Miracle-dz/UniFAR-FTUs huggingface dataset:
Analogy and explicit motor learning in dynamic balance: Posturography and performance analyses

Abstract Unlike explicit learning, analogy learning allows learners to acquire skills with a movement metaphor with fewer verbal knowledge accumulated during early learning, resulting in less reliance on cognitive resources for better motor performances. However, the efficacy of analogical instruction on balance is still unclear. This study examined learning and subsequent performance (including posturography) of a Y-balance task by explicit and analogical instructions. Forty female undergraduates were randomly assigned either into analogy (n = 20) or explicit (n = 20) learning. Both group learners completed pre-learning test-block on Day 1 (6 trials), five consecutive learning blocks from Days 3 to 7 (135 trials) and followed by test-blocks on Day 9 (retention 1 – dual-task – retention 2 design, 18 trials). Maximum reaching distances in anterior, posterolateral and posteromedial directions were measured to indicate Y-balance performance. During test-blocks (pre-learning, retention 1, dual-task, retention 2), CoM displacement and CoP excursion were quantified with the motion capturing system and force platform, respectively. Results indicated that maximum reach distances of two groups increased across learning days (p < .001). During test-blocks, explicit learners reduced maximum reaching distances under the dual-task test than the retention test 1 (p < .001), while analogy learners remained robust performance across test-blocks (p = .071). Moreover, analogy learners reported fewer explicit knowledge and demonstrated better counting backward performance than explicit learners. These findings suggest that introducing an analogical instruction in dynamic balance training is feasible and has implications to develop balance training strategies for injury prevention and performance enhancement.
ABO polymorphism and SARS-CoV-2 infection - a meta-analysis

At present, existing evidence about the association between SARS-CoV-2 infection and ABO blood group polymorphism is preliminary and controversial. In this meta-analysis we investigate this association and determine SARS-CoV-2 positive individuals odds of having a specific blood group compared to controls. We performed a systematic search on MEDLINE and LitCovid databases for studies published through July 12, 2020. 7 studies met inclusion criteria for meta-analysis, including a total of 13 subgroups of populations (7524 SARS-CoV-2 positive cases and 2962160 controls). We analysed the odds of having each blood group among SARS-CoV-2 positive patients compared with controls. Random-effects models were used to obtain the overall pooled odds ratio (OR). Subgroup and sensitivity analyses were performed in order to explore the source of heterogeneity and results consistency. The results of our meta-analysis indicate that SARS-CoV-2 positive individuals are more likely to have blood group A (pooled OR 1.21; 95%CI: 1.08-1.37) and less likely to have blood group O (pooled OR 0.76, 95%CI: 0.66-0.87). Further studies are needed to investigate the mechanisms at the basis of this association, which may affect the kinetics of the pandemic according to the blood group distribution within the population.
In silico drug discovery of IKK-β inhibitors from 2-amino-3-cyano-4-alkyl-6-(2-hydroxyphenyl) pyridine derivatives based on QSAR, docking, molecular dynamics and drug-likeness evaluation studies

Abstract The Inhibitor of IKK-β (nuclear factor kappa B kinase subunit beta), a specific modulator of NF-κB (nuclear factor-κB), is considered a valid target to discover new active compounds for various cancers and rheumatoid arthritis treatment. In this study a series of thirty 2-amino-3-cyano-4-alkyl-6-(2-hydroxyphenyl) pyridine derivatives was involved for a quantitative structure activity relationship model (QSAR) elaboration which allows the prediction of the pIC50 values of new designed compounds. The model can be used to predict the activity of new compounds within its applicability domain. Then a molecular docking study was carried out to identify the interactions between the compounds and the amino acids of the active site. After that, golden triangle, Veber’s rule, and Lipinski’s rule properties were calculated to identify the drug-likeness properties of the investigated compounds. Finally, in-silico-toxicity studies were performed to predict the toxicity of the new designed compounds. The analysis of the results of QSAR model and molecular docking succeeded to screen 21 interesting compounds with better inhibitory concentration having a good affinity to IKK-β. All compounds were within the range set by Veber’s rule and Lipinski’s rule. the analysis of golden triangle showed that the thirty 2-amino-3-cyano-4-alkyl-6-(2-hydroxyphenyl) pyridine derivatives would not have clearance and cell membrane permeability problems except comp6 comp12,comp20, comp21, and comp26.As for the new designed compounds, their properties may have these problems, except two compounds which are: A8m, A8p. The A1m, A1p, A3p and A11m compounds were predicted to be nontoxic. These findings indicate that the novel potent candidate drugs have promising potential to IKK-β enzyme inhibition and should motivate future experimental investigations. Communicated by Ramaswamy H. Sarma
Clinical pharmacy interventions in intensive care unit patients

