Miracle-dz/UniFAR-FTUs huggingface dataset:
On the risk of severe dengue during secondary infection: a systematic review coupled with mathematical modeling.

BACKGROUND & OBJECTIVES The present study aimed to systematically quantify the well known risk of severe dengue during secondary infection in literature and to understand how epidemiological mechanisms of enhancement during the secondary infection influence the empirically estimated risk of severe dengue by means of mathematical modeling. METHODS Two conditional risks of severe dengue, i.e. symptomatic illness and dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS), given secondary infection were explored based on systematically searched prospective studies. A two-strain epidemiological model was employed to simulate the transmission dynamics of dengue and to identify the relevant data gaps in empirical observations. RESULTS Using the variance-based weighting, the pooled relative risk (RR) of symptomatic illness during secondary infection was estimated at 9.4 [95% confidence interval (CI): 6.1-14.4], and similarly, RR of DHF/DSS was estimated to be 23.7 (95% CI: 15.3-36.9). A variation in the RR of DHF/DSS was observed among prospective studies. Using the mathematical modeling technique, we identified the duration of cross-protective immunity as an important modulator of the time-dependent behaviour of the RR of severe dengue. Different epidemiological mechanisms of enhancement during secondary infection yielded different RR of severe dengue. INTERPRETATION & CONCLUSION Optimal design of prospective cohort study for dengue should be considered, accounting for the time-dependence in the RR during the course of dengue epidemic. It is critical to statistically infer the duration of cross-protective immunity and clarify how the enhancement influences the epidemiological dynamics during secondary infection.
Low levels of plasma endothelin-1 in patients with retinitis pigmentosa

Purpose: The aim of this study was to elucidate the role of endothelin-1 (ET-1) in the pathophysiology of retinitis pigmentosa (RP). Methods: Plasma ET-1 levels and ophthalmic features in 50 RP patients were compared with those in 20 healthy-eye control subjects. Plasma ET-1 concentrations were determined using a commercially available enzyme-linked immunosorbent assay kit. Results: Mean plasma ET-1 levels of RP patients (1.88 ± 0.56 pg/mL) were significantly lower than those of control subjects (2.30 ± 0.30 pg/mL, Mann-Whitney’s U test; P < 0.01). However, ET-1 concentrations varied markedly in each patient. Among RP patients, a significant correlation of ET-1 concentrations was not observed in terms of its hereditary forms or other clinical factors. Conclusion: ET-1 may be important in the pathogenesis of RP, and measurement of its plasma concentrations may also contribute to additional insights into the retinal hemodynamics of RP.
The influence of curriculum elements on the perceived effectiveness of dfp tk. Pertama lipi

This study investigates which curriculum elements give the biggest influence on perceived training program effectiveness. In this study, Diklat Fungsional Peneliti Tk. Pertama (DFP Tk. Pertama) is chosen because this training program is the only training program in Indonesia that focuses on giving the basic knowledge and skills for researchers. This training program has the main goal to teach sufficient knowledge and skills for the researchers to conduct a high quality research. Therefore, the effectiveness of this training program is very important to ensure that the researchers are able to improve their knowledge and skills to conduct a high quality research in the future. This study intends to measure which curriculum elements give the biggest influences on the perceived effectiveness of DFP Tk. Pertama. To investigate the answer, a research was conducted through a questionnaire survey with a 5 Likert-scale. The measurement of curriculum elements' influence on the perceived training program effectiveness is based on the participants' responses which they put on the questionnaire form. The samples in this study are 30 participants of the DFP Tk. Pertama who have different gender, age, education degree, and education background (natural, technical, and social sciences). The result reveals that curriculum gives a significant influence to the effectiveness of the DFP Tk. Pertama. Measured per curriculum element, the result of the analysis shows that course of the study has the highest influence on the training program effectiveness. On the contrary, the other three of the curriculum elements: textbooks, classroom practices and supporting facilities, have no significant influence on the training program effectiveness. At the end of the training program, the participants agree that the DFP Tk. Pertama is effective to improve their knowledge and skills.
EFFECT OF DAILY WEIGHT GAIN ON AGE AT FIRST CALVING AND SUBSEQUENT MILK YIELD OF HOLSTEIN HEIFERS IN EGYPT

