Miracle-dz/UniFAR-FTUs huggingface dataset:
Peer review comments on drug trials submitted to medical journals differ depending on sponsorship, results and acceptance: a retrospective cohort study

Objective During peer review, submitted manuscripts are scrutinised by independent experts to assist journal editors in their decision-making and to help improve the quality of articles. In this retrospective cohort study, peer review comments for drug trials submitted to medical journals were analysed to investigate whether there is a relation between the content of these comments and sponsorship, direction of results and decision about acceptance. Design/setting Descriptive content analysis of reviewer comments made on manuscripts on drug trials submitted to eight medical journals (January 2010–April 2012). For each manuscript, the number of reviewers, decision about acceptance, sponsorship and direction of results were extracted. Reviewer comments were classified using a predefined checklist. Results Reviewer reports for 246 manuscripts were assessed. Industry-sponsored trials were more likely to receive comments about lack of novelty (8.9%) than industry-supported (2.5%) and non-industry trials (6.1%, overall p=0.038). Non-industry trials more often received comments about poor experimental design (69.7%) than industry-supported (58.8%) and industry-sponsored trials (52.9%, overall p=0.019). Non-industry trials were also more likely to receive comments regarding inappropriate statistical analyses (28.4%) than industry-supported (23.5%) and industry-sponsored trials (15.1%, overall p=0.006). Manuscripts with negative results were more likely to receive comments about inappropriate conclusions (29.3%) than those with positive results (18.9%, p=0.010). Rejected manuscripts had more often received comments on the research question not being clinically relevant (7.8%) than accepted manuscripts (1.6%, p=0.002), and also on lack of novelty (8.3% vs 2.6%, p=0.008) and poor experimental design (68.6% vs 50.5%, p<0.001). Conclusions Reviewers identified fewer shortcomings regarding design and statistical analyses in industry-related trials, but commented more often on a lack of novelty in industry-sponsored trials. Negative trial results did not significantly influence the nature of comments other than appropriateness of the conclusion. Manuscript acceptance was primarily related to the research question and methodological robustness of studies.
Combination of a Hepatitis C Virus NS3-NS4A Protease Inhibitor and Alpha Interferon Synergistically Inhibits Viral RNA Replication and Facilitates Viral RNA Clearance in Replicon Cells

ABSTRACT The present standard of care for hepatitis C virus (HCV) infection is pegylated alpha interferon (IFN-α) in combination with ribavirin. However, specific antivirals such as HCV NS3-NS4A protease inhibitors are now in clinical development, and these agents can potentially be used in combination with the present treatments. Therefore, it is important to investigate the potential benefits or adverse effects of these new combinations by using available in vitro HCV culture systems first. In the present study we demonstrate that the combination of a specific HCV NS3-NS4A protease inhibitor and IFN-α synergistically inhibits HCV RNA replication in replicon cells, with little or no increase in cytotoxicity. Furthermore, the benefit of the combination was sustained over time, such that a greater than 3-log reduction in HCV RNA levels was achieved following 9 days of treatment. The viral RNA appeared to be cleared from the replicon cells after 14 days of treatment, and no viral RNA rebound was observed upon withdrawal of the inhibitors. In each case, the antiviral effects obtained with higher concentrations of either the protease inhibitor alone or IFN-α alone can be achieved by a combination of both agents at lower concentrations, which may potentially reduce the risk of possible adverse effects associated with high doses of either agent.
Aerated Shewanella oneidensis in continuously fed bioelectrochemical systems for power and hydrogen production