The drug therapy of critically ill patients requires intensive evaluation and management due to their severity of illness. These patients often require complex medication regimens. This study analysed the pharmaceutical care provided by clinical pharmacists (CPs) in a single medical centre in Taiwan. In addition, we explored the drug‐related problems (DRPs) experienced by patients in intensive care units (ICUs) to determine how to improve the quality and safety of drug therapy.
Evaluating Serum Heat Shock Protein Levels as Novel Biomarkers for Atrial Fibrillation

Background: Staging of atrial fibrillation (AF) is essential to understanding disease progression and the accompanied increase in therapy failure. Blood-based heat shock protein (HSP) levels may enable staging of AF and the identification of patients with higher risk for AF recurrence after treatment. Objective: This study evaluates the relationship between serum HSP levels, presence of AF, AF stage and AF recurrence following electrocardioversion (ECV) or pulmonary vein isolation (PVI). Methods: To determine HSP27, HSP70, cardiovascular (cv)HSP and HSP60 levels, serum samples were collected from control patients without AF and patients with paroxysmal atrial fibrillation (PAF), persistent (PeAF) and longstanding persistent (LSPeAF) AF, presenting for ECV or PVI, prior to intervention and at 3-, 6- and 12-months post-PVI. Results: The study population (n = 297) consisted of 98 control and 199 AF patients admitted for ECV (n = 98) or PVI (n = 101). HSP27, HSP70, cvHSP and HSP60 serum levels did not differ between patients without or with PAF, PeAF or LSPeAF. Additionally, baseline HSP levels did not correlate with AF recurrence after ECV or PVI. However, in AF patients with AF recurrence, HSP27 levels were significantly elevated post-PVI relative to baseline, compared to patients without recurrence. Conclusions: No association was observed between baseline HSP levels and the presence of AF, AF stage or AF recurrence. However, HSP27 levels were increased in serum samples of patients with AF recurrence within one year after PVI, suggesting that HSP27 levels may predict recurrence of AF after ablative therapy.
Pathogenic Delivery: The Biological Roles of Cryptococcal Extracellular Vesicles

Extracellular vesicles (EVs) are produced by all domains of life. In fungi, these structures were first described in Cryptococcus neoformans and, since then, they were characterized in several pathogenic and non-pathogenic fungal species. Cryptococcal EVs participate in the export of virulence factors that directly impact the Cryptococcus–host interaction. Our knowledge of the biogenesis and pathogenic roles of Cryptococcus EVs is still limited, but recent methodological and scientific advances have improved our understanding of how cryptococcal EVs participate in both physiological and pathogenic events. In this review, we will discuss the importance of cryptococcal EVs, including early historical studies suggesting their existence in Cryptococcus, their putative mechanisms of biogenesis, methods of isolation, and possible roles in the interaction with host cells.
Giant Congenital Cholesteatoma of the Temporal Bone

