Miracle-dz/UniFAR-FTUs huggingface dataset:
Inhibitors of the Cyclin-Dependent Kinase and PIM Kinase Pathways in the Treatment of Myeloma

AbstractMultiple myeloma (MM) cells are characterized by genomic alternations that lead to increased cell proliferation and resistance to therapeutic interventions. Up-regulation of cyclins is a characteristic finding in a significant proportion of myeloma patients, mediated through a variety of mechanisms including chromosomal translocations. Cyclins and the cyclin-dependent kinases (CDKs) play a critical role in the cell proliferation seen in MM, especially in the high-risk disease. Given this, CDK inhibitors have been evaluated in this disease, and studies so far have led to a mixed picture. Recent studies with targeted CDK inhibitors have shown early promise, and trials of these drugs in combination with other myeloma drugs are ongoing. The malignant plasma cells in MM are highly dependent on the microenvironment for their growth and survival. Multiple signaling pathways have been found to mediate the interactions between the microenvironment and the plasma cells, whether mediated through cytokines or adhesion molecules. The PIM kinase pathway appears to play a major role in the myeloma cell survival, and PIM kinase inhibitors have shown efficacy in the laboratory, and a recent clinical trial also demonstrates important clinical activity.
Assessing Tax Risk: Practitioner Perspectives

This study examines whether the tax risk determinants identified by practitioners are incrementally informative of firms’ tax risk, compared to other measures used by recent research. We develop an empirical estimate of tax risk, relying on insights from managers, practitioners, and revenue authorities to identify firm characteristics and activities that generate tax risk. Our validation tests indicate that our estimate of tax risk is associated with higher UTBs and other firm- and market-based risk measures, lower future cash ETRs, and less persistent ETRs, consistent with our estimate representing firms’ tax risk. Moreover, our practitioner-based tax risk measure has incremental explanatory power for future cash ETRs relative to other tax avoidance and tax risk measures. Consistent with practitioners reacting to the factors that they argue create risk, we also find that auditors charge higher audit fee premiums to firms with greater tax risk. Finally, further tests reveal that our tax risk measure explains a substantial portion of UTBs, after controlling for measures of earnings management. Our results indicate that our practitioner-based tax risk measure represents a different construct from that captured by academic tax avoidance and tax risk measures and is useful for examining manager and practitioner decisions regarding tax risk.
The Pathophysiology of Disseminated Intravascular Coagulation

Introduction Disseminated intravascular coagulation (DIC) can be defined as “an acquired syndrome characterized by the activation of intravascular coagulation up to intravascular fibrin formation. The process may be accompanied by secondary fibrinolysis or inhibited fibrinolysis. ”1 Being an acquired disorder, DIC occurs in a wide range of underlying disease states, including sepsis (both by Gram positive and Gram negative bacteria), burns, preeclampsia, malignancy, and polytrauma.1 In the majority of conditions, the pathogenesis of DIC remains only partly understood, an exception is Gram negative septicemia. In the following chapter, we will discuss the presumed mechanism by which DIC is elicited in different pathological states. The initiation of DIC follows the presentation of the glycoprotein tissue factor (TF) at a cellular surface, being either an intact or perturbed cell, or a cell membrane remnant.2 The extracellular TF molecules may interact with circulating factor VIIa to form a catalytic complex. The complex binds the coagulation zymogen factors IX and X. This leads to proteolytic cleavage of these molecules, yielding enzymatically active factors IXa and Xa and promoting the activation of prothrombin to thrombin (Fig. 1).
Transformational leadership and horizontal trust as antecedentsof team performance in the healthcare context

