Miracle-dz/UniFAR-FTUs huggingface dataset:
A novel six-microRNA-based model to improve prognosis prediction of breast cancer

Current tumor-node-metastasis (TNM) stage is unable to accurately predict the overall survival (OS) in breast cancer (BC) patients. This study aimed to construct a microRNA (miRNA)-based model to improve survival prediction of BC. We confirmed 99 differentially expressed miRNAs (DEMs) in 1044 BC samples compared to 102 adjacent normal breast tissues from The Cancer Genome Atlas (TCGA) database. Prognostic DEMs were used to establish a miRNA-based nomogram via Cox regression model. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses (KEGG) were executed to analyze target genes of miRNAs. A six-miRNA signature was screened to effectively distinguish high-risk patients in the primary and validation cohort (all P<0.001). Furthermore, we established a novel prognostic model incorporating the six-miRNA signature and clinical risk factors to predict 5-year OS of BC. Time-dependent receiver operating characteristic analysis suggested that the predictive accuracy of the six-miRNA-based nomogram was distinctly higher than that of TNM stage (0.758 vs 0.650, P<0.001). GO and KEGG pathway analyses showed that the 39 target genes mainly enrichment in protein binding, cytoplasm and MAPK signaling pathway. Our six-miRNA-based model is a reliable prognostic tool for survival prediction and provides information for individualized treatment decisions in BC patients.
Lipid phosphatases SKIP and SHIP2 regulate fibronectin‐dependent cell migration in glioblastoma

Cell migration is an important process that occurs during development and has also been linked to the motility of cancer cells. Cytoskeleton reorganization takes place in the migration process leading to lamellipodia formation. Understanding the molecular underpinnings of cell migration is particularly important in studies of glioblastoma, a highly invasive and aggressive cancer type. Two members of the phosphoinositide 5‐phosphatase family, SKIP and SHIP2, have been associated with cell migration in glioblastoma; however, the precise role these enzymes play in the process—and whether they work in concert—remains unclear. Here, we compared phosphoinositide 5‐phosphatases expression in glioblastoma primary cells and cell lines and showed that SHIP2 and SKIP expression greatly varies between different cell types, while OCRL, another phosphoinositide 5‐phosphatase, is constitutively expressed. Upon adhesion of U‐251 MG cells to fibronectin, SHIP2, SKIP, and PI(4,5)P2 colocalized in membrane ruffles. Upregulation of PI(4,5)P2 was observed in SKIP‐depleted U‐251 MG cells compared to control cells, but only when cells were adhered to fibronectin. Both PTEN‐deficient (U‐251) and PTEN‐containing (LN229) glioblastoma cells showed a decrease in cell migration velocity in response to SKIP downregulation. Moreover, a SHIP2 catalytic inhibitor lowered cell migration velocity in the U‐251 MG cell line. We conclude that integrin activation in U‐251 cells leads to colocalization of both SKIP and SHIP2 in ruffles, where they act as potential drivers of cell migration. Depending on their expression levels in glioblastoma, phosphoinositide 5‐phosphatases could cooperate and synergize in the regulation of cell migration and adhesion.
Machine Learning in Modeling High School Sport Concussion Symptom Resolve.

INTRODUCTION Concussion prevalence in sport is well recognized, so too is the challenge of clinical and return-to-play management for an injury with an inherent indeterminant time course of resolve. A clear, valid insight into the anticipated resolution time could assist in planning treatment intervention. PURPOSE This study implemented a supervised machine learning-based approach in modeling estimated symptom resolve time in high school athletes who incurred a concussion during sport activity. METHODS We examined the efficacy of 10 classification algorithms using machine learning for the prediction of symptom resolution time (within 7, 14, or 28 d), with a data set representing 3 yr of concussions suffered by high school student-athletes in football (most concussion incidents) and other contact sports. RESULTS The most prevalent sport-related concussion reported symptom was headache (94.9%), followed by dizziness (74.3%) and difficulty concentrating (61.1%). For all three category thresholds of predicted symptom resolution time, single-factor ANOVA revealed statistically significant performance differences across the 10 classification models for all learners at a 95% confidence interval (P = 0.000). Naïve Bayes and Random Forest with either 100 or 500 trees were the top-performing learners with an area under the receiver operating characteristic curve performance ranging between 0.656 and 0.742 (0.0-1.0 scale). CONCLUSIONS Considering the limitations of these data specific to symptom presentation and resolve, supervised machine learning demonstrated efficacy, while warranting further exploration, in developing symptom-based prediction models for practical estimation of sport-related concussion recovery in enhancing clinical decision support.
Efficacy and safety of ospemifene in postmenopausal women with moderate-to-severe vaginal dryness: a phase 3, randomized, double-blind, placebo-controlled, multicenter trial

