Miracle-dz/UniFAR-FTUs huggingface dataset:
Can natural killer cell activity help screen patients requiring a biopsy for the diagnosis of prostate cancer?

ABSTRACT Purpose To evaluate the usefulness of natural killer cell activity (NKA) in diagnosing prostate cancer (PC). Materials and Methods The medical records of patients who underwent transrectal prostate biopsy (TRBx) at Korea University Ansan Hospital between May 2017 and December 2017 were retrospectively reviewed. NKA levels were measured using NK Vue® Tubes (ATgen, Sungnam, Korea). All blood samples were obtained at 8 AM on the day of biopsy. Patients with other malignancies, chronic inflammatory conditions, high prostate-specific antigen (PSA) level (>20ng/mL), or history of taking 5-alpha-reductase inhibitor or testosterone replacement therapy were excluded. Results A total of 102 patients who underwent TRBx for PC diagnosis were enrolled. Among them, 50 were diagnosed with PC. Significant differences in age and NKA level were observed between the PC and no-PC groups. Receiver operating characteristic (ROC) curve analysis showed that the optimal cut-off of NKA level for the prediction of PC was 500pg/dL, with a sensitivity of 68.0% and a specificity of 73.1%. In addition, NKA level (0.630) had the greatest area under the ROC curve compared to those for the ratio of total PSA to free PSA (0.597) and PSA density (0.578). Conclusions The results of this pilot study revealed that low NKA and high PSA levels were likely to be associated with a positive TRBx outcome. NKA detection was easy and improved the diagnostic accuracy of PC.
Periostin induces epithelial-to-mesenchymal transition via the integrin α5β1/TWIST-2 axis in cholangiocarcinoma

Periostin (PN) (also known as osteoblast-specific factor OSF-2) is a protein that in humans is encoded by the POSTN gene and has been correlated with a reduced survival of cholangiocarcinoma (CCA) patients, with the well-known effect of inducing epithelial-to-mesenchymal transition (EMT). The present study investigated the effect of PN, through integrin (ITG)α5β1, in EMT-mediated CCA aggressiveness. The alterations in EMT-related gene and protein expression were investigated by real-time PCR, western blot analysis and zymogram. The effects of PN on migration and the level of TWIST-2 were assessed in CCA cells with and without siITGα5 transfection. PN was found to induce CCA cell migration and EMT features, including increments in Twist-related protein 2 (TWIST-2), zinc finger protein SNAI1 (SNAIL-1), α-smooth muscle actin (ASMA), vimentin (VIM) and matrix metallopeptidase 9 (MMP-9), and a reduction in cytokeratin 19 (CK-19) together with cytoplasmic translocation of E-cadherin (CDH-1). Additionally, PN markedly induced MMP-9 activity. TWIST-2 was significantly induced in PN-treated CCA cells; this effect was attenuated in the ITGα5β1-knockdown cells and corresponded to reduced migration of the cancer cells. These results indicated that PN induced CCA migration through ITGα5β1/TWIST-2-mediated EMT. Moreover, clinical samples from CCA patients showed that higher levels of TWIST-2 were significantly correlated with shorter survival time. In conclusion, the ITGα5β1-mediated TWIST-2 signaling pathway regulates PN-induced EMT in CCA progression, and TWIST-2 is a prognostic marker of poor survival in CCA patients.
Patterns of Suffering in Palliative Care: A Descriptive Study

Suffering experiences are common phenomena in palliative care. In this study, we aim to explore the different patterns of suffering in palliative care. Adult palliative care patients were recruited from the University of Malaya Medical Centre. Suffering scores were charted 3 times a day for a week. The characteristics of the suffering charts were analyzed using SPSS. The patterns of suffering were analyzed using structural pattern recognition. A total of 53 patients participated. The overall trends of suffering were downward (64%), upward (19%), and stable (17%). Median minimum and maximum suffering scores were 2/10 and 6/10, with an average of 3.6/10. Nine patterns of suffering were recognized from categorizing two key characteristics of suffering (intensity and fluctuation)—named S1 to S9. Understanding the different patterns of suffering may lead to better suffering management.
Is pulmonary vein isolation enough for persistent atrial fibrillation?

