Miracle-dz/UniFAR-FTUs huggingface dataset:
An Interactive Web Portal for Tracking Oncology Patient Physical Activity and Symptoms: Prospective Cohort Study

Background Physical activity levels typically decline during cancer treatment and often do not return to prediagnosis or minimum recommended levels. Interventions to promote physical activity are needed. Support through the use of digital health tools may be helpful in this situation. Objective The goal of the research was to evaluate the feasibility, usability, and acceptability of an interactive Web portal developed to support patients with cancer to increase daily physical activity levels. Methods A Web portal for supportive cancer care which was developed to act as a patient-clinician information and coaching tool focused on integrating wearable device data and remote symptom reporting. Patients currently receiving or who had completed intensive anticancer therapy were recruited to 3 cohorts. All cohorts were given access to the Web portal and an activity monitor over a 10-week period. Cohort 2 received additional summative messaging, and cohort 3 received personalized coaching messaging. Qualitative semistructured interviews were completed following the intervention. The primary outcome was feasibility of the use of the portal assessed as both the number of log-ins to the portal to record symptoms and the completion of post-program questionnaires. Results Of the 49 people were recruited, 40 completed the intervention. Engagement increased with more health professional contact and was highest in cohort 3. The intervention was found to be acceptable by participants. Conclusions The portal was feasible for use by people with a history of cancer. Further research is needed to determine optimal coaching methods.
No Effect of Plazomicin on the Pharmacokinetics of Metformin in Healthy Subjects

Plazomicin is an aminoglycoside that was engineered to overcome aminoglycoside‐modifying enzymes, which are the most common aminoglycoside resistance mechanism in Enterobacteriaceae. Because plazomicin is predominantly eliminated via renal pathways, an in vitro study was conducted to determine whether plazomicin inhibits the organic cation transporter 2 (OCT2) and the multidrug and toxin extrusion (MATE1 and MATE2‐K) transporters, using metformin as a probe substrate. Plazomicin inhibited OCT2, MATE1, and MATE2‐K transporters with half‐maximal inhibition of the transporter values of 5120, 1300, and 338 µg/mL, respectively. To determine whether this in vitro inhibition translates in vivo, an open‐label, randomized, 2‐period, 2‐treatment crossover study (NCT03270553) was carried out in healthy subjects (N = 16), who received a single oral dose of metformin 850 mg alone and in combination with a single intravenous infusion of plazomicin 15 mg/kg. Geometric least‐squares mean ratios of the test treatment (combination) vs the reference treatment (metformin alone) and 90% confidence intervals were within the equivalence interval of 80% to 125% (peak plasma concentration, 104.5 [95.1–114.9]; area under the plasma concentration–time curve from time zero to time of last quantifiable concentration, 103.7 [93.5–115.0]; area under the plasma concentration–time curve from time zero to infinity, 104.0 [94.2–114.8]). The results demonstrate that there is no clinically significant drug‐drug interaction resulting from coadministration of single doses of intravenous plazomicin 15 mg/kg and oral metformin 850 mg in healthy subjects. Coadministration of plazomicin and metformin was well tolerated in healthy subjects.
Towards a consensus around standards for smartphone apps and digital mental health

Mental disorders impact one in four people worldwide, yet access to care is challenging for those who suffer from them. Mental health apps offer the potential to overcome access bar­ riers for the nearly three billion people projected to own a smart­ phone by 2020. Although there are over 10,000 mental health apps commer­ cially available, there are few resources available to help end users (patients, clinicians and health care organizations) to eval­ uate the quality and suitability of these products. Thus, there is an urgent need for an agreement about appropriate standards, principles and practices in research and evaluation of these tools. We represent leaders in mHealth research, industry and health care systems from around the globe, and we seek here to promote consensus on implementing these standards and principles for the evaluation of mental health apps. At a mini­ mum, standards should include consideration of: a) data safety and privacy, b) effectiveness, c) user experience/adherence, d) data integration. Our consensus on the challenges and recom­ mendations in each of these areas is presented below.
Decreased liver stiffness by transient elastography indicates lower incidence of hepatocellular carcinoma in patients with chronic hepatitis B

