Miracle-dz/UniFAR-FTUs huggingface dataset:
Transcellular retrograde labeling of radial glial cells with WGA‐HRP and diI in neonatal rat and hamster

Topographically distinct populations of radial glial cells in the diencephalon and mesencephalon of neonatal rats and hamsters were transcellularly labeled with wheat germ agglutinin conjugated to horseradish peroxidase (WGA‐HRP) and with the lipophilic tracer DiI. A comparison of the histological distribution of the two tracers is suggestive of two different mechanisms of transcellular labeling. Intraocular injections of WGA‐HRP resulted in the uptake of exogenously applied WGA‐HRP by retinal ganglion cells, followed by anterograde axonal transport and exocytosis within the optic target nuclei. In addition to the transneuronal labeling, which is typical of such injections, we observed the transcellular labeling of the processes and somata of radial glial cells that were topographically associated with the terminal fields of the labeled axons. Similar transcellular labeling of radial glial cells associated with the axon terminal fields of the colliculogeniculate projection to the medial geniculate nucleus was observed following injections of WGA‐HRP in the inferior colliculus. The transcellular labeling within the radial glial cells was discontinuous and somatopetally concentrated, indicating the existence of a retrograde active transport mechanism within the radial glial processes subsequent to its uptake following release of tracer from axons. This type of labeling can be referred to as transcellular retrograde glioplasmic transport. In contrast, DiI was used as a tracer through its capacity to diffuse within the plasmalemma. Topographically distinct populations of radial glial cells were transcellularly labeled following placements of DiI in the retina, inferior colliculus, or dorsal thalamus of fixed brains. The radial processes of labeled radial glial cells consistently extended into regions that also contained labeled axons. It is likely that the transcellular radial glial labeling with DiI occurred via transmembranous diffusion. These data indicate that a close structural and functional relation exists between axons and glial cells in the developing brain. © 1993 Wiley‐Liss, Inc.
Evolutionary mechanisms of circadian clocks

An intriguing question in biology is to know how circadian molecular networks could have evolved their particular topologies to adjust to a daily period. We analyze the mechanism of the evolution of such networks by using a computational design strategy that allows for the generation of synthetic networks with a targeted 24 hours oscillation. We have performed a systematic analysis of all possible two-gene network topologies based on a core activator-repressor frequently found in circadian mechanisms. We have considered transcriptional and post-translational regulations to implement this core. We have applied our analysis to both, eukaryotic and prokaryotic circadian machinery. Finally, we conjecture a possible mechanism for the evolution of circadian clocks.
HIV/AIDS Knowledge and Attitude among High School Students in Shiraz, Iran in 2015

Background & aim: Acquired immune deficiency syndrome (AIDS) is an infectious disease caused by human immunodeficiency virus (HIV). The awareness of HIV preventive measures and its transmission routes have an important role in controlling the HIV infection in the society. Regarding this, the present study aimed to investigate the awareness and attitudes of the high school students regarding HIV/AIDS infection in Shiraz, Iran, in 2015. Methods: This cross‐sectional study was conducted on 102 students, selected form six high schools. The students and schools were selected using the random sampling technique. The data were collected using a standard researcher-made questionnaire. The data analysis was performed using the Chi-square test through SPSS version 18. Results: As the results of the present study indicated, 55% of the participants were male, and the majority of them were about 17-18 years old. The participants’ general knowledge about HIV was found to be at moderate level. However, they had insufficient awareness of the associated transmission routes and major causes of this disease. The students majoring in biological sciences were more aware of this issue than other students. In addition, the majority of the students had highly positive attitudes towards the AIDS patients and confirmed their right to live and use all facilities. However, a large proportion of the students denied to share a location or personal items with these patients. Conclusion: According to the findings of this study, almost all students had high level of general information about HIV. Nonetheless, given the students’ low awareness and knowledge levels about the HIV transmission routes, the administration of the related educational programs is an urgent need to correct the students’ misconceptions about the HIV patients and improve their knowledge in this regard.
Novel drugs for treating angina

