Miracle-dz/UniFAR-FTUs huggingface dataset:
Prevention of resistance: a goal for dose selection for antimicrobial agents.

Drug-resistant microorganisms have become a major problem around the world. In nosocomial and community settings, many important pathogens have demonstrated high-grade resistance to many of our most important agents. In addition, the adverse impact of resistance has not been limited to the bacterial realm. In chemotherapy to treat human immunodeficiency virus (HIV) and other viral diseases, resistance has become a major problem. We are starting to see the beginnings of a resistance problem, even among fungi. Strangely, little attention has been focused on the impact of dosing on the probability with which emergence of resistance occurs. After delineation of the pharmacodynamically linked variable, it is possible to generate dosing regimens that can lower the probability of resistance. In addition, circumstances exist in which combination therapy may be required (e.g., therapy of HIV and tuberculosis). Here, too, it is possible to optimize therapy to prevent resistance by understanding how the drugs in the regimen interact. We can do better with our choices of dose, schedule, and combinations of agents. We will need to lower the probability of resistance and maintain the utility of the drugs currently in our therapeutic armamentarium.
Minimally Invasive Management of Biliary Tract Injury Following Percutaneous Nephrolithotomy

Introduction: Percutaneous nephrolithotomy is generally considered a safe option for the management of large complex or infectious upper urinary tract calculi. Biliary tract injury is a rare and potentially serious complication of percutaneous nephrolithotomy that can even lead to mortality, especially in cases where biliary peritonitis develops. All reported cases of biliary tract injury have been managed by either open or laparoscopic cholecystectomy. Case Presentation: Herein for the first time, we report a 39-year old woman with biliary tract injury following percutaneous nephrolithotomy who was managed less invasively by insertion of a percutaneous cholecystostomy tube. The patient was discharged home shortly thereafter, and the tube was later removed at a follow up visit after a normal cholangiogram. Conclusions: Biliary tract injury is a rare and potentially serious complication of percutaneous nephrolithotomy that can even lead to mortality. If a biliary tract injury is suspected during percutaneous renal procedures, diverting the bile away from the leak may resolve the problem without the need for a cholecystectomy. Ideally this can be done with ERCP and a stent, but in cases where this is not technically feasible; a percutaneous cholecystostomy can be successful at accomplishing the same result.
New roles for the GLUTAMATE RECEPTOR-LIKE 3.3, 3.5, and 3.6 genes as on/off switches of wound-induced systemic electrical signals

ABSTRACT Wounding induces systemic potentials in Arabidopsis thaliana that can be abolished by concomitant suppression of the GLUTAMATE RECEPTOR-LIKE GLR3.3 and GLR3.6 genes. However, the roles of specific GLR channels to these potentials remain unclear. Here I applied the Electrical Penetration Graph (EPG) to study the contribution of three GLR channels to wound-induced, systemically propagated electrical potentials in Arabidopsis thaliana. In contrast to recordings made with conventional rigs for whole-plant electrophysiology, the EPG allows for the unambiguous distinction of the phloem-propagated action potential (AP) from the electrical activity outside of the phloem. The data reported here suggest that: (a) the transmission of wound-induced, phloem-propagated AP to neighbor leaves, requires expression of GLR3.3 or GLR3.6, whereas GLR3.5 prevents its transmission to non-neighbor leaves; (b) the generation of wound-induced electrical signals outside the phloem network depends on GLR3.6 expression; and (c) wound-induced systemic potentials initiated in the shoot are transmitted to the root in the adult plant, which suggests a role for these electrical signals in coordinating the plant defenses in the shoot and in the root. Here, I propose a model for wound-induced systemic electrical signals at the molecular, cellular and anatomical level. In this model, GLR3.3 and GLR3.6 function as on switches for the propagation of wound-induced potentials beyond the wounded leaf, while GLR3.5 functions as an off switch that prevents the propagation of wound-induced electrical potentials to distal, non-neighbor leaves.
What approaches for promoting shared decision-making are used in child mental health? A scoping review.

OBJECTIVE Whilst the benefits of shared decision-making (SDM) have been promoted across different health settings, its implementation is complex, particularly for children and young people with mental health difficulties. The aim of this scoping review was to identify and describe SDM approaches (tools, techniques, and technologies) used in child and youth mental health. METHOD Electronic databases and grey literature were searched. Papers were included if they satisfied these criteria: English language; described an SDM approach (tool, technique, or technology); included sufficient detail on the SDM approach for quality assessment; did not use only a questionnaire to provide feedback on SDM or related concepts (e.g., therapeutic alliance) without another SDM approach; child or adolescent population (up to 18 years); carers of children or adolescents; and mental health setting. Screening and data extraction were performed by two co-authors, and each included record was quality assessed against a set of essential ingredients of SDM identified by previous studies. RESULTS Of the 8,153 initial results, 22 were eligible for final inclusion. These could be grouped into six approaches: therapeutic techniques, psychoeducational information, decision aids, action planning or goal setting, discussion prompts, and mobilizing patients to engage. The quality of approaches identified ranged from one to seven of the nine essential elements of SDM. CONCLUSION Evidence suggests that a range of approaches are being developed to support SDM in child and youth mental health. Rigorous research evaluating the effectiveness of these approaches is urgently needed, particularly from the perspective of children and young people.
Management of hyperglycaemia in the preterm infant

