Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of functional genetic variants in chemokine decoy receptors on the recurrence risk of breast cancer

Duffy antigen receptor for chemokine (DARC) and CCBP2, the two members of chemokine decoy receptor family, restrain cell proliferation and invasion through sequestrating cytotoxic chemokines. Our previous research clarified two functional nonsynonymous single nucleotide polymorphisms (SNPs): rs12075 in DARC and rs2228468 in CCBP2 were significantly correlated with lymph node metastasis. However, the role of their genetic variations on survival of breast cancer remains unclear. In the present study, rs12075 in DARC and rs2228468 in CCBP2 were genotyped in 806 patients with primary breast cancer. The endpoint was recurrence‐free survival (RFS). Cox regression model was used to explore the association between SNPs and patients’ survival. The results revealed that participants with GG genotype in rs12075 appeared a higher recurrence risk compared with AG/AA genotype after adjustment with clinical parameters including lymph node status (AG+AA vs GG: hazard ratio [HR] = 0.54, 95% confidence interval [CI], 0.31‐0.93, P = 0.027). Furthermore, subgroup analysis revealed that GG genotype frequency of rs12075 had a positive correlation with RFS compared with AG/AA genotype (AG+AA vs GG: HR = 0.22, 95% CI, 0.05‐0.91, P = 0.021) in triple‐negative breast cancer (TNBC) subtype but not in other subtypes. No significant association between the genotypic variants and relapse risk was found in rs2228468 (AC+AA vs CC: HR = 0.80, 95% CI, 0.56‐1.14, P = 0.222). There was also no significant difference in survival among rs2228468 polymorphism in any subtypes. Our study suggested that rs12075 could be served as a key predictive factor of recurrence risk in breast cancer, especially for TNBC subtype. Further researches to monitor SNPs will provide further opportunities to determine clinical prognosis.
ACVIM consensus statement: Guidelines for the identification, evaluation, and management of systemic hypertension in dogs and cats

An update to the 2007 American College of Veterinary Internal Medicine (ACVIM) consensus statement on the identification, evaluation, and management of systemic hypertension in dogs and cats was presented at the 2017 ACVIM Forum in National Harbor, MD. The updated consensus statement is presented here. The consensus statement aims to provide guidance on appropriate diagnosis and treatment of hypertension in dogs and cats.
GAN Augmentation: Augmenting Training Data using Generative Adversarial Networks

One of the biggest issues facing the use of machine learning in medical imaging is the lack of availability of large, labelled datasets. The annotation of medical images is not only expensive and time consuming but also highly dependent on the availability of expert observers. The limited amount of training data can inhibit the performance of supervised machine learning algorithms which often need very large quantities of data on which to train to avoid overfitting. So far, much effort has been directed at extracting as much information as possible from what data is available. Generative Adversarial Networks (GANs) offer a novel way to unlock additional information from a dataset by generating synthetic samples with the appearance of real images. This paper demonstrates the feasibility of introducing GAN derived synthetic data to the training datasets in two brain segmentation tasks, leading to improvements in Dice Similarity Coefficient (DSC) of between 1 and 5 percentage points under different conditions, with the strongest effects seen fewer than ten training image stacks are available.
Excitatory and inhibitory synapse reorganization immediately after critical sensory experience in a vocal learner

Excitatory and inhibitory synapses are the brain’s most abundant synapse types. However, little is known about their formation during critical periods of motor skill learning, when sensory experience defines a motor target that animals strive to imitate. In songbirds, we find that exposure to tutor song leads to elimination of excitatory synapses in HVC (used here as a proper name), a key song generating brain area. A similar pruning is associated with song maturation, because juvenile birds have fewer excitatory synapses, the better their song imitations. In contrast, tutoring is associated with rapid insertion of inhibitory synapses, but the tutoring-induced structural imbalance between excitation and inhibition is eliminated during subsequent song maturation. Our work suggests that sensory exposure triggers the developmental onset of goal-specific motor circuits by increasing the relative strength of inhibition and it suggests a synapse-elimination model of song memorization.
Multisystem Trajectories Over the Adult Life Course and Relations to Cardiovascular Disease and Death.

