Miracle-dz/UniFAR-FTUs huggingface dataset:
Velocity-specific knee strength between professional and under-17 female volleyball players

Background Many studies have investigated isokinetic performance in volleyball players but not through surface maps. Objectives The goals of this study were to assess velocity-specific isokinetic knee extensor–flexor muscle strength and to compare the isokinetic knee extensor–flexor muscles between professional (PRO) and under-17 (U17) female volleyball players. Method This cross-sectional laboratory study was developed with two groups: PRO (n = 12), medianage = 21.3 years, and U17 (n = 9), medianage = 15 years. Peak torque, total work, mean power, angle of peak torque, hamstring–quadriceps torque ratio (H–Q ratio) and torque–angle–velocity surface maps were analysed from knee extension–flexion at 60, 120 and 300 degrees per second (°/s). Results Significant differences were identified for extensor peak torque between PRO x = 202.3 Newton metre (N·m) (standard deviation [SD] = 24.4) and U17 x = 141.6 N·m (30.1) at 60 °/s (p < 0.001; d = 2.21) as well as flexor peak torque (PRO x = 75.7 N·m [10.3] and U17 x = 57.7 N·m [11.4]) at 120 °/s (p < 0.001; d = 1.65) for the dominant limb. There were also significant group differences for total work and mean power at all velocities for extension and flexion. Surface maps demonstrated higher torque at lower speeds for both groups with smaller torque changes across velocities for flexion. Conclusion Different groups of female volleyball players showed contrasting concentric knee muscle strength across isokinetic velocities. Clinical implications These results demonstrate the importance of specific strength training for different age groups, even within the same sport, and provide insight into muscle strength.
Further developments in the multiblock hybrid CFD solver elsA-H

Over the past few years, ONERA has been working on the extension of the multiblock structured solver elsA to hybrid-grid con gurations. By hybrid grids, we mean those in which structured (ijk-based) and unstructured blocks coexist within the same computational domain. We have called the new solver elsA-H. This approach has a number of advantages which are highlighted in this work. In this paper, we review the hybrid-grid algorithms upon which elsA-H relies, focusing on the particular handling of matching-grid interfaces. We also report recent progress on the parallelisation of such algorithms, as well as on the development of an appropriate hybrid-grid load-balancing tool. Finally, we present preliminary work on the implementation of a hybrid multigrid algorithm into elsA-H. A number of simulation results for several unstructured and hybrid-grid con gurations are reported in this paper.
Animal models of well-differentiated/dedifferentiated liposarcoma: utility and limitations

Abstract Liposarcoma is a malignant neoplasm of fat tissue. Well-differentiated and dedifferentiated liposarcoma (WDL/DDL) represent the two most clinically observed histotypes occurring in middle-aged to older adults, particularly within the retroperitoneum or extremities. WDL/DDL are thought to represent the broad spectrum of one disease, as they are both associated with the amplification in the chromosomal 12q13-15 region that causes MDM2 and CDK4 overexpression, the most useful predictor for liposarcoma diagnosis. In comparison to WDL, DDL contains additional genetic abnormalities, principally coamplifications of 1p32 and 6q23, that increase recurrence and metastatic rate. In this review, we discuss the xenograft and transgenic animal models generated for studying progression of WDL/DDL, highlighting utilities and pitfalls in such approaches that can facilitate or impede the development of new therapies.
Analgesic Effect of Toll-like Receptor 4 Antagonistic Peptide 2 on Mechanical Allodynia Induced with Spinal Nerve Ligation in Rats