Pulmonary vein isolation (PVI) is a well‐established treatment for atrial fibrillation (AF); however, studies report suboptimal outcomes in persistent AF. Adjuvant ablation targeting the substrate outside the pulmonary veins has been proposed to improve the success rates of the procedure. In this review, we summarize the current evidence regarding additional ablation over PVI in persistent AF. We describe the different approaches for adjuvant ablation, outcomes, and future perspectives.
Association of post‐reperfusion syndrome and ischemia‐reperfusion injury with acute kidney injury after liver transplantation

Acute kidney injury (AKI) is frequently observed after orthotopic liver transplantation (OLT) even in patients with previously normal renal function. In this study, we investigated the impact of factors such graft steatosis, post‐reperfusion syndrome (PRS), and hepatic ischemia reperfusion injury (HIRI) on the development of AKI after OLT in adult patients.
Enjoyable, engaging and individualised: A concept analysis of meaningful activity for older adults with dementia.

AIM The term "meaningful activity" is widely used in policy, practice and the research literature. However, definition and use of the term is unclear and inconsistent. A concept analysis was conducted to explore the fundamental attributes that make an activity meaningful for older adults with dementia and propose a conceptual model for understanding "meaningful activity" in this population. METHODS This study followed Walker and Avant's method of concept analysis. Searches were conducted in the Scopus, MEDLINE, CINAHL, PubMed, Academic Search Elite and Web of Science databases for literature using the term "meaningful activity. " Papers published before 1996 were excluded. RESULTS Twenty-nine papers concerned with "meaningful activity" were analysed. This analysis identified five attributes that make activities meaningful for people with dementia: (a) enjoyable; (b) suited to the individual's skills, abilities and preferences; (c) related to personally relevant goals; (d) engaging; and (e) related to an aspect of identity. The conceptual model illustrates how individual and opportunity factors influence participation in "meaningful activity" and the consequences of this participation as discussed in the existing literature. CONCLUSION The findings of this concept analysis provide insight into what characteristics make an activity meaningful. Specific activities that are meaningful are different for each person and participation in personally 'meaningful activities' has the potential to positively impact the lives of people with dementia. IMPLICATIONS FOR PRACTICE This understanding of 'meaningful activity' can be used by those involved in research, planning or delivery of services and care for people with dementia to encourage and support participation in activities that are meaningful to individuals.
Genetic Dissection of Alzheimer’s Disease Using Drosophila Models

Alzheimer’s disease (AD), a main cause of dementia, is the most common neurodegenerative disease that is related to abnormal accumulation of the amyloid β (Aβ) protein. Despite decades of intensive research, the mechanisms underlying AD remain elusive, and the only available treatment remains symptomatic. Molecular understanding of the pathogenesis and progression of AD is necessary to develop disease-modifying treatment. Drosophila, as the most advanced genetic model, has been used to explore the molecular mechanisms of AD in the last few decades. Here, we introduce Drosophila AD models based on human Aβ and summarize the results of their genetic dissection. We also discuss the utility of functional genomics using the Drosophila system in the search for AD-associated molecular mechanisms in the post-genomic era.
Plasma screening for the T790M mutation of EGFR and phase 2 study of osimertinib efficacy in plasma T790M–positive non–small cell lung cancer: West Japan Oncology Group 8815L/LPS study

Liquid biopsy allows the identification of patients whose tumors harbor specific mutations in a minimally invasive manner. No prospective data have been available for the efficacy of osimertinib in patients with non–small cell lung cancer (NSCLC) who develop resistance to first‐ or second‐generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) and who test positive for the TKI resistance–conferring T790M mutation of EGFR by liquid biopsy. Therefore, a phase 2 study was conducted to assess the efficacy and safety of osimertinib in such patients.
P2X7 receptor‐targeted regulation by tetrahydroxystilbene glucoside in alcoholic hepatosteatosis: A new strategy towards macrophage–hepatocyte crosstalk

