Miracle-dz/UniFAR-FTUs huggingface dataset:
Dysregulation of serine biosynthesis contributes to the growth defect of a Mycobacterium tuberculosis crp mutant

Mycobacterium tuberculosis CRPMt, encoded by Rv3676 (crp), is a CRP‐like transcription factor that binds with the serC–Rv0885 intergenic region. In the present study, we evaluated CRPMt's regulation of serC and Rv0885 in M. tuberculosis and M. bovis BCG, using site‐specific mutagenesis, promoter fusions and reverse‐transcriptase PCR (RT‐PCR). The CRPMt binding site was required for full expression of serC and Rv0885, and expression of both genes was reduced in M. tuberculosis and M. bovis BCG crp mutants. These data show that CRPMt binding directly activates both serC and Rv0885 expression. M. tuberculosis serC restored the ability of an Escherichia coli serC mutant to grow in serine‐dropout medium, demonstrating that M. tuberculosis serC encodes a phosphoserine aminotransferase. Serine supplementation, or overexpression of serC, accelerated the growth of M. tuberculosis and M. bovis BCG crp mutants in mycomedium, but not within macrophages. These results establish a role for CRPMt in the regulation of amino acid biosynthesis, and show that reduced serine production contributes to the slow‐growth phenotype of M. tuberculosis and M. bovis BCG crp mutants in vitro. Restoration of serine biosynthesis by serC expression will facilitate identification of additional CRPMt‐regulated factors required by M. tuberculosis during macrophage and host infection.
National case management standards in Australia--purpose, process and potential impact.

The use of case management has been increasing within Australia. The Case Management Society of Australia was established in 1996 to promote the developing case management profession and the viability of the service model in coordinating care and resources for clients with complex needs. In an effort to unify the debate around what is expected of a case manager, the Society has reviewed its interim standards of practice. This paper explains the purpose, process and potential impact of the National Standards of Practice for Case Management. The intent of this article is to describe a process that unifies a diverse range of professionals and non-professionals who practise under the banner of case management. The Standards are not described in detail in this article but are available at .
Interaction between Oxidative Stress Sensor Nrf2 and Xenobiotic-activated Aryl Hydrocarbon Receptor in the Regulation of the Human Phase II Detoxifying UDP-glucuronosyltransferase 1A10*

The defense against oxidative stress is a critical feature that prevents cellular and DNA damage. UDP-glucuronosyltransferases (UGTs) catalyze the glucuronidation of xenobiotics, mutagens, and reactive metabolites and thus act as indirect antioxidants. Aim of this study was to elucidate the regulation of UGTs expressed in the mucosa of the gastrointestinal tract by xenobiotics and the main mediator of antioxidant defense, Nrf2 (nuclear factor erythroid 2-related factor 2). Xenobiotic (XRE) and antioxidant (ARE) response elements were detected in the promoters of UGT1A8, UGT1A9, and UGT1A10. Reporter gene experiments demonstrated XRE-mediated induction by dioxin in addition to tert-butylhydroquinone (ARE)-mediated induction of UGT1A8 and UGT1A10, which are expressed in extrahepatic tissue in humans in vivo. The responsible XRE and ARE motifs were identified by mutagenesis. Small interfering RNA knockdown, electrophoretic mobility shifts, and supershifts identified a functional interaction of Nrf2 and the aryl hydrocarbon receptor (AhR). Induction of UGT1A8 and UGT1A10 requires Nrf2 and AhR. It proceeds by utilizing XRE- as well as ARE-binding motifs. In summary, we demonstrate the coordinated AhR- and Nrf2-dependent transcriptional regulation of human UGT1As. Cellular protection by glucuronidation is thus inducible by xenobiotics via AhR and by oxidative metabolites via Nrf2 linking glucuronidation to cellular protection and defense against oxidative stress.
Digitalis, A Targeted Therapy for Cancer?

The clinical benefit of digitalis for patients with heart disease is well established. However, recent studies have also suggested that digitalis has antineoplastic activities at clinically relevant serum concentrations. Much of the early evidence supporting the anticancer activity of digitalis has been circumstantial. Observational studies suggest a protective benefit and improved outcomes in patients who develop cancer while they are taking digitalis. The mechanism by which digitalis selectively affects the growth of malignant cells is complex, involving several important signaling pathways. Experiments to determine its mechanism of action have demonstrated that digitalis inhibits cell growth and angiogenesis and induces apoptosis in multiple cancer cell lines. Most, if not all, of these effects are mediated through its target enzyme, sodium- and potassium-activated adenosine triphosphatase. This article reviews the literature, which supports the use of digitalis in patients with malignancies with a discussion of the potential mechanisms of action. We hypothesize that sodium- and potassium-activated adenosine triphosphatase is an important new target for cancer therapy. It is reasonable to expect that the addition of digitalis to current cancer treatments will improve the clinical outcomes.
Improvement of the resonant cavity applicator for brain tumor hyperthermia - Experimental heating results -

