Miracle-dz/UniFAR-FTUs huggingface dataset:
STOPPFrail (Screening Tool of Older Persons Prescriptions in Frail adults with limited life expectancy): consensus validation

Objective to validate STOPPFrail, a list of explicit criteria for potentially inappropriate medication (PIM) use in frail older adults with limited life expectancy. Design a Delphi consensus survey of an expert panel comprising academic geriatricians, clinical pharmacologists, palliative care physicians, old age psychiatrists, general practitioners and clinical pharmacists. Setting Ireland. Subjects seventeen panellists. Methods STOPPFrail criteria were initially created by the authors based on clinical experience and literature appraisal. Criteria were organised according to the physiological system; each criterion accompanied by an explanation. Using Delphi consensus methodology, panellists ranked their agreement with each criterion on a 5-point Likert scale and provided written feedback. Criteria with a median Likert response of 4/5 (agree/strongly agree) and a 25th centile of ≥4 were included in the final list. Results all panellists completed three Delphi rounds. Thirty criteria were proposed, 27 were accepted. The first two criteria suggest deprescribing medications without indication or where compliance is poor. The remaining 25 criteria include lipid-lowering therapies, alpha-blockers for hypertension, anti-platelets, neuroleptics, memantine, proton-pump inhibitors, H2-receptor antagonists, anti-spasmodic agents, theophylline, leukotriene antagonists, calcium supplements, bone anti-resorptive therapy, selective oestrogen receptor modulators, non-steroidal anti-inflammatories, corticosteroids, 5-alpha-reductase inhibitors, alpha-1-selective blockers, muscarinic antagonists, oral diabetic agents, ACE-inhibitors, angiotensin receptor blockers, systemic oestrogens, multivitamins, nutritional supplements and prophylactic antibiotics. Consensus could not be reached on the inclusion of acetylcholinesterase inhibitors. Full consensus was reached on the exclusion of anticoagulants and antidepressants from the list. Conclusion STOPPFrail comprises 27 criteria relating to medications that are potentially inappropriate in frail older patients with limited life expectancy. STOPPFrail may assist physicians in deprescribing medications in these patients.
A System for Predictive Writing

Most predictive writing systems are based on n-gram model with different size. Systems designed for English are easier than those for flective languages since even smaller models allow reasonable coverage. However, the same corpus size is significantly insufficient for languages with many word forms. The paper presents a new predictive writing system based on n-grams calculated from a large corpus. We designed the high-performance server-side script that returns either the most probable endings of a word or the most probable following words. We also designed the client-side script that is suitable for desktop computers without touchscreens. We calculated 150 millions most frequent n-grams for n = 1, . , 12 from a Czech corpus and evaluated the writing system on Czech texts. The system was then extended by custom-built model that can consist of domain or user specific n-grams. We measured the key stroke per character (KSPC) rate in two different modes: one – called letter KSPC – excludes the control keys since they are input method specific, the other – called real KSPC – includes all key strokes. We have shown that the system performs well in general (letter KSPC on average was 0.64, real KSPC on average was 0.77) but performs even better on specific domains with the appropriate custom-built model (letter KSPC and real KSPC were on average 0.63 and 0.73 respectively). The system was tested on Czech, however it can easily be adapted an arbitrary language. Due to its performance, the system is suitable for languages with high inflection.
Impaired White Matter Integrity and Social Cognition in High-Function Autism: Diffusion Tensor Imaging Study

Objective It is known that many of the cognitive and social deficits associated with autism can arise from abnormal functional connectivity between brain networks. This aberrant functional connectivity in autism spectrum disorders (ASD) can be explained by impaired integrity of white matter tracts that link distant regions of the networks. Methods We investigated white matter in 9 children with high-function autism (HFA) compared to 13 typically developing controls using diffusion tensor imaging (DTI). The aim of this research is to provide supporting evidence for abnormalities in neural connectivity as an underlying pathophysiology of the main characteristics of ASD. Results We found impairment of neural connectivity, mainly in association fiber tracts as evidenced by decreased fractional anisotropy (FA), the index of white matter integrity, of these tracts. Among them, inferior fronto-occipital fasciculus (IFOF) had a significant relationship with ADI-R score. The inferior longitudinal fasciculus (ILF) and superior longitudinal fasciculus (SLF) also showed decreased FA. Decreased FA of ILF and SLF had negative correlations with scores of social interaction. Conclusion These findings suggest that widespread abnormalities in association fiber tracts may contribute to both core and associated symptoms of ASD.
The Random Finite Element Method (RFEM) in Probabilistic Slope Stability Analysis with Consideration of Spatial Variability of Soil Properties

