Miracle-dz/UniFAR-FTUs huggingface dataset:
A Novel MKL Method for GBM Prognosis Prediction by Integrating Histopathological Image and Multi-Omics Data

Glioblastoma multiforme (GBM) is one of the most malignant brain tumors with very short prognosis expectation. To improve patients’ clinical treatment and their life quality after surgery, researches have developed tremendous in silico models and tools for predicting GBM prognosis based on molecular datasets and have earned great success. However, pathology still plays the most critical role in cancer diagnosis and prognosis in the clinic at present. Recent advancement of storing and processing histopathological images has drawn attention of researchers. Models based on histopathological images are developed, which show great potential for computer-aided pathological diagnoses. But models based on both molecular and histopathological images that could predict GBM prognosis with high accuracy are not present yet. In our previous research, we used the simple MKL method to integrate multi-omics data to improve GBM prognosis prediction successfully. In this paper, we have developed a novel multiple kernel learning (MKL) method, named histopathological integrating multiple kernel learning (HI-MKL), that could integrate both histopathological images and multi-omics data efficiently. By using datasets from The Cancer Genome Atlas project, we have built a system that could predict the GBM prognosis with high accuracy. Our research shows that HI-MKL is an accurate, robust, and generalized MKL method, which performs well in a GBM prognosis task.
Efficient Copper Removal from an Aqueous Anvironment using a Novel and Hybrid Nanoadsorbent Based on Derived-Polyethyleneimine Linked to Silica Magnetic Nanocomposites

Due to the extreme rise of sludge pollution with heavy metals (e.g. copper), the options for its disposal or treatment are decreasing. On the contrary, properly heavy metal-cleaned sludge can be used as an alternative sustainable energy and agriculture source. The aim of this study was to develop a novel nanoadsorbent, based on irreversibly linked amino-rich polymer onto previously silica-coated magnetic nanoparticles (MNPs) that can be applied efficiently for metal removal. MNPs were coated uniformly by 3 nm thick silica layer (core-shell structure), and were additionally modified with systematic covalent attachment of derived branched polyethyleneimine (bPEI). The formed structure of synthesized MNPs composite was confirmed with several analytical techniques. Importantly, nanoadsorbents exhibit high density of chelating amino groups and large magnetic force for easier separation. The importance of introduced bPEI, effect of pH, initial heavy metal concentration onto copper uptake efficiency and, further, nanoadsorbent regeneration, were studied and explained in detail. The adsorption isotherm was well fitted with Langmuir model, and the maximum adsorption capacity was shown to be 143 mg·g−1 for Cu2+. The reusability and superior properties of silica-coated MNPs functionalized with derived-bPEI for copper adsorption underlie its potential for the removal application from heavy metals contaminated sludge
Development and Assessment of a Mobile Health Application for Monitoring the Linkage Among Treatment Factors of Type 1 Diabetes Mellitus.

BACKGROUND In the daily routine of type 1 diabetes mellitus (T1DM), the patients deal with many data and consider many variables to perform actions, decisions, and regimen adjustments. There is a need to apply filtering techniques to extract relevant information and provide appropriate data visualization methods to assist in clinical tasks and decision making. OBJECTIVE To present Soins DM, a mobile health tool, for monitoring the linkage among treatment factors of T1DM with an interactive data visualization approach. METHODS First, we performed a literature review, a commercial search, and ideation. Next, we created a prototype and an online survey for its feedback, with participation of 76 individuals. Afterward, the mobile app and its website version were built. Eventually, we conducted a pilot experiment with 4 patients, an online experiment for satisfaction assessment with 97 patients, and an online assessment by 9 health professionals. RESULTS Prototyping and feedback facilitated the design refinement. Soins DM enables the recording of data from routines of glycemia, insulin applications, meals, and physical exercises. From these logs, the app builds two different ways of interactive data visualization, a timeline and an integrated chart, providing personalized feedback on bad glycemia with its possible causes. The assessments revealed overall satisfaction with the app's characteristics. CONCLUSIONS Soins DM is a novel application with interactive visualization and personalized feedback for easy identification of the linkage among treatment factors of T1DM. The test scenario with patients and health professionals indicates Soins DM as a useful and reliable tool.
The Influence of Old Age and Poloxamer-407 on the Hepatic Disposition of Diazepam in the Isolated Perfused Rat Liver

