Miracle-dz/UniFAR-FTUs huggingface dataset:
An Electrophilic Deguelin Analogue Inhibits STAT3 Signaling in H-Ras-Transformed Human Mammary Epithelial Cells: The Cysteine 259 Residue as a Potential Target

Signal transducer and activator of transcription 3 (STAT3) is a point of convergence for numerous oncogenic signals that are often constitutively activated in many cancerous or transformed cells and some stromal cells in the tumor microenvironment. Persistent STAT3 activation in malignant cells stimulates proliferation, survival, angiogenesis, invasion, and tumor-promoting inflammation. STAT3 undergoes activation through phosphorylation on tyrosine 705, which facilitates its dimerization. Dimeric STAT3 translocates to the nucleus, where it regulates the transcription of genes involved in cell proliferation, survival, etc. In the present study, a synthetic deguelin analogue SH48, discovered by virtual screening, inhibited the phosphorylation, nuclear translocation, and transcriptional activity of STAT3 in H-ras transformed human mammary epithelial MCF-10A cells (MCF10A-ras). We speculated that SH48 bearing an α,β-unsaturated carbonyl group could interact with a thiol residue of STAT3, thereby inactivating this transcription factor. Non-electrophilic analogues of SH48 failed to inhibit STAT3 activation, lending support to the above supposition. By utilizing a biotinylated SH48, we were able to demonstrate the complex formation between SH48 and STAT3. SH48 treatment to MCF10A-ras cells induced autophagy, which was verified by staining with a fluorescent acidotropic probe, LysoTracker Red, as well as upregulating the expression of LC3II and p62. In conclusion, the electrophilic analogue of deguelin interacts with STAT3 and inhibits its activation in MCF10A-ras cells, which may account for its induction of autophagic death.
Prevalence of burnout among intensive care physicians: a systematic review

Objective We performed a systematic review to summarize the knowledge regarding the prevalence of burnout among intensive care unit physicians. Methods We conducted a systematic review of the MEDLINE and PubMed® databases (last update 04.02.2019) with the goal of summarizing the evidence on burnout among intensive care unit physicians. We included all studies reporting burnout in intensive care unit personnel according to the Maslach Burnout Inventory questionnaire and then screened studies for data on burnout among intensive care unit physician specifically. Results We found 31 studies describing burnout in intensive care unit staff and including different healthcare profiles. Among these, 5 studies focused on physicians only, and 12 others investigated burnout in mixed intensive care unit personnel but provided separate data on physicians. The prevalence of burnout varied greatly across studies (range 18% - 49%), but several methodological discrepancies, among them cut-off criteria for defining burnout and variability in the Likert scale, precluded a meaningful pooled analysis. Conclusion The prevalence of burnout syndrome among intensive care unit physicians is relatively high, but significant methodological heterogeneities warrant caution being used in interpreting our results. The lower reported levels of burnout seem higher than those found in studies investigating mixed intensive care unit personnel. There is an urgent need for consensus recommending a consistent use of the Maslach Burnout Inventory test to screen burnout, in order to provide precise figures on burnout in intensive care unit physicians.
Competitive Performance of Kenyan Runners Compared to their Relative Body Weight and Fat

Abstract Body fat values obtained with various measurement methods deviate substantially in many cases. The standardised brightness-mode ultrasound method was used in 32 Kenyan elite long-distance runners to measure subcutaneous adipose tissue thicknesses at an accuracy and reliability level not reached by any other method. Subcutaneous adipose tissue forms the dominating part of body fat. Additionally, body mass (m), height (h), sitting height (s), leg length, and the mass index MI1 =0.53m/(hs) were determined. MI1 considers leg length, which the body mass index ignores. MI1 values of all participants were higher than their body mass indices. Both indices for relative body weight were within narrow ranges, although thickness sums of subcutaneous adipose tissue deviated strongly (women: 20–82 mm; men: 3–36 mm). Men had 2.1 times more embedded fasciae in the subcutaneous adipose tissue. In the subgroup with personal best times below world record time plus 10%, no correlation between performance and body mass index was found, and there was also no correlation with sums of subcutaneous adipose tissue thicknesses. Within the data ranges found here, extremely low relative body weight or low body fat were no criteria for the level of performance, therefore, pressure towards too low values may be disadvantageous.
Glycemic Control and Variability of Diabetes Secondary to Total Pancreatectomy Assessed by Continuous Glucose Monitoring.

