Miracle-dz/UniFAR-FTUs huggingface dataset:
Renal protection in the 21st century

Purpose of reviewAmong critically ill patients, acute kidney injury (AKI) is still a common and serious complication with a tremendous impact on short-term and long-term outcomes. The objective of this review is to discuss strategies for renal protection and prevention of AKI in ICU patients. Recent findingsIt is fundamental to identify patients at risk for AKI as soon as possible and as accurately as possible. In order to achieve these goals, translational approaches implementing new biomarkers have shown promising results. Focusing on the role of potential preventive strategies, hemodynamic stabilization is the most important intervention with proven efficacy. Recent published data undermined any hope that high-dose statin therapy in statin-naïve patients could exert renoprotective effects. However, preliminary data revealed the renoprotective activity of dexmedetomidine when used as a sedative agent. Moreover, several studies demonstrated the protective effects of remote ischemic preconditioning in various organs including the kidneys. The use of balanced crystalloid instead of hyperchloremic solutions also contributes to the reduction of AKI in critically ill patients. SummaryTo prevent AKI, it is crucial to identify patients at risk as early as possible. Establishing hemodynamic stability and an adequate intravascular volume state to ensure a sufficient perfusion pressure is the only effective therapeutic intervention. It is self-evident that nephrotoxic agents should be avoided whenever it is possible.
Immunologic Analysis of a Phase I/II Study of Vaccination with MAGE-3 Protein Combined with the AS02B Adjuvant in Patients with MAGE-3-Positive Tumors

In a phase I/II study, patients with solid metastatic MAGE-3-positive tumors, mainly melanoma, were vaccinated with recombinant MAGE-3 protein combined with the immunologic adjuvant AS02B comprised of MPL and QS21 in an oil-in-water emulsion. The recombinant MAGE-3 protein was made up of a partial sequence of the protein D (ProtD) antigen of Haemophilus influenzae fused to the MAGE-3 sequence. The vaccine was given intramuscularly at 3-week intervals. Patients whose tumors stabilized or regressed after 4 vaccinations received 2 additional vaccinations at 6-week intervals. MAGE-3 and ProtD antibody and cellular immune responses were monitored after vaccination. Ninety-six percent (23/24) of the patients vaccinated with MAGE-3 protein in AS02B adjuvant elicited a significant anti-MAGE-3 IgG antibody response after 4 vaccinations, and all developed anti-ProtD IgG antibodies. For the detection of T-cell activity, total peripheral blood mononuclear cells were restimulated in vitro with MAGE-3- or ProtD-loaded autologous mature dendritic cells. In 30% of the evaluable patients vaccinated with the adjuvanted recombinant protein, IFN&ggr; production was increased in response to MAGE-3, and 2 patients (14% of evaluable patients) had a concomitant increase in IL-5 production. In 37% and 43% of the patients, respectively, IFN&ggr; or IL-5 production was increased in response to ProtD. It is concluded that vaccination of advanced cancer patients with MAGE-3 self-antigen in AS02B adjuvant is able to elicit MAGE-3-specific antibody and a T-cell response.
Differentiation potential of bone marrow stromal cells to enteric neurons in vitro.

