Miracle-dz/UniFAR-FTUs huggingface dataset:
The Spartacus Problem: Diagnostic Inefficiency of Neonatal Sepsis

* Abbreviation: EOS — : early-onset sepsis In the 1960 film Spartacus , the Roman army succeeds in trapping the rebellious slave army led by the eponymous hero.1 The Romans know that Spartacus is a dangerous foe who must not escape; unfortunately, they have no idea what he looks like. To ensure that Spartacus is eliminated, the Romans elect to execute everyone. It is easy to see the parallels between Spartacus and our current approaches to sepsis in the newborn. Nursery clinicians are well aware that neonatal sepsis is dangerous and must not be missed, but the challenge of identifying the septic needle from the uninfected haystack of neonates is challenging. The most common approach is to adopt a “when in doubt, test and treat” tactic. As a result, clinicians (me included) are both inefficient and subjective in our diagnostic approach to sepsis. In this issue of Pediatrics , Schulman et al2 highlight this inefficiency in their study of antimicrobial use in >326 000 infants in 116 California NICUs. Clinicians administered antibiotics to an average of 95 infants (SD ±71) for each case of … Address correspondence to Joseph B. Cantey, MD, Department of Pediatrics, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229. E-mail: cantey{at}uthscsa.edu
Beta-Blocker Use and Lung Cancer Mortality in a Nationwide Cohort Study of Patients with Primary Non–Small Cell Lung Cancer

Background: β-Adrenergic receptor blockers have been associated with improved survival among patients with different types of malignancies, but available data for patients with non–small cell lung cancer (NSCLC) are contradictory and limited to small hospital-based studies. We therefore aimed to investigate whether β-blocker use at the time of cancer diagnosis is associated with lung cancer mortality in the largest general population-based cohort of patients with NSCLC to date. Methods: For this retrospectively defined nationwide cohort study, we used prospectively collected data from Swedish population and health registers. Through the Swedish Cancer Register, we identified 18,429 patients diagnosed with a primary NSCLC between 2006 and 2014 with follow-up to 2015. Cox regression was used to estimate the association between β-blocker use at time of cancer diagnosis ascertained from the Prescribed Drug Register and cancer-specific mortality identified from the Cause of Death Register. Results: Over a median follow-up of 10.2 months, 14,994 patients died (including 13,398 from lung cancer). Compared with nonuse, β-blocker use (predominantly prevalent use, 93%) was not associated with lung cancer mortality [HR (95% confidence interval): 1.01 (0.97–1.06)]. However, the possibility that diverging associations for specific β-blockers and some histopathologic subtypes exist cannot be excluded. Conclusions: In this nationwide cohort of patients with NSCLC, β-blocker use was not associated with lung cancer mortality when assessed in aggregate in the total cohort, but evidence for some β-blockers is less conclusive. Impact: Our results do not indicate that β-blocker use at lung cancer diagnosis reduces the cancer-specific mortality rate in patients with NSCLC.
The Relationship between Patient-Centered Care and Outcomes in Specialist Drug and Alcohol Treatment: A Systematic Literature Review

Background: Patient-centered care is strongly advocated as a key for improving the quality of healthcare. Research examining the impact of patient-centered care in healthcare has concluded that there are demonstrable albeit inconsistent relationships between patient experience, quality of care, and healthcare outcomes. Knowledge of the impact of patient-centered care in the treatment of substance use disorder is limited. The aim of this review was to assess relationships between indicators of patient-centered care (satisfaction and patient-reported experience measures) and patient outcomes (substance use, psychological wellbeing, and service use) among people attending treatment for substance use disorder. Methods: A systematic electronic literature search of a range of databases was conducted with variations of the search terms ‘patient-centered care’, ‘substance use disorders’, and residential or community specialist ‘treatment’. The populations, interventions and outcomes were summarized and described according to the PRISMA statement. Results: A total of 25 articles were identified, of which only five included a patient-centered indicator other than satisfaction. Indicators of patient-centered care showed a generally positive association with improved outcomes, particularly between satisfaction with treatment and substance use. Nonetheless, mixed and contradictory results were not uncommon, more so for psychological wellbeing outcomes. Conclusions: There were demonstrable relationships between patient-centered indicators and outcomes for people receiving treatment for substance use disorder. However, conclusions are limited due to underrepresentation of patient-reported experience measures. Further research in the area is needed involving comparisons of patient centered indicators with outcomes and use of patient-reported experience measures together with satisfaction. Registration number: CRD42018092829
CD8αβ T Cells Are Not Essential to the Pathogenesis of Arthritis or Colitis in HLA-B27 Transgenic Rats1