CONTEXT The extent of the glycemic variability in diabetes secondary to total pancreatectomy is not fully understood. OBJECTIVE To evaluate glycemic variability in totally pancreatectomized (PX) patients and compare it to glycemic variability in HbA1c-matched patients with long-standing type 1 diabetes (T1D). DESIGN a case-control study was performed. SETTING Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen. PATIENTS OR OTHER PARTICIPANTS Ten PX patients (mean(SEM): age 64.3(9.8) years; Body Mass Index (BMI) 34.4(5.0) kg/m 2; duration of diabetes 3(2.8) years), 10 HbA1c-matched patients with T1D (63.9(8.6) years; 24.6(3.1) kg/m 2; 22(4) years) and 10 gender, age and BMI-matched healthy controls (CTRLs), All patients were managed on multiple daily injections of insulin. INTERVENTION Continuous glucose monitoring (CGM) (Medtronic MiniMed iPro 2) during twelve consecutive days. MAIN OUTCOME MEASURES Glycemic Variability. RESULTS HbA1c levels were similar in the PX group and the T1D group. The PX group had greater CONGA60min compared to the T1D group (mean(SEM): 9.5(0.3) vs 8.3(0.2) mmol/L, P<0.003) and mean plasma glucose values were higher in the PX group (10.6(0.9) vs 9.0(0.9) mmol/L, P<0.001) while CVpg and SDpg, respectively, were similar in the two groups. Time spent below range was not different between the PX and the T1D group (2.3(0.8) vs 4.5(0.8) %, P=0.065) while time spent above range was higher in the PX group (51.4(3.3) vs 37.6(1.9) %, P<0.001). CONCLUSIONS CGM-assessed glycemic variability showed higher CONGA60 min and time spent above range in our PX patients compared with HbA1c-matched T1D patients.
SCF FBXW17 E3 ubiquitin ligase regulates FBXL19 stability and cell migration

The Skp1‐Cul1‐F‐box protein (SCF) E3 ligase complex is one of the largest ubiquitin E3 ligase families. FBXL19, a F‐box protein in SCFFBXL19 E3 ligase complex, regulates a variety of cellular responses including cell migration. We have shown that FBXL19 is not stable and its degradation is mediated by the ubiquitin–proteasome system, while the ubiquitin E3 ligase for FBXL19 ubiquitination and degradation has not been identified. In the study, we discovered that a new ubiquitin E3 ligase, SCFFBXW17, ubiquitinates and induces FBXL19 degradation. Exogenous FBXW17 targets FBXL19 for its ubiquitination and degradation. Lysine 114 in FBXL19 is a potential ubiquitin acceptor site. Acetylation of FBXL19 attenuated SCFFBXW17‐mediated FBXL19 degradation. SCFFBXL19 E3 ligase reduced Rac1 levels and cell migration, while the effects were attenuated by exogenous FBXW17. Downregulation of FBXW17 attenuated lysophosphatidic acid‐induced lamellipodia formation and Rac1 accumulation at migration leading edge. Taken together with our previous studies, FBXL19 is degraded by the ubiquitin–proteasome system and its site‐specific ubiquitination is mediated by SCFFBXW17 E3 ligase, which promotes cell migration.
Evaluation of bed vacancy and occupancy times as governance parameters in patients admitted to a public intensive care unit

Objective To evaluate the vacancy and occupancy times of intensive care unit beds; to analyze differences in these times between the day and night shifts and weekdays, weekends, and holidays; and to identify predictors of vacancy and occupancy times. Methods This was a cross-sectional, observational, descriptive, analytical, inferential study. A total of 700 vacancy-to-occupancy records from 54 beds of an adult intensive care unit of a public hospital in Sergipe, Brazil, dated between January and December 2018 were analyzed. The nonparametric Mann-Whitney test was used for comparisons between groups. Several predictive models of length of stay were constructed. The incidence rate ratio was used to estimate the effect size. Results During the study period, there were 13,477 requests for the 54 intensive care unit beds, and only 5% (700 patients) were granted. The vacancy-to-occupancy times were shorter when beds were occupied at night (incidence rate ratio of 0.658; 95%CI 0.550 - 0.787; p < 0.0001) or on weekends (incidence rate ratio of 0.566; 95%CI 0.382 - 0.838; p = 0.004). Female sex (incidence rate ratio of 0.749; 95%CI 0.657 - 0.856; p < 0.0001) was a predictor of shorter vacancy-to-occupancy time. This time tended to increase with patient age (incidence rate ratio of 1.006; 95% CI 1.003 - 1.009; p < 0.0001). Conclusion Disparities in the waiting time for intensive care unit beds were identified, as the time was greater in the daytime and on weekdays, and women and younger patients experienced shorter vacancy-to-occupancy times.
Comparing the Use of Spatially Explicit Indicators and Conventional Indicators in the Evaluation of Healthy Cities: A Case Study in Shenzhen, China