Angina is the pain caused by myocardial ischaemia, usually as a result of obstructive coronary artery disease. Although angina typically presents as chest pain on exertion, patients can also present with atypical symptoms such as shortness of breath without pain. Guidelines1 2 recommend initial treatment with one or two antianginal drugs, plus aspirin, and a statin for secondary prevention of cardiovascular disease. If symptoms are not adequately controlled, coronary revascularisation by percutaneous coronary intervention or coronary artery bypass surgery is often effective.1 2 The antianginal drugs recommended for initial treatment are β blockers and calcium channel blockers, which reduce myocardial ischaemia by heart rate reduction and vasodilatory mechanisms, respectively. Either or both of these drug classes should be prescribed, together with a short acting nitrate for prompt alleviation of angina attacks (figure⇓) However, if these drugs are not tolerated, are contraindicated, or fail to correct symptoms, alternative antianginals are available, such as oral nitrates and newer antianginal drugs, which are the subject of this review. Although oral nitrates have been used for many years to treat stable angina, the National Institute for Health and Care Excellence concluded that evidence related to their efficacy was insufficient and hence advised that oral nitrates should be used as second line therapy after β blockers and calcium channel blockers. NICE also concluded that evidence was insufficient to make a firm recommendation about the choice of second line antianginals, which we present here in alphabetical order. Treatment algorithm for novel antianginal drugs. Modified from National Institute for Health and Care Excellence1 Alternative antianginal drugs include older less familiar ones such as nicorandil, which has been available for the past 20 years, and newer antianginal drugs such as ivabradine and ranolazine. Also available in many countries (not the United Kingdom) is trimetazidine. …
Arginine-enhanced enteral nutrition augments the growth of a nitric oxide-producing tumor.

BACKGROUND Arginine-enhanced diets have been shown to be beneficial in tumor-bearing hosts, but no data exist regarding their effects in hosts bearing nitric oxide (NO)-producting tumors. OBJECTIVE To examine the effect of arginine supplementation on the growth of a NO-producing murine breast cancer cell line. METHODS EMT-6 cells were grown in various concentrations of arginine in the presence or absence of the inducible nitric oxide synthase (iNOS) inhibitor, aminoguanidine (1 mmol/L). Forty-eight hours later, nitrite accumulation and viable cell number were assessed. BALB/c mice were then pair-fed basal purified diets (n = 10), 4% casein diets (isonitrogenous control, n = 5), or 4% arginine-enhanced diets (n = 10). One week later, 10(5) EMT-6 cells were implanted subcutaneously into the dorsal flank. After tumor implantation, five mice fed basal purified diets and five mice fed arginine-enhanced diets also received aminoguanidine (100 mg/kg subcutaneously twice daily). Two weeks after tumor cell implantation, tumor size (mean diameter), animal weight, serum and tumor nitrite and nitrate levels were measured. RESULTS There was minimal nitrite accumulation in arginine-free media, while increasing the arginine concentration increased nitrite levels. Viable cell number did not increase in arginine-free media, but increased nearly twofold in 100 and 1000 mumol/L arginine. In 5000 and 10,000 mumol/L arginine, the difference in viable cell number was not statistically different than that seen in arginine-free media, whereas the addition of aminoguanidine blocked nitrite accumulation and increased viable cell number at these arginine concentrations. Arginine-enhanced diets stimulated tumor growth in vivo more than twofold over tumor growth in mice fed isonitrogenous control or basal purified enteral diets. Mice fed arginine-enhanced diets also had increased serum nitrite and nitrate levels over mice fed basal purified enteral diets, whereas tumors from mice fed arginine-enhanced diets had nitrite and nitrate levels similar to mice fed basal purified enteral diets. Aminoguanidine blocked the increase in serum nitrite and nitrate, but failed to block the increased tumor growth in mice receiving the arginine-supplemented diets. CONCLUSIONS Arginine concentration influences the growth of EMT-6 tumor cells in vitro and dietary arginine supplementation augments tumor growth in vivo. The mechanism of the growth modulation in vitro is NO-dependent whereas the enhanced tumor growth in vivo is NO-independent.
Cardiac regeneration strategies: Staying young at heart

The human heart is continually operating as a muscular pump, contracting, on average, 80 times per minute to propel 8000 liters of blood through body tissues each day. Whereas damaged skeletal muscle has a profound capacity to regenerate, heart muscle, at least in mammals, has poor regenerative potential. This deficiency is attributable to the lack of resident cardiac stem cells, combined with roadblocks that limit adult cardiomyocytes from entering the cell cycle and completing division. Insights for regeneration have recently emerged from studies of animals with an elevated innate capacity for regeneration, the innovation of stem cell and reprogramming technologies, and a clearer understanding of the cardiomyocyte genetic program and key extrinsic signals. Methods to augment heart regeneration now have potential to counteract the high morbidity and mortality of cardiovascular disease.
Understanding the Metabolic Syndrome: A Modeling Perspective