Abstract Objective: To evaluate the safety and efficacy of ospemifene for the treatment of moderate to severe vaginal dryness in postmenopausal women with vulvovaginal atrophy (VVA). Methods: This 12-week, multicenter, double-blind phase 3 study randomized postmenopausal women (aged 40-80 years) with VVA and moderate to severe vaginal dryness as their most bothersome symptom to daily oral ospemifene 60 mg or placebo. Coprimary efficacy endpoints included changes from baseline to week 12 in percentages of vaginal parabasal and superficial cells, vaginal pH, and vaginal dryness severity with ospemifene versus placebo; other secondary endpoints were evaluated (weeks 4, 8, and 12). Safety was assessed by treatment-emergent adverse events (TEAEs) and endometrial biopsies. Results: Women (n = 631; ospemifene [n = 316], placebo [n = 315]) had a mean age of 59.8 years, a mean body mass index of 27.2 kg/m2, and most were white. Ospemifene significantly improved (P < 0.0001) the percentages of parabasal and superficial cells, vaginal pH, and severity of vaginal dryness severity compared with placebo at week 12; significant between-group differences were noted by week 4. Secondary endpoints of dyspareunia (P < 0.001), maturation value (P < 0.0001), and the Female Sexual Function Index (P < 0.05) also significantly improved with ospemifene versus placebo at week 12. Significantly more women responded (31.5% vs 6.0%; P < 0.0001) or were satisfied (49.2% vs 33.8%; P = 0.0007) with ospemifene versus placebo at week 12. No unexpected TEAEs, treatment-related serious TEAEs, thrombotic events, or endometrial hyperplasia or carcinoma were observed. Conclusions: Ospemifene was effective and well tolerated for the treatment of moderate-to-severe vaginal dryness in postmenopausal women with VVA.
Eye-tracker algorithms to detect saccades during static and dynamic tasks: a structured review

Objective: Eye-tracking devices have become widely used as clinical assessment tools in a variety of applied-scientific fields to measure saccadic eye movements. With the emergence of multiple static and dynamic devices, the concurrent need for algorithm development and validation is paramount. Approach: This review assesses the prevalence of current saccade detection algorithms, their associated validation methodologies and the suitability of their application. Medline, Embase, PsychInfo, Scopus, IEEEXplore and ACM Digital Library databases were searched. Two independent reviewers and an adjudicator screened articles describing the detection of saccades from raw infrared/video-based eye-tracker data. Main results: Thirteen articles were screened and met the inclusion criteria. Overall, the majority of reviewed saccadic detection algorithms used simple velocity-based classifications with static eye-tracking systems. Studies demonstrated validity but are limited by the static nature of testing. Heterogeneity in system design, proprietary and bespoke algorithmic methods used, processing strategies, and outcome reporting is evident. Significance: This paper suggests the use of a more standardised methodology to facilitate experimental validity and improve comparison of results across studies.
Systematic review of the impact of demographic and socioeconomic factors on quality of life in ostomized colorectal cancer survivors

Abstract Background: Formation of a fecal stoma may be necessary to ensure radical resection in colorectal cancer (CRC) patients but will substantially impact the health-related quality of life (HRQoL) in about 20% of cases. Little is known about patient-related risk factors for reduced HRQoL in patients with a permanent stoma. We, therefore, reviewed the current literature on how demographic and socioeconomic factors affect HRQoL in CRC survivors with a stoma. Material and methods: The databases Pubmed, Embase, CINAHL, and PsycINFO were systematically searched. Two independent reviewers extracted and quality-assessed eligible publications. Studies assessing HRQoL using a validated questionnaire at least 6 months after surgery for CRC were included if data on the impact of demographic and/or socioeconomic, factors on HRQoL were analyzed and presented. Results: Eligible studies predominantly presented small cross-sectional cohorts. Age showed equivocal results; hence, some studies found younger patients had inferior HRQoL compared with older patients, and others found no difference. Subdivision into age groups differed widely. Several studies found that both generic and stoma-specific HRQoL was lower in females compared with males. Most studies found that socioeconomic factors did not affect HRQoL while one study found lower education correlated to reduced HRQoL. Categorization of these factors also varied widely. Conclusions: This is to our knowledge the first systematic review on the impact of patient-related factors on HRQoL in long-term CRC survivors. We found that a stoma had more impact in younger ostomates than older and that HRQoL in females was reduced more than in males. Conclusions regarding other factors were difficult due to few studies and contradictory results. Further research in this subject is much needed in order to target preventive measures when planning surgery in patients in high risk of reduced HRQoL.
Enhanced Activation of HCN Channels Reduces Excitability and Spike-Timing Regularity in Maturing Vestibular Afferent Neurons