A total number of 1152 complete lactation records for 576 Holstein cows were collected from two commercial farms (Copenhagen and Sami Asaad farm) during the period from year 2007 to 2010 to determine the effect of average daily weight gain (ADG) from birth to conception of Holstein heifers on their age at first calving (AFC) and subsequent milk yield. Heifers were divided into four groups (G ,s ) based on their ADG as 650 g/day, 775 g/day, 875 g/day and 950 g/day for G1, G2, G3 and G4, respectively. Heifers of G4 reached the AFC 5.3 month earlier (P<0.001) than those of G1. ADG had positive effect on productive traits of the first two lactations. Cows of G4 had a similar 305 days milk yield in the first lactation compared to G1 but, scored non-significant higher milk yield in the second one by 535 kg. G4 had non-significant increase in milk yield / day of cow age till the end of the first lactation (MY1/DCA) compared with G1. Milk yield / day of cow age of G4 till the end of the second lactation (MY2/DCA) increased (P<0.01) by 12.7 % compared to G1. Days open of G4 in the first lactation (DO1) was shorter (P<0.05) than that of G1 by 44 days. This trend extended to the second lactation, however, it was insignificant. The present results showed that productive and reproductive performance of the faster growing Holstein heifers is better than that of slower ones. The ADG of Holstein heifers during the period from birth to conception affected significantly AFC, DO1 and MY2/DCA. G4 calved for the first time 5.3 months earlier, produced 535 kg more milk and had shorter days open by 67 days till the end of second lactation compared with G1.
Standard maximum likelihood analyses of alignments with gaps can be statistically inconsistent

Background Most statistical methods for phylogenetic estimation in use today treat a gap (generally representing an insertion or deletion, i.e., indel) within the input sequence alignment as missing data. However, the statistical properties of this treatment of indels have not been fully investigated. Results We prove that maximum likelihood phylogeny estimation, treating indels as missing data, can be statistically inconsistent for a general (and rather simple) model of sequence evolution, even when given the true alignment. Therefore, accurate phylogeny estimation cannot be guaranteed for maximum likelihood analyses, even given arbitrarily long sequences, when indels are present and treated as missing data. Conclusions Our result shows that the standard statistical techniques used to estimate phylogenies from sequence alignments may have unfavorable statistical properties, even when the sequence alignment is accurate and the assumed substitution model matches the generation model. This suggests that the recent research focus on developing statistical methods that treat indel events properly is an important direction for phylogeny estimation.
The dS/CFT Correspondence and the Big Smash

Recent observations suggest that the cosmological equation-of-state parameter w is close to -1. To say this is to imply that w could be slightly less than -1, which leads to R. Caldwell's ``Phantom cosmologies''. These often have the property that they end in a ``Big Smash'', a final singularity in which the Universe is destroyed in a finite proper time by excessive expansion. We show that, classically, this fate is not inevitable: there exist Smash-free Phantom cosmologies, obtained by a suitable perturbation of the de Sitter equation of state, in which the spacetime is in fact asymptotically de Sitter. [ Contrary to popular belief, such cosmologies, which violate the Dominant Energy Condition, do not necessarily violate causality. ] We also argue, however, that the physical interpretation of these classically acceptable spacetimes is radically altered by ``holography'', as manifested in the dS/CFT correspondence. It is shown that, if the boundary CFTs have conventional properties, then recent ideas on ``time as an inverse renormalization group flow'' can be used to rule out these cosmologies. Very recently, however, it has been argued that the CFTs in dS/CFT are of a radically unconventional form, and this opens up the possibility that Smash-free Phantom spacetimes offer a simple model of a ``bouncing'' cosmology in which the quantum-mechanical entanglement of the field theories in the infinite past and future plays an essential role.
Kinetics and crystal structure of catechol-o-methyltransferase complex with co-substrate and a novel inhibitor with potential therapeutic application.