Neuroinflammation is one of the key mechanisms of neuropathic pain, which is primarily mediated by the Toll-like receptor 4 (TLR4) signaling pathways in microglia. Therefore, TLR4 may be a reasonable target for treatment of neuropathic pain. Here, we examined the analgesic effect of TLR4 antagonistic peptide 2 (TAP2) on neuropathic pain induced by spinal nerve ligation in rats. When lipopolysaccharide (LPS)-stimulated BV2 microglia cells were treated with TAP2 (10 µM), the mRNA levels of proinflammatory mediators, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, cyclooxygenase (COX)-2, and inducible nitric oxide synthase (iNOS), were markedly decreased by 54–83% as determined by quantitative PCR (qPCR) analysis. Furthermore, when TAP2 (25 nmol in 20 µL PBS) was intrathecally administered to the spinal nerve ligation-induced rats on day 3 after surgery, the mechanical allodynia was markedly decreased for approximately 2 weeks in von Frey filament tests, with a reduction in microglial activation. On immunohistochemical and qPCR analyses, both the level of reactive oxygen species and the gene expression of the proinflammatory mediators, such as TNF-α, IL-1β, IL-6, COX-2, and iNOS, were significantly decreased in the ipsilateral spinal dorsal horn. Finally, the analgesic effect of TAP2 was reproduced in rats with monoiodoacetate-induced osteoarthritic pain. The findings of the present study suggest that TAP2 efficiently mitigates neuropathic pain behavior by suppressing microglial activation, followed by downregulation of neuropathic pain-related factors, such as reactive oxygen species and proinflammatory molecules. Therefore, it may be useful as a new analgesic for treatment of neuropathic pain.
Patients’ experiences of long-acting injectable antipsychotics: a qualitative study

Background In this study, we applied a qualitative approach to explore patients' subjective experiences of long-acting injectable antipsychotics (LAIs). Methods Patients undergoing psychiatric treatment from the chronic ward or outpatient department of a medical center in northern Taiwan who had experience with LAI treatment were enrolled. Information was obtained through semi-structured in-depth interviews. The interviews were audio-recorded and then translated verbatim, and the data were collected and analyzed concurrently to develop major themes and categories. Result In total, 14 participants (8 female) were interviewed. In a bio-psycho-social model, the participants used LAIs as a method to become “normal,” in order to achieve a balance between the “effects” and “side effects” that may influence their daily lives. Their past experiences constructed their concepts about and expectations regarding LAIs, and their relationships with their family members and co-workers also modeled their experiences. Conclusion In our study, we sought to understand the experience of LAI in the daily life context of the patients. We attempted to use a bio-psycho-social model to evaluate the subjective experience of the patients; an improved understanding can help mental health specialists gain a closer insight into patient experience.
Hibernation Impairs Odor Discrimination – Implications for Alzheimer’s Disease

Reversible formation of PHF-like phosphorylated tau, an early feature of Alzheimer’s disease (AD) was previously shown to occur in torpor during hibernation in the Golden hamster (Syrian hamster, Mesocricetus auratus). Here, we tackled the question to what extent hibernating Golden hamsters can serve as a model for the early stage of AD. During early AD, anosmia, the loss of olfactory function, is a common and typical feature. We, thus, investigated tau phosphorylation, synaptic plasticity and behavioral physiology of the olfactory system during hibernation. Tau was phosphorylated on several AD-relevant epitopes, and distribution of PHF-like phosphorylated tau in the olfactory bulb was quite similar to what is seen in AD. Tau phosphorylation was not associated with a destabilization of microtubules and did not lead to fibril formation. Previously, we observed a transient spine reduction in pyramidal cells in the hippocampus, which is correlated with the distribution of phosphorylated tau. Here we show that granule cells in the olfactory bulb are devoid of phosphorylated tau and maintain their spines number during torpor. No reduction of synaptic proteins was observed. However, hibernation did impair the recall performance in a two-odor discrimination task. We conclude that hibernation is associated with a specific olfactory memory deficit, which might not be attributed to the formation of PHF-like phosphorylated tau within the olfactory bulb. We discuss a possible involvement of modulatory input provided by cholinergic neurons in the basal forebrain, which are affected by hibernation.
Motor-Cognitive Neural Network Communication Underlies Walking Speed in Community-Dwelling Older Adults