This paper presents the results of probabilistic analyses in slope stability problems using the Random Finite Element Method (RFEM). The influence of spatially variable soil properties on design outcomes relating to slope stability analysis has been assessed through parametric studies, with focus on the "worst case" (critical) spatial correlation length that leads to a minimum reliability of the soil mass. This critical value is of particular interest, because it could be used for design in the absence of good site specific data.
Reciprocal associations of pain and post‐traumatic stress symptoms after whiplash injury: A longitudinal, cross‐lagged study

The objectives of the current study were to investigate (1) the longitudinal, reciprocal associations between pain and post‐traumatic stress symptoms as proposed by the mutual maintenance model, and (2) to assess the predictive value of the three clusters of post‐traumatic stress, where the model revealed that post‐traumatic stress symptoms maintained pain in a consecutive cohort of whiplash‐injured.
Structural basis of kindlin-mediated integrin recognition and activation

Significance Kindlin proteins play crucial roles in the integrin-signaling pathway by directly interacting with and activating integrins, which mediate the cell–extracellular matrix adhesion and signaling. Mutations of kindlins lead to diseases, such as Kindler syndrome, associated with skin blistering and atrophy; leukocyte adhesion deficiency; and cancers. However, the molecular basis underlying kindlin-mediated integrin activation remains to be determined. Here, we report the structural basis of the specific interaction between kindlins and integrins. Furthermore, we demonstrate that kindlins synergize integrin activation by forming a dimer, providing a model for understanding integrin signaling. Finally, we interpret disease-causing mutations found in kindlins at the atomic level, which can be useful for understanding and treating these diseases. Kindlins and talins are integrin-binding proteins that are critically involved in integrin activation, an essential process for many fundamental cellular activities including cell-matrix adhesion, migration, and proliferation. As FERM-domain–containing proteins, talins and kindlins, respectively, bind different regions of β-integrin cytoplasmic tails. However, compared with the extensively studied talin, little is known about how kindlins specifically interact with integrins and synergistically enhance their activation by talins. Here, we determined crystal structures of kindlin2 in the apo-form and the β1- and β3-integrin bound forms. The apo-structure shows an overall architecture distinct from talins. The complex structures reveal a unique integrin recognition mode of kindlins, which combines two binding motifs to provide specificity that is essential for integrin activation and signaling. Strikingly, our structures uncover an unexpected dimer formation of kindlins. Interrupting dimer formation impairs kindlin-mediated integrin activation. Collectively, the structural, biochemical, and cellular results provide mechanistic explanations that account for the effects of kindlins on integrin activation as well as for how kindlin mutations found in patients with Kindler syndrome and leukocyte-adhesion deficiency may impact integrin-mediated processes.
From chronic conditions to relevance in multimorbidity: a four-step study in family medicine.

BACKGROUND Chronic conditions and multimorbidity (MM) are major concerns in family medicine (FM). OBJECTIVES Based on the International Classification of Primary Care, Second Edition (ICPC-2), this study aimed to list (i)the chronic conditions and (ii)those most relevant to MM in FM. METHODS A panel of FM experts used a four-step process to identify chronic conditions among ICPC-2 items and list chronic conditions most relevant in MM. They also evaluated the importance of eight criteria, previously identified in the literature, for characterizing chronic conditions. Step one involved a focus group of five experts. Steps two, three and four involved 10, 25 and 25 experts, respectively. They rated ICPC-2 items via an online questionnaire using a Likert scale from 1 (never chronic/irrelevant in MM) to 9 (always chronic/always relevant in MM). A median value cut-off was used to evaluate appropriateness of each item and the inter-percentile range adjusted for symmetry to determine the agreement/disagreement between experts. In parallel, in steps two and three, experts rated the importance of eight criteria to characterize chronic conditions, using a Likert scale from 1 (strongly disagree) to 9 (strongly agree). RESULTS Of the ICPC-2's 686 items, experts identified 139 chronic conditions, of which 75 were deemed most relevant in the context of MM. Four of the eight criteria were retained as important to define chronic conditions: duration, sequelae, recurrence/pattern and the diagnosis itself. CONCLUSION Using this list of 75 chronic conditions most relevant in the context of MM should enhance the validity of studies of MM in FM.
Targeting the HGF-cMET Axis in Hepatocellular Carcinoma