Catechol-O-methyltransferase (COMT; E.C. 2.1.1.6) is a ubiquitous enzyme in nature that plays an important role in the metabolism of catechol neurotransmitters and xenobiotics. In particular, inactivation of drugs such as L-3,4-dihydroxyphenylalanine (L-DOPA) via O-methylation is of relevant pharmacological importance, because L-DOPA is currently the most effective drug used in the treatment of Parkinson's disease. This justified the interest in developing COMT inhibitors as potential adjuncts to L-DOPA therapy. The kinetics of inhibition by BIA 3-335 (1-[3,4-dihydroxy-5-nitrophenyl]-3-(N-3'-trifluormethylphenyl)-piperazine-1-propanone dihydrochloride) were characterized using recombinant rat soluble COMT. BIA 3-335 was found to act as a potent, reversible, tight-binding inhibitor of COMT with a K(i) of 6.0 +/- 1.6 nM and displaying a competitive inhibition toward the substrate binding site and uncompetitive inhibition toward the S-adenosyl-L-methionine (SAM) binding site. The 2.0-A resolution crystal structure of COMT in complex with its cosubstrate SAM and a novel inhibitor BIA 3-335 shows the atomic interactions between the important residues at the active site and the inhibitor. This is the first report of a three-dimensional structure determination of COMT complexed with a potent, reversible, and tight-binding inhibitor that is expected to have therapeutic applications.
Sarpogrelate Hydrochloride, a 5-HT2A Receptor Antagonist, Attenuates Neurogenic Pain Induced by Nucleus Pulposus in Rats

Study Design. An in vivo study using a rat lumbar disc herniation model. Objectives. To evaluate the effects of sarpogrelate hydrochloride on neurogenic pain induced by nucleus pulposus translocation and to elucidate its mechanism. Summary of Background Data. Sarpogrelate, an antiplatelet agent with selective 5-hydroxytryptamine (5-HT) receptor 2A antagonist activity, has been reported to improve low back pain, sciatica, and numbness of lower extremities in patients with lumbar disc herniation. However, the efficacy of sarpogrelate for pain relief in this situation has not been established by clinical studies and its mechanism remains unknown. Methods. The autologous nucleus pulposus was placed onto the left L4 and L5 nerve roots of 30 Sprague-Dawley rats allotted to sarpogrelate (100 mg/kg, n = 15) and control (vehicle, n = 15) treatment groups. Sarpogrelate or vehicle was administered orally once daily between days 7 and 14 after surgery. Mechanical allodynia was measured before and after treatment. The right and left nerve roots and dorsal root ganglions were isolated from 5 animals in each group to assay 5-HT, 5-hydroxyindoleacetic acid (5-HIAA), and norepinephrine on day 5 of administration (= day 11 after surgery). Results. Sarpogrelate treatment significantly reduced mechanical allodynia on days 5 and 8 of administration. The placement of the nucleus pulposus onto nerve roots increased norepinephrine but not 5-HT and 5-HIAA contents in inflamed nerve roots or dorsal root ganglions. Sarpogrelate did not affect these levels. Conclusions. Sarpogrelate attenuated pain-related behavior induced by the nucleus pulposus in the animal model. Although further investigation is needed concerning the mechanism of action, this study supported the hypothesis that sarpogrelate is efficacious for treating the pain of lumbar disc herniation.
Effect modification in the temperature extremes by mortality subgroups among the tropical cities of the Philippines