espanolEn el presente estudio analizamos el rol mediador de la confianza en el equipo de trabajo (i.e., confianza horizontal) entre el liderazgo transformacional, como recurso social, y el desempeno en equipo (i.e., desempeno intra y extra rol), tal como sugiere el Modelo HERO (HEalthy & Resilient Organizations Model; Salanova, Llorens, Cifre, & Martinez, 2012). La muestra corresponde a 388 trabajadores/as agrupados/as en 54 equipos de trabajo pertenecientes a cuatro organizaciones del sector sanitario. La confianza horizontal y el liderazgo transformacional fueron evaluados por los equipos de trabajo y el desempeno fue evaluado por los/as supervisores/as de esos equipos. Los modelos de Ecuaciones Estructurales revelaron, tal como se esperaba, que la confianza horizontal, tiene un papel mediador entre el liderazgo transformacional percibido por el equipo y el desempeno en equipo evaluado por el/la supervisor/a EnglishThe present study analyzes the mediator role of work-team trust (i.e., horizontal trust) in the relationship between transformational leadership, as a social resource, and team performance (i.e., intra- and extra-role performance), as suggested by the HERO model (HEalthy & Resilient Organizations Model; Salanova, Llorens, Cifre, & Martinez, 2012). The sample corresponds to 388 workers nested in 54 work teams from four organizations in the healthcare sector. Horizontal trust and transformational leadership were assessed by the work teams, and performance was assessed by the supervisors of these teams. Structural Equations models reveal, as expected, that horizontal trust has a fully mediating role between transformational leadership perceived at the team level and team performance assessed by the supervisor.
Energy Optimization of Routing Protocols in Wireless Sensor Networks

The hierarchical routing of data in WSNs is a specific class of routing protocols it encompasses solutions that take a restructuring of the physical network in a logical hierarchy system for the optimization of the consum-ption of energy. Several hierarchical routing solutions proposed, namely: the protocol LEACH (Low Energy Adaptive Clustering Hierarchy) consist of dividing the network in distributed clusters at one pop in order of faster data delivery and PEGASIS protocol (Power-Efficient Gathering in Sensor Information Systems) which uses the principle of constructing a chain’s sensor node. Our contribution consists of a hierarchical routing protocol, which is the minimization of the energy consumption by reducing the transmission distance of data and reducing the data delivery time. Our solution combines the two hierarchical routing approaches: chain based approach and the cluster based approach. Our approach allows for multi-hop communications, intra- and intercluster, and a collaborative aggregation of data in each Cluster, and a collaborative aggregation of data at each sensor node .
Mother-toddler problem solving: antecedents in attachment, home behavior, and temperament.

In a widely cited study, Matas, Arend, and Sroufe showed that mother-toddler interaction during problem solving at age 2 years was related to the child's prior attachment security. The current study asked (1) whether an independent laboratory could replicate this attachment finding, and (2) whether problem-solving interactions relate to mother-child interactions observed at home and to child temperament measured at 6, 13, and 24 months. Replicating Matas et al., secure dyads worked more competently, and mothers showed better quality of assistance and supportive presence. Mother-child home interaction also predicted problem solving: positive involvement at home predicted effective, unconflicted problem solving. Negative control at home did not predict problem-solving interaction. Unadaptable temperament was generally related to dependency in problem solving. Several patterns of correlations appeared to be mediated by sex of child, e.g., difficult temperament in boys predicted more effective, unconflicted problem solving, while for girls it predicted more conflict.
A Systematic Approach to Optimise Management in Global Sourcing Relationships

Despite a large number of studies, global IT sourcing projects are, in practice, performed ad-hoc and rely mostly on the manager’s experience. Outsourcing software development presents extra challenges because development is performed in an inter-organisational network. Although organisations collaborate by transferring knowledge from the customer to the vendor (e.g., requirements) and from the vendor to the client (e.g., product and status reports), each has its own interests and needs; which often conflict. Tacit requirements, conflicting interests and knowledge-domain gaps contribute to generate final solutions that cost more in terms of resources than what was originally planned or that do not help customers to meet their ambitions. In this work we propose eStudio, our semi-automatic quantitative-data based framework to provide guidance to reason about obstacles in, for instance, knowledge co-ordination.
How to Disseminate Professional Knowledge in Healthcare: The Case of Skaraborg Hospital

Undertaking to implement a knowledge management approach is inherently difficult and risky for organizations. This article describes and discusses an implementation of a knowledge management system that took place at Skaraborg Hospital, a group of hospitals in the South West of Sweden. The article describes how the implementation process was carried out. Based on the experiences from this case and some previous cases, the article suggests a number of best practices for implementing a knowledge management approach.
The Trends in Utilizing Nonvitamin K Antagonist Oral Anticoagulants in Patients With Nonvalvular Atrial Fibrillation