Under normal physiological conditions, the hepatocyte growth factor (HGF) and its receptor, the MET transmembrane tyrosine kinase (cMET), are involved in embryogenesis, morphogenesis, and wound healing. The HGF-cMET axis promotes cell survival, proliferation, migration, and invasion via modulation of epithelial-mesenchymal interactions. Hepatocellular cancer (HCC) is the third most common cause of worldwide cancer-related mortality; advanced disease is associated with a paucity of therapeutic options and a five-year survival rate of only 10%. Dysregulation of the HGF-cMET pathway is implicated in HCC carcinogenesis and progression through activation of multiple signaling pathways; therefore, cMET inhibition is a promising therapeutic strategy for HCC treatment. The authors review HGF-cMET structure and function in normal tissue and in HCC, cMET inhibition in HCC, and future strategies for biomarker identification.
Germination and inactivation of Bacillus subtilis spores induced by moderate hydrostatic pressure

In this study, we investigated the mechanisms of spore inactivation by high pressure at moderate temperatures to optimize the sterilization efficiency of high‐pressure treatments. Bacillus subtilis spores were first subjected to different pressure treatments ranging from 90 to 550 MPa at 40°C, with holding times from 10 min to 4 h. These treatments alone caused slight inactivation, which was related to the pressure‐induced germination of the spores. After these pressures treatments, the sensitivity of these processed spores to heat (80°C/10 min) or to high pressure (350 MPa/40°C/10 min) was tested to determine the pressure‐induced germination rate and the advancement of the spores in the germination process. The subsequent heat or pressure treatments were applied immediately after decompression from the first pressure treatment or after a holding time at atmospheric pressure. As already known, the spore germination is more efficient at low pressure level than at high pressure level. Our results show that this low germination efficiency at high pressure seemed not to be related either to a lower induction or a difference in the induction mechanisms but rather to an inhibition of enzyme activities which are involved in germination process. In fact, high pressure was necessary and very efficient in inducing spore germination. However, it seemed to slow the enzymatic digestion of the cortex, which is required for germinated spores to be inactivated by pressure. Although these results indicate that high‐pressure treatments are more efficient when the two treatments are combined, a small spore population still remained dormant and was not inactivated with any holding time or pressure level. Biotechnol. Bioeng. 2010;107: 876–883. © 2010 Wiley Periodicals, Inc.
Blood pressure‐lowering effects of sulodexide depend on albuminuria severity: post hoc analysis of the sulodexide microalbuminuria and macroalbuminuria studies

Aims It has been suggested that sulodexide is able to lower blood pressure (BP). This may be attributed to its ability to restore the endothelial surface layer (ESL). As ESL perturbation is known to be related to the degree of kidney damage, we investigated whether albuminuria, reflecting ESL status, modified the BP‐lowering potential of sulodexide. Methods A post hoc analysis of the double‐blind, randomized, placebo‐controlled sulodexide microalbuminuria (Sun‐MICRO) and macroalbuminuria (Sun‐MACRO) studies, including 1056 microalbuminuric and 843 macroalbuminuric subjects with type 2 diabetes receiving maximal tolerated renin–angiotensin‐aldosterone system inhibitor therapy, was carried out. We compared the effect of placebo and sulodexide on systolic BP (SBP) among albuminuria groups. Results Analysis of covariance, including data from both trials, showed that baseline urine albumin‐to‐creatinine ratio (UACR) was the only modifier of the SBP response (interaction with treatment P = 0.001). In subjects with an UACR >1000 mg g–1, sulodexide lowered SBP by 4.6 mmHg [95% confidence interval (CI) 3.6, 5.6; P < 0.001] compared with placebo, whereas a 2.3 mmHg (95% CI 0.9,3.7; P = 0.001) reduction was seen in subjects with a UACR of 300–1000 mg g–1. Sulodexide did not lower SBP in subjects with a UACR <300 mg g–1 (−0.2 mmHg, 95% CI −0.8, 0.5; P = 0.60). SBP‐lowering effects were not accompanied by changes in body weight. Conclusion The BP‐reducing potency of sulodexide is modified by the degree of albuminuria in subjects with type 2 diabetes. As ESL status deteriorates with increasing albuminuria and nephropathy severity, this suggests that ESL restoration may represent a new target for BP treatment in subjects with diabetic nephropathy.
Nanometric Integrated Temperature and Thermal Sensors in CMOS-SOI Technology

