Miracle-dz/UniFAR-FTUs huggingface dataset:
Mutations in Cancer Cause Gain of Cysteine, Histidine, and Tryptophan at the Expense of a Net Loss of Arginine on the Proteome Level

Accumulation of somatic mutations is critical for the transition of a normal cell to become cancerous. Mutations cause amino acid substitutions that change properties of proteins. However, it has not been studied as to what extent the composition and accordingly chemical properties of the cell proteome is altered as a result of the increased mutation load in cancer. Here, we analyzed data on amino acid substitutions caused by mutations in about 2000 protein coding genes from the Cancer Cell Line Encyclopedia that contains information on nucleotide and amino acid alterations in 782 cancer cell lines, and validated the analysis with information on amino acid substitutions for the same set of proteins in the Catalogue of Somatic Mutations in Cancer (COSMIC; v78) in circa 18,000 tumor samples. We found that nonsynonymous single nucleotide substitutions in the analyzed proteome subset ultimately result in a net gain of cysteine, histidine, and tryptophan at the expense of a net loss of arginine. The extraordinary loss of arginine may be attributed to some extent to composition of its codons as well as to the importance of arginine in the functioning of prominent tumor suppressor proteins like p53.
Substantial Contribution of Submicroscopical Plasmodium falciparum Gametocyte Carriage to the Infectious Reservoir in an Area of Seasonal Transmission

Background Man to mosquito transmission of malaria depends on the presence of the sexual stage parasites, gametocytes, that often circulate at low densities. Gametocyte densities below the microscopical threshold of detection may be sufficient to infect mosquitoes but the importance of submicroscopical gametocyte carriage in different transmission settings is unknown. Methodology/Principal Findings Membrane feeding experiments were carried out on 80 children below 14 years of age at the end of the wet season in an area of seasonal malaria transmission in Burkina Faso. Gametocytes were quantified by microscopy and by Pfs25-based quantitative nucleic acid sequence-based amplification assay (QT-NASBA). The children's infectiousness was determined by membrane feeding experiments in which a venous blood sample was offered to locally reared Anopheles mosquitoes. Gametocytes were detected in 30.0% (24/80) of the children by microscopy compared to 91.6% (65/71) by QT-NASBA (p<0.001). We observed a strong association between QT-NASBA gametocyte density and infection rates (p = 0.007). Children with microscopically detectable gametocytes were more likely to be infectious (68.2% compared to 31.7% of carriers of submicroscopical gametocytes, p = 0.001), and on average infected more mosquitoes (13.2% compared to 2.3%, p<0.001). However, because of the high prevalence of submicroscopical gametocyte carriage in the study population, carriers of sub-microscopical gametocytes were responsible for 24.2% of the malaria transmission in this population. Conclusions/Significance Submicroscopical gametocyte carriage is common in an area of seasonal transmission in Burkina Faso and contributes substantially to the human infectious reservoir. Submicroscopical gametocyte carriage should therefore be considered when implementing interventions that aim to reduce malaria transmission.
A short questionnaire to measure wellbeing at work (Short-SWELL) and to examine the interaction between the employee and organisation

The aim of the study was to develop a short measure of wellbeing at work which includes the interactions between the individual and the organisation. This was presented in an online survey to 210 employees doing a range of jobs. Regression analyses showed that positive wellbeing (e.g. job satisfaction; happiness) was predicted by a positive personality whereas negative wellbeing (stress; anxiety/depression) was predicted by negative job characteristics and passive coping. Organisational factors did not predict wellbeing.
Perceptual Enhancement of Low Light Images Based on Two-Step Noise Suppression