Abstract The prognositc value of dynamic liver stiffness (LS) variation on hepatocellular carcinoma (HCC) incidence in patients with chronic hepatitis B (CHB) remains to be explored. We aim to compare HCC incidence in patients with compensated CHB-related cirrhosis with increased and decreased LS after nucleos(t)ide analog (NA) regimens. A total of 168 patients with CHB-related compensated cirrhosis were divided into groups according to LS variation post to NA treatment. The laboratory results of 2 groups were reviewed and investigated. The probability of HCC development among each group was analyzed and compared. A total of 168 patients with CHB with compensated cirrhosis received NA treatment and Fibroscan. Child–Pugh score, alanine aminotransferase, total bilirubin level, status of hepatitis B e antigen, and serum hepatitis B virus DNA level were compared between groups. The cumulative probability of HCC development in patients with decreased LS was significantly lower than in patients with increased LS (P < .05). Multi-variant analysis indicated that decreased LS was significantly associated with lower probability of HCC development (hazard ratio, 0.65; 95% confidence interval range, 0.33–0.84, P < .05). Decreased LS after NA treatment indicates a lower HCC incidence in patients with CHB with compensated cirrhosis.
Fibroblast-like synoviocytes from fluid and synovial membrane from primary osteoarthritis demonstrate similar production of interleukin 6, and metalloproteinases 1 and 3.

OBJECTIVES The objective of the study was to compare the production of metalloproteinases (MMP)-1, -3 and interleukin (IL)-6 by fibroblast-like synoviocytes (FLS) derived from synovial fluid (FD-FLS), and FLS derived from synovial tissue (TD-FLS) of patients with primary osteoarthritis (OA). The more accessible FD-FLS could facilitate the study of the role of these cells in OA pathophysiology. METHODS MMP-1, MMP-3, and IL-6 levels were measured in the supernatant culture at baseline and 22 hours after stimulation with TNF-α and IL-1 β. RESULTS There was no difference at baseline between MMP-1, MMP-3 and IL-6 production by FD-FLS and TDFLS. Analogous to baseline, stimulation of FD-FLS and TD-FLS with IL-1β and TNF-α did not result in difference on MMP-3 and IL-6 production. However, TD-FLS produced more MMP-1 than FD-FLS after stimulation with IL-1β (p=0.01). Additionally, there was a positive correlation for production of MMP-1, MMP-3 and IL-6 between FD-FLS and TD-FLS (r=0.40 and p<0.0008; r=0.66 and p<0.0001; r=0.76 and p<0.0001, respectively). Supporting this statistical significant positive correlation, the Bland-Altman plotting, showed a homogeneous distribution of the values and low mean disagreement rates between all results of FD-FLS and TD-FLS (23.1%, 56.8% and 48.1%, respectively). CONCLUSIONS Our data demonstrated functional similarity between FD-FLS and TD-FLS and support the use of a more accessible source of FLS for the study of the pathogenesis of joint destruction and therapeutic targets in primary OA.
The impact of pharmacological and non‐pharmacological interventions to improve physical health outcomes in people with schizophrenia: a meta‐review of meta‐analyses of randomized controlled trials

We summarized and compared meta‐analyses of pharmacological and non‐pharmacological interventions targeting physical health outcomes among people with schizophrenia spectrum disorders. Major databases were searched until June 1, 2018. Of 3,709 search engine hits, 27 meta‐analyses were included, representing 128 meta‐analyzed trials and 47,231 study participants. While meta‐analyses were generally of adequate or high quality, meta‐analyzed studies were less so. The most effective weight reduction interventions were individual lifestyle counseling (standardized mean difference, SMD=–0.98) and exercise interventions (SMD=–0.96), followed by psychoeducation (SMD=–0.77), aripiprazole augmentation (SMD=–0.73), topiramate (SMD=–0.72), d‐fenfluramine (SMD=–0.54) and metformin (SMD=–0.53). Regarding waist circumference reduction, aripiprazole augmentation (SMD=–1.10) and topiramate (SMD=–0.69) demonstrated the best evidence, followed by dietary interventions (SMD=–0.39). Dietary interventions were the only to significantly improve (diastolic) blood pressure (SMD=–0.39). Switching from olanzapine to quetiapine or aripiprazole (SMD=–0.71) and metformin (SMD=–0.65) demonstrated best efficacy for reducing glucose levels, followed by glucagon‐like peptide‐1 receptor agonists (SMD=–0.39), dietary interventions (SMD=–0.37) and aripiprazole augmentation (SMD=–0.34), whereas insulin resistance improved the most with metformin (SMD=–0.75) and rosiglitazone (SMD=–0.44). Topiramate had the greatest efficacy for triglycerides (SMD=–0.68) and low‐density lipoprotein (LDL)‐cholesterol (SMD=–0.80), whereas metformin had the greatest beneficial effects on total cholesterol (SMD=–0.51) and high‐density lipoprotein (HDL)‐cholesterol (SMD=0.45). Lifestyle interventions yielded small effects for triglycerides, total cholesterol and LDL‐cholesterol (SMD=–0.35 to –0.37). Only exercise interventions increased exercise capacity (SMD=1.81). Despite frequent physical comorbidities and premature mortality mainly due to these increased physical health risks, the current evidence for pharmacological and non‐pharmacological interventions in people with schizophrenia to prevent and treat these conditions is still limited and more larger trials are urgently needed.
Buttonhole versus Stepladder Cannulation for Home Hemodialysis: A Multicenter, Randomized, Pilot Trial.