This paper reviews and compares the thermal and noise characterization of CMOS (complementary metal-oxide-semiconductor) SOI (Silicon on insulator) transistors and lateral diodes used as temperature and thermal sensors. DC analysis of the measured sensors and the experimental results in a broad (300 K up to 550 K) temperature range are presented. It is shown that both sensors require small chip area, have low power consumption, and exhibit linearity and high sensitivity over the entire temperature range. However, the diode’s sensitivity to temperature variations in CMOS-SOI technology is highly dependent on the diode’s perimeter; hence, a careful calibration for each fabrication process is needed. In contrast, the short thermal time constant of the electrons in the transistor’s channel enables measuring the instantaneous heating of the channel and to determine the local true temperature of the transistor. This allows accurate “on-line” temperature sensing while no additional calibration is needed. In addition, the noise measurements indicate that the diode’s small area and perimeter causes a high 1/f noise in all measured bias currents. This is a severe drawback for the sensor accuracy when using the sensor as a thermal sensor; hence, CMOS-SOI transistors are a better choice for temperature sensing.
Cyberbullying System Detection and Analysis

Abstract-Cyber-bullying has recently been reported as one that causes tremendous damage to society and economy. Advances in technology related to web-document annotation and the multiplicity of the online communities renders the detection and monitoring of such cases rather difficult and very challenging. This paper describes an online system for automatic detection and monitoring of Cyber-bullying cases from online forums and online communities. The system relies on the detection of three basic natural language components corresponding to Insults, Swears and Second Person. A classification system and ontology like reasoning have been employed to detect the occurrence of such entities in the forum / web documents, which would trigger a message to security in order to take appropriate action. The system has been tested on two distinct forums and achieves reasonable detection performances
Anomaly Detection in Cloud Applications

In very general terms, this internship report consist in analysing data from several experiments on the evolution of a virtual network over time. Using the available data, the objective was to develop a program which could perform online anomaly detection on virtual networks. The available data for this study consists of tables containing information regarding several virtual machines (i.e. the system) which are monitored every 15 seconds. Two sources of data are available: the first source provides data with 150 variables, and the second source with 250. In any case this number of variables is considered as high-dimensional. In addition, a qualitative variable classifies every entry into several possible categories, according to the state of the system, which is either exhibiting normal or anomalous behaviours. In statistical terms, the problem we deal with in this work implies creating a certain decision rule based on the data collected to be able to (accurately) forecast the state of the system (the value of the qualitative variable) knowing the value of the other variables. Therefore this is a classification problem. The main algorithm used for tackling the classification problem is Random forest from the work of Breiman & al.
Interaction of microtubules with the actin cytoskeleton via cross-talk of EB1-containing +TIPs and γ-actin in epithelial cells

Actin microfilaments and microtubules are both highly dynamic cytoskeleton components implicated in a wide range of intracellular processes as well as cell-cell and cell-substrate interactions. The interactions of actin filaments with the microtubule system play an important role in the assembly and maintenance of 3D cell structure. Here we demonstrate that cytoplasmic actins are differentially distributed in relation to the microtubule system. LSM, 3D-SIM, proximity ligation assay (PLA) and co-immunoprecipitation methods applied in combination with selective depletion of β- or γ-cytoplasmic actins revealed a selective interaction between microtubules and γ-, but not β-cytoplasmic actin via the microtubule +TIPs protein EB1. EB1-positive comet distribution analysis and quantification have shown more effective microtubule growth in the absence of β-actin. Our data represent the first demonstration that microtubule +TIPs protein EB1 interacts mainly with γ-cytoplasmic actin in epithelial cells.
Electroelastic Response of Cylindrical Fiber with D∞ Symmetry Exposed to Local Electric Field Through Opposed Electrode Pair