Dabigatran and rivaroxaban are novel nonvitamin K antagonist oral anticoagulants (NOACs) approved for thromboprophylaxis in atrial fibrillation (AF). In Turkey, like other countries, the efficacy of translation of the clinical trial results and current guideline recommendations into daily clinical practice is yet to be discovered. Using data from medical records of three tertiary care cardiology centers, we identified patients with nonvalvular AF on dabigatran or rivaroxaban treatment. Baseline characteristics and utilization trends were compared between dabigatran and rivaroxaban groups. Secondarily, clinical events including ischemic stroke and/or transient ischemic attack, systemic embolism, and bleeding were evaluated. Among 294 patients with AF included, dabigatran was utilized in 177 (60.2%) and rivaroxaban in 117 (39.8%). Overall, 76% of patients had received long-term warfarin therapy. The use of 110 mg twice a day (55.4%) was the prevailing strategy in dabigatran group, whereas in rivaroxaban group 20 mg every day (67.5%) was the preferred option. Of the patients, 37.3% had severe valvular disease in which mitral regurgitation was the predominant valve abnormality. Scores of CHADS2, CHA2DS2VASc, and HAS-BLED were similar in both the groups. Of the patients, 24% in dabigatran group and 13.7% in rivaroxaban group were prescribed the lower dose inappropriately. The two NOACs did not differ significantly in terms of clinical events. The results of this study indicate that in daily practice, the physicians’ behavior in utilizing the NOACs is shaped by the clinical trials and the guideline recommendations. On the other hand, in dose selection, this adherence is not of high quality.
Association of Coloproctology of Great Britain & Ireland (ACPGBI): Guidelines for the Management of Cancer of the Colon, Rectum and Anus (2017) – Multidisciplinary Management

*North Wales Cancer Treatment Centre, Glan Clwyd, UK, †Basingstoke & North Hampshire Hospital, Basingstoke,UK, ‡Cardiff University and Velindre Cancer Centre, Cardiff, UK, §John Radcliffe Hospital, Oxford, UK, ¶University of Birmingham and Queen Elizabeth Hospital,Birmingham, UK, **Clatterbridge Hospital, Wirral, UK, ††University of Manchester and Christie Hospital, Manchester, UK, ‡‡King’s College and Guy’s & St Thomas’ Hospital, London, UK, §§Guy’s & St Thomas’ Hospital, London, UK, ¶¶Birmingham Heartlands Hospital, Birmingham, UK, ***University of Sheffield, Sheffield, UK, and †††Queen Elizabeth Hospital, Birmingham, UK
Two-step Mechanism of Binding of Apolipoprotein E to Heparin

The interaction of apolipoprotein E (apoE) with cell-surface heparan sulfate proteoglycans is an important step in the uptake of lipoprotein remnants by the liver. ApoE interacts predominantly with heparin through the N-terminal binding site spanning the residues around 136–150. In this work, surface plasmon resonance analysis was employed to investigate how amphipathic α-helix properties and basic residue organization in this region modulate binding of apoE to heparin. The apoE/heparin interaction involves a two-step process; apoE initially binds to heparin with fast association and dissociation rates, followed by a step exhibiting much slower kinetics. Circular dichroism and surface plasmon resonance experiments using a disulfide-linked mutant, in which opening of the N-terminal helix bundle was prevented, demonstrated that there is no major secondary or tertiary structural change in apoE upon heparin binding. Mutations of Lys-146, a key residue for the heparin interaction, greatly reduced the favorable free energy of binding of the first step without affecting the second step, suggesting that electrostatic interaction is involved in the first binding step. Although lipid-free apoE2 tended to bind less than apoE3 and apoE4, there were no significant differences in rate and equilibrium constants of binding among the apoE isoforms in the lipidated state. Discoidal apoE3-phospholipid complexes using a substitution mutant (K143R/K146R) showed similar binding affinity to wild type apoE3, indicating that basic residue specificity is not required for the effective binding of apoE to heparin, unlike its binding to the low density lipoprotein receptor. In addition, disruption of the α-helix structure in the apoE heparin binding region led to an increased favorable free energy of binding in the second step, suggesting that hydrophobic interactions contribute to the second binding step. Based on these results, it seems that cell-surface heparan sulfate proteoglycan localizes apoE-enriched remnant lipoproteins to the vicinity of receptors by fast association and dissociation.
Analysis of Amplification Characteristics of Surface Plasmon Polaritons Based on the Rate-Equation Theory