Background Temperature–mortality relationships have been extensively probed with varying temperature range but with relatively similar patterns and in some instances are being modified by specific mortality groups such as causes of mortality, sex, and age. Objective This study aimed to determine the risk attributions in the extreme temperatures and also identified the risks associated with the various mortality subgroups. Design We used the 2006–2010 daily average meteorological and daily mortality variables from the Philippine Atmospheric Geophysical and Astronomical Services Administration and Philippine Statistics Authority–National Statistics Office, respectively. Mortality data were divided according to cause (cardiovascular and respiratory), sex, and age (0–14 years, 15–64 years, and >64 years). We performed a two-stage analysis to estimate the extreme temperature effects stratified by the different mortality subgroups to observe the effect modification. Results In the pooled analysis, greater risks were observed in the extreme high temperature (99th temperature percentile; RR (relative risk)=2.48 CI: 1.55–3.98) compared to the extreme low temperature (1st temperature percentile; RR=1.23 CI: 0.88–1.72). Furthermore, effect modification by mortality subgroups was evident, especially higher risks for extreme temperatures with respiratory-related diseases, women, and elderly. Conclusions Both sex and age were found to effect modify the risks in extreme temperatures of tropical cities; hence, health-related policies should take these risk variations into consideration to create strategies with respect to the risk population.
A Study of Educational Simulations Part I - Engagement and Learning

Interactive computer simulations with complex representations and sophisticated graphics are a relatively new addition to the classroom, and research in this area is limited. We have conducted over 200 individual student interviews during which the students described what they were thinking as they interacted with simulations. These interviews were conducted as part of the research and design of simulations for the Physics Education Technology (PhET) project. PhET is an ongoing project that has developed over 60 simulations for use in teaching physics, chemistry, and physical science. These interviews are a rich source of information about how students interact with computer simulations and what makes an educationally effective simulation. We have observed that simulations can be highly engaging and educationally effective, but only if the student’s interaction with the simulation is directed by the student’s own questioning. Here we describe our design process, what features are effective for engaging students in educationally productive interactions and the underlying principles which support our empirically developed guidelines. In a companion paper we describe in detail the design features used to create an intuitive simulation for students to use.
Malignant peripheral nerve sheath tumors: clinicopathological aspects, expression of p53 and survival

Malignant peripheral nerve sheath tumors (MPNSTs) arerare and highly aggressive neoplasms, representing only 5%of soft tissue sarcomas (1,2). Approximately half of MPNSTcases occur in association with neurofibromatosis type 1(NF1) (3). MPNSTs may appear de novo or develop from themalignant transformation of a benign neural neoplasm,generally a plexiform neurofibroma (1). Solitary (unasso-ciated with NF1) and localized (or discrete; multiple in NF1)neurofibromas do not have malignant transformationpotential (1,3). NF1 loss of heterozygosity (LOH) has beendemonstrated in NF1-associated and sporadic MPNSTs.Although NF1 LOH is believed to be sufficient for neu-rofibroma development, MPNST pathogenesis has beensuggested to be a multistage process that includes othermolecular alterations (4,5). TP53 mutations have been foundin a subgroup of MPNSTs, indicating that a p53-mediatedpathway is involved in their development (5,6). Some clinicopathological features (e.g., the presence ofNF1,high histologicalgrade,necrosis,andrhabdomyoblasticdifferentiation) have been indicated to be important factorsforlower survival in MPNST cases in some studies butnotinothers (2,7–10). The clinical significance of p53 expression inMPNSTs is also a controversial issue. We aimed to study p53expression in MPNSTs and investigate its impact, as well astheimpactsoftheclinicopathologicalfeaturesofMPNSTs,onthe survival rates. We also compared p53 expression inMPNSTswith theirclinicopathological features and with p53expression in neurofibromas.
GABAergic synapses: their plasticity and role in sensory cortex