Background and Purpose: The normal liver sinusoidal endothelium is thin and punctuated with fenestrations 50–200 nm in diameter that filter endobiotics and xenobiotics. Defenestration of the liver sinusoidal endothelium in old age and after pre-treatment with poloxamer-407 (P407) has been shown to prevent the transfer of small chylomicrons across the liver sinusoidal endothelium. The aim of this study was to investigate the impact of liver sinusoidal endothelium fenestrations on the hepatic uptake of the highly protein-bound drug diazepam. We hypothesized that defenestration will reduce the hepatic extraction of drugs which are highly bound to albumin. Methodology: The isolated perfused rat liver (IPRL) model and multiple indicator dilution technique were used to investigate the effect of fenestrations in the liver sinusoidal endothelium on the hepatic disposition of diazepam in old and young rats, and in young rats treated with P407 or vehicle. A bolus dose of 14C-diazpeam and non-extracted tracers (3H-sucrose and Evans blue) was injected into the portal vein. The single-pass recovery of diazepam and markers and the apparent volume of distribution were determined. Results: Scanning electron microscopy confirmed reduced porosity of the liver sinusoidal endothelial cells in P407-treated rats and old rats compared to young and control rats. The fractional recovery of diazepam was significantly increased in P407-treated rats compared to controls (0.20 ± 0.16, n = 12, P407; 0.08 ± 0.05, n = 8, controls; p = 0.0029), and in old rats compared to young rats (0.15 ± 0.03, n = 11, old; 0.10 ± 0.02, n = 11, young; p = 0.0004) following a single pass. Conclusion: Defenestration due to age-related pseudocapillarization and treatment with P407 resulted in reduced hepatic extraction of diazepam after a single pass through the IPRL. These results highlight the importance of the liver sinusoidal endothelium in the ultrafiltration of highly protein-bound drugs, and may also provide an additional mechanism for reduced hepatic clearance of diazepam in conditions associated with defenestration.
Euthanasia and advance directives in Huntington's disease: qualitative analysis of interviews with patients.

BACKGROUND In the literature there are few reports on euthanasia or physician-assisted suicide (PAS) or other matters concerning the end-of-life in patients with Huntington's disease (HD), although clinical experience suggests these issues do arise. OBJECTIVE To obtain in-depth information about patients' thoughts on and attitudes to euthanasia, PAS and the use of advance directives in HD. To assess the difficulties patients encounter when thinking about end-of-life wishes. METHODS Semi-structured in-depth interviews with 14 unselected HD patients from our out-patient clinic based on a topic list. Qualitative analysis of the interviews based on grounded theory. RESULTS We identified three patterns in our group of respondents: patients with distinct wishes, with general wishes and ideas and patients with no wishes. The most important frame of reference regarding end-of-life wishes in HD patients or known gene carriers is the experience with an affected parent. Family is important when thinking about the end of life and advance directives, even more so than the patient's physician. Knowledge about the (requirements of) law is limited. CONCLUSIONS The majority of interviewees expressed some kind of wish regarding end of life, probably more than they had revealed to their physician, but were sometimes hesitant to discuss it. Knowledge on how to deal with wishes, advance directives and response shift is limited. In general, patients underestimate the requirement for sound professional support when considering euthanasia or PAS and the value of an advance directive. In an attempt to improve knowledge and communication about end-of-life issues, physicians should ask the patient directly about their wishes.
Diversified Cycloisomerization/Diels-Alder Reactions of 1,6-Enynes through Bimetallic Relay Asymmetric Catalysis.

