptation to new conditions in the non-native ranges. In turn this adaptation is often hypothesized to contribute to the successful invasion of these species. There is good evidence for rapid evolution by many exotic invasives, but the extent to which these evolutionary changes actually drive invasiveness is unclear. One approach to resolving the relationship between adaptive responses and successful invasion is to compare traits between populations from the native and non-native ranges for both exotic invaders and congeners that are exotic but not invasive. We compared a suite of morphological traits that are commonly tested in the literature in the context of invasion for three very closely related species of Centaurea, all of which are sympatric in the same native and non-native ranges in Europe and North America. Of these, C. solstitialis is highly invasive whereas C. calcitrapa and C. sulphurea are not. For all three species, plants from non-native populations showed similar shifts in key traits that have been identified in other studies as important putative adaptive responses to post-introduction invasion. For example, for all three species plants from populations in non-native ranges were (i) larger and (ii) produced seeds that germinated at higher rates. In fact, the non-invasive C. calcitrapa showed the strongest trait shift between ranges. Centaurea solstitialis was the only species for which plants from the non-native range increased allocation to defensive spines, and allocated proportionally less resources to reproduction, patterns contrary to what would be predicted by theory and other empirical studies to enhance invasion. Our results suggest caution when interpreting the commonly observed increase in size and reproductive capacity as factors that cause exotics to become invaders.
Attenuated Pik3r1 Expression Prevents Insulin Resistance and Adipose Tissue Macrophage Accumulation in Diet-Induced Obese Mice

Obese white adipose tissue (AT) is characterized by large-scale infiltration of proinflammatory macrophages, in parallel with systemic insulin resistance; however, the cellular stimulus that initiates this signaling cascade and chemokine release is still unknown. The objective of this study was to determine the role of the phosphoinositide 3-kinase (PI3K) regulatory subunits on AT macrophage (ATM) infiltration in obesity. Here, we find that the Pik3r1 regulatory subunits (i.e., p85α/p55α/p50α) are highly induced in AT from high-fat diet–fed obese mice, concurrent with insulin resistance. Global heterozygous deletion of the Pik3r1 regulatory subunits (αHZ), but not knockout of Pik3r2 (p85β), preserves whole-body, AT, and skeletal muscle insulin sensitivity, despite severe obesity. Moreover, ATM accumulation, proinflammatory gene expression, and ex vivo chemokine secretion in obese αHZ mice are markedly reduced despite endoplasmic reticulum (ER) stress, hypoxia, adipocyte hypertrophy, and Jun NH2-terminal kinase activation. Furthermore, bone marrow transplant studies reveal that these improvements in obese αHZ mice are independent of reduced Pik3r1 expression in the hematopoietic compartment. Taken together, these studies demonstrate that Pik3r1 expression plays a critical role in mediating AT insulin sensitivity and, more so, suggest that reduced PI3K activity is a key step in the initiation and propagation of the inflammatory response in obese AT.
Coproduction of Research Questions and Research Evidence in Public Health: The Study to Prevent Teen Drinking Parties

Community-based participatory research (CBPR) provides a set of principles and practices intended to foster coproduction of knowledge. However, CBPR often has shortcomings when applied to population-level policy and practice interventions, including a focus on single communities and a lack of focus on policy change. At the same time, community trials focused on policy have shortcomings, including lack of stakeholder involvement in framing research questions and modest engagement in study implementation and interpretation and dissemination of results. We describe an attempt to hybridize CBPR and community trials by creating a partnership that included a national membership organization, a coalition advisory board, intervention and delayed intervention communities, and an academic study team, which collaborated on a study of community strategies to prevent underage drinking parties. We use qualitative and quantitative data to critically assess the partnership. Areas where the partnership was effective included (1) identifying a research question with high public health significance, (2) enhancing the intervention, and (3) improving research methods. Challenges included community coalition representatives' greater focus on their own communities rather than the production of broader scientific knowledge. This model can be applied in future attempts to narrow the gap between research, policy, and practice.
Fine-mapping the MHC locus in juvenile idiopathic arthritis (JIA) reveals genetic heterogeneity corresponding to distinct adult inflammatory arthritic diseases