The class I MHC allele HLA-B27 is highly associated with the human spondyloarthropathies, but the basis for this association remains poorly understood. Transgenic rats with high expression of HLA-B27 develop a multisystem inflammatory disease that includes arthritis and colitis. To investigate whether CD8αβ T cells are needed in this disease, we depleted these cells in B27 transgenic rats before the onset of disease by adult thymectomy plus short-term anti-CD8α mAb treatment. This treatment induced profound, sustained depletion of CD8αβ T cells, but failed to suppress either colitis or arthritis. To address the role of CD8α+β− cells, we studied four additional groups of B27 transgenic rats treated with: 1) continuous anti-CD8α mAb, 2) continuous isotype-matched control mAb, 3) the thymectomy/pulse anti-CD8α regimen, or 4) no treatment. Arthritis occurred in ∼40% of each group, but was most significantly reduced in severity in the anti-CD8α-treated group. In addition to CD8αβ T cells, two sizeable CD8α+β− non-T cell populations were also reduced by the anti-CD8α treatment: 1) NK cells, and 2) a CD4+CD8+CD11b/c+CD161a+CD172a+ monocyte population that became expanded in diseased B27 transgenic rats. These data indicate that HLA-B27-retricted CD8+ T cells are unlikely to serve as effector cells in the transgenic rat model of HLA-B27-associated disease, in opposition to a commonly invoked hypothesis concerning the role of B27 in the spondyloarthropathies. The data also suggest that one or more populations of CD8α+β− non-T cells may play a role in the arthritis that occurs in these rats.
Treatment of refractory conjunctivitis associated to dupilumab with topical pimecrolimus applied to the eyelid skin

Patients with atopic dermatitis commonly experience ophthalmic complications, and a higher incidence of conjunctivitis has been observed during treatment with dupilumab. We present the case of a 49‐year‐old woman with persistent severe atopic dermatitis who complained of refractory conjunctivitis associated with dupilumab. Ocular examination showed features of atopic conjunctivitis for which an external topical application to the eyelids of pimecrolimus 10 mg/g cream was prescribed. The patient showed substantial clinical remission after only 12 days. This case was remarkable as the medication applied externally to the eyelid skin was effective in treating the conjunctival involvement possibly due to penetration of pimecrolimus through the eyelid layers. Further studies are needed to support the use of this drug for dupilumab‐related conjunctivitis.
Risk Factors of Microbial Keratitis in Uganda: A Case Control Study

ABSTRACT Purpose: Microbial keratitis (MK), is a frequent cause of sight loss worldwide, particularly in low and middle-income countries. This study aimed to investigate the risk factors of MK in Uganda. Methods: Using a nested case control, we recruited healthy community controls for patients presenting with MK at the two main eye units in Southern Uganda between December 2016 and March 2018. Controls were individually matched for age, gender and village of the cases on a 1:1 ratio. We collected information on demographics, occupation, HIV and Diabetes Mellitus status. In STATA version 14.1, multivariable conditional logistic regression was used to generate odds ratios for risk factors of MK and a likelihood ratio test used to assess statistical significance of associations. Results: Two hundred and fifteen case-control pairs were enrolled. The HIV positive patients among the cases was 9% versus 1% among the controls, p = . 0003. Diabetes 7% among the cases versus 1.4% among the controls, p = . 012. Eye trauma was 29% versus 0% among the cases and controls. In the multivariable model adjusted for age, sex and village, HIV (OR 83.5, 95%CI 2.01–3456, p = .020), Diabetes (OR 9.38, 95% CI 1.48–59.3, p = .017) and a farming occupation (OR 2.60, 95%CI 1.21–5.57, p = .014) were associated with MK. Compared to a low socio-economic status, a middle status was less likely to be associated with MK (OR 0.29, 95%CI 0.09–0.89, p < .0001). Conclusion: MK was associated with HIV, Diabetes, being poor and farming as the main occupation. More studies are needed to explore how these factors predispose to MK.
Effect of Silver Nanoparticle Administration on Productive Performance, Blood Parameters, Antioxidative Status, and Silver Residues in Growing Rabbits under Hot Climate