OBJECTIVE To investigate whether bone marrow stromal cells (BMSC) can be induced to differentiate into enteric neurons and to produce more nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF). METHODS Bone marrow stromal cells were harvested from male Sprague-Dawley rats and cultured in Dulbecco's modified eagle medium supplemented with 20% fetal bovine serum. The BMSC were passaged six times and characterized by flow cytometry. The BMSC were pre-induced by basic fibroblast growth factor (10 ng/mL) for 24 h, then induced with GDNF in fetal gut condition medium (FGCM) for 10 days. The expressions of neuronal markers neural specific enolase (NSE), neurofilament (NF), glial cell marker, glial fibrillary acedic protein (GFAP), and enteric neuronal marker protein gene product 9.5 (PGP9.5), neural nitric oxide synthase (nNOS), and enteric neural transmitter vasoactive intestinal polypeptide (VIP) were detected by fluorescent immunohistochemistry. Expression levels of GDNF and NGF mRNA were determined by RT-PCR. RESULTS The cultured BMSC were CD90 (99.7%) positive and CD45 negative on flow cytometry. At day 10 of induction, 58.5 +/- 10.8% cells adopted neuron-like morphological changes and showed expression of NSE (47.6 +/- 7.5%), NF (75.6 +/- 8.4%), GFAP (negative), PGP9.5 (57.7 +/- 6.5%), nNOS (46.6 +/- 5.4%) and VIP (72.3 +/- 6.7%) by immunofluorescence. The BMSC expressed low levels of NGF and GDNF mRNA; however, after induction of GDNF in FGCM, the expression levels of NGF and GDNF mRNA were significantly increased. CONCLUSION Bone marrow stromal cells have the potential to be induced to differentiate into enteric neurons, express enteric neural transmitters, and produce more NGF and GDNF. Therefore, BMSC could be used as new method to treat gastrointestinal motility disorders associated with enteric neural lesions.
Perceived Effectiveness of Antismoking Ads and Association with Quit Attempts Among Smokers: Evidence from the Tips From Former Smokers Campaign

ABSTRACT Background. Measures of perceived effectiveness (PE) of ads have been validated to predict changes in cognitive precursors of quit attempts, but a relationship between PE and actual quit attempts has not been shown in population-based studies. We analyzed smokers’ PE ratings of ads from the national Tips From Former Smokers (Tips) campaign to (1) establish the validity of PE in predicting quit attempts in a large, nationally representative sample of smokers; (2) identify behavioral and demographic correlates of PE among respondents; and (3) examine whether PE is influenced by matching the race/ethnicity of ad participants with that of the ad viewer.Methods. We used survey data from two waves (baseline and follow-up) of a longitudinal online cohort of adult U.S. cigarette smokers. Respondents were shown one or more of 14 Tips campaign ads and were asked to assess each ad in terms of PE. We used multivariate models to estimate the association between baseline PE and prospective quit attempts; cross-sectional associations between PE and various respondent characteristics, including race/ethnicity, desire to quit, and health conditions; and the association between race/ethnicity of respondents and Tips ad participants.Results. Higher PE at baseline was associated with increased odds of a quit attempt at follow-up. Higher PE scores were associated with non-Hispanic black race, Hispanic ethnicity, higher desire to quit, presence of a chronic health condition, and presence of a mental health condition. There was no relationship between PE scores and matched race/ethnicity of the respondent and Tips ad participants.Conclusions. This is the first study to demonstrate an association between PE scores for antismoking ads and prospective quit attempts in a large, nationally representative sample of smokers. Our findings also provide strong evidence that racial/ethnic minority subpopulations, including non-Hispanic blacks and Hispanics, react more favorably to Tips campaign ads irrespective of race/ethnicity of the ad participant. This suggests that message characteristics (e.g., graphic visuals and emotional content) may play a more important role in PE than race/ethnicity of ad participants.
Sirtuin-2 Protects Neural Cells from Oxidative Stress and Is Elevated in Neurodegeneration

Sirtuins are highly conserved lysine deacetylases involved in ageing, energy production, and lifespan extension. The mammalian SIRT2 has been implicated in Parkinson's disease (PD) where studies suggest SIRT2 promotes neurodegeneration. We therefore evaluated the effects of SIRT2 manipulation in toxin treated SH-SY5Y cells and determined the expression and activity of SIRT2 in postmortem brain tissue from patients with PD. SH-SY5Y viability in response to oxidative stress induced by diquat or rotenone was measured following SIRT2 overexpression or inhibition of deacetylase activity, along with α-synuclein aggregation. SIRT2 in human tissues was evaluated using Western blotting, immunohistochemistry, and fluorometric activity assays. In SH-SY5Y cells, elevated SIRT2 protected cells from rotenone or diquat induced cell death and enzymatic inhibition of SIRT2 enhanced cell death. SIRT2 protection was mediated, in part, through elevated SOD2 expression. SIRT2 reduced the formation of α-synuclein aggregates but showed minimal colocalisation with α-synuclein. In postmortem PD brain tissue, SIRT2 activity was elevated compared to controls but also elevated in other neurodegenerative disorders. Results from both in vitro work and brain tissue suggest that SIRT2 is necessary for protection against oxidative stress and higher SIRT2 activity in PD brain may be a compensatory mechanism to combat neuronal stress.
E2f3a and E2f3b Contribute to the Control of Cell Proliferation and Mouse Development