Regulating macrophage–hepatocyte crosstalk through P2X7 receptors has led to new pharmacological strategies to reverse alcoholic hepatosteatosis. We investigated how tetrahydroxystilbene glucoside (2354glu), isolated from Polygonum multiflorum, modulates macrophage–hepatocyte crosstalk during alcoholic hepatosteatosis.
Understanding Failure and Improving Treatment Using HDAC Inhibitors for Prostate Cancer

Novel treatment regimens are required for castration-resistant prostate cancers (CRPCs) that become unresponsive to standard treatments, such as docetaxel and enzalutamide. Histone deacetylase (HDAC) inhibitors showed promising results in hematological malignancies, but they failed in solid tumors such as prostate cancer, despite the overexpression of HDACs in CRPC. Four HDAC inhibitors, vorinostat, pracinostat, panobinostat and romidepsin, underwent phase II clinical trials for prostate cancers; however, phase III trials were not recommended due to a majority of patients exhibiting either toxicity or disease progression. In this review, the pharmacodynamic reasons for the failure of HDAC inhibitors were assessed and placed in the context of the advancements in the understanding of CRPCs, HDACs and resistance mechanisms. The review focuses on three themes: evolution of androgen receptor-negative prostate cancers, development of resistance mechanisms and differential effects of HDACs. In conclusion, advancements can be made in this field by characterizing HDACs in prostate tumors more extensively, as this will allow more specific drugs catering to the specific HDAC subtypes to be designed.
Multifaceted Analyses of Epidermal Serine Protease Activity in Patients with Atopic Dermatitis

The serine proteases kallikrein-related peptidase (KLK) 5 and KLK7 cleave cell adhesion molecules in the epidermis. Aberrant epidermal serine protease activity is thought to play an important role in the pathogenesis of atopic dermatitis (AD). We collected the stratum corneum (SC) from healthy individuals (n = 46) and AD patients (n = 63) by tape stripping and then measuring the trypsin- and chymotrypsin-like serine protease activity. We also analyzed the p.D386N and p.E420K of SPINK5 variants and loss-of-function mutations of FLG in the AD patients. The serine protease activity in the SC was increased not only in AD lesions but also in non-lesions of AD patients. We found, generally, that there was a positive correlation between the serine protease activity in the SC and the total serum immunoglobulin E (IgE) levels, serum thymus and activation-regulated chemokine (TARC) levels, and peripheral blood eosinophil counts. Moreover, the p.D386N or p.E420K in SPINK5 and FLG mutations were not significantly associated with the SC’s serine protease activity. Epidermal serine protease activity was increased even in non-lesions of AD patients. Such activity was found to correlate with a number of biomarkers of AD. Further investigations of serine proteases might provide new treatments and prophylaxis for AD.
A framework to support the development of quality simulation-based learning programmes in speech-language pathology.

BACKGROUND Simulation-based learning provides students with a safe learning environment, guaranteed exposure to specific clinical scenarios and patients, time for reflection and repetition of tasks, and an opportunity to receive feedback from multiple sources. Research including studies specific to allied health training programmes have demonstrated that simulation-based learning also helps increase learners' confidence and reduces anxiety related to clinical environments, activities and skills. Such evidence, together with increasing challenges in provision of workplace clinical education, has supported an expansion of integrating simulation-based learning into university curricula. AIMS To provide detailed information about the processes and considerations involved in the development of a simulation-based learning programme for speech-language pathology. METHODS & PROCEDURES Through reflection on the development process of a 5-day simulation-based learning programme, and in light of existing research in simulation, this paper outlines the important steps and considerations required for the development of a simulation-based learning programme to support student competency development in adult speech pathology range of practice areas. MAIN CONTRIBUTION A proposed framework for the development of future simulation-based learning programmes in speech-language pathology. CONCLUSIONS & IMPLICATIONS The framework can be applied to simulation-based learning for university programmes and/or workplace training in speech-language pathology and across several other health disciplines.
Incidence of Celiac Disease Is Increasing Over Time: A Systematic Review and Meta-analysis.