Background Comprehensive conjoint characterization of long-term trajectories representing several biological systems are lacking. Methods We measured serially indicators representing 14 distinct biological systems in up to 3453 participants attending four Framingham Study examinations: bone mineral density, body mass index (BMI), C-reactive protein, glomerular filtration rate, forced vital capacity (FVC), one-second forced expiratory volume/FVC ratio (FEV1/FVC), gait speed, grip strength, glycosylated hemoglobin (HbA1c), heart rate, left ventricular mass, Mini-Mental State Examination (MMSE), pulse pressure, and total/high-density lipoprotein cholesterol ratio (TC/HDL). Results We observed that correlations among the 14 sex-specific trajectories were modest (r<0.30 for 169 of 182 sex-specific correlations). During follow-up (median 8 years), 232 individuals experienced a CVD event and 393 participants died. In multivariable regression models, CVD incidence was positively related to trajectories of BMI, HbA1c, TC/HDL, gait time, and pulse pressure (P<0.06); mortality risk was related directly to trajectories of gait time, C-reactive protein, heart rate, and pulse pressure but inversely to MMSE, and FEV1/FVC (P<0.006). A unit increase in the trajectory risk score was associated a 2.80-fold risk of CVD (95% confidence interval [CI], 2.04-3.84, P<0.001), and a 2.71-fold risk of death (95% CI, 2.30-3.20, P<0.001). Trajectory risk scores were suggestive of a greater increase in model c-statistic compared to single occasion measures (delta-c compared to age- and sex-adjusted models: 0.032 vs. 0.026 for CVD; 0.042 vs. 0.030 for mortality). Conclusion Biological systems age differentially over the life course. Longitudinal data on a parsimonious set of biomarkers reflecting key biological systems may facilitate identification of high-risk individuals.
Encoding of Reward and Decoding Movement from the Frontal Eye Field during Smooth Pursuit Eye Movements

Expectation of reward potentiates sensorimotor transformations to drive vigorous movements. One of the main challenges in studying reward is to determine how representations of reward interact with the computations that drive behavior. We recorded activity in smooth pursuit neurons in the frontal eye field (FEF) of two male rhesus monkeys while controlling the eye speed by manipulating either reward size or target speed. The neurons encoded the different reward conditions more strongly than the different target speed conditions. This pattern could not be explained by differences in the eye speed, since the eye speed sensitivity of the neurons was also larger for the reward conditions. Pooling the responses by the preferred direction of the neurons attenuated the reward modulation and led to a tighter association between neural activity and behavior. Therefore, a plausible decoder such as the population vector could explain how the FEF both drives behavior and encodes reward beyond behavior. SIGNIFICANCE STATEMENT Motor areas combine sensory and reward information to drive movement. To disambiguate these sources, we manipulated the speed of smooth pursuit eye movements by controlling either the size of the reward or the speed of the visual motion signals. We found that the relationship between activity in frontal eye field and eye kinematics varied: the eye speed sensitivity was larger for the different reward conditions than for the different target speed conditions. Decoders that pooled signals by the preferred direction of the neurons attenuated the reward modulations. These decoders may indicate how reward can be both encoded beyond eye kinematics at the single neuron level and drive movement at the population level.
Estimating Everyday Neuropsychological Functioning in Multiple Sclerosis: Reliability and Validity of the Greek Multiple Sclerosis Neuropsychological Questionnaire