BACKGROUND AND OBJECTIVES Canadian home hemodialysis guidelines highlight the potential differences in complications associated with arteriovenous fistula (AVF) cannulation technique as a research priority. Our primary objective was to determine the feasibility of randomizing patients with ESKD training for home hemodialysis to buttonhole versus stepladder cannulation of the AVF. Secondary objectives included training time, pain with needling, complications, and cost by cannulation technique. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS All patients training for home hemodialysis at seven Canadian hospitals were assessed for eligibility, and demographic information and access type was collected on everyone. Patients who consented to participate were randomized to buttonhole or stepladder cannulation technique. Time to train for home hemodialysis, pain scores on cannulation, and complications over 12 months was recorded. For eligible but not randomized patients, reasons for not participating in the trial were documented. RESULTS Patient recruitment was November 2013 to November 2015. During this time, 158 patients began training for home hemodialysis, and 108 were ineligible for the trial. Diabetes mellitus as a cause of ESKD (31% versus 12%) and central venous catheter use (74% versus 6%) were more common in ineligible patients. Of the 50 eligible patients, 14 patients from four out of seven sites consented to participate in the study (28%). The most common reason for declining to participate was a strong preference for a particular cannulation technique (33%). Patients randomized to buttonhole versus stepladder cannulation required a shorter time to complete home hemodialysis training. We did not observe a reduction in cannulation pain or complications with the buttonhole method. Data linkages for a formal cost analysis were not conducted. CONCLUSIONS We were unable to demonstrate the feasibility of conducting a randomized, controlled trial of buttonhole versus stepladder cannulation in Canada with a sufficient number of patients on home hemodialysis to be able to draw meaningful conclusions.
Proceedings of the Fourth European Conference on Artificial Life

Researchers in artificial life attempt to use the physical representation of lifelike phenomena to understand the organizational principles underlying the dynamics of living systems. The goal of the 1997 European Conference on Artificial Life is to provoke new understandings of the relationships between the natural and the artificial. Topics include self-organization, the origins of life, natural selection, evolutionary computation, neural networks, communication, artificial worlds, software agents, philosophical issues in artificial life, ethical problems, and learning and development.
Potential of the Probiotic Lactobacillus Plantarum ATCC 14917 Strain to Produce Functional Fermented Pomegranate Juice

In this research survey the application of probiotic strain Lactobacillus plantarum ATCC 14917 in pomegranate juice fermentation is sought. Pomegranate juice was fermented for 24 h and then it was stored 4 for 4 weeks. Cell viability retained in high levels after the 24 h of fermentation and storage for 4 weeks (above 8.8 log cfu/mL), while fermented pomegranate juice was scored better at the 4th week of storage compared to non-fermented pomegranate juice. The probiotic strain was effective regarding lactic acid fermentation as was proved through sugar and organic acids analysis. Concentration of ethanol was maintained at low levels (0.3–1% v/v). Fermented pomegranate juice contained more and in higher percentages desirable volatile compounds (alcohols, ketones and esters) even at the 4th week of cold storage compared to non-fermented juice. Antioxidant activity (150.63 mg Trolox equivalent (TE)/100 mL at the 2nd week) and total phenolic content (206.46 mg gallic acid equivalents (GAE)/100 mL at the 2nd week) were recorded in higher levels for all the storage time compared to non-fermented juice.
Identification of Genes Regulating Breast Cancer Dormancy in 3D Bone Endosteal Niche Cultures