ABSTRACT The E2f3 locus encodes two Rb-binding gene products, E2F3a and E2F3b, which are differentially regulated during the cell cycle and are thought to be critical for cell cycle progression. We targeted the individual inactivation of E2f3a or E2f3b in mice and examined their contributions to cell proliferation and development. Chromatin immunoprecipitation and gene expression experiments using mouse embryo fibroblasts deficient in each isoform showed that E2F3a and E2F3b contribute to G1/S-specific gene expression and cell proliferation. Expression of E2f3a or E2f3b was sufficient to support E2F target gene expression and cell proliferation in the absence of other E2F activators, E2f1 and E2f2, suggesting that these isoforms have redundant functions. Consistent with this notion, E2f3a−/− and E2f3b−/− embryos developed normally, whereas embryos lacking both isoforms (E2f3−/−) died in utero. We also find that E2f3a and E2f3b have redundant and nonredundant roles in the context of Rb mutation. Analysis of double-knockout embryos suggests that the ectopic proliferation and apoptosis in Rb−/− embryos is mainly mediated by E2f3a in the placenta and nervous system and by both E2f3a and E2f3b in lens fiber cells. Together, we conclude that the contributions of E2F3a and E2F3b in cell proliferation and development are context dependent.
Management strategies for atrial fibrillation

Atrial fibrillation is the most prevalent cardiac arrhythmia, affecting 10% of those aged over 80 years. Despite multiple treatment options, it remains an independent prognostic marker of mortality due to its association with clinical sequelae, particularly cerebrovascular events. Management can be broadly divided into treatment of the arrhythmia, via rhythm or rate control, and stroke thromboprophylaxis via anticoagulation. Traditional options for pharmacotherapy include negatively chronotropic drugs such as β-blockers, and/or arrhythmia-modifying drugs such as amiodarone. More recently, catheter ablation has emerged as a suitable alternative for selected patients. Additionally, there has been extensive research to assess the role of novel oral anticoagulants as alternatives to warfarin therapy. There is mounting evidence to suggest that they provide comparable efficacy, while being associated with lower bleeding complications. While these findings are promising, recent controversies have arisen with the use of novel oral anticoagulants. Further research is warranted to fully elucidate mechanisms and establish antidotes so that treatment options can be appropriately directed.
Environmental costs and benefits of growing Miscanthus for bioenergy in the UK

Planting the perennial biomass crop Miscanthus in the UK could offset 2–13 Mt oil eq. yr−1, contributing up to 10% of current energy use. Policymakers need assurance that upscaling Miscanthus production can be performed sustainably without negatively impacting essential food production or the wider environment. This study reviews a large body of Miscanthus relevant literature into concise summary statements. Perennial Miscanthus has energy output/input ratios 10 times higher (47.3 ± 2.2) than annual crops used for energy (4.7 ± 0.2 to 5.5 ± 0.2), and the total carbon cost of energy production (1.12 g CO2‐C eq. MJ−1) is 20–30 times lower than fossil fuels. Planting on former arable land generally increases soil organic carbon (SOC) with Miscanthus sequestering 0.7–2.2 Mg C4‐C ha−1 yr−1. Cultivation on grassland can cause a disturbance loss of SOC which is likely to be recovered during the lifetime of the crop and is potentially mitigated by fossil fuel offset. N2O emissions can be five times lower under unfertilized Miscanthus than annual crops and up to 100 times lower than intensive pasture. Nitrogen fertilizer is generally unnecessary except in low fertility soils. Herbicide is essential during the establishment years after which natural weed suppression by shading is sufficient. Pesticides are unnecessary. Water‐use efficiency is high (e.g. 5.5–9.2 g aerial DM (kg H2O)−1, but high biomass productivity means increased water demand compared to cereal crops. The perennial nature and belowground biomass improves soil structure, increases water‐holding capacity (up by 100–150 mm), and reduces run‐off and erosion. Overwinter ripening increases landscape structural resources for wildlife. Reduced management intensity promotes earthworm diversity and abundance although poor litter palatability may reduce individual biomass. Chemical leaching into field boundaries is lower than comparable agriculture, improving soil and water habitat quality.
Comprehensive review of epidemiology, scope, and impact of spinal pain.