The Multiple Sclerosis Neuropsychological Questionnaire is a brief screening questionnaire for the assessment of everyday neuropsychological competence of patients with Multiple Sclerosis. The aim of the present study was to examine psychometric properties of the Greek version of the instrument. One hundred and three MS patients and 60 informants participated in the present study and completed the questionnaire. From the initial patient sample, 51 participants completed broadly used neuropsychological tests and measures estimating cognitive failures and depression. Moreover, after a six-month interval the MSNQ was administered to 58 patients from the initial sample in order to explore test-retest reliability. Cronbach's α was 0.92 and 0.93 for patient and informant forms, respectively. The patient form was correlated significantly with measures of cognitive failures and depression. Low correlations were found between the informant form and performance on cognitive tests. In regard to the patient form, significant correlation was observed between repeated administrations and, psychometrically, the three-factor structure was preferable than the one-factor structure. The present study confirms the already established pattern of correlations among the two MSNQ forms, neuropsychological test performance and depression measurements. Additional research is needed in order to define a cut-off score for the MSNQ-I providing further information about the diagnostic interpretability of the instrument.
Entire Peroxidation Reaction System of Myeloperoxidase Correlates with Progressive Low-Density Lipoprotein Modifications via Reactive Aldehydes in Atherosclerotic Patients with Hypertension

Background/Aims: Reactive oxygen species (ROS) contribute to the dysfunction of serum lipoproteins, which triggers lipid metabolism abnormalities in the development of atherosclerosis and hypertension. Myeloperoxidase (MPO) is involved in ROS modifications, triggering lipid peroxidation and aldehyde formation. However, the relationship between the entirety of the MPO reaction system and oxidative modification of serum lipoproteins in atherosclerotic patients with hypertension remains unclear. Methods: We measured MPO activity (peroxidation and chlorination), 4-hydroxynonenal-modified low-density lipoprotein (HNE-LDL), malondialdehyde-modified low-density lipoprotein (MDA-LDL), H2O2, reduced glutathione (GSH), and oxidized glutathione (GSSG) using a corresponding commercial kit in atherosclerotic patients with hypertension and healthy participants. We used Spearman’s correlation analysis to investigate the correlation between MPO activity and the levels of these oxidative and anti-oxidative stress-related indices and performed response surface regression to investigate the relationship between the MPO reaction system and the levels of HNE-LDL, MDA-LDL, and the GSH/GSSG ratio. Results: Our results showed no association between the levels of MPO peroxidation activity, MPO chlorination activity, H2O2, and Cl- and those of HNE-LDL, MDA-LDL, GSH, and GSSG, and the GSH/GSSG ratio in healthy participants. In addition, no effects of the peroxidation reaction system of MPO (PRSM) and the chlorination reaction system of MPO (CRSM) on GSH/GSSG were found in this investigation. However, we found that the PRSM rather than the CRSM correlated with progressive low-density lipoprotein (LDL) modifications by HNE-LDL and MDA-LDL in atherosclerotic patients with hypertension. Conclusion: The PRSM rather than the CRSM correlated with progressive LDL modifications via reactive aldehydes in atherosclerotic patients with hypertension. Further investigation is warranted to evaluate whether the PRSM may serve as a potential index for monitoring LDL function in atherosclerosis and hypertension.
Subspecies differences in thermal acclimation of mitochondrial function and the role of uncoupling proteins in killifish

ABSTRACT Thermal effects on mitochondrial efficiency and ATP production can influence whole-animal thermal tolerance and performance. Thus, organisms may have the capacity to alter mitochondrial processes through acclimation or adaptation to mitigate these effects. One possible mechanism is through the action of uncoupling proteins (UCPs), which can decrease the proton-motive force independent of the production of ATP. To test this hypothesis, we examined the mRNA expression patterns of UCP isoforms and characterized the effects of thermal acclimation and putative local thermal adaptation on mitochondrial capacity, proton leak and P/O ratios in two subspecies of Atlantic killifish (Fundulus heteroclitus). Ucp1 was the dominant isoform in liver and was more highly expressed in northern killifish. We found that cold acclimation increased mitochondrial capacity (state III and maximum substrate oxidation capacity), state II membrane potential, proton leak and P/O ratios in northern, but not southern, killifish liver mitochondria. Palmitate-induced mitochondrial uncoupling was detected in northern, but not southern, killifish liver mitochondria, consistent with the differences in Ucp mRNA expression between the subspecies. Taken together, our data suggest that mitochondrial function is more plastic in response to thermal acclimation in northern killifish than in southern killifish and that UCP1 may play a role in regulating the proton-motive force in northern, but not southern, killifish in response to thermal acclimation. These data demonstrate the potential for adaptive variation in mitochondrial plasticity in response to cold. Summary: Changes in mitochondrial capacity, proton leak, uncoupling protein expression and fatty-acid-induced uncoupling with cold acclimation are greater in a putatively cold-adapted northern population of killifish compared with a southern population.
Presynaptic mGluRs Control the Duration of Endocannabinoid-Mediated DSI