Low-light images are seriously corrupted by noise due to the low signal-to-noise ratio. In low intensity, just-noticeable-difference (JND) is high, and thus the noise is not perceived well by human eyes. However, after contrast enhancement, the noise becomes obvious and severe, because JND decreases as intensity increases. Thus, contrast enhancement without considering human visual perception causes serious noise amplification in low-light images. In this paper, we propose perceptual enhancement of low-light images based on two-step noise suppression. We adopt two-step noise suppression based on noise characteristics corresponding to human visual perception. First, we perform noise aware contrast enhancement using a noise-level function. However, the increase of the intensity caused by contrast enhancement reduces JND in low intensity, which makes noise much more visible by human eyes. Second, we perceptually reduce noise in images while preserving details using a JND model, which represents noise visibility in contrast enhancement. We estimate the noise visibility based on the intensity change using luminance adaptation. Also, we extract image details by contrast masking and visual regularity, because textural regions have higher visibility thresholds than the smooth ones. Based on the human visual characteristics, we perform perceptual noise suppression using the JND model. Experimental results show that the proposed method perceptually enhances contrast in low-light images while successfully minimizing distortions and preserving details.
The association of trajectories of protein intake and age-specific protein intakes from 2 to 22 years with BMI in early adulthood

Abstract No study has analysed how protein intake from early childhood to young adulthood relate to adult BMI in a single cohort. To estimate the association of protein intake at 2, 11, 15, 19 and 22 years with age- and sex-standardised BMI at 22 years (early adulthood), we used linear regression models with dietary and anthropometric data from a Filipino birth cohort (1985–2005, n 2586). We used latent growth curve analysis to identify trajectories of protein intake relative to age-specific recommended daily allowance (intake in g/kg body weight) from 2 to 22 years, then related trajectory membership to early adulthood BMI using linear regression models. Lean mass and fat mass were secondary outcomes. Regression models included socioeconomic, dietary and anthropometric confounders from early life and adulthood. Protein intake relative to needs at age 2 years was positively associated with BMI and lean mass at age 22 years, but intakes at ages 11, 15 and 22 years were inversely associated with early adulthood BMI. Individuals were classified into four mutually exclusive trajectories: (i) normal consumers (referent trajectory, 58 % of cohort), (ii) high protein consumers in infancy (20 %), (iii) usually high consumers (18 %) and (iv) always high consumers (5 %). Compared with the normal consumers, ‘usually high’ consumption was inversely associated with BMI, lean mass and fat mass at age 22 years whereas ‘always high’ consumption was inversely associated with male lean mass in males. Proximal protein intakes were more important contributors to early adult BMI relative to early-childhood protein intake; protein intake history was differentially associated with adulthood body size.
Risks of Population Extinction from Demographic and Environmental Stochasticity and Random Catastrophes

Stochastic factors affecting the demography of a single population are analyzed to determine the relative risks of extinction from demographic stochasticity, environmental stochasticity, and random catastrophes. Relative risks are assessed by comparing asymptotic scaling relationships describing how the average time to extinction, T, increases with the carrying capacity of a population, K, under each stochastic factor alone. Stochastic factors are added to a simple model of exponential growth up to K. A critical parameter affecting the extinction dynamics is $$\tilde r,$$ the long-run growth rate of a population below K, including stochastic factors. If r̃ is positive, with demographic stochasticity T increases asymptotically as a nearly exponential function of K, and with either environmental stochasticity or random catastrophes T increases asymptotically as a power of K. If r̃ is negative, under any stochastic demographic factor, T increases asymptotically with the logarithm of K. Thus, for sufficiently large populations, the risk of extinction from demographic stochasticity is less important than that from either environmental stochasticity or random catastrophes. The relative risks of extinction from environmental stochasticity and random catastrophes depend on the mean and environmental variance of population growth rate, and the magnitude and frequency of catastrophes. Contrary to previous assertions in the literature, a population of modest size subject to environmental stochasticity or random catastrophes can persist for a long time, if r̃ is substantially positive.
Factors associated with non-response to second course indomethacin for PDA treatment in preterm neonates