The prevalence of obesity is growing at an alarming rate, placing many at risk for developing diabetes, hypertension, sleep apnea, or a combination of disorders known as “metabolic syndrome”. The evidence to date suggests that metabolic syndrome results from an imbalance in the mechanisms that link diet, physical activity, glucose-insulin control, and autonomic cardiovascular control. There is also growing recognition that sleep-disordered breathing and other forms of sleep disruption can contribute significantly to autonomic dysfunction and insulin resistance. Chronic sleep deprivation resulting from sleep-disordered breathing or behavioral causes can lead to excessive daytime sleepiness and lethargy, which in turn contribute to increasing obesity. Analysis of this complex dynamic system using a model-based approach can facilitate the delineation of the causal pathways that lead to the emergence of the metabolic syndrome. In this paper, we provide an overview of the main physiological mechanisms associated with obesity and sleep-disordered breathing that are believed to result in metabolic and autonomic dysfunction, and review the models and modeling approaches that are relevant in characterizing the interplay among the multiple factors that underlie the development of the metabolic syndrome.
Strengthening surgical handover: Developing and evaluating the effectiveness of a handover tool to improve patient safety

Abstract The European Working Time Directive and economic challenges have led to a paradigm of shift-work becoming common, and yet the continuation of high-quality patient care remains paramount. Effective and safe transfer of clinical information is critical as emphasised by the Royal College of Surgeons document 'Safe handover: Guidance from the Working Time Directive working party (March 2007)'. The aim of this project was to design and implement a handover proforma in order to deliver a more efficient and safer system for patient care over the weekend. The surgical weekend handover proforma was designed following consultation with nursing and medical colleagues. It included a traffic light scoring system to alert the on-call team of the urgency of clinical review. An educational session was delivered to junior doctors on the surgical rotation to ensure accurate completion of the proforma. All trainee surgical doctors from Foundation Year 1 to Specialist Registrars were asked to complete a pre- and post-intervention questionnaire. Improvement was noted in all categories measured. 85% of the firms were using the new surgical weekend handover sheet. 78% of junior doctors were confident in understanding the patient's condition and executing the clinical jobs faster, with ward rounds lasting less than 3 hours. On average, 20% of patients were discharged per weekend during the trial period. Robust patient handover is vital to maintain patient safety and avoid adverse events. Our findings support the use of a surgical proforma to provide a consistent and structured approach to inpatient handover during the weekend.
Barriers to Optimal Care for Patients with Coexisting Substance Use and Mental Health Disorders

Objective: This paper describes qualitative research that was carried out as part of a project aimed at drawing up a series of guidelines for the assessment and management for people with coexisting substance use and mental health disorders, or dual diagnosis [1]. Method: A core consultation team of 14 experts with experience in the areas of both substance use and mental health in New Zealand was established to advise on the development of eight clinical scenarios. The clinical scenarios were selected to highlight a range of real life issues in the treatment of people with coexisting substance use and mental health disorders and were presented at 12 focus groups around New Zealand. The 261 participants of the focus groups were asked to comment on what was optimal management for each of the scenarios and to identify barriers to optimal care in their region. Written notes were analysed for recurring and strongly stated themes and these comprise the results of the study. Results: While there was marked regional variation in treatment approaches and service structures, many of the barriers to optimal care that were identified were common to all regions. The results are considered under the headings of systems issues, clinical issues and attitudes. Conclusions: A wide variety of barriers that impede the delivery of optimal care have been identified. These range from the attitudes of individual clinicians to the structure of the systems within which they work. A system of key principles and processes for organizing treatment in a way which helps overcome these barriers is proposed.
On delayed uncertain genetic regulatory networks: robust stability analysis

In this paper, the problem of stability analysis for uncertain genetic regulatory networks with time-varying delays is investigated. The time-varying delay function in this paper is not required to be either continuously differentiable, or its derivative less than one. By choosing an appropriate Lyapunov–Krasovskii functional and employing some free-weighting matrices, some new delay-dependent and delay-derivative-dependent stability criteria are presented in terms of linear matrix inequality. And the new criteria are applicable to both fast and slow time-varying delays. Finally, three numerical examples are used to demonstrate the usefulness of the main results and less conservativeness of the proposed method.
New biologically active hybrid bacteriocins constructed by combining regions from various pediocin-like bacteriocins: the C-terminal region is important for determining specificity