Simple Summary Silver nanoparticles (AgNPs) were used for their antibacterial effects, which increase productive performance and immune response in poultry and rabbits. On the other hand, residues of silver in meat and the internal organs of treated animals may be toxic for human beings. The current results of using two doses of injecting AgNPs revealed that body weight significantly improved in rabbits given a low dose of AgNPs compared with control animals. For consumers’ health concerns, it is of interest to note that the amount of accumulated silver in blood plasma and meat increased dramatically with an increasing dose. Abstract The influence of subcutaneous injections of silver nanoparticles (AgNPs) on rabbit performance, hematological and biochemical parameters of blood, antioxidant status, and the residues of silver in meat and blood in two breeds (New Zealand White (NZW) and Jabali) of rabbits growing under high ambient temperature was evaluated. A total of 90 six-week-old rabbits (45 NZW and 45 Jabali) were randomly distributed into three equal treatment groups (control, 0.5 mg, and 1.0 mg AgNPs/kg body weight). The treated rabbits were injected twice a week for four consecutive weeks. The results revealed that AgNPs administration had no significant effect on average daily gain (ADG), feed intake, and feed conversion ratio (FCR). The NZW breed surpassed the Jabali breed in growth performance traits, carcass weight, dressing percentage, and cuts of mid parts and hind cuts. Administration of AgNPs had a significant effect on hematocrit (HCT) and platelet (PLT) values. Rabbits injected with AgNPs at a dose of 0.5 mg showed a lower plasma concentration of total cholesterol and triglycerides than that of control rabbits. The NZW breed had significantly low platelet, total cholesterol, and triglyceride values. Rabbits injected with 0.5 mg/kg BW had the lowest total antioxidant capacity and highest malondialdehyde (MDA) and glutathione peroxidase. The Ag residues were higher in blood than those in meat in treated rabbits. The local breed (Jabali) had significantly lower residues than the imported one (NZW) either in meat or in blood. However, the amount of accumulated silver in blood plasma and meat increased with increasing dose.
The influence of individuals' beliefs about learning and nature of knowledge on educating a competent workforce

In light of recent initiatives in re-engineering training and workplace education and the multitude of programmes that have since evolved, there is still a lack of evidence that the new initiatives developed by the Australian government facilitate better learning outcomes. The current focus may increase participation of workers in training programmes but there is still a need to consider the micro processes in learning and instruction that influence the quality of learning outcomes. Two such micro processes are investigated in the study reported in this article. Firstly, the relationship between trainees' beliefs about knowledge and learning and learning outcomes is investigated and secondly, beliefs and learning outcomes of trainees who gained entry into the programmes via work experience and those who enrolled directly from secondary schools are compared. Twenty-three male students enrolled in an electronics subject at a tertiary institution were interviewed regarding their beliefs about learning and later tested on a problem task. The trainees indicated unsophisticated conceptions of learning which were also reflected in their poor learning outcomes as measured by knowledge representations. The comparisons of work experience and non-work experience trainees indicated no difference in their beliefs about learning and the learning outcomes. The results, on the whole, demonstrated a limited knowledge base by all trainees when compared to the knowledge necessary to solve the problem task as determined from experts' knowledge representation. The findings indicate that the current initiatives may not be producing a competent workforce. Though the sample involved in the study is small, the results suggest that a closer look at the training reform process is warranted, especially at the learning and instruction phase.
Biomechanical quality assurance criteria for deformable image registration algorithms used in radiotherapy guidance

Image-guided radiation therapy (IGRT) allows radiation dose deposition with a high degree of geometric accuracy. Previous studies have demonstrated that such therapies may benefit from the employment of deformable image registration (DIR) algorithms, which allow both the automatic tracking of anatomical changes and accumulation of the delivered radiation dose over time. In order to ensure patient care and safety, however, the estimated deformations must be subjected to stringent quality assurance (QA) measures. In the present study we propose to extend the state-of-the-art methodology for QA of DIR algorithms by a set of novel biomechanical criteria. The proposed biomechanical criteria imply the calculation of the normal and shear mechanical stress, which would occur within the observed tissues as a result of the estimated deformations. The calculated stress is then compared to plausible physiological limits, providing thus the anatomical plausibility of the estimated deformations. The criteria were employed for the QA of three DIR algorithms in the context of abdominal conebeam computed tomography and magnetic resonance radiotherapy guidance. An initial evaluation of organ boundary alignment capabilities indicated that all three algorithms perform similarly. However, an analysis of the deformations within the organ boundaries with respect to the proposed biomechanical QA criteria revealed different degrees of anatomical plausibility. Additionally, it was demonstrated that violations of these criteria are also indicative of errors within the dose accumulation process. The proposed QA criteria, therefore, provide a tissue-dependent assessment of the anatomical plausibility of the deformations estimated by DIR algorithms, showcasing potential in ensuring patient safety for future adaptive IGRT treatments.
3‐Acetyl‐11‐keto‐β‐boswellic acid attenuated oxidative glutamate toxicity in neuron‐like cell lines by apoptosis inhibition

