Miracle-dz/UniFAR-FTUs huggingface dataset:
Use of Intravenous Fentanyl Against Morphine Tolerance in Breakthrough Cancer Pain

Palliative care physicians are accustomed to using transdermal fentanyl patch for cancer pain control but not so familiar with its intravenous administration. Historically, fentanyl has been used to treat breakthrough pain because it is a very potent analgesic with a rapid onset and short duration of action. Although several formulations of fentanyl have been recently developed for breakthrough cancer pain, these are unavailable or too expensive in some countries. Also, all opioids can induce tolerance potentially and different opioids cause significantly different degrees of tolerance. Therefore, sequential opioid trials may be a reasonable approach in patients with poor analgesic effect after dose escalation. Here, we present 2 morphine-tolerant patients with cancer in whom the intravenous fentanyl was effectively used for their refractory breakthrough pain.
Mortality in diabetes: pancreas transplantation is associated with significant survival benefit.

BACKGROUND Pancreas transplantation in complicated type 1 (insulin dependent) diabetes mellitus improves the quality of life, increases longevity and stabilizes diabetic complications. There may be clinician reticence due to perceived poor outcomes with published associated mortality rates of 5-8% due to significant co-morbidities, particularly cardiovascular impairment. METHODS Retrospective analysis was performed on patients undergoing pancreas transplantation in a single centre since the programme's initiation [simultaneous pancreas kidney (SPK) = 148, pancreas after kidney (PAK) = 33 and pancreas transplant alone (PTA) = 11] compared with a control group accepted contemporaneously onto the waiting list. The primary endpoint was patient mortality. The risk factors including medical and diabetic history, demographics, transplant type and waiting time were analysed. RESULTS The waiting list mortality was 30% (35 of 120) compared with a mortality of 9% (20 of 193) post-transplantation (P < 0.001). Deaths on the waiting list compared with transplantation up to 1 year had a relative risk of 2.67 (95% CI: 0.81-3.51; P = 0.19), whilst those surviving >1 year had a relative risk of 5.89 of dying on the waiting list (95% CI: 1.70-3.20; P < 0.0005). There were no differences in terms of cardiovascular or renal-associated risk factors, nor in other potential confounding factors other than duration of diabetes (P = 0.02). Median survival from listing was shorter in younger patients (<50; P < 0.0001). CONCLUSIONS Type 1 diabetics with renal failure listed for pancreas transplantation are at a significant risk of mortality even without surgery. Transplantation offers considerable survival benefits, despite associated surgical and immunosuppressive risks. In selected patients, pancreas transplantation remains the benchmark treatment for type 1 diabetes mellitus.
Biologically plausible learning in a deep recurrent spiking network

Artificial deep convolutional networks (DCNs) meanwhile beat even human performance in challenging tasks. Recently DCNs were shown to also predict real neuronal responses. Their relevance for understanding the neuronal networks in the brain, however, remains questionable. In contrast to the unidirectional architecture of DCNs neurons in cortex are recurrently connected and exchange signals by short pulses, the action potentials. Furthermore, learning in the brain is based on local synaptic mechanisms, in stark contrast to the global optimization methods used in technical deep networks. What is missing is a similarly powerful approach with spiking neurons that employs local synaptic learning mechanisms for optimizing global network performance. Here, we present a framework consisting of mutually coupled local circuits of spiking neurons. The dynamics of the circuits is derived from first principles to optimally encode their respective inputs. From the same global objective function a local learning rule is derived that corresponds to spike-timing dependent plasticity of the excitatory inter-circuit synapses. For deep networks built from these circuits self-organization is based on the ensemble of inputs while for supervised learning the desired outputs are applied in parallel as additional inputs to output layers. Generality of the approach is shown with Boolean functions and its functionality is demonstrated with an image classification task, where networks of spiking neurons approach the performance of their artificial cousins. Since the local circuits operate independently and in parallel, the novel framework not only meets a fundamental property of the brain but also allows for the construction of special hardware. We expect that this will in future enable investigations of very large network architectures far beyond current DCNs, including also large scale models of cortex where areas consisting of many local circuits form a complex cyclic network.
Worst-case communication delay analysis for many-cores using a Limited Migrative Model