A re-entrant type resonant cavity applicator for deep tumor hyperthermia treatment was presented. In this method, a human body is placed between the gap of the inner re-entrant cylinders, and is heated with electromagnetic fields stimulated in the cavity without contact between the surface of the human body and the applicator. In this paper, two methods to control the heating pattern were proposed. In the first method, a human body was moved towards the electrode. In the second method, the diametric ratio of the inner electrode was changed. The controllable range of heating pattern was about 20% of the distance from the center of the agar phantom in the direction of depth
Why is license plate rationing not a good transport policy?

ABSTRACT License plate rationing (LPR) has become an increasingly popular travel demand management strategy in developing countries. This paper aims to show that such a trend is concerning because of the inherent flaws of the policy. Using a conceptual mathematical model that explicitly considers mode choice and user heterogeneity, we prove that LPR is not a first-best policy, even though it can help reduce congestion under certain conditions. There is however no guarantee that LPR can even be a second-best policy: it may never improve the system cost, regardless of its configuration. More important, we show when it does improve the system cost, LPR makes it impossible to maximize the system efficiency by using other complementary policies. Our analysis also reveals unintended consequences of the policy. Notably, a more restrictive LPR could actually make congestion worse when imposed on a rich population that can bypass the policy through acquiring additional cars. Finally, numerical results confirm that LPR is likely regressive in many (if not most) practical cases. Specifically, the wealthier users tend to benefit more from LPR, especially when they can buy additional cars. The regressivity of the policy may be corrected only when LPR is highly restrictive and additional vehicle acquisition is tightly controlled. However, such a correction may only be achieved at the expense of significant welfare losses.
‘Just a GP’: a mixed method study of undermining of general practice as a career choice in the UK

Objectives Failure to recruit sufficient applicants to general practice (GP) training has been a problem both nationally and internationally for many years and undermining of GP is one possible contributing factor. The aim of our study was to ascertain what comments, both negative and positive, are being made in UK clinical settings to GP trainees about GP and to further explore these comments and their influence on career choice. Methodology We conducted a mixed methods study. We surveyed all foundation doctors and GP trainees within one region of Health Education England regarding any comments they experienced relating to a career in GP. We also conducted six focus groups with early GP trainees to discuss any comments that they experienced and whether these comments had any influence on their or others career choice. Results Positive comments reported by trainees centred around the concept that choosing GP is a positive, family-focused choice which facilities a good work–life balance. Workload was the most common negative comment, alongside the notion of being ‘just a GP’; the belief that GP is boring, a waste of training and a second-class career choice. The reasons for and origin of the comments are multifactorial in nature. Thematic analysis of the focus groups identified key factors such as previous exposure to and experience of GP, family members who were GPs, GP role models, demographics of the clinician and referral behaviour. Trainees perceived that negative comments may be discouraging others from choosing GP as a career. Conclusion Our study demonstrates that negative comments towards GP as a career do exist within clinical settings and are having a potential impact on poor recruitment rates to GP training. We have identified areas in which further negative comments could be prevented by changing perceptions of GP as a career. Additional time spent in GP as undergraduates and postgraduates, and positive GP role models, could particularly benefit recruitment. We recommend that undermining of GP as a career choice be approached with a zero-tolerance policy.
Fetal-Specific CD8+ Cytotoxic T Cell Responses Develop during Normal Human Pregnancy and Exhibit Broad Functional Capacity

Tolerance of the semiallogeneic fetus presents a significant challenge to the maternal immune system during human pregnancy. T cells with specificity for fetal epitopes have been detected in women with a history of previous pregnancy, but it has been thought that such fetal-specific cells were generally deleted during pregnancy as a mechanism to maintain maternal tolerance of the fetus. We used MHC-peptide dextramer multimers containing an immunodominant peptide derived from HY to identify fetal-specific T cells in women who were pregnant with a male fetus. Fetal-specific CD8+ T lymphocytes were observed in half of all pregnancies and often became detectable from the first trimester. The fetal-specific immune response increased during pregnancy and persisted in the postnatal period. Fetal-specific cells demonstrated an effector memory phenotype and were broadly functional. They retained their ability to proliferate, secrete IFN-γ, and lyse target cells following recognition of naturally processed peptide on male cells. These data show that the development of a fetal-specific adaptive cellular immune response is a normal consequence of human pregnancy and that unlike reports from some murine models, fetal-specific T cells are not deleted during human pregnancy. This has broad implications for study of the natural physiology of pregnancy and for the understanding of pregnancy-related complications.
Hepatitis A among schoolchildren in a US-Mexico border community.

