Miracle-dz/UniFAR-FTUs huggingface dataset:
Hemodynamic physiology during perioperative intracranial hypertension

Background : During an endoscopic neurosurgical procedure (ENP) a sudden increase in intracranial pressure (ICP) may occur at any time. In the literature little attention has been paid to the early detection of such an increase. In particular the occurrence of a „Cushing reflex‟ has not been discussed in this context. We now present a prospective study of haemodynamic changes during ENP. Methods : In 17 consecutive patients who underwent an ENP under general anaesthesia, physiological data was recorded over the whole operative procedure. Monitoring included invasive blood pressure, intracranial pressure, electrocardiogram, end-expired carbon dioxide, pulse oximetry and heart rate. Pressure-and ECG waveforms were recorded at 100Hz and evaluated in a subsequent off-line analysis. Results : In almost every case, the occurrence of hypertension and tachycardia was clearly the result of an increase in ICP. Also, in almost every case where the cerebral perfusion pressure (CPP) dropped below 15mmHg, a Cushing reflex developed. The occurrence of bradycardia was rather occasional and not systematically associated with a low CPP. Conclusion : In this study, we describe the haemodynamic effects of an increased ICP during ENP and their respective sequence of events at high temporal resolution. Although most clinicians rely on the occurrence of bradycardia to diagnose intracranial hypertension during ENP, we show that a simultaneous onset of hypertension and tachycardia is a much faster approach to determine impeded brain perfusion. Waiting for a persistent bradycardia to alert the surgeon during ENP could allow severe bradycardia or even asystole to develop.
Cognitive bias in software engineering

Developer's thought processes are a fundamental area of concern. Cognitive scientist have discovered that people's intiative inferences and probality judgments do not strictly conform to the laws of logic or mathematics, and that people are willing to provide plausible explanations for random events. This article examines the role these phenomena might have in software development, ultimately concluding that what are cast as one-sided software development guidelines often can be recast beneficially as two-sided trade-offs.
Radiate and Planar Multipolar Neurons of the Mouse Anteroventral Cochlear Nucleus: Intrinsic Excitability and Characterization of their Auditory Nerve Input

Radiate and planar neurons are the two major types of multipolar neurons in the ventral cochlear nucleus (VCN). Both cell types receive monosynaptic excitatory synaptic inputs from the auditory nerve, but have different responses to sound and project to different target regions and cells. Although the intrinsic physiology and synaptic inputs to planar neurons have been previously characterized, the radiate neurons are less common and have not been as well studied. We studied both types of multipolar neurons and characterized their properties including intrinsic excitability, synaptic dynamics of their auditory nerve inputs, as well as their neural firing properties to auditory nerve stimulation. Radiate neurons had a faster member time constant and higher threshold current to fire spikes than planar neurons, but the maximal firing rate is the same for both cell types upon large current injections. Compared to planar neurons, radiate neurons showed spontaneous postsynaptic currents with smaller size, and slower but variable kinetics. Auditory nerve stimulation progressively recruited synaptic inputs that were smaller and slower in radiate neurons, over a broader range of stimulus strength. Synaptic inputs to radiate neurons showed less depression than planar neurons during low rates of repetitive activity, but the synaptic depression at higher rates was similar between two cell types. However, due to the slow kinetics of the synaptic inputs, synaptic transmission in radiate neurons showed prominent temporal summation that contributed to greater synaptic depolarization and a higher firing rate for repetitive auditory nerve stimulation at high rates. Taken together, these results show that radiate multipolar neurons integrate a large number of weak synaptic inputs over a broad dynamic range, and have intrinsic and synaptic properties that are distinct from planar multipolar neurons. These properties enable radiate neurons to generate powerful inhibitory inputs to target neurons during high levels of afferent activity. Such robust inhibition is expected to dynamically modulate the excitability of many cell types in the cochlear nuclear complex.
Salient Region Detection via Integrating Diffusion-Based Compactness and Local Contrast