OBJECTIVES To conduct a systematic review and meta-analysis that defines the worldwide incidence of celiac disease (CD) and examines temporal trends. METHODS MEDLINE and EMBASE were searched for population-based studies reporting the incidence of CD in the overall population, children, or adults. No limits were placed on year or language of publication. Studies solely examining at-risk populations (e.g., patients with type 1 diabetes) were excluded. Random-effects models were performed to meta-analyze sex- and age-specific incidence in the 21st century. Temporal trend analyses assessed the average annual percent change in CD incidence over time. RESULTS Of 11,189 citations, 86 eligible studies were identified for inclusion, of which 50 were deemed suitable for analyses. In the 21st century, the pooled female incidence of CD was 17.4 (95% confidence interval [CI]: 13.7, 21.1) (I = 99.5%) per 100,000 person-years, compared with 7.8 (95% CI: 6.3, 9.2) (I = 98.6%) in males. Child-specific incidence was 21.3 per 100,000 person-years (95% CI: 15.9, 26.7) (I = 99.7%) compared with 12.9 (95% CI: 7.6, 18.2) (I = 99.9%) in adults. Pooling average annual percent changes showed the incidence of CD to be increasing by 7.5% (95% CI: 5.8, 9.3) (I = 79.6%) per year over the past several decades. DISCUSSION Incidence of CD is highest in females and children. Overall, the incidence has been significantly rising in the latter half of the 20th century and into the 21st century throughout the Western world. Population-based studies in Africa, Asia, and Latin America are needed to provide a comprehensive picture of the global incidence of CD.
A Randomized Trial of Empagliflozin to Increase Plasma Sodium Levels in Patients with the Syndrome of Inappropriate Antidiuresis.

BACKGROUND Treatment options to address the hyponatremia induced by the syndrome of inappropriate antidiuresis (SIAD) are inadequate. The sodium glucose cotransporter 2 (SGLT2) inhibitor empagliflozin promotes osmotic diuresis via urinary glucose excretion and therefore, might offer a novel treatment option for SIAD. METHODS In this double-blind, randomized trial, we recruited 88 hospitalized patients with SIAD-induced hyponatremia <130 mmol/L at the University Hospital Basel from September 2016 until January 2019 and assigned patients to receive, in addition to standard fluid restriction of <1000 ml/24 h, a once-daily dose of oral empagliflozin or placebo for 4 days. The primary end point was the absolute change in plasma sodium concentration after 4 days of treatment. Secondary end points included predisposing factors for treatment response and safety of the intervention. RESULTS Of the 87 patients who completed the trial, 43 (49%) received treatment with empagliflozin, and 44 (51%) received placebo. Baseline plasma sodium concentrations were similar for the two groups (median 125.5 mmol/L for the empaflozin group and median 126 mmol/L for the placebo group). Patients treated with empagliflozin had a significantly higher increase of median plasma sodium concentration compared with those receiving placebo (10 versus 7 mmol/L, respectively; P=0.04). Profound hyponatremia (<125 mmol/L) and lower baseline osmolality levels increased the likelihood of response to treatment with empagliflozin. Treatment was well tolerated, and no events of hypoglycemia or hypotension occurred among those receiving empagliflozin. CONCLUSIONS Among hospitalized patients with SIAD treated with fluid restriction, those who received empagliflozin had a larger increase in plasma sodium levels compared with those who received placebo. This finding indicates that empagliflozin warrants further study as a treatment for the disorder.
Robotics for catheter ablation of cardiac arrhythmias: Current technologies and practical approaches

Robotic technology has emerged as an important tool to facilitate catheter ablation of arrhythmias. Robotic cardiac electrophysiology technology includes remote magnetic navigation and manual robotic navigation. Robotics can confer advantages with respect to ease of catheter manipulation in anatomically challenging spaces, minimization of fluoroscopic exposure to both patients and operators, and reduction in operator fatigue. This review provides a comprehensive summary of robotic electrophysiology technology, its practical applications and its safety and efficacy for targeting cardiac arrhythmias.
Structure and function of crocodilian hemoglobins and allosteric regulation by chloride, ATP and CO2.