We report the combination of transition-metal-catalyzed diversified cycloisomerization of 1,6-enynes with chiral Lewis acid promoted asymmetric Diels-Alder reaction to realize asymmetric cycloisomerization/Diels-Alder relay reactions of 1,6-enynes with electron-deficient alkenes. A broad spectrum of chiral [5,6]-bicyclic products could be acquired in high yields (up to 99 %) with excellent diastereoselectivy (>19:1 dr) and enantioselectivity (up to 99 % ee).
Integrated Tele-Assistance Platform - TELEASIS

Abstract The diversification of telecommunication networks and advances in communication technologies, including the Internet, has considerable potential as an environment supporting telemedicine applications. Within eRomania government programme a special focus is on public and private electronic services development. During the last decade, communications systems development and expansion of Internet enabled more and more users to access public electronic services. In this context, National Communication Research Institute - INSCC is coordinating a Romanian telemedicine project called Complex System on NGN support offering Home Telecare Services for Elders - TELEASIS. This paper presents the integrated tele-assistance platform - TELEASIS, as a support for implementation and development of homecare electronic integrated services, allowing tele-assistance of elder people, at their residence, with a medical and as well, a social target. The presentation includes the context, issues regarding project management, hardware and software platforms, devices, and patients/clients benefits.
Interventions to Prevent Perinatal Depression: Evidence Report and Systematic Review for the US Preventive Services Task Force

Importance Depression during pregnancy and the postpartum period is relatively common and can have adverse effects on both mother and child. Objective To systematically review benefits and harms of primary care–relevant interventions to prevent perinatal depression, a major or minor depressive episode during pregnancy or up to 1 year after childbirth, to inform the US Preventive Services Task Force. Data Sources MEDLINE, PubMED (for publisher-supplied records only), PsycINFO, and the Cochrane Central Register of Controlled Trials; surveillance through December 5, 2018. Study Selection Randomized clinical trials (RCTs) and nonrandomized controlled intervention studies of interventions (eg, behavior-based, antidepressants, dietary supplements) to prevent perinatal depression in general populations of pregnant and postpartum individuals or in those at increased risk of perinatal depression. Large cohort studies were considered for harms of antidepressant use only. Data Extraction and Synthesis Two investigators independently reviewed abstracts and full-text articles and quality rated included studies. Random-effects meta-analysis was used to estimate the benefits of the interventions. Main Outcomes and Measures Depression status; depression symptoms; maternal, infant, and child health outcomes. Results Fifty studies (N = 22 385) that met inclusion criteria were identified. Counseling interventions were the most widely studied interventions. Compared with controls, counseling interventions were associated with a lower likelihood of onset of perinatal depression (pooled risk ratio [RR], 0.61 [95% CI, 0.47-0.78]; 17 RCTs [n = 3094]; I2 = 39.0%). The absolute difference in the risk of perinatal depression ranged from 1.3% greater reduction in the control group to 31.8% greater reduction in the intervention group. Health system interventions showed a benefit in 3 studies (n = 5321) and had a pooled effect size similar to that of the counseling interventions, but the pooled effect was not statistically significant using a method appropriate for pooling a small number of studies (restricted maximum likelihood RR, 0.58 [95% CI, 0.22-1.53]; n = 4738; I2 = 66.3%; absolute risk reduction range, −3.1% to −13.1%). None of the behavior-based interventions reported on harms directly. A smaller percentage of participants prescribed sertraline had a depression recurrence compared with those prescribed placebo (7% vs 50%, P = .04) at 20 weeks postpartum in 1 very small RCT (n = 22 analyzed) but with an increased risk of adverse effects to the mother. Conclusions and Relevance Counseling interventions can be effective in preventing perinatal depression, although most evidence was limited to women at increased risk for perinatal depression. A variety of other intervention approaches provided some evidence of effectiveness but lacked a robust evidence base and need further research.
How does T cell receptor clustering impact on signal transduction?