A steady increase in the number of cores within many-core platforms causes increasing contentions for the interconnect medium and leads to non-negligible latencies of intercore communication. In order to study the worst-case execution times of applications, it is no longer sufficient to only take into account schedulability requirements, but the communication delays also have to be considered. In this paper we focus on the worst-case communication delays of applications, assuming a Limited Migrative Model (LMM). LMM is an approach based on the multi-kernel paradigm - a promising step towards scalable and predictable many-cores. The contribution of this paper is threefold. First, we extend LMM by allowing inter-application communication, and adapt the existing worst-case communication delay analysis, to make it applicable to the enhanced model. Then, we propose a novel analysis. Finally, we compare these two methods. The experiments show that the new approach renders tighter upper-bound estimates in more than 90% of the cases, while demonstrating a comparable runtime performance.
[Lipid peroxidation and copper-zinc superoxide dismutase activity in patients treated with fluoxetine during the first episode of depression].

UNLABELLED In recent years researchers have made a lot of studies to determine the molecular and neurochemical mechanisms which are the basis of depressive disorders. Apoptosis is a cause of the limbic system neuronal cells defect in patients suffering from depression. The antioxidant system is the best known molecular mechanism which protects the cells from apoptosis. This system exists inside and outside of the cells compartments. There is much evidence that antioxidant enzymes keep neuronal cells safe from apoptosis, which is a result of oxidative stress. It also limits the premature ageing of cells. AIM We tried to give an answer to three questions. 1. Is the activity of cooper-zinc superoxide dismutase (CuZnSOD) and lipid peroxydation level (TBARS) different in patients and the healthy control group? 2. Does the activity of CuZnSOD change due to fluoxetine treatment? 3. What is the difference of TBARS concentration in platelets isolated from patients before and after treatment? METHOD The study comprised of 32 patients diagnosed with depression. The activity of CuZnSOD in platelets was measured by Misra and Fridovich's method. The thrombocyte concentration of TBARS was measured by Placer and coop. method. RESULTS AND CONCLUSIONS 1. The activity of CuZnSOD in platelets of depressive patients is lower than in the healthy control group, but the differences are not significant. 2. The activity of CuZnSOD rises after fluoxetine treatment. 3. The concentration of TBARS is higher in patients than in the healthy control group. 4. The intensity of lipid peroxydation is statistically lower after fluoxetine treatment.
Use of design and modeling in agile software development

Agile Software Development targets rapid delivery of solutions with ongoing involvement of customer. Thorough requirements analysis and comprehensive documentation are not a priority in this scheme. Traditional software engineering emphasizes the positive relationship between quality documentation and success of projects. In case of agile development, lack of Good Design, Modeling and Sound Architecture can prove to be very expensive. A survey has been conducted in two software development companies in the UAE, which use agile technologies. The results are presented in this paper which includes recommendations for both the companies.
Pooling in Chronic Orthostatic Intolerance: Arterial Vasoconstrictive but not Venous Compliance Defects