3‐Acetyl‐11‐keto‐β‐boswellic acid (AKBA), a pentacyclic triterpenic acid present in gum resin of Boswellia serrata, has been found to possess antioxidant and neuroprotective properties. In this study, we aimed to examine protective properties of AKBA against glutamate‐induced neuronal injury. To investigate the effects of AKBA (2.5‐10 µM) on glutamate injury in neuron‐like cells PC12 and N2a, two treatment regimens (incubation for 2 or 0 hours before glutamate exposure) were used. Then, the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide method was used to determine viability of the cells. Cellular redox status was evaluated using fluorimetry and comet assays. Annexin V/propidium iodide double staining and Western blot analysis of relative apoptotic proteins were conducted. Based on the results, 24 hours incubation with glutamate (8 mM) increased the cell mortality of PC12 and N2a (P < .001). However, AKBA (2.5‐10 µM) enhanced the cell viability in both treatment regimens (P < .001). Also co‐ and pretreatment with AKBA significantly attenuated lipid peroxidation, reactive oxygen species production, and DNA injury (P < .05 and P < .001). AKBA also restored the activity of cellular superoxide dismutase under glutamate toxicity; this effect was seen to be more significant during the pretreatment regimen (P < .001). Moreover, Western blot analysis indicated that AKBA inhibited glutamate‐induced programmed cell death through depressing the elevation of the expression ratio of Bax/Bcl‐2 and cleaved‐caspase‐3 proteins, concentration‐dependently. Overall, the present findings suggest the neuroprotective activities of AKBA against glutamate‐induced cell injury probably by inhibiting oxidative damage and reducing apoptotic cell death.
Active vision: on the relevance of a bio-inspired approach for object detection

Starting from biological systems, we review the interest of active perception for object recognition in an autonomous system. Foveated vision and control of the eye saccade introduce strong benefits related to the differentiation of a ‘what’ pathway recognizing some local parts in the image and a ‘where’ pathway related to moving the fovea in that part of the image. Experiments on a dataset illustrate the capability of our model to deal with complex visual scenes. The results enlighten the interest of top-down contextual information to serialize the exploration and to perform some kind of hypothesis test. Moreover learning to control the occular saccade from the previous one can help reducing the exploration area and improve the recognition performances. Yet our results show that the selection of the next saccade should take into account broader statistical information. This opens new avenues for the control of the ocular saccades and the active exploration of complex visual scenes.
Isolation, structural elucidation, and antimicrobial evaluation of the metabolites from a marine-derived fungus Penicillium sp. ZZ1283

Abstract A crude extract prepared from a culture of marine-sourced fungus Penicillum ZZ1283 in the medium of potato dextrose broth was found to have antimicrobial activities. Chemical investigation on this active extract resulted in the isolation of eighteen metabolites, including purpuride D, a new analogue of drimane-type sesquiterpene lactones conjugated with N-acetyl-L-valine. Structure of the new purpuride D was determined based on its HRESIMS data, NMR spectroscopic analyses, single-crystal X-ray diffraction and ECD calculation. Purpuride D showed activities in inhibiting the growth of methicillin-resistant Staphylococcus aureus, Escherichia coli and Candida albicans with MIC values of 4, 3 and 8 μg/mL, respectively. Graphical Abstract
Processes and determinants of integration of eGFR in physicians’ drug prescriptions: a qualitative study of semi-structured interviews

Abstract Aim: Our objective was to explore the processes and determinants leading physicians to integrate estimated glomerular filtration rate (eGFR) in their drug prescriptions Background: Access to patients’ eGFR would allow primary care pharmacists to optimise their role in the procedure of safe prescribing. Some rare physicians actively integrate eGFR in their prescriptions, in a sporadically and uncoordinated manner. Methods: Qualitative study using semi-directed interviews conducted among 12 French physicians who integrated eGFR in their drug prescriptions, (February 2016–April 2017). These voluntary participants were recruited through different means: Twitter®, forums, direct contact and snowball sampling. Data analysis was based on the grounded theory approach, underpinned by a comprehensive perspective of interactionist orientation. Findings: Residency and training, professional experience – including experiences of adverse drug reactions – and the membership in various communities of professionals were key drivers for the integration of eGFR in prescriptions. The theoretical aim was above all safe prescribing in order to reduce adverse drug reactions, with the control by a dispensing pharmacist and/or other healthcare professionals. Nevertheless, none of the physicians had received any feedback from any healthcare professionals. Despite their disappointment, the physicians remained convinced of the interest of integrating eGFR in their prescriptions and would continue to do so. Characteristics associated with integration of eGFR in drug prescriptions belong partly to Roger’s theory of innovations. If a widespread diffusion of this habit takes place, it will be necessary to evaluate its adoption by both physicians and pharmacists.
Adverse Effects of Proton Pump Inhibitors—Evidence and Plausibility

Proton pump inhibitors (PPIs) have been increasingly used over the last decades and there are concerns about overuse and the numerous reported side-effects. It is uncertain whether associations between PPI use and potential side effects are causal. However, important evidence from experimental and mechanistic studies that could support a causal relationship may have been underestimated by epidemiologists and meta-analysists. In the current manuscript we review the combined epidemiological and mechanistic evidence of the adverse effects of PPI use.