A rate-equation theory model with the amplified spontaneous emission (ASE) effect considered for the surface plasmon polariton (SPP) waveguide amplifier is presented for analyzing the SPP amplifications with both side and SPP pumping techniques. By partitioning the cross section of the waveguide to suitable small units and introducing the overlapping integrated factor in each unit, the 3-D coupled equations of the model can be simplified to 1-D equations, which could be solved more conveniently. With our model, the gain and noise properties of a dielectric-loaded SPP waveguide amplifier are simulated. The results show that the ASE effect reduces the signal gain and deteriorates the signal-to-noise ratio of the SPP amplifier. For both the pumping schemes, the gains and noises for SPP multimode amplifications depend on the waveguide structure. By optimizing the waveguide structure, the gain-equalized amplification for different SPP modes may be achieved.
CKD and the Risk of Acute, Community-Acquired Infections Among Older People With Diabetes Mellitus: A Retrospective Cohort Study Using Electronic Health Records

Background Hospital admissions for community-acquired infection are increasing rapidly in the United Kingdom, particularly among older individuals, possibly reflecting an increasing prevalence of comorbid conditions such as chronic kidney disease (CKD). This study describes associations between CKD (excluding patients treated by dialysis or transplantation) and community-acquired infection incidence among older people with diabetes mellitus. Study Design Retrospective cohort study using primary care records from the Clinical Practice Research Datalink linked to Hospital Episode Statistics admissions data. Setting & Participants 191,709 patients 65 years or older with diabetes mellitus and no history of renal replacement therapy, United Kingdom, 1997 to 2011. Predictor Estimated glomerular filtration rate (eGFR) and history of proteinuria. Outcomes Incidence of community-acquired lower respiratory tract infections (LRTIs, with pneumonia as a subset) and sepsis, diagnosed in primary or secondary care, excluding hospital admissions from time at risk. Measurements Poisson regression was used to calculate incidence rate ratios (IRRs) adjusted for age, sex, smoking status, comorbid conditions, and characteristics of diabetes. Estimates for associations of eGFR with infection were adjusted for proteinuria, and vice versa. Results Strong graded associations between lower eGFRs and infection were observed. Compared with patients with eGFRs ≥ 60 mL/min/1.73 m2, fully adjusted IRRs for pneumonia among those with eGFRs < 15, 15 to 29, 30 to 44, and 45 to 59 mL/min/1.73 m2 were 3.04 (95% CI, 2.42-3.83), 1.73 (95% CI, 1.57-1.92), 1.19 (95% CI, 1.11-1.28), and 0.95 (95% CI, 0.89-1.01), respectively. Associations between lower eGFRs and sepsis were stronger, with fully adjusted IRRs up to 5.56 (95% CI, 3.90-7.94). Those associations with LRTI were weaker but still clinically relevant at up to 1.47 (95% CI, 1.34-1.62). In fully adjusted models, a history of proteinuria remained an independent marker of increased infection risk for LRTI, pneumonia, and sepsis (IRRs of 1.07 [95% CI, 1.05-1.09], 1.26 [95% CI, 1.19-1.33], and 1.33 [95% CI, 1.20-1.47]). Limitations Patients without creatinine results were excluded. Conclusions Strategies to prevent infection among people with CKD are needed.
Funnel plots for comparing provider performance based on patient-reported outcome measures