Congenital or primitive cholesteatoma is a benign disease with slow progressive growth that destroys neighboring structures. It is a rare disease considered an epidermal cyst originating from the remnants of squamous keratinized epithelium, in several regions of the temporal bone such as in the middle ear (most frequent) as well as in the petrous apex, cerebellopontine cistern, external acoustic meatus and mastoid process. In this case report, we present a giant congenital cholesteatoma, occupying a part of the petrous part of the temporal bone, including middle ear and mastoid process discovered at a 12-years-old girl as an acute right otomastoiditis complicated with retro auricular abscess. There were no history of ear infections, trauma or previous surgeries on this area, the eardrum was intact, all the accusing starts after an infection of the naospharynx –typical for congenital cholesteatoma. In emergency using a retro auricular approach we drain the abscess located sub-periosteal and finally we remove the cholesteatoma using a radical mastoidectomy with canal wall down procedure with a large meatoplasty. Even with a minutia’s excision of the cholesteatoma and a permanent follow up recurrence was discovered after 4 years at 16 years old –without signs of infection but with tinnitus and vertigo and we explore the cavity and remove the new cholesteatoma. Now at 22 years old our patient now a lady, is free of accuses except deafness ,with a clean large tympani-mastoid cavity–she return at every 6 month for a check –up with cleaning the cavity at the microscope –we remove the epithelial debris and wax . The aim of this report was to present a rare case of giant . congenital cholesteatoma of the temporal bone with all required characters and also to share our experience after a brief review of the literature and to discuss the new classification used and the best attitude in such a serious problem as long as we still don’t know how to stop recurrence of the cholesteatoma.
Effects of Resistance Training at Different Loads on Inflammatory Biomarkers, Muscle Mass, Muscular Strength, and Physical Performance in Postmenopausal Women

Abstract Carneiro, MAS, de Oliveira Júnior, GN, de Sousa, JFR, Murta, EFC, Orsatti, CL, Michelin, MA, Cyrino, ES, and Orsatti, FL. Effects of resistance training at different loads on inflammatory biomarkers, muscle mass, muscular strength, and physical performance in postmenopausal women. J Strength Cond Res 36(6): 1582–1590, 2022—It has been suggested that the effect of resistance training (RT) on circulating proinflammatory biomarkers may be dependent on muscle mass gain. A few recent studies have suggested that lower-load RT (LLRT; loads <50% of 1 repetition maximum [1RM] and repetition performed until, or close to, voluntary concentric failure) may be superior to higher-load RT (HLRT; loads >70% of 1RM) in increasing muscle mass. Hence, this study aimed to test whether LLRT is superior to HLRT for increasing muscle mass (total fat-free mass [TFFM] and leg fat-free mass [LFFM]) and improving circulating inflammatory biomarkers (interleukin [IL]-6, IL1-ra, tumor necrosis factor [TNF]-α, and extracellular heat shock protein [eHSP]70) in postmenopausal women (PW) (primary outcome). The secondary outcome was to compare the changes in muscular strength and physical performance (4-meter walking test [4-M], timed-up-and-go [TUG] test, and sit-to-stand [STS] test) between the LLRT and HLRT. The PW were randomized into 2 groups: LLRT (n = 14; loads necessary to perform 30–35 repetitions) and HLRT (n = 15; loads necessary to perform 8–12 repetitions). The greater magnitude of increase in LFFM (p = 0.033) was observed in LLRT when compared with HLRT. Moreover, there was a trend for a greater increase in TFFM in LLRT over HLRT (p = 0.070). However, there were similar improvements in TNF-α and muscular strength (p < 0.001). Furthermore, there was no significant difference between the RT schemes on IL-6, IL-1ra, and eHSP70 levels. Thus, although performing LLRT until, or close to, voluntary concentric failure seems to provide a greater stimulus for an increase in muscle mass than HLRT, it does not seem to affect the responses in circulating inflammatory biomarkers, muscular strength, and physical performance in PW.
Effect of Plastrum Testudinis Extracts on the Proliferation and Osteogenic Differentiation of rBMSCs by Regulating p38 MAPK-Related Genes

Extracts from plastrum testudinis (PTE) are active compounds that have been used to treat bone diseases in traditional Chinese medicine for thousands of years. In previous studies, we demonstrated their effects on glucocorticoid-induced osteoporosis both in vivo and in vitro. However, the mechanisms by which PTE regulates the osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells (rBMSCs) in vitro remain poorly understood. In this study, rBMSCs were treated with medium (CON), PTE, osteogenic induction (OI), and a combination of PTE and OI (PTE+OI) over a 21-day period. We found that PTE significantly promoted rBMSCs osteogenic differentiation and mineralisation after 21 days of culturing. Moreover, PTE+OI further enhanced the differentiation and mineralisation process. PTE upregulated STE20, IGF1R, and p38 MAPK mRNA expression and downregulated TRAF6 mRNA expression. The extracts inhibited TRAF6 protein expression and promoted STE20, IGF1R, and phosphorylated p38 MAPK protein expression. Our results imply that PTE promotes the proliferation and osteogenic differentiation of rBMSCs by upregulating p38 MAPK, STE20, and IGF1R and downregulating TRAF6 expression, which may provide experimental evidence of the potential of PTE in the treatment of osteoporosis.
The Immunotherapy Revolution in Kidney Cancer Treatment