We studied the effects of aeration of Shewanella oneidensis on potentiostatic current production, hydrogen production in a microbial electrolysis cell, and electric power generation in a microbial fuel cell (MFC). The potentiostatic performance of aerated S. oneidensis was considerably enhanced to a maximum current density of 0.45 A/m2 or 80.3 A/m3 (mean: 0.34 A/m2, 57.2 A/m3) compared to anaerobically grown cultures. Biocatalyzed hydrogen production rates with aerated S. oneidensis were studied within the applied potential range of 0.3–0.9 V and were highest at 0.9 V with 0.3 m3 H2/m3 day, which has been reported for mixed cultures, but is ∼10 times higher than reported for an anaerobic culture of S. oneidensis. Aerated MFC experiments produced a maximum power density of 3.56 W/m3 at a 200‐Ω external resistor. The main reasons for enhanced electrochemical performance are higher levels of active biomass and more efficient substrate utilization under aerobic conditions. Coulombic efficiencies, however, were greatly reduced due to losses of reducing equivalents to aerobic respiration in the anode chamber. The next challenge will be to optimize the aeration rate of the bacterial culture to balance between maximization of bacterial activation and minimization of aerobic respiration in the culture. Biotechnol. Bioeng. 2010;105: 880–888. © 2009 Wiley Periodicals, Inc.
Empathy in Clinical Practice: How Individual Dispositions, Gender, and Experience Moderate Empathic Concern, Burnout, and Emotional Distress in Physicians

To better understand clinical empathy and what factors can undermine its experience and outcome in care-giving settings, a large-scale study was conducted with 7,584 board certified practicing physicians. Online validated instruments assessing different aspects of empathy, distress, burnout, altruistic behavior, emotional awareness, and well-being were used. Compassion satisfaction was strongly associated with empathic concern, perspective taking and altruism, while compassion fatigue (burnout and secondary traumatic stress) was more closely related to personal distress and alexithymia. Gender had a highly selective effect on empathic concern, with women displaying higher values, which led to a wide array of negative and devalued feelings. Years of experience did not influence dispositional measures per se after controlling for the effect of age and gender. Participants who experienced compassion fatigue with little to no compassion satisfaction showed the highest scores on personal distress and alexithymia as well as the strongest indicators of compassion fatigue. Physicians who have difficulty regulating their negative arousal and describing and identifying emotions seem to be more prone to emotional exhaustion, detachment, and a low sense of accomplishment. On the contrary, the ability to engage in self-other awareness and regulate one’s emotions and the tendency to help others, seem to contribute to the sense of compassion that comes from assisting patients in clinical practice.
Neural-Cardiac Coupling in Threat-Evoked Anxiety

Anxiety is a debilitating symptom of many psychiatric disorders including generalized anxiety disorder, mood disorders, schizophrenia, and autism. Anxiety involves changes in both central and peripheral biology, yet extant functional imaging studies have focused exclusively on the brain. Here we show, using functional brain and cardiac imaging in sequential brain and cardiac magnetic resonance imaging (MRI) sessions in response to cues that predict either threat (a possible shock) or safety (no possibility of shock), that MR signal change in the amygdala and the prefrontal and insula cortices predicts cardiac contractility to the threat of shock. Participants with greater MR signal change in these regions show increased cardiac contractility to the threat versus safety condition, a measure of the sympathetic nervous system contribution to the myocardium. These findings demonstrate robust neural-cardiac coupling during induced anxiety and indicate that individuals with greater activation in brain regions identified with aversive emotion show larger magnitude cardiac contractility increases to threat.
Opposing regulation of T cell function by Egr‐1/NAB2 and Egr‐2/Egr‐3