Persistent pain interfering with daily activities is common. Chronic pain has been defined in many ways. Chronic pain syndrome is a separate entity from chronic pain. Chronic pain is defined as, "pain that persists 6 months after an injury and beyond the usual course of an acute disease or a reasonable time for a comparable injury to heal, that is associated with chronic pathologic processes that cause continuous or intermittent pain for months or years, that may continue in the presence or absence of demonstrable pathologies; may not be amenable to routine pain control methods; and healing may never occur. " In contrast, chronic pain syndrome has been defined as a complex condition with physical, psychological, emotional, and social components. The prevalence of chronic pain in the adult population ranges from 2% to 40%, with a median point prevalence of 15%. Among chronic pain disorders, pain arising from various structures of the spine constitutes the majority of the problems. The lifetime prevalence of spinal pain has been reported as 54% to 80%. Studies of the prevalence of low back pain and neck pain and its impact in general have shown 23% of patients reporting Grade II to IV low back pain (high pain intensity with disability) versus 15% with neck pain. Further, age related prevalence of persistent pain appears to be much more common in the elderly associated with functional limitations and difficulty in performing daily life activities. Chronic persistent low back and neck pain is seen in 25% to 60% of patients, one-year or longer after the initial episode. Spinal pain is associated with significant economic, societal, and health impact. Estimates and patterns of productivity losses and direct health care expenditures among individuals with back and neck pain in the United States continue to escalate. Recent studies have shown significant increases in the prevalence of various pain problems including low back pain. Frequent use of opioids in managing chronic non-cancer pain has been a major issue for health care in the United States placing a significant strain on the economy with the majority of patients receiving opioids for chronic pain necessitating an increased production of opioids, and escalating costs of opioid use, even with normal intake. The additional costs of misuse, abuse, and addiction are enormous. Comorbidities including psychological and physical conditions and numerous other risk factors are common in spinal pain and add significant complexities to the interventionalist's clinical task. This section of the American Society of Interventional Pain Physicians (ASIPP)/Evidence-Based Medicine (EBM) guidelines evaluates the epidemiology, scope, and impact of spinal pain and its relevance to health care interventions.
Experiments on behavioral coordinated control of an Unmanned Aerial Vehicle manipulator system

This work tackles the problem of controlling an Unmanned Aerial Vehicle equipped with a robotic Manipulator and it has been developed within the framework of the EU-funded ARCAS (Aerial Robotics Cooperative Assembly System) project. A behavioral control, based on the Null Space-based Behavioral (NSB) paradigm, is proposed to tackle the coordination between the arm and vehicle motions. To this aim, a set of basic functionalities (called elementary behaviors) are designed and combined in a priority order to attain complex tasks (called compound behaviors). The proposed controller has been experimentally validated on a multirotor aircraft with an attached 6 Degree of Freedoms manipulator. Two experimental case studies, involving several compound behaviors, have been reported and the results show the effectiveness of the approach.
Characterization of the resting-state brain network topology in the 6-hydroxydopamine rat model of Parkinson’s disease

Resting-state functional MRI (rsfMRI) is an imaging technology that has recently gained attention for its ability to detect disruptions in functional brain networks in humans, including in patients with Parkinson’s disease (PD), revealing early and widespread brain network abnormalities. This methodology is now readily applicable to experimental animals offering new possibilities for cross-species translational imaging. In this context, we herein describe the application of rsfMRI to the unilaterally-lesioned 6-hydroxydopamine (6-OHDA) rat, a robust experimental model of the dopamine depletion implicated in PD. Using graph theory to analyse the rsfMRI data, we were able to provide meaningful and translatable measures of integrity, influence and segregation of the underlying functional brain architecture. Specifically, we confirm that rats share a similar functional brain network topology as observed in humans, characterised by small-worldness and modularity. Interestingly, we observed significantly reduced functional connectivity in the 6-OHDA rats, primarily in the ipsilateral (lesioned) hemisphere as evidenced by significantly lower node degree, local efficiency and clustering coefficient in the motor, orbital and sensorimotor cortices. In contrast, we found significantly, and bilaterally, increased thalamic functional connectivity in the lesioned rats. The unilateral deficits in the cortex are consistent with the unilateral nature of this model and further support the validity of the rsfMRI technique in rodents. We thereby provide a methodological framework for the investigation of brain networks in other rodent experimental models of PD, as well as of animal models in general, for cross-comparison with human data.
Evaluating the development of leadership self-efficacy among the aspiring school leaders