Abstract Background: Failure of first course of indomethacin (FCI) for patent ductus arteriosus (PDA) treatment in preterm neonates often prompts clinicians to consider a second course (SCI). Objective: To identify factors including baseline characteristics and response to FCI that are associated with non-response to SCI for PDA treatment in preterm neonates. Methods: In this retrospective observational study, neonates ≤32 weeks admitted to a tertiary NICU over 5 years who received two indomethacin courses for PDA treatment were reviewed. Only neonates with echocardiograms (ECHO) immediately before and after receipt of each indomethacin course were included. Primary outcome was non-response to SCI. Baseline characteristics and response to FCI were compared between responders and non-responders of SCI. Results: Of the 98 neonates enrolled, 47 (48%) had non-response to SCI. Of them, 27 patients (57%) had prior non-response to FCI, while of the 51 neonates who responded to SCI, 24 neonates (47%) had prior non-response to FCI. The adjusted risk of non-response to SCI in patients who had non-response to FCI was 37% higher (relative risk = 1.37, 95%CI: 0.87–1.80; p = .07) compared to those who had response to FCI. Multivariable analysis showed that increasing gestational age (AOR: 1.6, 95%CI: 1.1–2.3, p = .03) was associated with a higher odds of non-response to SCI while the odds of non-response to SCI increased by 90% in patients with non-response to FCI (AOR: 1.9, 95%CI: 0.8–4.5; p = .15) compared to those with success of FCI, although no statistical significance was observed. Conclusions: Advanced gestational age was the predictor of non-response to SCI in preterm neonates.
Craniofacial shape differs in patients with tooth agenesis: geometric morphometric analysis

Aim To evaluate the shape of the craniofacial complex in patients with tooth agenesis and compare it to matched controls. Subjects and methods The sample comprised 456 patients that were allocated to three groups: the agenesis group of 100 patients with at least one missing tooth, excluding third molars, the third molar agenesis group (3dMAG; one to four missing third molars) of 52 patients and the control group (CG) of 304 patients with no missing teeth. The main craniofacial structures depicted on lateral cephalograms were digitized and traced with 15 curves and 127 landmarks. These landmarks were subjected to Procrustes superimposition and principal component analysis in order to describe shape variability of the cranial base, maxilla and mandible, as well as of the whole craniofacial complex. For statistical analysis, permutation tests were used (10 000 permutations without replacement). Results Approximately half of the sample's variability was described by the first three principal components. Comparisons within the whole sample revealed sexual dimorphism of the craniofacial complex and its structures (P < 0.01). Differences between the agenesis group and matched controls were found in the shape of all craniofacial structures except for the cranial base (P < 0.05). Specifically, patients with agenesis presented with Class III tendency and hypodivergent skeletal pattern. However, the comparison between the 3dMAG and matched CG revealed no differences. Conclusion The shape of the craniofacial complex differs in patients with tooth agenesis suggesting that common factors are implicated in tooth development and craniofacial morphology.
Individual brain structure and modelling predict seizure propagation

See Lytton (doi:10.1093/awx018) for a scientific commentary on this article. Patients with drug-resistant epilepsy show different seizure propagation patterns and postsurgical outcomes. Proix et al. merge structural information from brain imaging with mathematical modelling to generate personalized brain network models. Validation of the models against presurgical stereotactic EEGs and clinical data shows that they can account for the variability observed.
Comparison of time to obtain intraosseous versus jugular venous catheterization on canine cadavers

OBJECTIVE To compare the time required and the success rate of personnel with 4 different levels of experience to place a humeral intraosseous (IO) catheter versus a jugular venous catheter (IV) in cadaver dogs. DESIGN Prospective study. SETTING Veterinary university teaching hospital. INTERVENTIONS Canine cadavers from recently euthanized dogs were obtained from the cadaver donation program between May and December 2014. Catheter placers (CPs) with varying clinical experience, including a first year emergency and critical care resident, a senior emergency veterinary technician (VTS certified), a final year veterinary student, and an ACVECC diplomate, participated in the study. Each CP catheterized a total of 6 dogs so that there was a total of 6 IO and 6 IV catheters placed, by automatic rotary insertion device (with an EZ-IO gun) and vascular cut-down technique, respectively, for each CP. Time for IO catheterization and IV catheterization was recorded and compared. The success of IO catheterization and IV catheterization was verified by visualization of an injection of iodinated contrast material under fluoroscopy within the medullary cavity or vessel. ANIMALS Twenty-four canine cadavers. MEASUREMENTS AND MAIN RESULTS Outcomes were analyzed using the Wilcoxon rank-sum test and the Kruskal-Wallis one-way analysis of variance. The median time for all IO catheterization operators was faster at 55.4 seconds (range 15.0-153.0 s) compared to the median time for all IV catherization operators at 217.3 seconds (range 55.6-614 s). The success rate for IO and IV was equal at 87.5%. CONCLUSION IO catheterization using an automatic rotary insertion device was performed more rapidly and successfully than jugular venous catheterization using a cut-down technique in canine cadaver. These findings suggest IO catheterization may be more efficient for gaining vascular access in the appropriate emergency clinical situations when preexisting IV access does not exist.
All‐pass filters using DDCC‐ and MOSFET‐based electronic resistor