Vestibular ganglion neurons (VGNs) transmit information along parallel neuronal pathways whose signature distinction is variability in spike-timing; some fire at regular intervals while others fire at irregular intervals. The mechanisms driving timing differences are not fully understood but two opposing (but not mutually exclusive) hypotheses have emerged. In the first, regular-spiking is inversely correlated to the density of low-voltage-gated potassium currents (IKL). In the second, regular spiking is directly correlated to the density of hyperpolarization-activated cyclic nucleotide-sensitive currents (IH). Supporting the idea that variations in ion channel composition shape spike-timing, VGNs from the first postnatal week respond to synaptic-noise-like current injections with irregular-firing patterns if they have IKL and with more regular firing patterns if they do not. However, in vitro firing patterns are not as regular as those in vivo. Here we considered whether highly-regular spiking requires IH currents and whether this dependence emerges later in development after channel expression matures. We recorded from rat VGN somata of either sex aged postnatal day (P)9–P21. Counter to expectation, in vitro firing patterns were less diverse, more transient-spiking, and more irregular at older ages than at younger ages. Resting potentials hyperpolarized and resting conductance increased, consistent with developmental upregulation of IKL. Activation of IH (by increasing intracellular cAMP) increased spike rates but not spike-timing regularity. In a model, we found that activating IH counter-intuitively suppressed regularity by recruiting IKL. Developmental upregulation in IKL appears to overwhelm IH. These results counter previous hypotheses about how IH shapes vestibular afferent responses. SIGNIFICANCE STATEMENT Vestibular sensory information is conveyed on parallel neuronal pathways with irregularly-firing neurons encoding information using a temporal code and regularly-firing neurons using a rate code. This is a striking example of spike-timing statistics influencing information coding. Previous studies from immature vestibular ganglion neurons (VGNs) identified hyperpolarization-activated mixed cationic currents (IH) as driving highly-regular spiking and proposed that this influence grows with the current during maturation. We found that IH becomes less influential, likely because maturing VGNs also acquire low-voltage-gated potassium currents (IKL), whose inhibitory influence opposes IH. Because efferent activity can partly close IKL, VGN firing patterns may become more receptive to extrinsic control. Spike-timing regularity likely relies on dynamic ion channel properties and complementary specializations in synaptic connectivity.
Ecological and Construct Validity of a Repeated Sprint Test in Male Youth Soccer Players

Abstract Fernandes-Da-Silva, J, Castagna, C, Teixeira, AS, Carminatti, LJ, Francini, L, Póvoas, SCA, and Antonacci Guglielmo, LG. Ecological and construct validity of a repeated sprint test in male youth soccer players. J Strength Cond Res 35(7): 2000–2009, 2021—This study aimed to examine the relationship between a repeated sprint ability (RSA) test (5 bouts of 30-m sprints interspersed by 30 seconds of recovery) and match-related physical performance in male youth soccer players. Although 60 outfield players were evaluated, only data from players who participated in the full matches (n = 39) were retained (8 central defenders, 7 external defenders, 8 central midfielders, 8 external midfielders, and 8 forwards). To verify the ecological validity of this RSA protocol, the association between the best (RSAbest) and mean (RSAmean) sprint time in the 5 × 30-m and physical match performance during friendly youth soccer games was examined. Physical match demands were assessed using global positioning system technology (10 Hz) considering distance covered in selected arbitrary speed categories. The absolute speed thresholds were the same for all the players. Players were categorized into 2 groups based on the 5 × 30-m performance: RSAmean times below (i.e., faster) and above (i.e., slower) the median value. Players with faster RSAmean times covered significantly more distance sprinting during friendly matches (606 ± 204 m, +47.0%; t = 4.953; effect size = 1.88, 1.24; 2.52, p ≤ 0.001) compared to their slower counterparts (322 ± 145 m). A large negative correlation (r = −0.63, −0.77; −0.44, p ≤ 0.001) was found between RSAbest time (4.59 ± 0.27 seconds) and match sprint distance (457 ± 229 m). Likewise, RSAmean time (4.76 ± 0.25 seconds) was also largely associated (r = −0.60, −0.75; −0.39; p ≤ 0.001) with in-game sprinting performance. The results of this study provided evidence to support the construct and ecological validity of the 5 × 30-m protocol in male youth soccer players. Furthermore, differences in 5 × 30-m performance explained the amount of sprinting activity performed during the match.
The red pepper’s spicy ingredient capsaicin activates AMPK in HepG2 cells through CaMKKβ