The pediocin-like bacteriocins, produced by lactic acid bacteria, are bactericidal polypeptides with very similar primary structures. Peptide synthesis followed by reverse-phase and ion-exchange chromatographies yielded biologically active pediocin-like bacteriocins in amounts and with a purity sufficient for characterizing their structure and mode of action. Despite similar primary structures, the pediocin-like bacteriocins, i.e., pediocin PA-1, sakacin P, curvacin A, and leucocin A, differed in their relative toxicities against various bacterial strains. On the basis of the primary structures, the polypeptides of these bacteriocins were divided into two modules: the relatively hydrophilic and well conserved N-terminal region, and the somewhat more diverse and hydrophobic C-terminal region. By peptide synthesis, four new biologically active hybrid bacteriocins were constructed by interchanging corresponding modules from various pediocin-like bacteriocins. All of the new hybrid bacteriocin constructs had bactericidal activity. The relative sensitivity of different bacterial strains to a hybrid bacteriocin was similar to that to the bacteriocin from which the C-terminal module was derived and quite different from that to the bacteriocin from which the N-terminal was derived. Thus, the C-terminal part of the pediocin-like bacteriocins is an important determinant of the target cell specificity. The synthetic bacteriocins were more stable than natural isolates, presumably as a result of the absence of contaminating proteases. However, some of the synthetic bacteriocins lost activity, but this was detectable only after months of storage. Mass spectrometry suggested that this instability was due to oxidation of methionine residues, resulting in a 10- to 100-fold reduction in activity.
Adding CNNs to the Mix: Stacking models for sentiment classification

In the recent years, sentiment analysis has emerged as a major research problem in the field of Natural Language Processing. Here, the problem is to identify the sentiment/emotion in given sentence/paragraph. Usually it is positive, negative and neutral. Here, we consider only binary classification task (positive and negative). We have considered the best performing sentiment analysis model which is a ensemble of NB-SVM, Paragraph2Vec and RNN. We added CNN into this stacking model and showed that our ensemble model perform better than the existing one. We achieved the state of the art performance on IMDB Movie review dataset, Stanford sentiment treebank dataset (SST) and Elec reviews dataset.
Introduction of Adonis aestivalis as a new source of effective cytotoxic cardiac glycoside

Abstract Cardiac glycosides are used for treatment of irregular heartbeats, cardiac arrhythmia and congestive heart failures. In this research, digitoxin as a cardiac glycoside was identified and isolated for the first time in the world from Adonis aestivalis and investigated for its cytotoxic activity against cervical cancer cell (HeLa) lines and human lymphocytes by MTT test. Digitoxin extracted from the aerial parts of the plant collected from west of Iran and purified by column and thin layer chromatographic techniques. The structure of isolated cardiac glycoside was identified by IR, 1H NMR and 13C NMR methods and so the presence of digitoxin was established. The half maximal inhibitory concentration values for cervical cancer and lymphocyte cells were obtained to be 5.62 and 412.94 μg/mL. The results of this study introduced the new resource of digitoxin which has considerable cytotoxic effects against HeLa cancer cells but did not damage normal human lymphocyte cells.
The 5-HT3A receptor is essential for fear extinction

The 5-HT3 receptor, the only ionotropic 5-HT receptor, is expressed in limbic regions, including the hippocampus, amygdala, and cortex. However, it is not known whether it has a role in fear memory processes. Analysis of 5-HT3A receptor knockout mice in fear conditioning paradigms revealed that the 5-HT3A receptor is not required for the acquisition or retention of fear memory but is essential for the extinction of contextual and tone-cued fear. Our data suggest that the 5-HT3A receptor could be a key molecule regulating fear memory processes and a potential therapeutic target for fear disorders.
Long-term results of intestinal transplantation for pseudo-obstruction in children.

PURPOSE The aim of this study was to determine long-term results of intestinal transplantation in children with pseudo-obstruction, particularly when stomach and colon are not part of the allograft. METHODS The authors conducted a case-record review of all children who underwent transplantation at our center for a primary diagnosis of pseudo-obstruction. Supplementary information was obtained from outpatient charts, computerized database, and telephone survey of parents. RESULTS Six small bowel and 3 liver-small bowel transplants were carried out in 8 patients between 1993 and 1999. Median follow-up is 40 months (range, 13 to 73 months). Median age at transplantation was 2.7 years (range, 0.7 to 12.8 years). Median graft survival in this series is 15 months (range, 1 day to 71 months). Stomach and colon were excluded from all allografts. Two children died 5 and 368 days after transplant and 2 graft losses occurred in 1 patient. Two children had lymphoproliferative disease; both are alive with functioning grafts. Five survivors with functioning grafts receive full enteral feedings at home. Four of the 5 have had ileostomies closed, and 3 have normal bowel movements. CONCLUSIONS Intestinal transplantation without stomach or colon provides children with chronic intestinal pseudo-obstruction with a good quality of life. The underlying disease poses special challenges in management.
Uterine Artery Embolization: A Systematic Review of the Literature and Proposal for Research

Abstract : Uterine leiomyomata are a common cause of gynecologic symptoms and major gynecologic surgery. Common treatments for these benign tumors include medical therapy, hysterectomy, and myomectomy. The objective of this project was to review and synthesize the existing literature on a minimally invasive technique for reducing symptoms from uterine leiomyomata, uterine artery embolization (UAE); and, using an expert panel approach, develop an agenda for research into the long and short term outcomes of this technique.