Abstract The recent discovery of immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment, including the treatment for renal cell carcinoma (RCC). Following the eras of cytokines and molecularly targeted therapies including vascular endothelial growth factor–directed agents and mammalian target of rapamycin (mTOR) inhibitors, ICIs have become the latest addition to the RCC armamentarium. To understand the scientific rationale behind this revolution in RCC treatment, we have reviewed the fundamental discoveries underlying the transition from old (cytokines) to new (ICIs) immunotherapies. We summarize the pivotal trials (CheckMate 025, CheckMate 214, KEYNOTE-426, JAVELIN Renal 101, IMmotion151) of checkpoint inhibitors for clear cell RCC in various treatment settings. With the availability of many different combination therapies and many more currently under investigation, clear cell RCC treatment is becoming more complex. Patient preferences, disease volumes, and adverse event profiles are essential in determining which option is the best for an individual patient. In the future, biomarkers currently under development could guide these treatment decisions.
A higher ctDNA fraction decreases survival in regorafenib‐treated metastatic colorectal cancer patients. Results from the regorafenib's liquid biopsy translational biomarker phase II pilot study

The predictive effect of circulating tumor DNA (ctDNA) in colorectal cancer (CRC) treatment is still highly discussed. The primary objective of our study was to investigate a possible prognostic/predictive value of ctDNA under regorafenib treatment. This prospective multicenter translational biomarker phase II pilot study enrolled 30 metastatic CRC patients (67% men, 33% women) treated with regorafenib. ctDNA was assessed in plasma before treatment start and at defined time points during administration. Measurement of tumor fraction as well as mutation and copy number analysis of CRC driver genes were performed by next‐generation sequencing approaches. Multivariate analyses for survival and treatment efficacy were adjusted to age, gender and Eastern Cooperative Oncology Group. Disease control rate was 30%. Median tumor fraction at baseline was 18.5% (0‐49.9). Mutations in CRC driver genes or genes involved in angiogenesis were identified in 25 patients (83.3%). KRAS mutations were detected in 13 of 14 KRAS‐positive tumors; in three patients without KRAS mutation in the respective tumors, acquired mutations as a consequence of prior anti‐EGFR treatment were detected. In a subset of patients, novel occurring mutations or focal amplifications were detected. A tumor fraction of 5% and higher at baseline was significantly associated with a decreased OS (P = .022; hazard ratio 3.110 (95% confidence interval: 1.2‐8.2). ctDNA is detectable in a high proportion of mCRC patients. Higher ctDNA levels are associated with survival among regorafenib treatment. Moreover, our data highlight the benefit of a combined evaluation of mutations and somatic copy number alterations in advanced cancer patients.
Lessons from Bacillus Calmette-Guérin: Harnessing Trained Immunity for Vaccine Development

Vaccine design traditionally focuses on inducing adaptive immune responses against a sole target pathogen. Considering that many microbes evade innate immune mechanisms to initiate infection, and in light of the discovery of epigenetically mediated innate immune training, the paradigm of vaccine design has the potential to change. The Bacillus Calmette-Guérin (BCG) vaccine induces some level of protection against Mycobacterium tuberculosis (Mtb) while stimulating trained immunity that correlates with lower mortality and increased protection against unrelated pathogens. This review will explore BCG-induced trained immunity, including the required pathways to establish this phenotype. Additionally, potential methods to improve or expand BCG trained immunity effects through alternative vaccine delivery and formulation methods will be discussed. Finally, advances in new anti-Mtb vaccines, other antimicrobial uses for BCG, and “innate memory-based vaccines” will be examined.
Acoustic Evidences about the Setting of the Coda Parameter in Brazilian Portuguese