OBJECTIVES A cross-sectional study investigated the association of hepatitis A seropositivity with environmental and personal risk factors among children in a United States-Mexico border community. METHODS Hepatitis A serological markers and a questionnaire identifying risk factors were evaluated for 523 primary school children. RESULTS Of the children studied, 16.9% tested positive for total antihepatitis A virus. Risk factors included being in the first grade, low maternal educational attainment, living in Mexico for more than 6 months, household crowding, and inadequate excreta disposal systems. CONCLUSIONS To decrease enteric disease, improvements in excreta disposal infrastructures and educational programs are needed. Hepatitis A vaccine should be administered before school age.
C-terminal Movement during Gating in Cyclic Nucleotide-modulated Channels*

Activation of cyclic nucleotide-modulated channels such as CNG and HCN channels is promoted by ligand-induced conformational changes in their C-terminal regions. The primary intersubunit interface of these C termini includes two salt bridges per subunit, formed between three residues (one positively charged and two negatively charged amino acids) that we term the SB triad. We previously hypothesized that the SB triad is formed in the closed channel and breaks when the channel opens. Here we tested this hypothesis by dynamically manipulating the SB triad in functioning CNGA1 channels. Reversing the charge at positions Arg-431 and Glu-462, two of the SB triad residues, by either mutation or application of charged reagents increased the favorability of channel opening. To determine how a charge reversal mutation in the SB triad structurally affects the channel, we solved the crystal structure of the HCN2 C-terminal region with the equivalent E462R mutation. The backbone structure of this mutant was very similar to that of wild type, but the SB triad was rearranged such that both salt bridges did not always form simultaneously, suggesting a mechanism for the increased ease of opening of the mutant channels. To prevent movement in the SB triad, we tethered two components of the SB triad region together with cysteine-reactive cross-linkers. Preventing normal movement of the SB triad region with short cross-linkers inhibited channel opening, whereas longer cross-linkers did not. These results support our hypothesis that the SB triad forms in the closed channel and indicate that this region expands as the channel opens.
Fracture Risk in Monoclonal Gammopathy of Undetermined Significance

To assess fractures in monoclonal gammopathy of undetermined significance (MGUS), the precursor of multiple myeloma, we followed 488 Olmsted County, MN, residents with MGUS in a retrospective cohort study. There was a 2.7‐fold increase in the risk of axial fractures but no increase in limb fractures. The pathophysiologic basis for the increased axial fractures should be determined.
Prediction of ingredient quality and the effect of a combination of xylanase, amylase, protease and phytase in the diets of broiler chicks. 1. Growth performance and digestible nutrient intake

1. A total of 2208 broiler chicks were used in two growth experiments (8 treatments and 12 replicate pens in each experiment) to assess the effects of xylanase, amylase, protease and phytase in maize-based diets. 2. A positive control diet was formulated containing adequate nutrient concentrations. A negative control diet was formulated to contain approximately 628 kJ/kg, 0·13%, 0·12% and 1 to 2% less metabolisable energy (ME), phosphorus (P), calcium (Ca) and amino acids, respectively, than the positive control. In addition, two further negative control diets that contained 167 or 334 kJ/kg more ME, respectively, than negative control 1 were formulated. 3. A further 4 dietary treatments were made by supplementing each of the 4 negative control diets with a combination of xylanase, amylase, protease and phytase, resulting in 8 dietary treatments in a 4 by 2 factorial arrangement. 4. The scale of the removal of energy, P, Ca and amino acids from the positive control diet was determined using least square models based on in vivo data for both the xylanase/amylase/protease cocktail and for phytase and it was predicted that performance of birds fed on negative control 1 would be returned by supplemental enzymes to that of those fed on the positive control. 5. In both experiments there was a significantly poorer performance in birds fed on the negative control 1 than in those fed on the positive control. The poorer weight gain and feed conversion ratio could be attributed in part to a reduced intake of digestible energy, P, nitrogen (N) and amino acids associated with birds fed on the negative control diet. 6. Supplementation of the negative control diets with the enzyme combination returned performance to that of the positive control in both experiments. 7. These data indicate that exogenous xylanase, amylase, protease and phytase can be used successfully in a strategically formulated low nutrient density diet to maintain performance to that of birds fed on a nutritionally adequate diet.
The Effects of Organizational Downsizing on Product Innovation