While walking was once thought to be a highly automated process, it requires higher-level cognition with older age. Like other cognitive tasks, it also becomes further challenged with increased cognitive load (e.g., the addition of an unrelated dual task) and often results in poorer performance (e.g., slower speed). It is not well known, however, how intrinsic neural network communication relates to walking speed, nor to this “cost” to gait performance; i.e., “dual-task cost (DTC). ” The current study investigates the relationship between network connectivity, using resting-state functional MRI (rs-fMRI), and individual differences in older adult walking speed. Fifty participants (35 females; 84 ± 4.5 years) from the MOBILIZE Boston Study cohort underwent an MRI protocol and completed a gait assessment during two conditions: walking quietly at a preferred pace and while concurrently performing a serial subtraction task. Within and between neural network connectivity measures were calculated from rs-fMRI and were correlated with walking speeds and the DTC (i.e., the percent change in speed between conditions). Among the rs-fMRI correlates, faster walking was associated with increased connectivity between motor and cognitive networks and decreased connectivity between limbic and cognitive networks. Smaller DTC was associated with increased connectivity within the motor network and increased connectivity between the ventral attention and executive networks. These findings support the importance of both motor network integrity as well as inter-network connectivity amongst higher-level cognitive networks in older adults’ ability to maintain mobility, particularly under dual-task (DT) conditions.
Valproate Exposure in ovo Attenuates the Acquisition of Social Preferences of Young Post-hatch Domestic Chicks

Embryonic exposure to valproic acid (VPA) is known to produce sociability deficits, resembling human autistic phenotypes, in several vertebrate species. Animals living in groups prefer the proximity of peers and have the ability to perceive and to respond to social signals for modifying behavior. Chicks of Galliform birds, known to display early preference behaviors, have been used extensively for adaptive learning studies. Young precocial birds seem to be useful models also for studying the effect of embryonic VPA treatment. Here, domestic chicken eggs were injected with sodium valproate (200 μl of 35 μmol/L solution) or with vehicle (distilled water) on the 14th day of incubation. After hatching, the chicks were tested for one-trial passive avoidance learning at day 1, vocalization due to isolation as a measure of stress level (day 2), approach preference to large versus small groups of age-matched conspecifics (day 5), and to those with normal versus blurred head features (day 7). In addition, we tested the preference of birds to conspecifics reared in group versus those reared in isolation (day 9), as well as the preference of chicks to familiar versus non-familiar conspecifics (day 21). Our findings confirm previous reports concerning an adverse effect of VPA on embryonic development, including a tendency for aborted or delayed hatching and, occasionally, for locomotor disorders in a small percentage of birds (eliminated from later studies). Otherwise, VPA treatment did not impair motor activity or distress level. Memory formation for the aversive stimulus and discrimination of colors were not impaired by VPA treatment either. Innate social predispositions manifested in approach preferences for the larger target group or for the birds with natural facial features remained unaffected by VPA exposure. The most prominent finding was attenuation of social exploration in VPA-exposed birds (expressed as the frequency of positional switches between two stimulus chicks after the first choice), followed by a deficit in the recognition of familiar conspecifics, unfolding at the end of the third week. Social exploration and recognition of familiar individuals are the key elements impaired at this stage. The results underline the importance of early social exploration in ASD.
The Utilization of Freezing Steps in Mesenchymal Stromal Cell (MSC) Manufacturing: Potential Impact on Quality and Cell Functionality Attributes

Some recent reports suggest that cryopreserved and thawed mesenchymal stromal cells (MSCs) may have impaired functional properties as compared to freshly harvested MSCs from continuous cultures. A cryopreservation step in the manufacturing process brings important benefits, since it enables immediate off-the-shelf access to the products and a completion of all quality testing before batch release and administration to the patient. Cryopreservation is also inevitable in MSC banking strategies. In this study, we present the results from the MSC stability testing program of our in-house manufactured clinical-grade allogeneic bone marrow-derived MSC product that is expanded in platelet lysate and frozen in passage 2. The current manufacturing protocol contains only one freezing step and the frozen MSC product is thawed bed-side at the clinic. We can conclude superior viability and cell recovery of the frozen and thawed MSC product utilizing the validated freezing and thawing protocols we have developed. The MSC phenotype and differentiation potential was generally found to be unaltered after thawing, but the thawed cells exhibited a 50% reduced, but not completely abolished, performance in an in vitro immunosuppression assay. The in vitro immunosuppression assay results should, however, be interpreted with caution, since the chosen assay mainly measures one specific immunosuppressive mechanism of MSCs to suppress T-cell proliferation. Since at least two freezing steps are usually necessary in MSC banking strategies, we went on to investigate the impact of repeated freezing on MSC quality attributes. We can conclude that two freezing steps with a preceding cell culture phase of at least one passage before freezing is feasible and does not substantially affect basic cell manufacturing parameters or quality attributes of the final frozen and thawed product. Our results suggest, however, that an exhaustive number of freezing steps (≥4) may induce earlier senescence. In conclusion, our results support the utilization of frozen MSC products and MSC banking strategies, but emphasize the need of always performing detailed studies on also the cryopreserved MSC counterpart and to carefully report the cryopreservation and thawing protocols.
SPEECH DEVELOPMENT IN PREVIOUSLY APHONIC CHILDREN AFTER AIRWAY RECONSTRUCTION RECAPITULATES EVOLUTION OF SPOKEN LANGUAGE