ABSTRACT The essential function of the T cell receptor (TCR) is to translate the engagement of peptides on the major histocompatibility complex (pMHC) into appropriate intracellular signals through the associated cluster of differentiation 3 (CD3) complex. The spatial organization of the TCR–CD3 complex in the membrane is thought to be a key regulatory element of signal transduction, raising the question of how receptor clustering impacts on TCR triggering. How signal transduction at the TCR–CD3 complex encodes the quality and quantity of pMHC molecules is not fully understood. This question can be approached by reconstituting T cell signaling in model and cell membranes and addressed by single-molecule imaging of endogenous proteins in T cells. We highlight such methods and further discuss how TCR clustering could affect pMHC rebinding rates, the local balance between kinase and phosphatase activity and/or the lipid environment to regulate the signal efficiency of the TCR–CD3 complex. We also examine whether clustering could affect the conformation of cytoplasmic CD3 tails through a biophysical mechanism. Taken together, we highlight how the spatial organization of the TCR–CD3 complex – addressed by reconstitution approaches – has emerged as a key regulatory element in signal transduction of this archetypal immune receptor. Summary: Understanding of the mechanisms involved in T cell receptor activation has been greatly advanced by reconstitution systems. Here, we review how clustering of the T cell receptor impacts on signal transduction in T cells and how reconstitution systems have contributed to this knowledge.
Linaclotide and Prucalopride for Management of Constipation in Patients with Parkinsonism

Background: Constipation is a common condition in patients with neurodegenerative parkinsonism, including Parkinson’s disease (PD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP). Chronic constipation negatively impacts quality of life and decrease the absorption of antiparkinsonian drugs. Linaclotide (guanylate cyclase C agonist) and prucalopride (selective 5-HT 4 receptor agonist) are emerging effective drugs for the management of chronic idiopathic constipation (CIC). To date, neither of these drugs has been tested in controlled trials in parkinsonism patients and their efficacy is unknown in this population. Aims: We aimed to identify patients who received linaclotide or prucalopride in our clinic database and to review the change in bowel movement frequency and the patient perception of drug effect. Methods: We searched our patient database for patients diagnosed with neurodegenerative parkinsonism and constipation who had received linaclotide or prucalopride. Constipation was defined by Rome III criteria. Demographics, treatment characteristics, BM frequency, side effects were captured from medical records. Objective improvement was defined as post-treatment BM frequency of 3 or more per week. Subjective improvement was assessed by clinical or telephone interview and defined as agreement or strong agreement in a 5-point Likert scale. Continuous variables were expressed as median[range] or mean±SD (Wilcoxon signed-rank or Fisher’s exact test). Results: Among the 31 patients identified, 13 patients received linaclotide, 11 received prucalopride, and 7 individuals initially received prucalopride, which was switched to linaclotide. The number
Adult attachment as a moderator of treatment outcome for generalized anxiety disorder: Comparison between cognitive-behavioral therapy (CBT) plus supportive listening and CBT plus interpersonal and emotional processing therapy.

OBJECTIVE To determine whether baseline dimensions of adult insecure attachment (avoidant and anxious) moderated outcome in a secondary analysis of a randomized controlled trial comparing cognitive-behavioral therapy (CBT) plus supportive listening (CBT + SL) versus CBT plus interpersonal and emotional processing therapy (CBT + I/EP). METHOD Eighty-three participants diagnosed with generalized anxiety disorder (GAD) were recruited from the community and assigned randomly to CBT + SL (n = 40) or to CBT + I/EP (n = 43) within a study using an additive design. PhD-level psychologists treated participants. Blind assessors evaluated participants at pretreatment, posttreatment, 6-month, 12-month, and 2-year follow-up with a composite of self-report and assessor-rated GAD symptom measures (Penn State Worry Questionnaire, Hamilton Anxiety Rating Scale, Clinician's Severity Rating). Avoidant and anxious attachment were assessed using self-reported dismissing and angry states of mind, respectively, on the Perceptions of Adult Attachment Questionnaire. RESULTS Consistent with our prediction, at all assessments higher levels of dismissing styles in those who received CBT + I/EP predicted greater change in GAD symptoms compared with those who received CBT + SL for whom dismissiveness was unrelated to the change. At postassessment, higher angry attachment was associated with less change in GAD symptoms for those receiving CBT + I/EP, compared with CBT + SL, for whom anger was unrelated to change in GAD symptoms. Pretreatment attachment-related anger failed to moderate outcome at other time points and therefore, these moderation effects were more short-lived than the ones for dismissing attachment. CONCLUSIONS When compared with CBT + SL, CBT + I/EP may be better for individuals with GAD who have relatively higher dismissing styles of attachment.
Individual Variability in Reaction Time and Prediction of Clinical Response to Methylphenidate in Adult ADHD: A Prospective Open Label Study Using Conners’ Continuous Performance Test II