The main motivation in this paper is to draw attention to the tunability and input‐signal amplitude limitations when a nonlinear device is used as a resistor. For this purpose, two first‐order all‐pass filters are proposed using differential difference current conveyor (DDCC), a capacitor and a resistor without element‐matching restriction. These all‐pass filter circuits can be made electronically tunable with electronic resistors. Tunability and input‐signal amplitude limitations of the proposed circuits due to the operational restrictions of the electronic resistors are examined. PSPICE simulations confirm the validity and the practical utility of the proposed circuits. Copyright © 2010 John Wiley & Sons, Ltd.
Balance Performance During Perturbed Standing Is Not Associated With Muscle Strength and Power in Young Adults

ABSTRACT The authors investigate the ways in which varied postural responses to translating platform perturbations are associated with the variables of strength and power. Twenty-four physically active and 27 sedentary young adults were exposed to a set of postural perturbations at varied velocities (10 and 20 cm/s) and the respective accelerations (6.4 and 6.9 m/s2), constant distance (6 cm), and 4 directions of platform motion (forward, backward, left-lateral, and right-lateral). They also performed maximum voluntary isometric contraction (MVC) and chair rising/chair jumping tests. The analysis of variance revealed significant interaction effect for peak center of pressure displacement, direction by velocity: F3,129 = 24.43, p = . 002; and direction by acceleration: F3,129 = 34.18, p = . 001. There were no significant correlations between peak center of pressure displacements and peak force and peak rate of force development measured during MVC in either standing (r = .27–57) or sitting positions (r = .12–51) and peak power during chair jumping (r = .47–.59) in all participants. As such, only a small proportion of variance was explained (9–39%, 3–23%, and 23–41%, respectively). In conclusion, interaction effects indicate that the composition of stimuli strongly influences compensatory responses and this effect is more pronounced in sedentary than in physically active young adults. Nevertheless, the dynamic balance is not associated with muscle strength and power in either group.
Impact of Target‐Mediated Elimination on the Dose and Regimen of Evolocumab, a Human Monoclonal Antibody Against Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9)

Understanding the pharmacokinetic (PK) and pharmacodynamic (PD) relationship of a therapeutic monoclonal antibody against proprotein convertase subtilisin/kexin type 9 (PCSK9) exhibiting target‐mediated drug disposition (TMDD) is critical for selecting optimal dosing regimens. We describe the PK/PD relationship of evolocumab using a mathematical model that captures evolocumab binding and removal of unbound PCSK9 as well as reduction in circulating low‐density lipoprotein cholesterol (LDL‐C). Data were pooled from 2 clinical studies: a single‐dose escalation study in healthy subjects (7‐420 mg SC; n = 44) and a multiple‐dose escalation study in statin‐treated hypercholesterolemic patients (14 mg weekly to 420 mg monthly [QM] SC; n = 57). A TMDD model described the time course of unbound evolocumab concentrations and removal of unbound PCSK9. The estimated linear clearance and volume of evolocumab were 0.256 L/day and 2.66 L, respectively, consistent with other monoclonal antibodies. The time course of LDL‐C reduction was described by an indirect response model with the elimination rate of LDL‐C being modulated by unbound PCSK9. The concentration of unbound PCSK9 associated with half‐maximal inhibition (IC50) of LDL‐C elimination was 1.46 nM. Based on simulations, 140 mg every 2 weeks (Q2W) and 420 mg QM were predicted to achieve a similar time‐averaged effect of 69% reduction in LDL‐C in patients on statin therapy, suggesting that an approximate 3‐fold dose increase is required for a 2‐fold extension in the dosing interval. Evolocumab dosing regimens of 140 mg Q2W or 420 mg QM were predicted to result in comparable reductions in LDL‐C over a monthly period, consistent with results from recently completed phase 3 studies.
Improved long-term outcomes in double-inlet left ventricle and tricuspid atresia with transposed great arteries: systemic outflow tract obstruction present at birth defines long-term outcome