Seven previously aphonic children underwent airway reconstruction enabling them to obtain phonation for the first time between the ages of 13 and 34 months. Prior to surgical intervention, children had normal language exposure but expressive language was severely limited due to an inability to phonate. Spoken language development was accelerated, but still occurred step-wise with the following distinct periods after reconstruction: (1) Exclusively vegetative functions of the larynx; (2) Voluntary control over vegetative laryngeal functions; (3) Babbling; (4) Simple words; (5) Speech. These findings suggest that control of laryngeal function is a prerequisite for speech development and can develop independently of language skills. A similar pattern for the evolutionary development of speech is proposed.
Regulation of Proteasome Activity by (Post-)transcriptional Mechanisms

Intracellular protein synthesis, folding, and degradation are tightly controlled processes to ensure proper protein homeostasis. The proteasome is responsible for the degradation of the majority of intracellular proteins, which are often targeted for degradation via polyubiquitination. However, the degradation rate of proteins is also affected by the capacity of proteasomes to recognize and degrade these substrate proteins. This capacity is regulated by a variety of proteasome modulations including (1) changes in complex composition, (2) post-translational modifications, and (3) altered transcription of proteasomal subunits and activators. Various diseases are linked to proteasome modulation and altered proteasome function. A better understanding of these modulations may offer new perspectives for therapeutic intervention. Here we present an overview of these three proteasome modulating mechanisms to give better insight into the diversity of proteasomes.
Genome Analysis Reveals Genetic Admixture and Signature of Selection for Productivity and Environmental Traits in Iraqi Cattle

The Near East cattle are adapted to different agro-ecological zones including desert areas, mountains habitats, and humid regions along the Tigris and Euphrates rivers system. The region was one of the earliest and most significant areas of cattle husbandry. Currently, four main breeds of Iraqi cattle are recognized. Among these, the Jenoubi is found in the southern more humid part of Iraq, while the Rustaqi is found in the middle and drier region of the country. Despite their importance, Iraqi cattle have up to now been poorly characterized at the genome level. Here, we report at a genome-wide level the diversity and signature of positive selection in these two breeds. Thirty-five unrelated Jenoubi cattle, sampled in the Maysan and Basra regions, and 60 Rustaqi cattle, from around Baghdad and Babylon, were genotyped using the Illumina Bovine HD BeadChip (700K). Genetic population structure and diversity level were studied using principal component analysis (PCA), expected heterozygosity (He), observed heterozygosity (Ho), and admixture. Signatures of selection were studied using extended haplotype homozygosity (EHH) (iHS and Rsb) and inter-population Wright’s Fst. The results of PCA and admixture analysis, including European taurine, Asian indicine, African indicine, and taurine indicate that the two breeds are crossbreed zebu × taurine, with more zebu background in Jenoubi cattle compared with Rustaqi. The Rustaqi has the greatest mean heterozygosity (He = 0.37) among all breeds. iHS and Rsb signatures of selection analyses identify 68 candidate genes under positive selection in the two Iraqi breeds, while Fst analysis identifies 220 candidate genes including genes related to the innate and acquired immunity responses, different environmental selection pressures (e.g., tick resistance and heat stress), and genes of commercial interest (e.g., marbling score).
A Job-Scheduling Problem Involving Sequence-Dependent Changeover Costs