Various indicator systems have been developed to monitor and assess healthy cities. However, few of them contain spatially explicit indicators. In this study, we assessed four health determinants in Shenzhen, China, using both indicators commonly included in healthy city indicator systems and spatially explicit indicators. The spatially explicit indicators were developed using detailed building information or social media data. Our results showed that the evaluation results of districts and sub-districts in Shenzhen based on spatially explicit indicators could be positively, negatively, or not associated with the evaluation results based on conventional indicators. The discrepancy may be caused by the different information contained in the two types of indicators. The spatially explicit indicators measure the quantity of the determinants and the spatial accessibility of these determinants, while the conventional indicators only measure the quantity. Our results also showed that social media data have great potential to represent the high-resolution population distribution required to estimate spatially explicit indicators. Based on our findings, we recommend that spatially explicit indicators should be included in healthy city indicator systems to allow for a more comprehensive assessment of healthy cities.
Amino Acid Sensing in Metabolic Homeostasis and Health.

Sensing and responding to changes in nutrient levels, including those of glucose, lipids and amino acids, by the body is necessary for survival. Accordingly, perturbations in nutrient sensing are tightly linked with human pathologies, particularly metabolic diseases such as obesity, type 2 diabetes mellitus and other complications of metabolic syndromes. The conventional view is that amino acids are fundamental elements for protein and peptide synthesis, while recent studies have revealed that amino acids are also important bioactive molecules that play key roles in signaling pathway and metabolic regulation. Different pathways that sense intracellular and extracellular levels of amino acids are integrated and coordinated at the organismal level, and together, these pathways maintain whole metabolic homeostasis. In this review, we discuss the studies describing how important sensing signals respond to amino acid availability and how these sensing mechanisms modulate metabolic processes, including energy, glucose and lipid metabolism. We further discuss whether dysregulation of amino acid sensing signals can be targeted to promote metabolic disorders, and discuss how to translate these mechanisms to treat human diseases. This review will help to enhance our overall understanding of the correlation between amino acid sensing and metabolic homeostasis, which would be important implications for human health.
Influence of Abdominal Hollowing Maneuver on the Core Musculature Activation during the Prone Plank Exercise

This cross-sectional study of repeated measures investigated whether integrating the abdominal hollowing maneuver (AHM) into the prone plank performance is an effective strategy for increasing both the activation of the deep and superficial core musculature. Electromyographical (EMG) responses of rectus abdominis (RA), external oblique (EO), internal oblique (IO), and lumbar erector spinae (LES), and ratings of perceived exertion (RPE) of 20 participants (13 male, 7 female; mean ± standard deviation (SD) age: 24.25 ± 3.54 years; body mass: 66.42 ± 8.40 kg; height: 1.70 ± 9.51 m) were compared across two experimental conditions: the traditional prone plank (STANDARD); and a variation including the AHM (HOLLOWING). Regarding Total Intensity, HOLLOWING resulted in significantly greater EMG response than STANDARD (p < 0.001; Effect size (ES) = 3.01). Specifically, RA showed no significant differences between STANDARD and HOLLOWING (p = 0.056; ES = 0.285). However, for the remaining analyzed muscles, HOLLOWING significantly provided higher EMG activation compared to STANDARD (LES: p = 0.004; ES = 0.619; left EO: p < 0.001; ES = 1.031; right EO: p < 0.001; ES = 1.419; left IO: p < 0.001; ES = 2.021; right IO: p < 0.001; ES = 2.269). Regarding RPE, HOLLOWING reported values significantly greater than STANDARD (p < 0.001; ES = 2.94). In conclusion, integrating the AHM into the prone plank exercise enhances overall abdominal activity, particularly in both obliques. These findings provide updated guidelines for lumbar stabilization and core strengthening in health-related physical fitness programs.
Cardiovascular Events throughout the Disease Course in Chronic Myeloid Leukaemia Patients Treated with Tyrosine Kinase Inhibitors—A Single-Centre Retrospective Study