TCR‐induced NF‐AT activation leads to the up‐regulation of multiple genes involved in T cell anergy. Since NF‐AT is also involved in T cell activation, we have endeavored to dissect TCR‐induced activating and inhibitory genetic programs. This approach revealed roles for the early growth response (Egr) family of transcription factors and the Egr coactivator/corepressor NGFI‐A‐binding protein (NAB)2 in regulating T cell function. TCR‐induced Egr‐1 and NAB2 enhance T cell function, while Egr‐2 and Egr‐3 inhibit T cell function. In this report, we demonstrate that Egr‐2 and Egr‐3 are induced by NF‐AT in the absence of AP‐1, while Egr‐1 and NAB2 both require AP‐1‐mediated transcription. Our data suggest that Egr‐3 is upstream of Egr‐2, and that mechanistically Egr‐2 and Egr‐3 suppress Egr‐1 and NAB2 expression. Functionally, T cells from Egr‐2 and Egr‐3 null mice are hyperresponsive while T cells from Egr‐3 transgenic, overexpressing mice are hyporesponsive. Furthermore, an in vivo model of autoimmune pneumonitis reveals that T cells from Egr‐3 null mice hasten death while Egr‐3‐overexpressing T cells cause less disease. Overall, our data suggest that just as the Egr/NAB network of genes control cell fate in other systems, TCR‐induced Egr‐1, 2, 3 and NAB2 control the fate of antigen recognition in T cells.
A study on the l1 analysis of discrete-time systems

This paper studies computing the l∞-induced norm of multi-input/multi-output (MIMO) linear time-invariant (LTI) discrete-time systems, which is called the l1 analysis problem. Because such a computation involves an infinite-dimensional matrix, this paper employs a truncation idea to approximately deal with the l1 analysis problem. More precisely, this paper develops two methods for computing the l∞-induced norm, in which upper bounds and lower bounds of the l∞-induced norm are derived on the truncated treatment. Furthermore, it is shown that the gaps between the computed upper and lower bounds converge to 0 at an exponential rate of N, where N is the truncation parameter. Finally, a numerical exampled is provided to demonstrate the effectiveness of the developed computation methods.
Litho-stratigraphic and hydrogeological evaluation of groundwater system in parts of Benin Metropolis, Benin City Nigeria: The key to groundwater sustainability

Previous studies revealed that soil properties play a significant role in aquifer contamination. Consequently, it is necessary to understand the nature and properties of soil in carrying out groundwater evaluation. This study evaluates the subsurface geology and groundwater flow direction in Okpagha, Iguomo, Ikhueniro and Okhuahe suburbs in Benin City, Nigeria. Six boreholes were drilled by means of manual (rotary) method in different parts of the study area and each borehole was logged in order to understand the lithology, depth to water table, static water level as well as flow direction. The results obtained show that aquifer within the study areas were confined, semi confined to unconfined and was dominated by sands with minor clay and lignite interbed. It was observed that aquifer becomes shallower towards eastern portion of the study areas with increase in sand and decrease in clay materials. It was also observed that groundwater flow map revealed a flow direction of North-West to South-East from North West to South East. The decrease in the depth of aquifer and increase in sand material could be explained by the closeness to sea level. This phenomenon can enhance the infiltration of contaminants into aquifer thereby contaminating the groundwater bodies. It is therefore necessary to constantly monitor the groundwater quality in this suburbs in order to be aware of the quality of water resources being consumed because poor water quality can impact public health negatively. Furthermore, the authors advise that boreholes should be drilled in the direction of groundwater flow for maximum yield Keywords : Groundwater, lithology, borehole, aquifer, water quality and contaminants
The Palliative Care Clinical Evaluation Exercise (CEX): An Experience-Based Intervention for Teaching End-of-Life Communication Skills

Purpose To pilot test the “Palliative Care Clinical Evaluation Exercise (CEX),” a new experience-based intervention to teach communication skills in giving bad news and discussing code status. The intervention allows faculty to observe, evaluate, and give feedback to housestaff in their discussions with patients and families. Method In 2002–03, the intervention was piloted among 60 first-year residents in the categorical Internal Medicine Residency Programs at the University of Pittsburgh. The authors collected feasibility measurements at the time of intervention, and interns’ attitudes were measured before and one week after intervention and at the end of the intern year. Results Forty-four residents (73%) completed the intervention. Discussions averaged a total of 49.5 minutes (SD 24.1), divided among 12.7 minutes (SD 7.5) for prediscussion counseling between the resident and faculty observer, 25.6 minutes (SD 16.1) for the resident–patient discussion, and 12.1 minutes (SD 5.7) for postdiscussion feedback. Residents rated the Palliative Care CEX favorably (>3 on a five-point scale) on ease of arranging the exercise, educational value, quality of the experience, effect on their comfort with discussions, importance to their education, and value of preceptor feedback. Self-ratings of communication competence showed improvement one week after the intervention. Conclusions The Palliative Care CEX is feasible and positively valued by residents. The findings from this initial pilot study support the value of further efforts to refine the intervention, to confirm its feasibility in other settings, and to validate its use as an educational and assessment tool.
Plantar Flexor Muscle Architecture Changes as a Result of Eccentric Exercise in Patients With Achilles Tendinosis