Tumor cell dormancy is a significant clinical problem in breast cancer. We used a three-dimensional (3D) in vitro model of the endosteal bone niche (EN), consisting of endothelial, bone marrow stromal cells, and fetal osteoblasts in a 3D collagen matrix (GELFOAM), to identify genes required for dormancy. Human triple-negative MDA-MB-231 breast cancer cells, but not the bone-tropic metastatic variant, BoM1833, established dormancy in 3D-EN cultures in a p38-MAPK–dependent manner, whereas both cell types proliferated on two-dimensional (2D) plastic or in 3D collagen alone. “Dormancy-reactivation suppressor genes” (DRSG) were identified using a genomic short hairpin RNA (shRNA) screen in MDA-MB-231 cells for gene knockdowns that induced proliferation in the 3D-EN. DRSG candidates enriched for genes controlling stem cell biology, neurogenesis, MYC targets, ribosomal structure, and translational control. Several potential DRSG were confirmed using independent shRNAs, including BHLHE41, HBP1, and WNT3. Overexpression of the WNT3/a antagonists secreted frizzled-related protein 2 or 4 (SFRP2/4) and induced MDA-MB-231 proliferation in the EN. In contrast, overexpression of SFRP3, known not to antagonize WNT3/a, did not induce proliferation. Decreased WNT3 or BHLHE41 expression was found in clinical breast cancer metastases compared with primary-site lesions, and the loss of WNT3 or BHLHE41 or gain of SFRP1, 2, and 4 in the context of TP53 loss/mutation correlated with decreased progression-free and overall survival. Implications: These data describe several novel, potentially targetable pathways controlling breast cancer dormancy in the EN.
Use of Hyperspectral/Multispectral Imaging in Gastroenterology. Shedding Some–Different–Light into the Dark

Hyperspectral/Multispectral imaging (HSI/MSI) technologies are able to sample from tens to hundreds of spectral channels within the electromagnetic spectrum, exceeding the capabilities of human vision. These spectral techniques are based on the principle that every material has a different response (reflection and absorption) to different wavelengths. Thereby, this technology facilitates the discrimination between different materials. HSI has demonstrated good discrimination capabilities for materials in fields, for instance, remote sensing, pollution monitoring, field surveillance, food quality, agriculture, astronomy, geological mapping, and currently, also in medicine. HSI technology allows tissue observation beyond the limitations of the human eye. Moreover, many researchers are using HSI as a new diagnosis tool to analyze optical properties of tissue. Recently, HSI has shown good performance in identifying human diseases in a non-invasive manner. In this paper, we show the potential use of these technologies in the medical domain, with emphasis in the current advances in gastroenterology. The main aim of this review is to provide an overview of contemporary concepts regarding HSI technology together with state-of-art systems and applications in gastroenterology. Finally, we discuss the current limitations and upcoming trends of HSI in gastroenterology.
What role might cardioneuroablation strategy have in syncope guidelines ?

Özet– Vazovagal senkop (VVS), senkopun en sık rastlanan tipidir. Mortalite riskinde artış olmamasına rağmen tekrarlayan senkop atakları ciddi sakatlanmalara ve yaşam kalitesinde azalmaya neden olabilir. Günümüzde etkin ve önerilen bir tedavi stratejisi bulunmamaktadır. Bu durum özellikle kardiyoinhibitör tip VVS olguları için geçerlidir. Kardiyonöroablasyon VVS esnasında vagal efferent çıktıların ortadan kaldırılmasını amaçlayan göreceli olarak yeni bir tekniktir. Biz bu derleme yazısında senkop kılavuzunda kardiyonöroablasyon stratejisinin yeri ne olabilirdi? sorusunun olası cevabını bulmayı amaçladık. Summary– Vasovagal syncope (VVS) is the most common type of syncope. Although it is not related to an increase in mortality, recurrent syncope episodes may be disabling and reduce the quality of life. There are no optimal treatment strategies currently available, especially for the cardioinhibitory type of VVS. Cardioneuroablation (CNA) is a relatively novel technique that aims to eliminate vagal efferent output during VVS. The objective of this review was to explore the potential role of CNA strategy in syncope guidelines. 69
Predictive models for designing potent tyrosine kinase inhibitors in chronic myeloid leukemia for understanding its molecular mechanism of resistance by molecular docking and dynamics simulations