Background—Orthostatic intolerance is characterized by postural tachycardia syndrome (POTS) with exaggerated tachycardia, orthostatic symptoms, and “pooling” (which comprises acrocyanosis and dependent edema when upright). My colleagues and I tested the hypothesis that pooling results from increased venous compliance in POTS patients. Methods and Results—Fifteen patients aged 13 to 19 years were compared with 11 healthy, age-matched controls. The POTS group was divided into patients with high venous pressure (Pv>20 mm Hg) and normal Pv on the basis of resting supine Pv obtained in previous work. Subjects were studied using strain gauge plethysmography to measure blood flow, Pv, and the venous compliance volume-pressure relation while supine and during incremental head-up tilt testing at −10°, 0°, 20°, and 35°. Volume-pressure relations of controls and POTS patients with normal Pv and high Pv were not different and were unchanged by orthostasis. Supine leg peripheral resistance was greater than control resistance in patients with high Pv (54±9 versus 30±6 mm Hg · mL−1 · 100 mL−1 · min−1) and less than control resistance in patients with normal Pv (17±2 mm Hg · mL−1 · 100 mL−1 · min−1). On upright tilt, resistance decreased in high Pv to approximate resistance in normal Pv. Resistance in controls increased throughout tilt. Leg Pv increased in patients with normal Pv and in controls but remained unchanged in the high Pv group. Conclusions—The findings suggest that pooling in POTS is due to blunted arterial vasoconstriction, which produces passive redistribution of blood within peripheral venous capacitance beds. Venous compliance in POTS is similar to that in control subjects.
PDS Based Bilateral Control System of Flexible Master-Slave Arms with Random Delay Considering Contact with Obstacle

A PDS based bilateral control system of flexible master-slave arms with random delay is investigated in this paper. Moreover, a flexible slave arm employed in this research is affected by a contact force. A rigid master arm and a flexible slave arm which is actuated by a high-geared servomotor construct the proposed bilateral control system. Both arms are connected by a communication network. It is considered that this network occurs a random delay. Furthermore, the contact force is added to the flexible arm during its motion. Thus, the motion of this arm is restricted by the contact force. A Kalman filter is designed to estimate signals and controllers for both arms are designed as the PDand PDS-controllers, respectively. Numerical simulations are achived to confirm the performance of the proposed system such as the instability of its motion and the adaptivity of the Kalman filter.
Up-Regulation of VCAM-1 and Differential Expansion of β Integrin-Expressing T Lymphocytes Are Associated with Immunity to Pulmonary Mycobacterium tuberculosis Infection1

Immune responses rely on an intricate system of adhesion molecules to coordinate the homing and retention of lymphocytes in both secondary lymphoid tissues and at sites of infection. To define the events associated with pulmonary immune responses, the expression of endothelial addressins and integrins on T cells was analyzed during Mycobacterium tuberculosis infection. In infected lung, expression of endothelial VCAM-1, but not mucosal addressin cell adhesion molecule-1, was up-regulated from 4 wk postinfection and persisted to at least 12 wk. Subsequent analysis of the corresponding integrins expressed on lung CD4+ and CD8+ T cells revealed an accumulation of β1high/β7−/low, and to a lesser extent β7high, integrin-expressing T cells during infection. Examination of integrin heterodimers showed that while α4 integrin was predominantly expressed on β1high/β7−/low cells, αE integrin was primarily associated with β7high. The majority of activated/memory T cells recruited during infection expressed high levels of β1 integrin and undetectable or low levels of β7 integrin. These T cells were capable of producing IFN-γ, a cytokine crucial for controlling M. tuberculosis infection. Rapid expansion of β1high, β7−, and β7high T cell populations in the lung upon secondary mycobacterial infection indicates the participation of these populations in the acquired immune response to the infection. Furthermore, treatment of infected mice with mAb to α4 or α4β7 integrin led to a reduction in lymphocytes and increase in granulocytes in the pulmonary infiltrate. These results reveal a crucial role for adhesion molecules in the generation of an effective pulmonary immune response to M. tuberculosis infection.
Guideline for screening, assessment and treatment in problem gambling