Salient region detection is a challenging problem and an important topic in computer vision. It has a wide range of applications, such as object recognition and segmentation. Many approaches have been proposed to detect salient regions using different visual cues, such as compactness, uniqueness, and objectness. However, each visual cue-based method has its own limitations. After analyzing the advantages and limitations of different visual cues, we found that compactness and local contrast are complementary to each other. In addition, local contrast can very effectively recover incorrectly suppressed salient regions using compactness cues. Motivated by this, we propose a bottom-up salient region detection method that integrates compactness and local contrast cues. Furthermore, to produce a pixel-accurate saliency map that more uniformly covers the salient objects, we propagate the saliency information using a diffusion process. Our experimental results on four benchmark data sets demonstrate the effectiveness of the proposed method. Our method produces more accurate saliency maps with better precision-recall curve and higher F-Measure than other 19 state-of-the-arts approaches on ASD, CSSD, and ECSSD data sets.
Role of leptin in female reproduction

Abstract Reproductive function is dependent on energy resources. The role of weight, body composition, fat distribution and the effect of diet have been largely investigated in experimental female animals as well as in women. Any alteration in diet and/or weight may induce abnormalities in timing of sexual maturation and fertility. However, the cellular mechanisms involved in the fine coordination of energy balance and reproduction are largely unknown. The brain and hypothalamic structures receive endocrine and/or metabolic signals providing information on the nutritional status and the degree of fat stores. Adipose tissue acts both as a store of energy and as an active endocrine organ, secreting a large number of biologically important molecules termed adipokines. Adipokines have been shown to be involved in regulation of the reproductive functions. The first adipokine described was leptin. Extensive research over the last 10 years has shown that leptin is not only an adipose tissue-derived messenger of the amount of energy stores to the brain, but also a crucial hormone/cytokine for a number of diverse physiological processes, such as inflammation, angiogenesis, hematopoiesis, immune function, and most importantly, reproduction. Leptin plays an integral role in the normal physiology of the reproductive system with complex interactions at all levels of the hypothalamic-pituitary gonadal (HPG) axis. In addition, leptin is also produced by placenta, where it plays an important autocrine function. Observational studies have demonstrated that states of leptin excess, deficiency, or resistance can be associated with abnormal reproductive function. This review focuses on the leptin action in female reproduction.
Identification of CiaR Regulated Genes That Promote Group B Streptococcal Virulence and Interaction with Brain Endothelial Cells

Group B Streptococcus (GBS) is a major causative agent of neonatal meningitis due to its ability to efficiently cross the blood-brain barrier (BBB) and enter the central nervous system (CNS). It has been demonstrated that GBS can invade human brain microvascular endothelial cells (hBMEC), a primary component of the BBB; however, the mechanism of intracellular survival and trafficking is unclear. We previously identified a two component regulatory system, CiaR/H, which promotes GBS intracellular survival in hBMEC. Here we show that a GBS strain deficient in the response regulator, CiaR, localized more frequently with Rab5, Rab7 and LAMP1 positive vesicles. Further, lysosomes isolated from hBMEC contained fewer viable bacteria following initial infection with the ΔciaR mutant compared to the WT strain. To characterize the contribution of CiaR-regulated genes, we constructed isogenic mutant strains lacking the two most down-regulated genes in the CiaR-deficient mutant, SAN_2180 and SAN_0039. These genes contributed to bacterial uptake and intracellular survival. Furthermore, competition experiments in mice showed that WT GBS had a significant survival advantage over the Δ2180 and Δ0039 mutants in the bloodstream and brain.
Altered Fermentative Metabolism in Chlamydomonas reinhardtii Mutants Lacking Pyruvate Formate Lyase and Both Pyruvate Formate Lyase and Alcohol Dehydrogenase[W]