OBJECTIVES In 2 subtypes of functional single ventricle, double inlet left ventricle (DILV) and tricuspid atresia with transposed great arteries (TA-TGA), systemic output passes through an outflow chamber before entering the aorta. Intracardiac obstruction to this pathway causing systemic outflow tract obstruction (SOTO) may be present at birth or develop over time. Long-term survival after Fontan has not been defined. We defined outcomes utilizing records from 2 centres that were cross-checked with data from a bi-national Fontan Registry for completeness and accuracy. METHODS Two hundred and eleven patients were identified, 59 TA-TGA,152 DILV. Median follow-up was 17 years (range 4 days to 49.8 years). The Kaplan-Meier method was used for all of the time to event analyses and the log-rank test was used to compare the time-to-events. Cox proportional hazard models were used to test the association between potential predictors and time-to-event end-points. RESULTS TA-TGA had reduced survival compared to DILV (cumulative risk of death 28.8% vs 11%, hazard ratio (HR) 3.1 (95% confidence interval (CI) 1.6-6.1), P = 0.001). In both groups, SOTO at birth carried a worse prognosis HR 3.54 (1.36-9.2, P = 0.01). SOTO was not more common in either morphology at birth ( P = 0.20). Periprocedural mortality accounted for 40% of deaths. Fontan was achieved in 82%, DILV were more likely to achieve Fontan than TA-TGA (91% vs 60%, P <0.001). After Fontan there were 9 deaths (4%) with no difference according to morphology. CONCLUSIONS Patients with TA-TGA have poorer outcomes than those with DILV, affecting survival and likelihood of achieving Fontan. SOTO at birth carries a high risk of mortality suggesting that, when present, initial surgical management should address this.
Role of El Niño Southern Oscillation (ENSO) Events on Temperature and Salinity Variability in the Agulhas Leakage Region

This study explores the relationship between the Agulhas Current system and El Nino Southern Oscillation (ENSO) events. Specifically, it addresses monthly to yearly variations in Agulhas leakage where the Agulhas Current sheds waters into the Atlantic Ocean, in turn affecting meridional overturning circulation (MOC). Sea surface temperature (SST) data from the National Oceanic and Atmospheric Administration’s (NOAA) Advanced Very High Resolution Radiometer (AVHRR) combined with sea surface salinity (SSS) from Soil Moisture Ocean Salinity (SMOS) and Simple Ocean Data Assimilation (SODA) reanalysis are used to explore changes in Agulhas leakage dynamics. Agulhas leakage is anomalously warm in response to El Nino and anomalously cool in response to La Nina. The corresponding SSS signal shows both a primary and secondary signal response. At first, the SSS signal of Agulhas leakage is anomalously fresh in response to El Nino, but this primary signal is replaced by a secondary anomalously saline signal. In response to La Nina, the primary SSS signal of Agulhas leakage is anomalously saline, while the secondary SSS signal is anomalously fresh. The lag between the peak of ENSO and the response in SST and the corresponding primary SSS signal of Agulhas leakage is about 20 months, followed by the secondary SSS signal at a lag of about 26 months. In general, increasing ENSO strength increases the extremes of the resulting anomalous SST and SSS signal and impacts the Agulhas leakage region earlier during El Nino and slightly later during La Nina.