This article examines the impact of downsizing on product innovation. It compares the experiences of product innovators in companies with a high degree of downsizing with those in companies with less downsizing. Higher downsizing hinders innovation by reducing people's ability to connect their product strategically to the firm. Specifically, downsizing breaks the network of relationships that innovators use to make these vital strategic connections. To overcome the negative consequences of downsizing on product innovation, managers should support innovation sponsors and champions, and retain "old timers" who constitute the network. They should also bolster the network by building more connections among departments, and between new and established businesses. Finally, they should incorporate innovation directly into their firm's strategy.
Smoking Related to Anxiety and Depression in Greek Medical Staff

We assessed the relation of anxiety and depression to smoking behavior in a sample of 80 physicians and surgeons, using the Spielberger State-Trait Anxiety Scale and the Beck Depression Inventory. 27 doctors were nonsmokers, 14 were former smokers, and 39 were current smokers. Current smokers showed significantly higher Anxiety and Depression scores compared to nonsmokers and former smokers, while the latter presented significantly lower Anxiety scores than nonsmokers. In current smokers, the daily quota of cigarettes was not correlated with Anxiety or Depression scores. From our results we can hypothesize that, among medical staff, smoking behavior is more anxiery-related than depression-related. In conclusion, we believe that interventions such as stress management techniques could be effective in lessening Anxiety and diminishing the need for relief searched for in smoking.
Radiofrequency Thermocoagulation in Relieving Refractory Pain of Knee Osteoarthritis

To investigate the efficacy of radiofrequency thermocoagulation (RFTC) in relieving refractory pain of knee osteoarthritis (OA), we selected 54 patients with chronic knee OA pain, 27 treated with RFTC (case group) and 27 receiving regular treatments (control group). Response evaluations were conducted before treatment, and at the termination of treatment, and 3-month follow-up, applying the visual analog scale, the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), and American Knee Society Score (AKSS). Data analyses were performed with SPSS 21.0. At the termination of treatments and 3-month follow-ups, cases gained significantly increased scores in vitality, bodily pain, general health perceptions, physical functioning, and social role functioning by SF-36 scaling and in pain, range of motion, stability, walking, and stair climbing by AKSS (all P < 0.05). Controls received higher scores by AKSS in pain at the termination of treatments and in pain, range of motion, and walking at the termination of 3-month follow-ups (all P < 0.05). Both cases and controls presented significant difference between visual analog scale scores before treatments and those at the termination of 3-month follow-ups (both P < 0.05). All patients felt less pain after treatments, cases presenting better improvement (P < 0.05). Pain was stronger in females compared with males and in a positive correlation with age while had no obvious relation to disease course. In conclusion, RFTC may have better efficacy in relieving refractory pain and promoting function recovery in patients with knee OA than regular treatment.
Participatory organic research in the USA and Italy: Across a continuum of farmer–researcher partnerships

Abstract Organic agriculture continues to expand in the USA and in the European Union (EU), particularly in Italy, which had 48,650 organic farms in 2014 compared with 19,474 in the USA. Additionally, EU support for organic research is nearly double than that of the USA. Along with increased support for organic research, the EU organic community has achieved recognition at the European Commission policy level for a dedicated innovation platform, advocating the practice of farmer-first models for participatory research. The US land-grant universities have a long history of on-farm research, primarily through the Extension Service, but the need exists for more inclusive, second-loop, co-research with organic farmers. A survey was conducted of organic farmers and researchers in Italy and in the USA to ascertain the extent of participatory organic research activities and experiences, and explore the vision each group had for the future of co-innovation between organic farmers and researchers. Results indicated that, despite the higher level of organic research support in the EU, the percentage of researchers involved in on-farm/participatory organic research was equivalent in Italy and the USA, presumably due to the more recent emphasis in Italian/EU agricultural research agendas on the importance of farmer knowledge and participation in organic research. Overall, 60% of surveyed organic researchers in both countries cited involvement in on-farm/participatory organic research, with ‘farming systems’ and ‘nutrient/pest management’ the main research focus in the USA, compared with ‘farming systems’ and ‘equipment’ in Italy. Both countries’ researchers expressed their vision of participatory research as helping to improve communication between researchers and farmers, to enable work on relevant research, and to allow farmers to adapt technologies to their own conditions. Organic farmers in Italy completed survey questionnaires as part of a field day activity, leading to more Italian farmers responding to the survey, compared with USA counterparts who were queried via e-mail. Organic farmers in Italy identified ‘knowledge-sharing’ as a critical value of participatory research, and were conducting on-farm research with less compensation than US farmers. The ‘lack of time’ was cited as the most important constraint limiting participatory research by Italian and US farmers, although the ‘lack of common language’ also was rated as potentially impairing full participation. Lessons shared between EU and US organic researchers as a result of this project included methods to institute policies aimed at increasing support for organic research and co-innovations with organic farming communities, and connecting experienced on-farm researchers in the US with Italian colleagues to enhance collaborative activities with organic farmers.