Capsaicin is a natural compound present in chili and red peppers and the responsible of their spicy flavor. It has recently provoked interest because of its antitumoral effects in many cell types although its action mechanism is not clearly understood. As metabolic dysregulation is one of the hallmarks of cancer cells and the key metabolic sensor in the AMP-activated kinase (AMPK), in this study we explored the ability of capsaicin to modulate AMPK activity. We found that capsaicin activated AMPK in HepG2 cells by increasing AMPK phosphorylation and its downstream target ACC. Mechanistically, we determined that capsaicin activated AMPK through the calcium/calmodulin-dependent protein kinase kinase β, CaMKKβ as either the CaMKK inhibitor STO-609 or CaMKK knock down with siRNA abrogated the activation of AMPK. Moreover, capsaicin decreased cell viability, inhibited Akt/mTOR pathway and increased reactive oxygen species (ROS) in HepG2 cells. AMPK activation was involved in the underpinning mechanism of capsaicin-induced cell death.
Microbiological Aspects of Acute and Chronic Pediatric Rhinosinusitis

The microbiology of acute and chronic rhinosinusitis has been extensively studied, but there are still some differences of view concerning the etiology of the former, and many disagreements regarding the microbiology of the latter. Establishing the concomitant distribution of the causative micro-organisms in cases that involve multiple sinuses is scientifically and practically important. The main problems are the variety of aerobes and anaerobes that may be involved, and the fact that different tracts of the sinuses of the same patient may be simultaneously affected. Rhinosinusitis may also involve the formation of biofilm, which may play a significant role in its pathogenesis and persistence. Biofilms have a number of advantages in terms of bacterial survival, and their perpetuation can create a certain degree of instability in host-bacteria interactions. Sinonasal microflora may further complicate pathogenesis and the identification of the pathogen(s) involved. Furthermore, the concentration, uniformity, and type/number of strains of nasal microbiota may vary from one site to another. The relative and total micro-organism counts can also be affected by various factors, and microbiota can modulate the course of both acute and chronic rhinosinusitis.
Nurses' decision-making, practices and perceptions of patient involvement in medication administration in an acute hospital setting.

AIMS To describe nurses' decision-making, practices and perceptions of patient involvement in medication administration in acute hospital settings. BACKGROUND Medication errors cause unintended harm to patients. Nurses have a major role in ensuring patient safety in medication administration practices in hospital settings. Investigating nurses' medication administration decision-making and practices and their perceptions of patient involvement, may assist in developing interventions by revealing how and when to involve patients during medication administration in hospital. DESIGN A descriptive exploratory study design. METHODS Twenty nurses were recruited from two surgical and two medical wards of a major metropolitan hospital in Australia. Each nurse was observed for 4 hr, then interviewed after the observation. Data were collected over six months in 2015. Observations were captured on an electronic case report form; interviews were audio-recorded and transcribed verbatim. Data were analysed using descriptive statistics and content and thematic analysis. RESULTS Ninety-five medication administration episodes, of between two and eight episodes per nurse, were observed. A total of 56 interruptions occurred with 26 of the interruptions being medication related. Four major themes emerged from the interviews: dealing with uncertainty; facilitating, framing and filtering information; managing interruptions and knowing and involving patients. CONCLUSION Nurses work in complex adaptive systems that change moment by moment. Acknowledging and understanding the cognitive workload and complex interactions are necessary to improve patient safety and reduce errors during medication administration. Knowing and involving the patient is an important part of a nurses' medication administration safety strategies.
Structure, regulation and related diseases of the actin-binding protein gelsolin

Abstract Gelsolin (GSN), one of the most abundant actin-binding proteins, is involved in cell motility, shape and metabolism. As a member of the GSN superfamily, GSN is a highly structured protein in eukaryotic cells that can be regulated by calcium concentration, intracellular pH, temperature and phosphatidylinositol-4,5-bisphosphate. GSN plays an important role in cellular mechanisms as well as in different cellular interactions. Because of its participation in immunologic processes and its interaction with different cells of the immune system, GSN is a potential candidate for various therapeutic applications. In this review, we summarise the structure of GSN as well as its regulating and functional roles, focusing on distinct diseases such as Alzheimer's disease, rheumatoid arthritis and cancer. A short overview of GSN as a therapeutic target in today's medicine is also provided.
The role of lipid rafts in cell entry of human metapneumovirus

Human metapneumovirus (hMPV) is a crucial pathogen in children. A cell entry is the first step for infection. Our previous study indicated that there was an endocytosis pathway for hMPV cell entry. Lipid raft is a specific structure at the cell surface and it has been demonstrated to play an important role in endocytosis process of many viruses. In this study, we investigated whether and how lipid raft can take part in the hMPV entry. The confocal microscope was used to detect colocalization of hMPV and lipid raft marker. We demonstrated that colocalizations were increased along with the viral infection and hMPV particles transferred to the perinuclear region with lipid raft. When specific lipid raft inhibitors: methyl‐β cyclodextrin and nystatin were used, hMPV cell entry was inhibited and viral titer decreased dramatically. With the replenishment of exogenous cholesterol, hMPV recovered quickly. These data suggest that lipid raft plays an important role in hMPV endocytosis and maybe one of the pathways for hMPV cell entry.