Introduction. Cardiovascular risk factors, pre-existing comorbidities, molecular factors, and the direct effects of second- and third-generation BCR-ABL1 tyrosine kinase inhibitors on the vascular endothelium contribute to the progression of cardiovascular (CV) events, especially atherothrombotic conditions. The study objective was to evaluate comorbidities, the cardiovascular risk profile, and events throughout the chronic myeloid leukaemia disease course. Methods. Retrospective data from adults who experienced haematology treatment at a single centre were continuously updated and followed throughout the disease course. A total of 43 subjects conforming with the inclusion and exclusion criteria of the study protocol were finally recruited. The median disease course was 77.0 ± 17.5 months. Statistical analyses were performed. Results. More than three CV risk factors were identified in 41.9% of cases. Almost half of the cases had relevant comorbidities (Charlson Comorbidity Index (CCI) ≥ 4), and no statistically significant comorbidities were found when comparing the tyrosine kinase inhibitor (TKI) treatment subgroups (p = 0.53). The patients at high and very high CV risk, according to Systematic Coronary Risk Evaluation (SCORE) risk classification, had 75.0% CV events (12/22 patients), p = 0.45. Throughout the disease course, 19 cardiovascular events were reported in 37.2% patients (13 males/3 females, p < 0.03). Conclusion. To the best of our knowledge, this is the first study exploring cardiovascular risk factors in Romanian chronic myeloid leukaemia patients. This study reinforces the need for close long-term follow-up that should be performed by a multidisciplinary team. The target should be not only the disease and specific drug-related toxicities but, also, the identification of cardiovascular and metabolic risk factors before the commencement of and throughout TKI therapy.
The relationship between disability and clinical outcomes in maintenance dialysis patients

Background Dialysis patients are prone to having disabilities. We aimed to evaluate the association between disability and various clinical outcomes in Korean dialysis patients. Methods This study consisted of 1,615 dialysis patients from 27 centers. We evaluated disability by using four questions on the activities of daily living (ADLs) concerning whether help was needed for feeding, dressing/undressing, getting in/out of bed, or taking a bath/shower. We divided the patients into three groups: no disability (Non-D, none of the four ADL domains required help; n=1,312), mild disability (Mild-D, one ADL domain required some/full help; n=163), or moderate to severe disability (MS-D, two or more ADL domains required some/full help; n=140). We evaluated falls, frailty, health-related quality of life (HRQoL), mortality, and hospitalization. Results The numbers of participants with a fall during the last 1 year were 199 (15.2%), 42 (25.8%), and 44 (31.4%) in the Non-D, Mild-D, and MS-D groups, respectively (p<0.001). The numbers of participants with frailty in the Non-D, Mild-D, and MS-D groups were 381 (29.0%), 84 (51.5%), and 93 (66.4%), respectively (p<0.001). In both univariate and multivariate analyses, the physical component scale and mental component scale scores decreased as the grade of disability increased (p<0.001 for both scores). Hospitalization-free survival rate at 500 days was 64.2%, 56.7%, and 51.1% in the Non-D, Mild-D, and MS-D, respectively (p=0.001 for trend). Patient survival rate at 500 days was 95.3%, 89.5%, and 92.3% in the Non-D, Mild-D, and MS-D, respectively (p=0.005 for trend). Conclusion Disability was associated with falls, frailty, HRQoL scales, and survival trends in Korean dialysis patients.
Is Thulium laser enucleation of prostate an alternative to Holmium and TURP surgeries -A systematic review?