Disclaimer This document is a general guide to appropriate practice, to be followed subject to the circumstances, clinician's judgement and patient's preferences in each individual case. It is designed to provide information to assist decision making. Recommendations contained herein are based on the best available evidence published up to March 2010. The relevance and appropriateness of the information and recommendations in this document depend on the individual circumstances. Moreover, the recommendations and guidelines are subject to change over time. Each of the parties involved in developing this document expressly disclaims and accepts no responsibility for any undesirable consequences arising from relying on the information or recommendations contained herein. In approving these guidelines the NHMRC considers that they meet the NHMRC standard for clinical practice guidelines. This approval is valid for a period of 5 years. NHMRC is satisfied that they are based on the systematic identification and synthesis of the best available scientific evidence and make clear recommendations for health professionals practising in an Australian health care setting. The NHMRC expects that all guidelines will be reviewed no less than once every five years. Foreword The guideline summarises the research and the current state of knowledge concerning problem gambling and includes a series of evidence-based recommendations concerning screening, assessment and treatment practices for problem gambling. The development of this guideline is an endorsed activity of the International Gambling Think Tank. The Think Tank is an invitational meeting of the world's leading scientists in gambling and addiction and the jurisdictions within which they operate with representation from the US, Canada, European Union, UK and Nordic countries, Asia, Australia and New Zealand. The guideline has been developed in response to a growing research base in problem gambling and the need for problem gambling services, practitioners and policy makers to have evidence-based guidance in the design and delivery of treatments for people with gambling problems. It should be noted that for the purpose of this Australian guideline, the term " problem gambling " is used to refer to the full continuum of gambling-related harm, which is in accordance with standard practice in the Australian context. The term " pathological gambling " is only used in the context of the DSM classification in this guideline. It is acknowledged that in some other jurisdictions the term " pathological gambling " is used to refer to people with a diagnosed or diagnosable gambling disorder and that …
A general solution of the n-dimensional B-tree problem

We present a generic solution to a problem which lies at the heart of the unpredictable worst-case performance characteristics of a wide class of multi-dimensional index designs: those which employ a recursive partitioning of the data space. We then show how this solution can produce modified designs with fully predictable and controllable worst-case characteristics. In particular, we show how the recursive partitioning of an n-dimensional dataspace can be represented in such a way that the characteristics of the one-dimensional B-tree are preserved in n dimensions, as far as is topologically possible i.e. a representation guaranteeing logarithmic access and update time, while also guaranteeing a one-third minimum occupancy of both data and index nodes.
Homologous Recombination but Not Nucleotide Excision Repair Plays a Pivotal Role in Tolerance of DNA-Protein Cross-links in Mammalian Cells*

DNA-protein cross-links (DPCs) are unique among DNA lesions in their unusually bulky nature. The steric hindrance imposed by cross-linked proteins (CLPs) will hamper DNA transactions, such as replication and transcription, posing an enormous threat to cells. In bacteria, DPCs with small CLPs are eliminated by nucleotide excision repair (NER), whereas oversized DPCs are processed exclusively by RecBCD-dependent homologous recombination (HR). Here we have assessed the roles of NER and HR for DPCs in mammalian cells. We show that the upper size limit of CLPs amenable to mammalian NER is relatively small (8–10 kDa) so that NER cannot participate in the repair of chromosomal DPCs in mammalian cells. Moreover, CLPs are not polyubiquitinated and hence are not subjected to proteasomal degradation prior to NER. In contrast, HR constitutes the major pathway in tolerance of DPCs as judged from cell survival and RAD51 and γ-H2AX nuclear foci formation. Induction of DPCs results in the accumulation of DNA double strand breaks in HR-deficient but not HR-proficient cells, suggesting that fork breakage at the DPC site initiates HR and reactivates the stalled fork. DPCs activate both ATR and ATM damage response pathways, but there is a time lag between two responses. These results highlight the differential involvement of NER in the repair of DPCs in bacterial and mammalian cells and demonstrate the versatile and conserved role of HR in tolerance of DPCs among species.
Quality of life in patients with skin diseases in central Saudi Arabia