GABA synapses in the brain undergo depolarization-induced suppression of inhibition (DSI) that requires activation of presynaptic cannabinoid type 1 receptors (CB1Rs). The brevity of DSI, lasting ∼1 min in most brain regions, has been ascribed to the transient production of 2-arachidonoylglycerol (2-AG). Here, we propose that the duration of DSI is controlled by heterologous interactions between presynaptic mGluRs and CB1Rs. By examining GABA synapses on parvocellular corticotropin-releasing hormone-expressing neurons in the paraventricular nucleus of the hypothalamus (PVN) of male and female mice, we show that DSI decays quickly in experimental conditions in which both GABA and glutamate are released from adjacent nerve terminals. Pharmacological inhibition of group I mGluRs prolongs DSI, whereas prior activation of mGluRs inhibits DSI, collectively suggesting that group I mGluRs quench presynaptic CB1R signaling. When photostimulation of genetically identified terminals is used to release only GABA, CB1R-dependent DSI persists for many minutes. Under the same conditions, activation of group I mGluRs reestablishes classical, transient DSI. The long-lasting DSI observed when GABA synapses are independently recruited functionally uncouples inhibitory input to PVN neurons. These observations suggest that heterologous interactions between mGluRs and CB1Rs control the temporal window of DSI at GABA synapses, providing evidence for a powerful new way to affect functional circuit connectivity in the brain. SIGNIFICANCE STATEMENT Postsynaptic depolarization liberates endocannabinoids, resulting in a rapid and transient decrease in release probability at GABA synapses. We discovered that mGluRs control the duration of depolarization-induced suppression of inhibition (DSI), most likely through heterologous desensitization of cannabinoid type 1 receptors by presynaptic mGluR5. By shortening the duration of DSI, mGluRs control the temporal window for retrograde signaling at GABA synapses. Physiological or pathological changes that affect glutamate spillover may profoundly affect network excitability by shifting the duration of cannabinoid inhibition at GABA synapses.
Requirements Analysis Skills: How to Train Practitioners?

One of the goals of any software development organization (SDO) is the assurance of a high quality software. To achieve this, it is important to perform all the software related activities, especially those of the requirements engineering (RE) phase, in the right way and ideally by experts. However, the current practice reveals that this crucial phase is commonly performed by people with limited experience in RE, indeed, some of them ignoring the basic activities. We present a training plan in order to improve practitioners' RE analysis skills. The training plan was applied to 44 practitioners working at a Mexican SDO. We developed such a plan based on the idea of considering six main dimensions that include theory, tests and mentoring sessions. The so called dimensions are: understanding the organization's domain, basic concepts of RE, requirements elicitation, requirements expression, requirements prioritization and requirements analysis. In this paper we present what are the topics discussed in each dimension, the feedback received by the practitioners after the training and how we envision the evolution of the training plan.
Student perceptions of cultural immersion during an Interprofessional programme

ABSTRACT In New Zealand undergraduate health professional degrees focus on aspects of indigenous (Maori) health. Formal and informal feedback suggests that for individual students the impact of those components in respect of Maori health varies. Separate and sequential interprofessional groups of students from seven health professions participated in an innovative and immersive Interprofessional programme. All participating students had prior exposure during their respective degrees to theoretical perspectives of indigenous health. At the end of each and every 5-week long programme each cohort of student contributed to a focus group discussion. Analysis revealed that for these groups of students the real-life exposure to an indigenous community was positively regarded and, in some instances, transformative. The students also reported that the ‘lived’ experience in an indigenous community built upon and in many cases extended prior learning of indigenous health. Whilst the results are encouraging it must be noted that the students who were exposed to this experience represented less than 10% of the entire student population. It is clear that a key challenge for us is to enable more students to be exposed to this powerful learning experience.
Development of Novel Protocol to Al3+ Stress Tolerance at Germination Stage in Indica Rice through Statistical Approaches