Objectives Juvenile idiopathic arthritis (JIA) is a heterogeneous group of diseases, comprising seven categories. Genetic data could potentially be used to help redefine JIA categories and improve the current classification system. The human leucocyte antigen (HLA) region is strongly associated with JIA. Fine-mapping of the region was performed to look for similarities and differences in HLA associations between the JIA categories and define correspondences with adult inflammatory arthritides. Methods Dense genotype data from the HLA region, from the Immunochip array for 5043 JIA cases and 14 390 controls, were used to impute single-nucleotide polymorphisms, HLA classical alleles and amino acids. Bivariate analysis was performed to investigate genetic correlation between the JIA categories. Conditional analysis was used to identify additional effects within the region. Comparison of the findings with those in adult inflammatory arthritic diseases was performed. Results We identified category-specific associations and have demonstrated for the first time that rheumatoid factor (RF)-negative polyarticular JIA and oligoarticular JIA are genetically similar in their HLA associations. We also observe that each JIA category potentially has an adult counterpart. The RF-positive polyarthritis association at HLA-DRB1 amino acid at position 13 mirrors the association in adult seropositive rheumatoid arthritis (RA). Interestingly, the combined oligoarthritis and RF-negative polyarthritis dataset shares the same association with adult seronegative RA. Conclusions The findings suggest the value of using genetic data in helping to classify the categories of this heterogeneous disease. Mapping JIA categories to adult counterparts could enable shared knowledge of disease pathogenesis and aetiology and facilitate transition from paediatric to adult services.
Dopaminergic neuromodulation of high gamma stimulus phase‐locking in gerbil primary auditory cortex mediated by D1/D5‐receptors

Cortical release of the neurotransmitter dopamine has been implied in adapting cortical processing with respect to various functions including coding of stimulus salience, expectancy, error prediction, behavioral relevance and learning. Dopamine agonists have been shown to modulate recurrent cortico‐thalamic feedback, and should therefore also affect synchronization and amplitude of thalamo‐cortical oscillations. In this study, we have used multitaper spectral and time–frequency analysis of stimulus‐evoked and spontaneous current source density patterns in primary auditory cortex of Mongolian gerbils to characterize dopaminergic neuromodulation of the oscillatory structure of current sources and sinks. We systemically applied D1/D5‐receptor agonist SKF‐38393 followed by competitive D1/D5‐receptor antagonist SCH‐23390. Our results reveal an increase in stimulus phase‐locking in the high gamma‐band (88–97 Hz) by SKF‐38393, specifically in layers III/IV at the best frequency, which occurred at 20 ms after tone onset, and was reversed by SCH‐23390. However, changes in induced oscillatory power after SKF‐38393 treatment occurred stimulus‐independently in the background activity in different layers than phase‐locking effects and were not reversed by SCH‐23390. These effects might either reflect longer‐lasting changes in neural background noise, non‐specific changes due to ketamine anesthesia, or an interaction of both. Without concomitant stimulus‐induced power increase, increased stimulus phase‐locking in layers III/IV indicates enhanced phase‐resetting of neural oscillations by the stimulus after D1/D5‐receptor activation. The frequency characteristics, together with the demonstrated stimulus specificity and layer specificity, suggest that changes in phase‐resetting originate from dopaminergic neuromodulation of thalamo‐cortical interactions. Enhanced phase‐resetting might be a key step in the recruitment of cortical activity modes interpreting sensory input.
Hypoxia modulates the purine salvage pathway and decreases red blood cell and supernatant levels of hypoxanthine during refrigerated storage

Hypoxanthine catabolism in vivo is potentially dangerous as it fuels production of urate and, most importantly, hydrogen peroxide. However, it is unclear whether accumulation of intracellular and supernatant hypoxanthine in stored red blood cell units is clinically relevant for transfused recipients. Leukoreduced red blood cells from glucose-6-phosphate dehydrogenase-normal or -deficient human volunteers were stored in AS-3 under normoxic, hyperoxic, or hypoxic conditions (with oxygen saturation ranging from <3% to >95%). Red blood cells from healthy human volunteers were also collected at sea level or after 1–7 days at high altitude (>5000 m). Finally, C57BL/6J mouse red blood cells were incubated in vitro with 13C1-aspartate or 13C5-adenosine under normoxic or hypoxic conditions, with or without deoxycoformycin, a purine deaminase inhibitor. Metabolomics analyses were performed on human and mouse red blood cells stored for up to 42 or 14 days, respectively, and correlated with 24 h post-transfusion red blood cell recovery. Hypoxanthine increased in stored red blood cell units as a function of oxygen levels. Stored red blood cells from human glucose-6-phosphate dehydrogenase-deficient donors had higher levels of deaminated purines. Hypoxia in vitro and in vivo decreased purine oxidation and enhanced purine salvage reactions in human and mouse red blood cells, which was partly explained by decreased adenosine monophosphate deaminase activity. In addition, hypoxanthine levels negatively correlated with post-transfusion red blood cell recovery in mice and – preliminarily albeit significantly - in humans. In conclusion, hypoxanthine is an in vitro metabolic marker of the red blood cell storage lesion that negatively correlates with post-transfusion recovery in vivo. Storage-dependent hypoxanthine accumulation is ameliorated by hypoxia-induced decreases in purine deamination reaction rates.