Background Patient-reported outcome measures (PROMs) often produce skewed distributions of individual scores after a healthcare intervention. For health performance indicators derived from skewed distributions, funnel plots designed with symmetric control limits may increase the risk of false alarms about poor performance. Aim To investigate the accuracy of funnel plots with symmetric control limits when comparing provider performance based on PROMs. Methods The authors used a database containing condition-specific PROMs for 17 453 hip replacements and 7656 varicose vein procedures performed by providers in the English NHS. The mean postoperative PROM score, adjusted for patient characteristics, was used as the measure of performance. To compare performance, symmetric 99.8% control limits were calculated on funnel plots, 3 SDs away from the overall mean on either side. These were compared to control limits derived directly from percentiles of simulated (bootstrap) distributions of mean scores. Results The simulated control limits on funnel plots for both procedures were asymmetric. The empirical probability of falling outside the symmetric 99.8% ‘poor performance’ control limit was inflated from the stipulated rate of 0.1% to 0.2–0.3% for provider sample sizes of up to 150 procedures. The authors observed that, out of 237 providers of hip replacement, eight had adjusted mean scores that exceeded the symmetric ‘poor performance’ limit compared with only five that exceeded the corresponding simulated limit. In other words, three (1.3%) were differently classified. For varicose vein surgery, five out of 160 providers exceeded the symmetric limit and four exceeded the simulated limit, that is, 1 (0.6%) was differently classified. Conclusions When designing funnel plots for comparisons of provider performance based on highly skewed data, the use of simulated control limits should be considered.
The performance of commercial banks and the determinants of profitability: Evidence from Kosovo

Financial intermediaries perform indirect financing, and in this context, commercial banks are very important participants. They carry out the bulk of indirect financing transactions. On the other hand, the implementation mechanism of monetary policy is closely linked to the functioning of the banking system. Kosovo’s Commercial Banks performance is satisfactory compared with regional. In this paper we provide some of the performance indicators. The rates of return of commercial banks are greatly and directly affected by the net interest margin, provisions for loan losses, revenues and expenses by the non-interest, taxes and the equity multiplier. In this context, liquid assets do not appear to be of high impact in determining and variability the rate of return, high liquidity with low returns. Also, we address the impact of the global financial crisis “2008-20012” in the commercial banks performance in Kosovo, mainly through the impact of the decline in the asset use ratio. We think that was a positive approach that banks have followed the course of returns fall by the reduction in interest-expenditures, while the costs of provisions for loan losses to total average assets marked constant level throughout the period, despite the increasing ratio of nonperforming loans. Drawing on these findings it is recommended that banks even further engage in reducing operational costs; diversify income sources in order not to rely exclusively on the interests of loans, and to strengthen credit risk management in order to minimize the credit risk.
Is Basel the Right Gateway for a More Efficient Debt Market? An International Comparison

Current literature does not agree on the impact that Basel regulation is having onto the banking system, small and medium size enterprises (SMEs) and the single country economies. Moreover, recent crises cast some doubts on the efficacy of the regulation itself. With this paper, we investigate this issue by comparing the credit allocation capabilities of different countries. In particular, we compare two Anglo-Saxon Countries (the USA and the UK) with a group of eight European Countries where Basel rules are fully implemented. We find that, without the competition of well-developed risk capital markets, Basel regulation struggles to be effective.
Clinical and radiographic evaluation of immediately loaded one-piece implants placed into fresh extraction sockets.

OBJECTIVE To assess clinical survival and success rates of one-piece implants placed at the time of tooth extraction with immediate provisionalization and to evaluate radiographic peri-implant bone loss around one-piece implants 1 year after functional loading. METHOD AND MATERIALS Forty-six patients (20 men and 26 women) with a mean age of 45.5 years (range, 24 to 74 years) were recruited from four centers for this case series report. Immediately following the extraction of untreatable teeth, all patients received one-piece implants. The implants were immediately restored and placed into function with no occlusal contact. Outcome assessments included clinical and radiographic evaluations. RESULTS Of the one-piece implants placed after extraction in the maxilla and mandible, 95.7% integrated successfully. The mean marginal bone loss after 1 year was 0.80 mm (SD, 0.53 mm). Overall peri-implant bone loss at maxillary sites was compared with overall bone loss at mandibular sites. At the 1-year follow-up, no statistically significant difference was found. The deeper the implants were placed below the crest, the more marginal bone loss was observed. However, no difference in marginal bone loss was observed as a consequence of the following three variables: implant length (10, 11.5, or 13 mm), implant diameter (3, 3.7, or 4.7 mm); and 3- and 6-month time periods after implant prosthesis placement. CONCLUSION Based on data obtained from this sample size study, it can be concluded that one-piece implants can be successfully placed immediately after extraction with minimal peri-implant bone loss.