Background Previous national and international studies of quality of life (QoL) in patients with skin diseases have revealed different levels of QoL impairment. The aims of this study were to assess QoL in patients with skin diseases in central Saudi Arabia using the newly validated Skindex-16 instrument and to determine the association between QoL in patients with skin disease, sociodemographic data, and disease characteristics. Methods A cross-sectional study was conducted in 283 adult patients who visited the outpatient dermatology clinics of King Abdulaziz Medical City, Riyadh, Saudi Arabia, over 3 months. The patients were interviewed using a pretested Arabic version of the Skindex-16 to measure the effect of skin disorders on their QoL during the previous 7 days. Patient characteristics, medical history, and clinical findings were collected. Multiple linear regression analyses were used to relate the demographic and clinical characteristics to the percentage mean QoL score, and P ≤ 0.05 was considered to be statistically significant. Results QoL was good in 69% of the respondents, with a total percent mean score of 31.80 ± 20.16. The emotional domain was the most affected (mean percentage score 44.27 ± 27.06), followed by symptoms (31.45 ± 28.40) and functioning (14.61 ± 22.75). After adjustment for potential confounders, poorer QoL was significantly associated with female gender (P = 0.03), older age (P = 0.003), rural origin (P = 0.03), positive family history of the same lesion(s) (P = 0.01), shorter duration of ≤6 months (P = 0.02), generalized spread (P ≤ 0.02), and lack of isotretinoin treatment (P = 0.02). Conclusion . The QoL results in this study were generally more optimistic than those of many previous studies. This discrepancy may be due to biases in questionnaire responses or to cultural differences in experience of skin disease and perception of disability. Significant predictors of QoL were not the same for the three domains of the Skindex scale. Further studies of specific diseases and educational programs targeting patients at higher risk for QoL impairments are recommended.
Integral models in mixed characteristic (0,2) of Shimura varieties of PEL type

We prove the existence and the uniqueness of integral canonical models of Shimura varieties of PEL type in unramified mixed characteristic (0, 2). The existence part for the A and C (i.e. the unitary and symplectic) cases was known before, with the works of Mumford (1965), Zink (1983), and Rapoport–Langlands (1987) as the main references. So the new parts of this result are the existence part for the D (i.e. the hermitian orthogonal) case and the uniqueness part. As an additional feature, for the D case we also construct relative PEL embeddings into Shimura varieties involving a reductive group over Q that over Q 2 is a split GSO group. Shimura varieties are the main testing ground for many parts of Langlands' program. The understanding of the zeta functions of these varieties depends on a good theory of their integral models. Such a theory was obtained in [42] for cases of good reduction of Shimura varieties of preabelian type with respect to primes of characteristic at least 5. But for refined applications to zeta functions it is important to have also a good theory in mixed characteristic (0, p), with p ∈ {2, 3}. As in future work we will present a complete theory of good reductions for p = 3, in this paper we report on recent progress for p = 2.2 for a general theory of integral (canonical) models of Shimura varieties (the precise definitions of such models are not relevant for what follows). The previous status of the existence of smooth such integral models in mixed characteristic (0, 2) can be summarized as follows.1 for a translation of this result in the language of Shimura varieties). The proof uses geometric invariant theory and standard deformations of abelian varieties.
Building Concordant Ontologies for Drug Discovery

— In this study we demonstrate how we interconnect three different ontologies, the BioAssay Ontology (BAO), LINCS Information FramEwork ontology (LIFEo), and the Drug Target Ontology (DTO). The three ontologies are built and maintained for three different projects: BAO for the BioAssay Ontology Project, LIFEo for the Library of Integrated Network-Based Cellular Signatures (LINCS) project, and DTO for the Illuminating the Druggable Genome (IDG) project. DTO is a new ontology that aims to formally describe drug target knowledge relevant to drug discovery. LIFEo is an application ontology to describe information in the LIFE software system. BAO is a highly accessed NCBO ontology; it has been extended formally to describe several LINCS assays. The three ontologies use the same principle architecture that allows for re-use and easy integration of ontology modules and instance data. Using the formal definitions in DTO, LIFEo, and BAO and data from various resources one can quickly identify disease-relevant and tissue-specific genes, proteins, and prospective small molecules. We show a simple use case example demonstrating knowledge-based linking of life science data with the potential to empower drug discovery.