Trainings given to aspiring school leaders (ASLs) play a crucial role in setting the direction for successful schools. The inadequate ability of leadership preparatory training to prepare and support ASLs to take on the challenging task of school leadership has been severely criticized and continues to be a major concern locally and internationally. Literature on training has focused on training design, individual and organizational factors but studies on self-efficacy, especially among school leaders’ have not been given due consideration. The study evaluated the effectiveness of the National Professional Qualification for Educational Leaders (NPQELs) preparatory training in developing the leadership self-efficacy beliefs of ASLs. This encompassed an investigation of individual characteristics and determination of training design characteristics and how these contributed to the self-efficacy development of the ASLs. The study adopted a sequential explanatory mixed methodology. A survey was carried out on 226 NPQEL trained ASLs and in-depth interviews were conducted on seven selected ASLs based on criterion sampling. Non-parametric statistical techniques were used to analyse the quantitative data. The findings showed that among the individual characteristics, only age and experience significantly influenced the improvement of the ASLs’ self-efficacy beliefs. Among the four training design characteristics, training internship revealed a moderate influence in all the self-efficacy dimensions and this was followed by the relevancy of coursework to practice sub-factor. Thematic analysis of the qualitative data based on Bandura’s concept revealed that three of Bandura’s sources of efficacy beliefs, namely mastery experience, vicarious experience and physiological arousal were evident in the NPQEL training design. However, there was only a low level of social persuasion, the fourth source in the training. Overall, the findings showed that there were insufficient conditions of these sources of efficacy in the NPQEL training to give significant impact on the development of the ASLs’ self-efficacy beliefs. The study proposed a framework for self-efficacy development initiatives in the preparatory educational leadership training of ASLs in Malaysia.
Validating the Location of Fluorescent Protein Fusions in the Endomembrane System

Assessment of gene function generally requires knowledge of the sites of action of gene products. Several experimental approaches can provide relevant information, but all have their limitations and the potential for experimental artifact. In this article we focus on the endomembrane organelles and on the methods that can be used to validate the location of fluorescent protein fusions. We discuss the utility of redundant localization techniques, complementation of mutant phenotypes, and integration of localization data with expected biological function as methods to achieve consensus. We argue that no single piece of evidence is sufficient to address the issue, and that all approaches can reveal useful information about the true steady state location of a protein or about other aspects of its transport and dynamics. As ever, the critical point is the subjective interpretation one puts on each observation in light of the experimental conditions and other pertinent data. We illustrate these points with some successes and failures in our own work.
miR-1271 inhibits ERα expression and confers letrozole resistance in breast cancer

Attenuation of estrogen receptor α (ERα) expression via unknown mechanism(s) is a hallmark of endocrine-resistant breast cancer (BCa) progression. Here, we report that miR-1271 was significantly down-regulated in letrozole-resistant BCa tissues and in letrozole-resistant BCa cells. miR-1271 directly targeted the chromatin of DNA damage-inducible transcript 3 (DDIT3) gene. miR-1271 expression level was inversely correlated to DDIT3 mRNA level in BCa biopsies. Form a mechanistic standpoint, reintroduction of exogenous miR-1271 could effectively restore ERα level via inhibiting DDIT3 expression, thereby potentiating letrozole sensitivity in BCa cells. Moreover, DDIT3 deregulation promoted letrozole-resistance by acting as a potent corepressor of ESR1 transcription. Taken together, we have identified that disruption of the miR-1271/DDIT3/ERα cascade plays a causative role in the pathogenesis of letrozole resistance in BCa.