This article describes novel ways that algae may adjust metabolite trafficking when specific branches of fermentation metabolism are blocked. This rerouting of metabolites allows for continued glycolytic energy production under anoxic conditions, which is critical for the cell’s survival. Mechanisms associated with this reengineering of metabolism are almost completely unexplored. Chlamydomonas reinhardtii, a unicellular green alga, often experiences hypoxic/anoxic soil conditions that activate fermentation metabolism. We isolated three Chlamydomonas mutants disrupted for the pyruvate formate lyase (PFL1) gene; the encoded PFL1 protein catalyzes a major fermentative pathway in wild-type Chlamydomonas cells. When the pfl1 mutants were subjected to dark fermentative conditions, they displayed an increased flux of pyruvate to lactate, elevated pyruvate decarboxylation, ethanol accumulation, diminished pyruvate oxidation by pyruvate ferredoxin oxidoreductase, and lowered H2 production. The pfl1-1 mutant also accumulated high intracellular levels of lactate, succinate, alanine, malate, and fumarate. To further probe the system, we generated a double mutant (pfl1-1 adh1) that is unable to synthesize both formate and ethanol. This strain, like the pfl1 mutants, secreted lactate, but it also exhibited a significant increase in the levels of extracellular glycerol, acetate, and intracellular reduced sugars and a decrease in dark, fermentative H2 production. Whereas wild-type Chlamydomonas fermentation primarily produces formate and ethanol, the double mutant reroutes glycolytic carbon to lactate and glycerol. Although the metabolic adjustments observed in the mutants facilitate NADH reoxidation and sustained glycolysis under dark, anoxic conditions, the observed changes could not have been predicted given our current knowledge of the regulation of fermentation metabolism.
Early dropout predictive factors in obesity treatment

Diet attrition and failure of long term treatment are very frequent in obese patients. This study aimed to identify pre-treatment variables determining dropout and to customise the characteristics of those most likely to abandon the program before treatment, thus making it possible to modify the therapy to increase compliance. A total of 146 outpatients were consecutively enrolled; 73 patients followed a prescriptive diet while 73 followed a novel brief group Cognitive Behavioural Treatment (CBT) in addition to prescriptive diet. The two interventions lasted for six months. Anthropometric, demographic, psychological parameters and feeding behaviour were assessed, the last two with the Italian instrument VCAO Ansisa; than, a semi-structured interview was performed on motivation to lose weight. To identify the baseline dropout risk factors among these parameters, univariate and multivariate logistic models were used. Comparison of the results in the two different treatments showed a higher attrition rate in CBT group, despite no statistically significant difference between the two treatment arms (P = 0.127). Dropout patients did not differ significantly from those who did not dropout with regards to sex, age, Body Mass Index (BMI), history of cycling, education, work and marriage. Regardless of weight loss, the most important factor that determines the dropout appears to be a high level of stress revealed by General Health Questionnaire-28 items (GHQ-28) score within VCAO test. The identification of hindering factors during the assessment is fundamental to reduce the dropout risk. For subjects at risk, it would be useful to dedicate a stress management program before beginning a dietary restriction.
Genome-wide identification of in vivo Drosophila Engrailed-binding DNA fragments and related target genes

Chromatin immunoprecipitation after UV crosslinking of DNA/protein interactions was used to construct a library enriched in genomic sequences that bind to the Engrailed transcription factor in Drosophila embryos. Sequencing of the clones led to the identification of 203 Engrailed-binding fragments localized in intergenic or intronic regions. Genes lying near these fragments, which are considered as potential Engrailed target genes, are involved in different developmental pathways, such as anteroposterior patterning, muscle development, tracheal pathfinding or axon guidance. We validated this approach by in vitro and in vivo tests performed on a subset of Engrailed potential targets involved in these various pathways. Finally, we present strong evidence showing that an immunoprecipitated genomic DNA fragment corresponds to a promoter region involved in the direct regulation of frizzled2 expression by engrailed in vivo.
Mother to Mother (M2M) Peer Support for Women in Prevention of Mother to Child Transmission (PMTCT) Programmes: A Qualitative Study