This paper studies a problem of job scheduling in a production line having various adjustable settings or ‘states’ that can process a variety of jobs. Each job can be processed when the line is in one of the several states at a cost dependent on the state used. One state is sufficient for the processing of each job. In addition, a sequence-dependent changeover cost is also incurred between states. The problem is to determine an optimal sequence of the states of the line, and allocation of jobs to states that minimizes the overall operating cost. An exact implicit enumeration algorithm, which exploits the similarity of this problem with the simple plant location problem, is proposed. Computational experience with the algorithm shows that any reasonable size problem can be solved in comparatively small computational effort.
SGLT-2 inhibitors as promising therapeutics for non-alcoholic fatty liver disease: pathophysiology, clinical outcomes, and future directions

Abstract Nonalcoholic fatty liver disease (NAFLD) is increasingly recognized as a major expanding national and international health problem. Despite numerous investigations using a variety of therapeutic agents, the positive result on any single medication has not been established enough to gain widespread approval. This is in part related to concerns regarding side effects of agents, but is also related to the complex etiology of NAFLD. An often discussed question has been whether insulin resistance that is frequently present in those with NAFLD is a cause of NAFLD or is merely associated with the condition. Nevertheless, it is clear that a very high proportion of patients with NAFLD are obese, have elements of metabolic syndrome, or have type 2 diabetes (T2DM). Also, much progress has been made toward a better understanding of the pathophysiology of NAFLD. Life-style interventions resulting in weight loss remain the foundation for the prevention and treatment of NAFLD. In addition, agents such as Vitamin E and pioglitazone as well as other glycemia-lowering agents including Glucagon Like Peptide-1 (GLP-1) receptor agonists and Sodium Glucose Contransporter-2 inhibitors (SGLT-2i(s)) exhibit positive effects on the clinical course of NAFLD. This narrative review summarizes the current understanding of the diagnosis, epidemiology, and pathophysiology of NAFLD and specifically focuses on the efficacy of SGLT2i(s) as a potentially promising group of agents for the management of patients with NAFLD.
In Vitro Evaluation of the Biological Availability of Hyaluronic Acid Polyethylene Glycols-Cross-Linked Hydrogels to Bovine Testes Hyaluronidase

During last years, hyaluronic acid- (HA-) based dermal fillers have grown rapidly and continuously, as reported by the American Society of Aesthetic Plastic Surgery (ASAPS). In fact, HA fillers are considered the gold standard technique for soft tissue augmentation, deep skin hydration, and facial recontouring, playing a key role as an alternative to plastic surgery. HA fillers are less invasive, more biocompatible, and safer and with a more natural and immediate result if compared to plastic surgery. Hence, the safety of HA-based dermal fillers plays a crucial role, mostly in terms of biocompatibility and adjustability in case of unpleasant results and side effects such as, tyndall effect, edema, or granulomas. Hyaluronidase is a naturally occurring enzyme, present in the human body, and can degrade HA fillers avoiding more severe complications. In this article, we analyzed the bioavailability of hyaluronidase degradation of five fillers of Neauvia® hydrogels line (MatexLab SA, Lugano, CH), composed of pure hyaluronic acid and based on PEGDE cross-linking (polyethylene glycol) technology that guarantees a higher biocompatibility and an optimal biointegration and rheological characteristics. The performed in vitro testing is based on the colorimetric determination of the N-acetyl-D-glucosamine (NAG) present in solution after incubation with hyaluronidase, determined at different time points in order to assess the kinetic of each product degradation (1h, 3h, 6h, 24h, 48h, 72h, 120h, and 168h). The aim of this study was to assess, in vitro, how the difference in HA content and PEGDE concentration of the analyzed fillers can influence the product biocompatibility, intended as product enzymatic clearance and duration in time. The results demonstrated that the method was reproducible and easy to perform and that all the analyzed fillers are naturally immediately available for hyaluronidase-mediated degradation.