Objective: The aim of this study was to examine whether reaction time parameters in adult patients with ADHD could predict their response to methylphenidate (MPH). Method: Previously unmedicated patients (N = 123) were administered the Conners’ Continuous Performance Test II (CPT II) at baseline and after 6 weeks of treatment with immediate-release MPH. In addition to traditional CPT measures, we extracted intraindividual raw data and analyzed time series using linear and nonlinear mathematical models. Results: Clinical responders, assessed with the Clinical Global Impression-Improvement scale, showed significant normalization of target failures, reduced variability and skewness, and increased complexity of reaction time series after 6 weeks of treatment, while nonresponders showed no significant changes. Prior to treatment, responders had significantly higher variability and skewness, combined with lower complexity, compared with nonresponders. Conclusion: These results show that the CPT test is useful in the evaluation of treatment response to MPH.
Differentiation of the human liver progenitor cell line (HepaRG) on a microfluidic‐based biochip

HepaRG is a bipotent stem cell line that can be differentiated towards hepatocyte‐like and biliary‐like cells. The entire cultivation process requires 1 month and relies on the addition of 2% dimethyl sulfoxide (DMSO) to the culture. Our motivation in this research is to differentiate HepaRG cells (progenitor cells and undifferentiated cells) towards hepatocyte‐like cells by minimizing the cultivation time and without using DMSO treatment by instead using a microfluidic device combined with the following strategies: (a) comparison of extracellular matrices (matrigel and collagen I), (b) types of flow (one or both sides), and (c) effects of DMSO. Our results demonstrate that matrigel promotes the differentiation of progenitor cells towards hepatocytes and biliary‐like cells. Moreover, the frequent formation of HepaRG cell clusters was observed by a supply of both sides of flow, and the cell viability and liver specific functions were influenced by DMSO. Finally, differentiated HepaRG progenitor cells cultured in a microfluidic device for 14 days without DMSO treatment yielded 70% of hepatocyte‐like cells with a highly polarized organization that reacted to stimulation with IL‐6 to produce C‐reactive protein (CRP). This culture model has high potential for investigating cell differentiation and liver pathophysiology research.
Differential effects of split and continuous sleep on neurobehavioral function and glucose tolerance in sleep-restricted adolescents

Abstract Study Objectives Many adolescents are exposed to sleep restriction on school nights. We assessed how different apportionment of restricted sleep (continuous vs. split sleep) influences neurobehavioral function and glucose levels. Methods Adolescents, aged 15–19 years, were evaluated in a dormitory setting using a parallel-group design. Following two baseline nights of 9-hour time-in-bed (TIB), participants underwent either 5 nights of continuous 6.5-h TIB (n = 29) or 5-hour nocturnal TIB with a 1.5-hour afternoon nap (n = 29). After two recovery nights of 9-hour TIB, participants were sleep restricted for another three nights. Sleep was assessed using polysomnography (PSG). Cognitive performance and mood were evaluated three times per day. Oral glucose tolerance tests (OGTT) were conducted on mornings after baseline sleep, recovery sleep, and the third day of each sleep restriction cycle. Results The split sleep group had fewer vigilance lapses, better working memory and executive function, faster processing speed, lower level of subjective sleepiness, and more positive mood, even though PSG-verified total sleep time was less than the continuous sleep group. However, vigilance in both sleep-restricted groups was inferior to adolescents in a prior sample given 9-hour nocturnal TIB. During both cycles of sleep restriction, blood glucose during the OGTT increased by a greater amount in the split sleep schedule compared with persons receiving 6.5-hour continuous sleep. Conclusions In adolescents, modest multinight sleep restriction had divergent negative effects on cognitive performance and glucose levels depending on how the restricted sleep was apportioned. They are best advised to obtain the recommended amount of nocturnal sleep. Trial registration https://clinicaltrials.gov/ct2/show/NCT03333512