The research on the acquisition of the rhotic consonants by Brazilian children developed by Miranda (1996), which presents a detailed analysis of the process of acquisition of the rhotic sounds in all the syllabic positions, discussing their phonological status in the system of Brazilian Portuguese, left out a question related to the acquisition of the rhotic in the coda position for further development. The results of the work showed that there is a big difference in the process of acquisition of the medial coda and the final coda. The children who were analysed produced the 'r' of final coda, while the production of the rhotic in medial coda only occurs much later. This fact favoured the hypothesis of a possible compensatory lengthening of the vowel in non final CVC syllables in words like 'porco' (pig) and 'perna' (leg), for example. This lengthening of the vowel, phenomenon already referred by Jakobson (1941/68), has a clear explanation in non-linear phonology as proposed by Clements & Keyser (1983) and can clearly show that the parameter of the coda has already been set by the child. To test this hypothesis on the lengthening of the vowel, the data from Miranda (1996) underwent an acoustic analysis with the help of the Phonédit programme, to verify whether there is the lengthening of the vowel or not when the child does not produce the rhotic, and the consequent maintenance of the position in the skeletal tier in the speech of children who produce the rhotic in the final coda, but do not produce it in the medial position.
Multivariate relationships among nucleus and Golgi properties during fibrillar migration are robust to and unchanged by epithelial-to-mesenchymal transition

Epithelial-to-mesenchymal transition (EMT) and maturation of a fibrillar tumor microenvironment play important roles in breast cancer progression. A better understanding of how these events promote cancer cell migration and invasion could help identify new strategies to curb metastasis. The nucleus and Golgi affect migration in a microenvironment-dependent manner. Nucleus size and mechanics influence the ability of a cell to squeeze through confined tumor microenvironments. Golgi positioning determines front-rear polarity necessary for migration. While the roles of individual attributes of nucleus and Golgi in migration are being clarified, how their manifold features are inter-related and work together remains to be understood at a systems level. Here, to elucidate relationships among nucleus and Golgi properties, we quantified twelve morphological and positional properties of these organelles during fibrillar migration of human mammary epithelial cells. Principal component analysis (PCA) reduced the twelve-dimensional space of measured properties to three principal components that capture 75% of the variations in organelle features. Unexpectedly, nucleus and Golgi properties that co-varied in a PCA model built with data from untreated cells were largely similar to co-variations identified using data from TGFβ-treated cells. Thus, while TGFβ-mediated EMT significantly alters gene expression and motile phenotype, it did not significantly affect the relationships among nucleus size, aspect ratio and orientation with migration direction and among Golgi size and nucleus-Golgi separation distance. Indeed, in a combined PCA model incorporating data from untreated and TGFβ-treated cells, scores of individual cells occupy overlapping regions in principal component space, indicating that TGFβ-mediated EMT does not promote a unique “Golgi-nucleus phenotype” during fibrillar migration. These results suggest that migration along spatially-confined fiber-like tracks employs a conserved nucleus-Golgi arrangement that is independent of EMT state.
Dynamic Cerebral Autoregulation Post Endovascular Thrombectomy in Acute Ischemic Stroke

The development of the endovascular thrombectomy (EVT) technique has revolutionized acute stroke management for patients with large vessel occlusions (LVOs). The impact of successful recanalization using an EVT on autoregulatory profiles is unknown. A more complete understanding of cerebral autoregulation in the context of EVT may assist with post-procedure hemodynamic optimization to prevent complications. We examined cerebral autoregulation in 107 patients with an LVO in the anterior circulation (proximal middle cerebral artery (M1/2) and internal cerebral artery (ICA) terminus) who had been treated using an EVT. Dynamic cerebral autoregulation was assessed at multiple time points, ranging from less than 24 h to 5 days following last seen well (LSW) time, using transcranial Doppler ultrasound recordings and transfer function analysis. Complete (Thrombolysis in Cerebral Infarction (TICI) 3) recanalization was associated with a more favorable autoregulation profile compared with TICI 2b or poorer recanalization (p < 0.05), which is an effect that was present after accounting for differences in the infarct volumes. Less effective autoregulation in the first 24 h following the LSW time was associated with increased rates of parenchymal hematoma types 1 and 2 hemorrhagic transformations (PH1–PH2). These data suggest that patients with incomplete recanalization and poor autoregulation (especially within the first 24 h post-LSW time) may warrant closer blood pressure monitoring and control in the first few days post ictus.