Hemoglobins (Hbs) of crocodilians are reportedly characterized by unique mechanisms of allosteric regulatory control, but there are conflicting reports regarding the importance of different effectors such as chloride ions, organic phosphates, and CO2. Progress in understanding the unusual properties of crocodilian Hbs has also been hindered by a dearth of structural information. Here we present the first comparative analysis of blood properties and Hb structure and function in a phylogenetically diverse set of crocodilian species. We examine mechanisms of allosteric regulation in the Hbs of 13 crocodilian species belonging to the families Crocodylidae and Alligatoridae. We also report new amino acid sequences for the α- and β-globins of these taxa which, in combination with structural analyses, provide insights into molecular mechanisms of allosteric regulation. All crocodilian Hbs exhibited a remarkably strong sensitivity to CO2, which would permit effective O2 unloading to tissues in response to an increase in metabolism during intense activity and diving. Although the Hbs of all crocodilians exhibit similar intrinsic O2-affinities, there is considerable variation in sensitivity to Cl- ions and ATP, which appears to be at least partly attributable to variation in the extent of N-terminal acetylation. Whereas chloride appears to be a potent allosteric effector of all crocodile Hbs, ATP has a strong, chloride-independent effect on Hb-O2 affinity only in caimans. Modeling suggests that allosteric ATP-binding has a somewhat different structural basis in crocodilian and mammalian Hbs.
Gradients in the mammalian cerebellar cortex enable Fourier-like transformation and improve storing capacity

Cerebellar granule cells (GCs) make up the majority of all neurons in the vertebrate brain, but heterogeneities among GCs and potential functional consequences are poorly understood. Here, we identified unexpected gradients in the biophysical properties of GCs in mice. GCs closer to the white matter (inner-zone GCs) had higher firing thresholds and could sustain firing with larger current inputs than GCs closer to the Purkinje cell layer (outer-zone GCs). Dynamic Clamp experiments showed that inner- and outer-zone GCs preferentially respond to high- and low-frequency mossy fiber inputs, respectively, enabling dispersion of the mossy fiber input into its frequency components as performed by a Fourier transformation. Furthermore, inner-zone GCs have faster axonal conduction velocity and elicit faster synaptic potentials in Purkinje cells. Neuronal network modeling revealed that these gradients improve spike-timing precision of Purkinje cells and decrease the number of GCs required to learn spike-sequences. Thus, our study uncovers biophysical gradients in the cerebellar cortex enabling a Fourier-like transformation of mossy fiber inputs.
Interactions of sprint interval exercise and psychological need-support on subsequent food intake among physically inactive men and women.

The aim of this study was to investigate the effect of sprint interval exercise (SIT) and psychological need-support in exercise on post-exercise appetite and energy intake. Forty physically inactive men and women (BMI 24.6 ± 4.8 kg·m-2, V̇O2peak 26.6 ± 4.9 mL·kg-1·min-1) were randomised to either a need-support or no-support condition, with each participant completing two experimental trials involving 30 min of moderate-intensity continuous cycling (MICT; 60% V̇O2peak) and SIT (alternating 15 s at 170% V̇O2peak and 60 s at 32% V̇O2peak) matched for total work. Perceptions of appetite and appetite-related blood variables were assessed, together with ad libitum energy intake for three hours following exercise using a laboratory test meal and available snacks. Greater enjoyment, perceived exertion, heart rate, and blood lactate were observed in SIT compared with MICT (all p ≤ 0.006). Ratings of perceived appetite were similar across conditions and trials (p > 0.05); however, active ghrelin was lower following SIT compared with MICT (p < 0.001), and there was a significant condition-by-type interaction for energy intake (p = 0.033), with participants in the support group consuming less energy from foods following SIT (1895 ± 1040 kJ) than MICT (2475 ± 1192 kJ). Findings from this work highlight the need to reconsider traditional exercise guidelines where dietary intake is a concern. Novel points: - Enjoyment was greater during SIT compared with MICT - Enjoyment and choice were higher among participants provided with psychological need-support - In a need-supportive environment, SIT reduced subsequent energy intake compared with MICT.