Rice production is decreasing by abiotic stresses like heavy metals. In such circumstances, producing food for growing human population is a challenge for plant breeders. Excess of Al3+ in soil has become threat for high yield of rice. Improvement of crop is one of potential solution for high production. The aim of this study was to develop the new method for optimization of Al3+ toxicity tolerance in indica rice at germination stag using two-way ANOVA and Duncan's multiple-range test (DMRT). Seeds of two indica rice cultivars (Pokkali and Pak Basmati) were exposed in different concentrations (control, 5 mM, 15 mM, and 20 mM) of Al3+ toxicity at pH 4 ±0.2 for two weeks. Germination traits such as final germination percentage (FG%), germination energy (GE), germination speed (GS), germination index (GI), mean time of germination (MGT), germination value (GV), germination velocity (GVe), peak value of germination (GPV), and germination capacity (GC) and growth traits such as root length (RL), shoot length (SL), total dry biomass (TDB), and germination vigour index (GVI) were measured. To obtain the maximum number of significance (≤ 0.01%) parameters in each concentration of Al3+ toxicity with control, two-way ANOVA was established and comparison of mean was done using DMRT. The results showed that 5 mM, 10 mM, and 15 mM have less significant effects on the above-mentioned parameters. However, 20 mM concentration of Al3+ produced significant effects (≤ 0.01%). Therefore, 20 mM of Al3+ is considered optimized limit for indica cultivars (Pokkali and Pak Basmati).
IL-33 ( Interleukin 33 ) / sST 2 ( Soluble Suppression of Tumorigenicity 2 ) Axis in Hypertension and Heart Failure

IL-33 (interleukin 33) is type of cytokine designated an alarmin, which is released under stress conditions or by cell death to induce protective measures in neighboring cells. It signals via the ST2 (suppression of tumorigenicity 2) receptor, which is also expressed as a truncated and soluble form that acts as a decoy receptor soluble ST2 (sST2). Substantial evidence supports the use of sST2 measurement as an indicator of cardiac stress and remodeling in hypertension, heart failure, cardiomyopathies, and aortic stenosis (AS). However, as discussed here, there are gaps in our understanding of the IL-33/sST2 axis, including the source of the components, stimuli for their expression and release, what it actually assesses, and the role of immune cells. Moreover, as discussed, the fundamental assumption that Il-33 has beneficial actions that are thwarted by sST2 requires further scrutiny.
Estimation of quadriceps femoris muscle dysfunction in the early period after surgery of the knee joint using shear-wave elastography

Objectives Orthopaedic surgery of the knee joint results in functional deterioration of the quadriceps femoris muscle. However, little is known about quadriceps femoris muscle dysfunction in the early postsurgical period. Therefore, we examined the stiffness of the quadriceps femoris muscle in the early postsurgical period. Methods Seven patients and seven healthy controls performed quadriceps contraction exercises. In resting and contraction conditions, the shear modulus, muscle thickness and pennation angle were measured for the vastus medialis (VM), vastus lateralis (VL) and the rectus femoris (RF) using ultrasound elastography. Results The shear moduli of the VM, VL and RF in the control group did not significantly interact, while the shear moduli in the patient group did show a significant interaction. In the resting condition, there was no difference between the unaffected and affected sides in the patient group, but the shear moduli of the VM and VL in the contraction condition was significantly lower on the affected side than the unaffected side. The contraction ratios between muscles by limbs did not significantly interact. However, there were main effects due to muscle and limb factors. The VM and VL had a significantly higher contraction ratio than the RF, and the control and unaffected limbs had a higher contraction ratio than the affected limb. Conclusion The results demonstrated a decrease in muscle stiffness during contraction in patients with quadriceps femoris dysfunction. Measurement of the shear modulus has potential as a new evaluation index and with high sensitivity to decreases in muscle contraction.