ABSTRACT To obtain practical information on the electroelastic behavior of poly-l-lactic acid microtweezers or catheters, a previously constructed analytical technique is used to obtain the electroelastic field solution of a poly-l-lactic acid cylindrical fiber exposed to a local electric field, which is applied through an opposed pair of square-sectioned electrodes. The numerical representation of the solution reveals the detailed field quantity distributions, their importance in the design of microtweezers and catheters, the overall deformation of such devices, and the effects of the electrode dimensions on the deformation. GRAPHICAL ABSTRACT
Indoor Air Quality Analysis Using Deep Learning with Sensor Data

Indoor air quality analysis is of interest to understand the abnormal atmospheric phenomena and external factors that affect air quality. By recording and analyzing quality measurements, we are able to observe patterns in the measurements and predict the air quality of near future. We designed a microchip made out of sensors that is capable of periodically recording measurements, and proposed a model that estimates atmospheric changes using deep learning. In addition, we developed an efficient algorithm to determine the optimal observation period for accurate air quality prediction. Experimental results with real-world data demonstrate the feasibility of our approach.
Effect of Oral Prednisolone on Symptom Duration and Severity in Nonasthmatic Adults With Acute Lower Respiratory Tract Infection: A Randomized Clinical Trial

Importance Acute lower respiratory tract infection is common and often treated inappropriately in primary care with antibiotics. Corticosteroids are increasingly used but without sufficient evidence. Objective To assess the effects of oral corticosteroids for acute lower respiratory tract infection in adults without asthma. Design, Setting, and Participants Multicenter, placebo-controlled, randomized trial (July 2013 to final follow-up October 2014) conducted in 54 family practices in England among 401 adults with acute cough and at least 1 lower respiratory tract symptom not requiring immediate antibiotic treatment and with no history of chronic pulmonary disease or use of asthma medication in the past 5 years. Interventions Two 20-mg prednisolone tablets (n = 199) or matched placebo (n = 202) once daily for 5 days. Main Outcomes and Measures The primary outcomes were duration of moderately bad or worse cough (0 to 28 days; minimal clinically important difference, 3.79 days) and mean severity of symptoms on days 2 to 4 (scored from 0 [not affected] to 6 [as bad as it could be]; minimal clinically important difference, 1.66 units). Secondary outcomes were duration and severity of acute lower respiratory tract infection symptoms, duration of abnormal peak flow, antibiotic use, and adverse events. Results Among 401 randomized patients, 2 withdrew immediately after randomization, and 1 duplicate patient was identified. Among the 398 patients with baseline data (mean age, 47 [SD, 16.0] years; 63% women; 17% smokers; 77% phlegm; 70% shortness of breath; 47% wheezing; 46% chest pain; 42% abnormal peak flow), 334 (84%) provided cough duration and 369 (93%) symptom severity data. Median cough duration was 5 days (interquartile range [IQR], 3-8 days) in the prednisolone group and 5 days (IQR, 3-10 days) in the placebo group (adjusted hazard ratio, 1.11; 95% CI, 0.89-1.39; P = .36 at an &agr; = .05). Mean symptom severity was 1.99 points in the prednisolone group and 2.16 points in the placebo group (adjusted difference, −0.20; 95% CI, −0.40 to 0.00; P = .05 at an &agr; = .001). No significant treatment effects were observed for duration or severity of other acute lower respiratory tract infection symptoms, duration of abnormal peak flow, antibiotic use, or nonserious adverse events. There were no serious adverse events. Conclusions and Relevance Oral corticosteroids should not be used for acute lower respiratory tract infection symptoms in adults without asthma because they do not reduce symptom duration or severity. Trial Registration ISRCTN.com Identifier: ISRCTN57309858