Introduction Mother-to-Mother (M2M) or “Mentor Mother” programmes utilise HIV positive mothers to provide support and advice to HIV positive pregnant women and mothers of HIV exposed babies. Médecins Sans Frontières (MSF) supported a Mentor Mother programme in Bulawayo, Zimbabwe from 2009 to 2012; with programme beneficiaries observed to have far higher retention at 6–8 weeks (99% vs 50%, p<0.0005) and to have higher adherence to Prevention of Mother to Child Transmission (PMTCT) guidelines, compared to those not opting in. In this study we explore how the M2M progamme may have contributed to these findings. Methods In this qualitative study we used thematic analysis of in-depth interviews (n = 79). This study was conducted in 2 urban districts of Bulawayo, Zimbabwe’s second largest city. Results Interviews were completed by 14 mentor mothers, 10 mentor mother family members, 30 beneficiaries (women enrolled both in PMTCT and M2M), 10 beneficiary family members, 5 women enrolled in PMTCT but who had declined to take part in the M2M programme and 10 health care staff members. All beneficiaries and health care staff reported that the programme had improved retention and provided rich information on how this was achieved. Additionally respondents described how the programme had helped bring about beneficial behaviour change. Conclusions M2M programmes offer great potential to empower communities affected by HIV to catalyse positive behaviour change. Our results illustrate how M2M involvement may increase retention in PMTCT programmes. Non-disclosure to one’s partner, as well as some cultural practices prevalent in Zimbabwe appear to be major barriers to participation in M2M programmes.
Regional Expression Levels of Drug Transporters and Metabolizing Enzymes along the Pig and Human Intestinal Tract and Comparison with Caco-2 Cells

Intestinal transporter proteins and metabolizing enzymes play a crucial role in the oral absorption of a wide variety of drugs. The aim of the current study was to characterize better available intestinal in vitro models by comparing expression levels of these proteins and enzymes between porcine intestine, human intestine, and Caco-2 cells. We therefore determined the absolute protein expression of 19 drug transporters and the mRNA expression of 12 metabolic enzymes along the pig intestinal tract (duodenum, jejunum, ileum; N = 4), in human intestine (jejunum; N = 9), and Caco-2 cells. Expression of the included transporters and enzymes was in general well comparable between porcine and human intestinal tissue, although breast cancer resistance protein, monocarboxylate transporter 5, multidrug resistance protein (MRP) 1, MRP1, MRP3 (∼2-fold), and organic anion-transporting polypeptide (OATP) 4A1 (∼6-fold) was higher expressed in pig compared with human jejunum. Alternatively, expression level of relevant transporter proteins (glucose transporter 1, OATP4A1, MRP2, MRP1, and OATP2B1) was significantly higher (3- to 130-fold) in Caco-2 cells compared with human jejunum. Moreover, all examined CYPs showed at least a fivefold lower gene expression in Caco-2 cells compared with human jejunum, with the smallest differences for CYP1A1 and CYP3A5 and the largest difference for CYP3A4 (871-fold higher expression in human jejunum compared with Caco-2 cells). In conclusion, a comprehensive overview is provided of the expression levels of clinically relevant transporter proteins and metabolic enzymes in porcine and human intestinal tissue and Caco-2 cells, which may assist in deciding upon the most suitable model to further improve our understanding of processes that determine intestinal absorption of compounds.
Temporal Dynamics of Distinct CA1 Cell Populations during Unconscious State Induced by Ketamine

Ketamine is a widely used dissociative anesthetic which can induce some psychotic-like symptoms and memory deficits in some patients during the post-operative period. To understand its effects on neural population dynamics in the brain, we employed large-scale in vivo ensemble recording techniques to monitor the activity patterns of simultaneously recorded hippocampal CA1 pyramidal cells and various interneurons during several conscious and unconscious states such as awake rest, running, slow wave sleep, and ketamine-induced anesthesia. Our analyses reveal that ketamine induces distinct oscillatory dynamics not only in pyramidal cells but also in at least seven different types of CA1 interneurons including putative basket cells, chandelier cells, bistratified cells, and O-LM cells. These emergent unique oscillatory dynamics may very well reflect the intrinsic temporal relationships within the CA1 circuit. It is conceivable that systematic characterization of network dynamics may eventually lead to better understanding of how ketamine induces unconsciousness and consequently alters the conscious mind.
A sensitive assay reveals structural requirements for α-synuclein fibril growth