In the fetus, the predominant energy supply is glucose transported across the placenta from the mother. As pregnancy progresses, the amount of glucose transported increases, with glycogen and fat stores being laid down, principally in the third trimester. In the well-term baby, there is hormonal and metabolic adaptation in the perinatal period to ensure adequate fuel supply to the brain and other vital organs after delivery, but in the preterm infant, abnormalities of glucose homeostasis are common. After initial hypoglycaemia, due to limited glycogen and fat stores, preterm babies often become hyperglycaemic because of a combination of insulin resistance and relative insulin deficiency. Hyperglycaemia is associated with increased morbidity and mortality in preterm infants, but what should be considered optimal glucose control, and how best to achieve it, has yet to be defined in these infants.
Bevacizumab for the treatment of glioblastoma

Glioblastoma (GB) is the most common adult malignant primary brain tumor that arises from glial precursor cells. Survival in GB is variable ranging from 6 to 20 months notwithstanding current standard of care (SOC) treatment. Therapy has improved, but nonetheless GB is still invariably recurrent and incurable. Treatment options at recurrence include re-operation with or without carmustine (BCNU) wafer implantation (Gliadel), re-irradiation and standard/experimental chemo- or targeted therapy. Recurrent GB radiographic response rates to cytotoxic chemotherapy are less than 10% and median 6-month progression-free survival (PFS6) is 15%. With the recognition of the importance of tumor angiogenesis and the development of targeted therapy based on angiogenic inhibition, two pivotal trials of the VEGF-directed monoclonal antibody, bevacizumab (BEV, Avastin), were conducted in recurrent GB. Based upon the results of these two prospective US trials (median radiographic response rate: 25%; PFS6: 40%), BEV as a single agent was granted accelerated approval in the USA for recurrent GB. This review is a summary of current literature and clinical trials research in the role of BEV for the treatment of newly diagnosed and recurrent GB and potential future use of anti-angiogenic therapies in the management of GB.
Time‐dependent rates of molecular evolution

For over half a century, it has been known that the rate of morphological evolution appears to vary with the time frame of measurement. Rates of microevolutionary change, measured between successive generations, were found to be far higher than rates of macroevolutionary change inferred from the fossil record. More recently, it has been suggested that rates of molecular evolution are also time dependent, with the estimated rate depending on the timescale of measurement. This followed surprising observations that estimates of mutation rates, obtained in studies of pedigrees and laboratory mutation‐accumulation lines, exceeded long‐term substitution rates by an order of magnitude or more. Although a range of studies have provided evidence for such a pattern, the hypothesis remains relatively contentious. Furthermore, there is ongoing discussion about the factors that can cause molecular rate estimates to be dependent on time. Here we present an overview of our current understanding of time‐dependent rates. We provide a summary of the evidence for time‐dependent rates in animals, bacteria and viruses. We review the various biological and methodological factors that can cause rates to be time dependent, including the effects of natural selection, calibration errors, model misspecification and other artefacts. We also describe the challenges in calibrating estimates of molecular rates, particularly on the intermediate timescales that are critical for an accurate characterization of time‐dependent rates. This has important consequences for the use of molecular‐clock methods to estimate timescales of recent evolutionary events.
Modifications to the Arabidopsis Defense Proteome Occur Prior to Significant Transcriptional Change in Response to Inoculation with Pseudomonas syringae1[W][OA]

Alterations in the proteome of Arabidopsis (Arabidopsis thaliana) leaves during responses to challenge by Pseudomonas syringae pv tomato DC3000 were analyzed using two-dimensional gel electrophoresis. Protein changes characteristic of the establishment of disease, basal resistance, and resistance-gene-mediated resistance were examined by comparing responses to DC3000, a hrp mutant, and DC3000 expressing avrRpm1, respectively. The abundance of each protein identified was compared with that of selected transcripts obtained from comparable GeneChip experiments. We report changes in three subcellular fractions: total soluble protein, chloroplast enriched, and mitochondria enriched over four time points (1.5–6 h after inoculation). In total, 73 differential spots representing 52 unique proteins were successfully identified. Many of the changes in protein spot density occurred before significant transcriptional reprogramming was evident between treatments. The high proportion of proteins represented by more than one spot indicated that many of the changes to the proteome can be attributed to posttranscriptional modifications. Proteins found to show significant change after bacterial challenge are representative of two main functional groups: defense-related antioxidants and metabolic enzymes. Significant changes to photosystem II and to components of the mitochondrial permeability transition were also identified. Rapid communication between organelles and regulation of primary metabolism through redox-mediated signaling are supported by our data.
Effects of meat and poultry recalls on firms' stock prices