Eccentric training for Achilles tendinosis (AT) has been reported to significantly improve patient symptoms. There has been no biomechanical explanation on the mechanism for specific rehabilitation technique. The purpose of this study was to determine changes in muscle architecture that occurred as a result of Achilles tendinosis injury and a subsequent eccentric rehabilitation program. Twenty-five patients (age, 53.3 ± 17.5 years) diagnosed with AT participated in 6 weeks of rehabilitation. Specific exercises for the ankle plantar flexors consisted of maximal load eccentric muscle action using 3 sets of 15 repetitions. Patients also completed a protocol for AT, which consisting of traditional rehabilitation. Medial gastrocnemius (GM) and lateral gastrocnemius (GL) muscle fascicle length and thickness were measured with ultrasound at 2-week intervals from initial treatment day to the end of 6 weeks of rehabilitation. Medial gastrocnemius fascicle length increased (45.1 ± 10.5 mm to 51.4 ± 10.5 mm; P = .22) between the initial day of rehabilitation and after 6 weeks of rehabilitation. But, GM thickness (16.3 ± 3.5 mm to 16.8 ± 2.0 mm), GL fascicle length (47.2 ± 10.0 mm to 47.1 ± 7.4 mm), and GL thickness (14.9 ± 5.2 mm to 14.4 ± 2.7 mm) did not change as a result of rehabilitation. A 6-week eccentric-biased exercise increased the GM muscle fascicle length by 12%, but GM thickness, GL fascicle length, and GL thickness did not change as a result of rehabilitation. Eccentric training for the treatment of AT is well recognized, but the mechanism of action has not been previously reported. A 6-week eccentric training protocol increased the GM muscle fascicle length by 12%, and this correlated with improvement in a validated patient outcome scoring system. Further study is warranted to determine a predictive relationship between improvement of GM fascicle length and outcome scores. Levels of Evidence: Therapeutic, Level IV: Case series
Anthrax Toxins Induce Shock in Rats by Depressed Cardiac Ventricular Function

Anthrax infections are frequently associated with severe and often irreversible hypotensive shock. The isolated toxic proteins of Bacillus anthracis produce a non-cytokine-mediated hypotension in rats by unknown mechanisms. These observations suggest the anthrax toxins have direct cardiovascular effects. Here, we characterize these effects. As a first step, we administered systemically anthrax lethal toxin (LeTx) and edema toxin (EdTx) to cohorts of three to twelve rats at different doses and determined the time of onset, degree of hypotension and mortality. We measured serum concentrations of the protective antigen (PA) toxin component at various time points after infusion. Peak serum levels of PA were in the µg/mL range with half-lives of 10–20 minutes. With doses that produced hypotension with delayed lethality, we then gave bolus intravenous infusions of toxins to groups of four to six instrumented rats and continuously monitored blood pressure by telemetry. Finally, the same doses used in the telemetry experiments were given to additional groups of four rats, and echocardiography was performed pretreatment and one, two, three and twenty-four hours post-treatment. LeTx and EdTx each produced hypotension. We observed a doubling of the velocity of propagation and 20% increases in left ventricular diastolic and systolic areas in LeTx-treated rats, but not in EdTx-treated rats. EdTx-but not LeTx-treated rats showed a significant increase in heart rate. These results indicate that LeTx reduced left ventricular systolic function and EdTx reduced preload. Uptake of toxins occurs readily into tissues with biological effects occurring within minutes to hours of serum toxin concentrations in the µg/mL range. LeTx and EdTx yield an irreversible shock with subsequent death. These findings should provide a basis for the rational design of drug interventions to reduce the dismal prognosis of systemic anthrax infections.
Free time optimal control problems with time delays