The mammalian neocortex is composed of a variety of cell types organized in a highly interconnected circuit. GABAergic neurons account for only about 20% of cortical neurons. However, they show widespread connectivity and a high degree of diversity in morphology, location, electrophysiological properties and gene expression. In addition, distinct populations of inhibitory neurons have different sensory response properties, capacities for plasticity and sensitivities to changes in sensory experience. In this review we summarize experimental evidence regarding the properties of GABAergic neurons in primary sensory cortex. We will discuss how distinct GABAergic neurons and different forms of GABAergic inhibitory plasticity may contribute to shaping sensory cortical circuit activity and function.
The Retrograde Ventriculovenous Shunts: The El-Shafei Retrograde Ventriculojugular and Ventriculosinus Shunts

Retrograde ventriculovenous (RVV) shunts utilize the impact pressure of the venous bloodstream to maintain the intraventricular pressure more than the pressure in the draining venous channel and to maintain a continuous flow of cerebrospinal fluid (CSF) to the venous circulation at a rate equal to and dependent upon the rate of its formation regardless of changes in posture or intrathoracic pressure, create impact zones which discourage stagnation and clotting of blood at the venous end of the connection and utilize collapse of the internal jugular vein in the erect posture to prevent siphonage. During the past 40 years, 229 RVV shunts were implanted; 219 of the patients (95.63%) benefited from the shunt, and only 2 of them needed a single shunt revision. The manifestations of increased intracranial pressure disappeared, different degrees of regression of the ventriculomegaly occurred in patients with closed craniums but not in infants and young children with open craniums, and there were no problems related to improper CSF drainage or venous thrombosis. The follow-up period is up to 40 years (mean 9 years 8 months).
Dosing and monitoring of enoxaparin (Low molecular weight heparin) therapy in children

Low molecular weight heparins (LMWHs) are commonly used in paediatric tertiary institutions for primary prophylaxis and treatment of thromboembolic events. Despite this widespread use, the therapeutic and prophylactic guidelines for LMWH therapy in children are extrapolated from adult guidelines. In fact, there is very little information regarding the pharmacokinetics, clinical effectiveness, adverse event profile and optimal dose schedule for LMWH therapy in children. This study was designed to determine whether paediatric‐specific dosage requirements for LMWH are justified, by investigating the doses required to achieve target therapeutic ranges. Patients who were treated with enoxaparin between October 2003 and July 2007 were identified for inclusion in this study. One hundred forty patients had an anti‐activated factor X assay result with a total of 55 (39%) patients achieving therapeutic levels 4–6 h post dose. Children younger than 1 year required the highest dose of enoxaparin/kg and highest number of dose changes to achieve the target therapeutic range. Major bleeding occurred in one patient, equating to 0·7%, with complete clot resolution recorded in 16 (11%) patients. This study demonstrated a 2–3‐fold variation in individual dose requirements for LMWH in children ≤5 years of age, and further mandates the need for age‐specific dosage requirements in children receiving enoxaparin.
Surgical Technique in Distal Pancreatectomy: A Systematic Review of Randomized Trials

Despite recent improvements in surgical technique, the morbidity of distal pancreatectomy remains high, with pancreatic fistula being the most significant postoperative complication. A systematic review of randomized controlled trials (RCTs) dealing with surgical techniques in distal pancreatectomy was carried out to summarize up-to-date knowledge on this topic. The Cochrane Central Registry of Controlled Trials, Embase, Web of Science, and Pubmed were searched for relevant articles published from 1990 to December 2013. Ten RCTs were identified and included in the systematic review, with a total of 1286 patients being randomized (samples ranging from 41 to 450). The reviewers were in agreement for application of the eligibility criteria for study selection. It was not possible to carry out meta-analysis of these studies because of the heterogeneity of surgical techniques and approaches, such as varying methods of pancreas transection, reinforcement of the stump with seromuscular patch or pancreaticoenteric anastomosis, sealing with fibrin sealants and pancreatic stent placement. Management of the pancreatic remnant after distal pancreatectomy is still a matter of debate. The results of this systematic review are possibly biased by methodological problems in some of the included studies. New well designed and carefully conducted RCTs must be performed to establish the optimal strategy for pancreatic remnant management after distal pancreatectomy.