Food recalls have been an issue of great concern in the food industry. Stakeholder responses to food safety scares can cause significant economic losses for food firms. Assessing the overall impact that may result from a food recall requires a thorough understanding of the costs incurred by firms. However, quantifying these costs is daunting if not impossible. A direct measurement of a firm’s total costs and losses of revenue associated with a food recall requires firm-level data that is not available. The method utilized in this study overcomes this severe limitation. Using an event study, the impact of meat and poultry recalls is quantified by analyzing price reactions in financial markets, where it is expected that stock prices would reflect the overall economic impact of a recall. A unique contribution of this study is evaluating whether recall and firm specific characteristics are economic drivers of the magnitude of impact of meat and poultry recalls on stock prices. Results indicate that on average shareholders’ wealth is reduced by 1.15% within 5 days after a firm is implicated in a recall involving serious food safety hazards. However, when recalls involve less severe hazards, stock markets do not react negatively. Also, reductions in company valuations return to pre-recall levels after day 20. Firm size, firm’s experience, media information and recall size are drivers of the economic impact of meat and poultry recalls. That is, firms recalling a larger amount of product perceive greater reductions in company valuations. Additionally, recalls issued by larger firms are less likely to present negative effects on stock prices, compared to smaller firms. Moreover, firms that have recently issued a recall are less harmed by a new recall compared to those firms issuing a recall for first time. Thus, suggesting that investors take into consideration the past performance of a company when dealing with food recalls. Furthermore, media information has a negative impact on shareholder’s wealth. Findings from this study provide essential information to the meat industry. In particular, understanding the likely impact of such “black swan” events is critical for firm’s investing in food safety technologies and protocols. EFFECTS OF MEAT AND POULTRY RECALLS ON FIRMS’ STOCK PRICES
Autobiographical Memory in Children with Temporal Lobe Epilepsy

Abstract Autobiographical memory involves the recall of personal facts (semantic memory) and re-experiencing of specific personal events (episodic memory). Although impairments in autobiographical memory have been found in adults with unilateral temporal lobe epilepsy (TLE) and attributed to compromised hippocampal integrity, it is not yet known whether this occurs in children with TLE. In the current study, 21 children with TLE and 24 healthy controls of comparable age, sex, and socioeconomic status were administered the Children's Autobiographical Interview. Compared to controls, children with TLE recalled fewer episodic details, but only when no retrieval prompts were provided. There was no difference between the groups for semantic autobiographic details. Interestingly, the number of episodic details recalled increased significantly from 6 to 16 years of age in healthy control children, but not in children with TLE. Exploratory analyses revealed that, within the group of children with TLE, epilepsy factors, including presence or absence of structural hippocampal abnormalities, did not relate to the richness of episodic recall. Our results provide first evidence of autobiographical episodic memory deficits in children with TLE. (JINS, 2013, 19, 1–12)
Adaptor Protein Complex-2 (AP-2) and Epsin-1 Mediate Protease-activated Receptor-1 Internalization via Phosphorylation- and Ubiquitination-dependent Sorting Signals*

Background: Internalization of protease-activated receptor-1 (PAR1) occurs through clathrin-coated pits independent of β-arrestins. Results: The clathrin adaptors AP-2 and epsin-1 mediate agonist-induced PAR1 internalization via recognition of discrete sorting signals. Conclusion: In addition to the β-arrestins, other clathrin adaptors can mediate internalization of mammalian G protein-coupled receptors (GPCR) through clathrin-coated pits. Significance: AP-2 and epsin-1 increase the diversity of adaptor molecules that can regulate GPCRs. Signaling by protease-activated receptor-1 (PAR1), a G protein-coupled receptor (GPCR) for thrombin, is regulated by desensitization and internalization. PAR1 desensitization is mediated by β-arrestins, like most classic GPCRs. In contrast, internalization of PAR1 occurs through a clathrin- and dynamin-dependent pathway independent of β-arrestins. PAR1 displays two modes of internalization. Constitutive internalization of unactivated PAR1 is mediated by the clathrin adaptor protein complex-2 (AP-2), where the μ2-adaptin subunit binds directly to a tyrosine-based motif localized within the receptor C-tail domain. However, AP-2 depletion only partially inhibits agonist-induced internalization of PAR1, suggesting a function for other clathrin adaptors in this process. Here, we now report that AP-2 and epsin-1 are both critical mediators of agonist-stimulated PAR1 internalization. We show that ubiquitination of PAR1 and the ubiquitin-interacting motifs of epsin-1 are required for epsin-1-dependent internalization of activated PAR1. In addition, activation of PAR1 promotes epsin-1 de-ubiquitination, which may increase its endocytic adaptor activity to facilitate receptor internalization. AP-2 also regulates activated PAR1 internalization via recognition of distal C-tail phosphorylation sites rather than the canonical tyrosine-based motif. Thus, AP-2 and epsin-1 are both required to promote efficient internalization of activated PAR1 and recognize discrete receptor sorting signals. This study defines a new pathway for internalization of mammalian GPCRs.
Enhanced Crankback Signaling for Multi-Domain Traffic Engineering