Abstract BCR-ABL fusion protein drives chronic myeloid leukemia (CML) which constitutively activates tyrosine kinase involved in the initiation and maintenance of CML phenotype. Ponatinib, an oral drug, was discovered as an efficient BCR-ABL inhibitor by addressing imatinib drug resistance arising due to the point mutations at its active sites. In this study, 44 BCR-ABL kinase inhibitors, which are derivatives of ponatinib, were used to develop a robust two-dimensional quantitative structure–activity relationship (2D-QSAR) and 3D-Pharmacophore models by dividing dataset into 32 training sets and 12 test set molecules. 2D-QSAR model was developed using Genetic Function Approximation (GFA) algorithm consisting of four types of information-rich molecular descriptors, electrotopological (ES_Count_aasN and ES_Sum_aaaC), electronic (Dipole_X), spatial (PMI_Y) and thermodynamic (LogD), primarily contributing to BCR-ABL kinase inhibitory activity. For the best 2D-QSAR model, the statistics were R2 = 0.8707, R2pred = 0.8142 and N = 32 for the training set molecules. Phase module of Schrödinger suit was employed for 3D-Pharmacophore model development showing five different pharmacophoric features – ADHHPRR with good R2 of 0.9629, F of 175.3, Q2 of 0.645 and root-mean-square error (RMSE) of 0.214 that are essential for an effective BCR-ABL kinase inhibition. These two models were further validated by cross-validation, test set predictions, enrichment factor calculations and predictions based on the external dataset. The molecular mechanism of resistance arising due to gate keeper mutation T315I of ABL kinase in complex with its inhibitors was also studied using molecular docking and molecular dynamics simulations. Our developed models predicted key chemical features for designing potent inhibitors against BCR-ABL kinase activity and its resistance mechanism to CML disease therapy. Communicated by Ramaswamy H. Sarma
An upstream enhancer regulates Gpihbp1 expression in a tissue-specific manner[S]

Glycosylphosphatidylinositol-anchored high density lipoprotein–binding protein 1 (GPIHBP1), the protein that shuttles LPL to the capillary lumen, is essential for plasma triglyceride metabolism. When GPIHBP1 is absent, LPL remains stranded within the interstitial spaces and plasma triglyceride hydrolysis is impaired, resulting in severe hypertriglyceridemia. While the functions of GPIHBP1 in intravascular lipolysis are reasonably well understood, no one has yet identified DNA sequences regulating GPIHBP1 expression. In the current studies, we identified an enhancer element located ∼3.6 kb upstream from exon 1 of mouse Gpihbp1. To examine the importance of the enhancer, we used CRISPR/Cas9 genome editing to create mice lacking the enhancer (Gpihbp1Enh/Enh). Removing the enhancer reduced Gpihbp1 expression by >90% in the liver and by ∼50% in heart and brown adipose tissue. The reduced expression of GPIHBP1 was insufficient to prevent LPL from reaching the capillary lumen, and it did not lead to hypertriglyceridemia—even when mice were fed a high-fat diet. Compound heterozygotes (Gpihbp1Enh/− mice) displayed further reductions in Gpihbp1 expression and exhibited partial mislocalization of LPL (increased amounts of LPL within the interstitial spaces of the heart), but the plasma triglyceride levels were not perturbed. The enhancer element that we identified represents the first insight into DNA sequences controlling Gpihbp1 expression.
Sensory plasticity of carotid body is correlated with oxidative stress in paraventricular nucleus during chronic intermittent hypoxia

Chronic intermittent hypoxia (CIH) is known to induce hypertension, but the mechanism is not well understood. We hypothesized that sensory plasticity of the carotid body (CB) and oxidative stress in the paraventricular nucleus (PVN) are involved in CIH‐induced hypertension. In this study, rats were exposed to CIH for 28 days (intermittent hypoxia of 21% O2 for 60 s and 5% O2 for 30 s, cyclically repeated for 8 hr/day) and then randomly grouped for intracerebroventricular injection of 5‐HT2 receptor antagonist ritanserin, Rho‐associated protein kinase (ROCK) inhibitor Y‐27632, and NADPH oxidase (NOX) inhibitor diphenyleneiodonium (DPI), respectively. We found that CIH increased blood pressure (BP), elevated carotid sinus nerve (CSN) and renal sympathetic nerve (RSN) activities, oxidative stress, and cell apoptosis in PVN. NOX‐derived reactive oxygen species (ROS) production and cell apoptosis decreased when CIH‐induced activation of 5‐HT/5‐HT2AR/PKC signaling was inhibited by ritanserin. In addition, RhoA expression was downregulated when oxidative stress was attenuated by DPI, while Y‐27632 decreased the expression of endothelin‐1, which is overexpressed in the vascular wall during hypertension. Moreover, treatment with ritanserin, DPI or Y‐27632 attenuated the sensory plasticity and sympathetic hyperactivity as well as CIH‐induced elevation of BP. In conclusion, CIH‐induced activation of 5‐HT/5‐HT2AR/PKC signaling contributes to NOX‐derived oxidative stress in PVN, which may cause sensory plasticity of CB, RSN hyperactivity, and elevated BP.