Solutions to optimal control problems for retarded systems, on a fixed time interval, satisfy a form of the Maximum Principle, in which the co-state equation is an advanced differential equation. In this paper we present an extension of this well-known necessary condition of optimality, to cover situations in which the data is non-smooth, and the final time is free. The fact that the end-time is a choice variable is accommodated by an extra transversality condition. A traditional approach to deriving this extra condition is to reduce the free end-time problem to a fixed end-time problem by a parameterized change of the time variable. This approach is problematic for time delay problems because it introduces a parameter dependent time-delay that is not readily amenable to analysis; to avoid this difficulty we instead base our analysis on direct perturbation of the end-time. Formulae are derived for the gradient of the minimum cost as a function of the end-time. It is shown how these formulae can be exploited to construct two-stage algorithms for the computation of solutions to optimal retarded control problems with free-time, in which a sequence of fixed time problems are solved by means of Guinn's transformation, and the end-time is adjusted according to a rule based on the earlier derived gradient formulae for the minimum cost function. Numerical examples are presented.
Peripheral and Thymic Foxp3+ Regulatory T Cells in Search of Origin, Distinction, and Function

Over the past decade, much has been learnt and much more to discover about Foxp3+ regulatory T cells (Tregs). Initially, it was thought that Tregs were a unique entity that originates in the thymus. It is now recognized that there is a fraternal twin sibling that is generated in the periphery. The difficulty is in the distinction between these two subsets. The ability to detect, monitor, and analyze these two subsets in health and disease will provide invaluable insights into their functions and purposes. The plasticity and mechanisms of action can be unique and not overlapping within these subsets. Therefore, the therapeutic targeting of a particular subset of Tregs might be more efficacious. In the past couple of years, a vast amount of data have provided a better understanding of the cellular and molecular components essential for their development and stability. Many studies are implicating their preferential involvement in certain diseases and immunologic tolerance. However, it remains controversial as to whether any phenotypic markers have been identified that can differentiate thymic versus peripheral Tregs. This review will address the validity and controversy regarding Helios, Lap/Garp and Neuropilin-1 as markers of thymic Tregs. It also will discuss updated information on distinguishing features of these two subsets and their critical roles in maternal-fetal tolerance and transplantation.
A Mathematical Model to Estimate Out of Focus Blur

Blur identification is one of the most important parts of image restoration. The most conventional blur that occurs in images is out of focus, which is generated because of lens defocus. In this paper, a new method is presented to estimate out of focus blur parameters robustly. This method is based on mathematical modeling of zero crossing in log of Fourier spectrum. We have presented a formula to calculate out of focus blur parameters using circular hough transform and statistical measures. Experimental results show the error tolerance of the method is about 2% and this works on noisy images with SNR ges 55 dB, robustly.
Big Data Analytics Capability: Antecedents and Business Value

Big data has managed in a very short time to dominate the interest of researchers and managers, vastly changing the way information is generated and used in decision making. Nevertheless, there has been disproportionate focus on the technical aspects of this emerging technology, and limited attention on other relevant organizational elements. Past research in IT business value has demonstrated that investments alone do not generate business value; rather, firms need to develop idiosyncratic and difficult to imitate capabilities. Drawing on the resource based view and dynamic capabilities view of the firm, this study examines the resources that are necessary to develop a big data analytics capability, identifies the organizational capabilities they enable, and determines factors that moderate or condition the value of a big data analytics capability. Employing a multiple case study approach on six international firms, we develop a deeper understanding of the importance of big data analytics resources and the mechanisms through which they leveraged towards the strengthening of organizational capabilities.