To assess efficacy and safety of Thulium laser enucleation of prostate (ThuLEP) for benign prostatic hyperplasia. It is a systemic review based on a comprehensive search of PubMed, Cochrane, and Google scholar databases from inception to 31 March 2020. All studies in English evaluating ThuLEP as well as those comparing it with Transurethral resection of prostate (TURP) and Holmium Laser enucleation of prostate (HoLEP) were enrolled. The primary outcome was to evaluate operative, postoperative, and functional outcomes (IPSS, QoL, Qmax, PVR) in patients undergoing ThuLEP. Secondary outcome was to compare operative, postoperative, and functional outcomes with TURP and HoLEP in comparative studies. Fourteen studies with a total of 2,562 patients were included in this review. 2,034 underwent ThuLEP, 349 underwent TURP, and remaining 139 had HoLEP. We found that ThuLEP is safe as well as efficacious in all age groups as well as across all prostate sizes and with all four functional outcomes (IPSS, QoL, Qmax, PVR) revealing marked improvement at 3, 6, 12, and 24 months. Compared to TURP and HoLEP, Thulep is non-inferior in terms of operative and functional outcomes and, in fact, is associated with lesser catheterization duration as well as shorter hospital stay. Further, Thulium fiber laser (TFL) has advantages of being light weight, having high frequency, less fiber degradation, and less energy consumption, making it cost effective for operational and maintenance purpose. ThuLEP is a safe, efficacious, and cost-effective procedure for BPE.
Multi-Target Device-Free Wireless Sensing Based on Multiplexing Mechanisms

Device-free wireless sensing (DFWS) is a promising technology which could sense target states without requiring them equipped with any device. In recent years, it has drawn considerable attention due to its potential application in the fields of fatigue driving detection, vital sign monitoring, human-computer interaction, etc. State-of-the-art work has achieved excellent sensing performance when there is one target only. However, when there are multiple targets need to be sensed simultaneously, the influenced signals from different targets will be mixed together, and thus traditional DFWS methods will fail. There still lacks an effective system solution to this problem. Inspired by the multiplexing mechanisms utilized in communication systems, in this paper, we explore and exploit the idea of separating and extracting the influenced signal from each target by leveraging three novel multiplexing mechanisms, i.e., angle division multiplexing sensing, range division multiplexing sensing, and source division multiplexing sensing, and thus realize multi-target DFWS accordingly. Meanwhile, we also give theory analysis on the sensing capability of the proposed multiplexing mechanism based multi-target sensing systems. Furthermore, taking multi-target vital sign monitoring as a case study, we develop a 77 GHz FMCW hardware based prototype system, and evaluate the proposed mechanisms extensively. Experimental results reveal the effectiveness of the proposed mechanisms.
Living-Lab and Experimental Workshops for Design of I-RobEka Assistive Shopping Robot: ELSI Aspects with MEESTAR

If robotic assistance is to be used in the near future by aging adults, it must have an acceptable design. In the process of applying a MEESTAR model in project to measure, predict, and justify the acceptance of robot assistants in a supermarket setting, we investigated the ethical ramifications of these robots. The method used was very well suited for participatory technology development. Does the appearance of the robot affect acceptance? The aim of the exploratory workshops was to gain insights into this question before evaluation in tangible environment. Our research approach, in addition to the construction of the robot, poses a significant difference to the traditional design and evaluation procedure.
Convergent and Concurrent Validity between Clinical Recovery and Personal-Civic Recovery in Mental Health †

Several instruments have been developed by clinicians and academics to assess clinical recovery. Based on their life narratives, measurement tools have also been developed and validated through participatory research programs by persons living with mental health problems or illnesses to assess personal recovery. The main objective of this project is to explore possible correlations between clinical recovery, personal recovery, and citizenship by using patient-reported outcome measures. All study participants are currently being treated and monitored after having been diagnosed either with (a) psychotic disorders or (b) anxiety and mood disorders. They have completed questionnaires for clinical evaluation purposes (clinical recovery) will further complete the Recovery Assessment Scale and Citizenship Measure (personal-civic recovery composite index). Descriptive and statistical analyses will be performed to determine internal consistency for each of the subscales, and assess convergent-concurrent validity between clinical recovery, citizenship and personal recovery. Recovery-oriented mental health care and services are particularly recognizable by the presence of Peer Support Workers, who are persons with lived experience of recovery. Upon training, they can personify personalized mental health care and services, that is to say services that are centered on the person’s recovery project and not only on their symptoms. Data from our overall research strategy will lay the ground for the evaluation of the effects of the intervention of Peer Support Workers on clinical recovery, citizenship and personal recovery.