Multi-domain traffic engineering is a major focus area for carriers and crankback signaling offers a very promising alternative. However, even though various crankback studies have been done, there remains significant latitude for improved multi-domain designs. To address these challenges, this work develops a novel solution for intra/inter-domain signaling crankback in IP/MPLS networks. Namely, dynamic intra-domain link-state routing information is coupled with inter-domain path/distance-vector routing state to improve the search process. Mechanisms are also added to limit setup signaling overheads and track crankback history from congested links. The performance of the proposed solution is analyzed using simulation and compared against other techniques including hierarchical inter-domain routing.
Serum Hepatocyte Growth Factor Is Associated with Small Vessel Disease in Alzheimer’s Dementia

Background: While hepatocyte growth factor (HGF) is known to exert cell growth, migration and morphogenic effects in various organs, recent studies suggest that HGF may also play a role in synaptic maintenance and cerebrovascular integrity. Although increased levels of HGF have been reported in brain and cerebrospinal fluid (CSF) samples of patients with Alzheimer’s disease (AD), it is unclear whether peripheral HGF may be associated with cerebrovascular disease (CeVD) and dementia. In this study, we examined the association of baseline serum HGF with neuroimaging markers of CeVD in a cohort of pre-dementia (cognitive impaired no dementia, CIND) and AD patients. Methods: Serum samples from aged, Non-cognitively impaired (NCI) controls, CIND and AD subjects were measured for HGF levels. CeVD (cortical infarcts, microinfarcts, lacunes, white matter hyperintensities (WMH) and microbleeds) were assessed by magnetic resonance imaging (MRI). Results: After controlling for covariates, higher levels of HGF were associated with both CIND and AD. Among the different CeVD MRI markers in CIND and AD, only small vessel disease, but not large vessel disease markers were associated with higher HGF levels. Conclusion: Serum HGF may be a useful peripheral biomarker for small vessel disease in subjects with cognitive impairment and AD.
Teachers' processes of negotiating meaning of new curriculum

This qualitative study addresses the question of how teachers negotiate meaning of new curriculum to better understand how curriculum is transformed from a theoretical construct to a practical one. Through interviews with 5 teachers, their experiences were examined as they negotiated the process of implementing new curriculum. Three theoretical constructs provided the entry point into the study: epistemology, teacher knowledge, and teacher learning. Using inductive analysis, 4 points or attributes of negotiation emerged: reference, growth, autonomy, and reconciliation. These attributes provided a theoretical framework from which a constructivist conceptualization of teacher learning and teacher knowledge could serve to understand the process of how teachers negotiate meaning of curriculum. Studied and theorized in this way, teacher knowledge and teacher learning are seen to be inextricably linked in a relationship that is dynamically changed by forces of stability and instability. Theorizing the negotiation of meaning from a constructivist epistemology also strengthened the assertion that negotiating meaning is a unique structural process, and that knowledge construction is therefore unique to each knower and subject to experience in a particular time and place. The implications for such a theory are, first, that it questions the legitimacy of privatized teacher practice and, second, that it calls for a renewed conceptualization of collegial network and relationship to strengthen the capacity for negotiating meaning of curricular initiatives. Understanding the relationship of curricular theory and negotiating meaning also has implications for curriculum development. In particular, the study highlights the necessity of professional discretion and the generative process of negotiating meaning.
Functional role of the prefrontal cortex in retrieval of memories: a PET study

Retrieval of information from episodic memory involves the processes invoked by the attempt to remember (retrieval attempt) as well as processes associated with the successful retrieval of stored information (ecphory). Previous PET studies of memory have shown an activation of the prefrontal cortex in memory retrieval tasks, and we hypothesised that this activation represents retreival attempt, not ecphory. This hypothesis was directly directed using [15O]H2 PET imaging in 19 healthy subjects who performed three matched tasks which involved different levels of retrieval attempt and ecphory. The results showed that retrieval attempt was associated with activation of the prefrontal cortex, right greater than left, while ecphory involved the posterior cortical regions. These findings illuminate the functional role of the different neuroanatomical regions involved in episodic remembering.