The accumulation of α-synuclein (α-syn) fibrils in neuronal inclusions is the defining pathological process in Parkinson's disease (PD). A pathogenic role for α-syn fibril accumulation is supported by the identification of dominantly inherited α-syn (SNCA) gene mutations in rare cases of familial PD. Fibril formation involves a spontaneous nucleation event in which soluble α-syn monomers associate to form seeds, followed by fibril growth during which monomeric α-syn molecules sequentially associate with existing seeds. To better investigate this process, we developed sensitive assays that use the fluorescein arsenical dye FlAsH (fluorescein arsenical hairpin binder) to detect soluble oligomers and mature fibrils formed from recombinant α-syn protein containing an N-terminal bicysteine tag (C2-α-syn). Using seed growth by monomer association (SeGMA) assays to measure fibril growth over 3 h in the presence of C2-α-syn monomer, we observed that some familial PD-associated α-syn mutations (i.e. H50Q and A53T) greatly increased growth rates, whereas others (E46K, A30P, and G51D) decreased growth rates. Experiments with wild-type seeds extended by mutant monomer and vice versa revealed that single-amino acid differences between seed and monomer proteins consistently decreased growth rates. These results demonstrate that α-syn monomer association during fibril growth is a highly ordered process that can be disrupted by misalignment of individual amino acids and that only a subset of familial-PD mutations causes fibril accumulation through increased fibril growth rates. The SeGMA assays reported herein can be utilized to further elucidate structural requirements of α-syn fibril growth and to identify growth inhibitors as a potential therapeutic approach in PD.
Local selection modifies phenotypic divergence among Rana temporaria populations in the presence of gene flow

In ectotherms, variation in life history traits among populations is common and suggests local adaptation. However, geographic variation itself is not a proof for local adaptation, as genetic drift and gene flow may also shape patterns of quantitative variation. We studied local and regional variation in means and phenotypic plasticity of larval life history traits in the common frog Rana temporaria using six populations from central Sweden, breeding in either open‐canopy or partially closed‐canopy ponds. To separate local adaptation from genetic drift, we compared differentiation in quantitative genetic traits (QST) obtained from a common garden experiment with differentiation in presumably neutral microsatellite markers (FST). We found that R. temporaria populations differ in means and plasticities of life history traits in different temperatures at local, and in FST at regional scale. Comparisons of differentiation in quantitative traits and in molecular markers suggested that natural selection was responsible for the divergence in growth and development rates as well as in temperature‐induced plasticity, indicating local adaptation. However, at low temperature, the role of genetic drift could not be separated from selection. Phenotypes were correlated with forest canopy closure, but not with geographical or genetic distance. These results indicate that local adaptation can evolve in the presence of ongoing gene flow among the populations, and that natural selection is strong in this system.
Breathing pattern and thoracoabdominal motion in healthy individuals: influence of age and sex.

OBJECTIVE to describe the breathing pattern and thoracoabdominal motion of healthy individuals, taking age and sex into consideration. METHODS the study included 104 individuals aged 20 to 39, 40 to 59, and 60 to 80 years (41 males and 63 females), with normal body mass index and spirometric values. Participants were evaluated at rest in the supine position, by means of respiratory inductive plethysmography. The following variables were measured: tidal volume (Vt), respiratory frequency (f), minute ventilation (VE), inspiratory duty cycle (Ti/Ttot), mean inspiratory flow (Vt/Ti), rib cage motion (%RC), inspiratory phase relation (PhRIB), expiratory phase relation (PhREB), and phase angle (PhaseAng). Comparisons between the age groups were performed using one-way ANOVA or Kruskal-Wallis H, while comparisons between the sexes were performed using Student's t test or the Mann-Whitney U test, depending on the data distribution; p<0.05 was taken to be significant. RESULTS comparison between the sexes showed that, in the age groups 20 to 39 and 60 to 80 years, women presented significantly lower values for Vt, VE, and Ti/Ttot than men, and there was no significant difference in the age group 40 to 59 years. Comparisons between the age groups showed that participants aged 60 to 80 presented significantly greater PhRIB and PhaseAng than participants aged 20 to 39 years, without significant differences in the breathing pattern. CONCLUSION the data suggest that breathing pattern is influenced by sex whereas thoracoabdominal motion is influenced by age.