Miracle-dz/UniFAR-FTUs huggingface dataset:
The Effects of 6% Hydroxyethyl Starch Compared with Normal Saline on Controlling Undesirable Hemodynamic Changes Following Spinal Anesthesia in Patients Undergoing Orthopedic Surgery: A Randomized Clinical Trial

Abstract Objective: The aim of the current study was to compare the effects of normal saline solution and 6% hydroxyethyl starch (HES/HAES) solution on hemodynamic changes after spinal anesthesia in patients undergoing lower limb orthopedic surgery. Method: This randomized clinical trial was performed on 50 patients undergoing surgery, aged 20-60, with physical status of ASA I, II. Before surgery, the hemodynamic status of each patient including systolic and diastolic blood pressure, heart rate, and central venous pressure was measured. Then, the patients were randomly divided into two groups and for the control group, 7 ml/kg 9% (or normal) saline and for the experimental group 6% hydroxyethyl starch were administered. Hemodynamic indices were re-measured after the completion of infusion, and then spinal anesthesia was performed. After anesthesia, hemodynamic indices were measured every 5 minutes for 1 hour and then every 10 minutes for 2 hours. The analysis of variance (ANOVA) for repeated measures was used to evaluate the significant changes in hemodynamic indices. Results: The mean and standard deviation of systolic and diastolic blood pressure, heart rate, and central venous pressure in the control group were 113.0 (7.3), 73.0 (6.0), 95.6 (5.7), and 5.8 (0.9), respectively, and in the intervention group were 104.8 (5.5), 66.1 (4.2), 95.8 (8.2), and 4.3 (0.9(. ANOVA for repeated measures showed that the incidence of decreasing changes in systolic and diastolic blood pressure, heart rate, and central venous pressure of the patients for whom hydroxyethyl starch was prescribed was significantly less than that of the patients for whom normal saline was prescribed. Conclusion: Hydroxyethyl starch has a more effective role in controlling hemodynamic changes before spinal anesthesia than normal saline.
Targeting human Plasmacytoid dendritic cells through BDCA2 prevents inflammation and fibrosis in xenotransplant mouse model of Scleroderma

Plasmacytoid dendritic cells (pDC) have been implicated in the pathogenesis of Scleroderma (SSc) through their ability to infiltrate the skin and secrete interferons (IFN) and proinflammatory chemokines. Blood Dendritic Cells Antigen 2 (BDCA2) is an inhibitory type II C-type lectin expressed by human pDC. Here we determined the effects of BDCA2 internalisation on pDC mediated skin inflammation and fibrosis in human preclinical models of skin inflammation and fibrosis in vitro and in vivo. BDCA2 targeting reversed TLR-signalling induced transcriptome and differentiation of pDC and suppressed their ability to induce IFN response in organotypic 3D human skin cultures in vitro. In vivo, xenotransplantation of human pDC into immunocompromised mice (XenoSCID) significantly increased IFN induced responses to topical TLR7/9 agonist and separately enhanced the fibrotic response to bleomycin. Targeting of BDCA2 strongly suppressed both of these pathological responses ameliorating skin inflammation and fibrosis. Together, these preclinical data strongly support the notion that human pDC play a key role in immune driven skin fibrosis, which can be effectively blocked by targeting BDCA2.
Ultrasonographically Observed Grade III Placenta at 36 Weeks’ Gestation: Maternal and Fetal Outcomes

INTRODUCTION: The placenta is essential to fetal well-being, growth and development; it can be demonstrated reliably and accurately by ultrasound (1) . The association of ultrasonically detectable placental changes with increasing gestational age was first reported by Winsberg (2) , but it was Grannum et al. (3) who introduced a grading system based on the ultrasonographic appearance of placentas. They graded placentas from 0 (Immature) to III (mature) on the basis of changes in the appearance of the chorionic plate, placental structure and basal layer. By 38 gestational weeks, 5-10% of placentas present
Organ-specificity of sterol and triterpene accumulation in Arabidopsis thaliana

Sterols serve essential functions as membrane constituents and hormones (brassinosteroids) in plants, while non-sterol triterpenoids have been implicated in defense responses. Surprisingly little is known about the sterol and triterpene profiles in different plant organs. To enhance our understanding of organ-specific sterol and triterpene accumulation, we quantified these metabolite classes in four different organs (root, stem, leaf, seed) of Arabidopsis thaliana (L.). Based on these data sets we developed kinetic mathematical models of sterol biosynthesis to capture flux distribution and pathway regulation in different organs. Simulations indicated that an increased flux through the sterol pathway would not only result in an increase of sterol end products but also a concomitant build-up of certain intermediates. These computational predictions turner out to be consistent with experimental data obtained with transgenic plants ectopically overexpressing 3-hydroxy-3-methylglutary-coenzyme A reductase (HMG1 gene). The opportunities and limitations of incorporating mathematical modeling into the design of approaches to engineer sterol biosynthesis are discussed.
Resistance to dieldrin evolution in African malaria vectors is driven by interspecific and interkaryotypic introgression

The evolution of insecticide resistance mechanisms in natural populations of Anopheles malaria vectors is a major public health concern across Africa. Using genome sequence data, we study the evolution of resistance mutations in the resistance to dieldrin gene (Rdl), a GABA receptor targeted by several insecticides, but most notably by the long-discontinued cyclodiene, dieldrin. The two Rdl resistance mutations (296G and 296S) spread across West and Central African Anopheles via two independent hard selective sweeps that included likely compensatory nearby mutations, and were followed by a rare combination of introgression across species (from A. gambiae and A. arabiensis to A. coluzzii) and across non-concordant karyotypes of the 2La chromosomal inversion. Rdl resistance evolved in the 1950s as the first known adaptation to a large-scale insecticide-based intervention, but the evolutionary lessons from this system highlight contemporary and future dangers for management strategies designed to combat development of resistance in malaria vectors
Prevalence of scabies and its associated factors among school age children in Arba Minch zuria district, Southern Ethiopia, 2018

Background Scabies, a common human skin disease with a prevalence range of 0.2% to 71.4% in the world. It can have considerable impact on general health leading to illness and death not only through direct effect of its infestation and as a result of secondary bacterial infection. The aim of this study was to assess the prevalence of scabies and its associated factors among school age children in Arba Minch zuria district, Gamo zone, Southern Ethiopia. Methods A community based cross sectional study was carried out in 845 school age children from February 20 to March 30, 2018. Multi-stage sampling technique was used to select study populations. Logistic regression an analysis was used to identify factors associated with scabies. Findings were presented using 95% CI of Crude Odds Ratios (COR) and Adjusted Odds Ratios (AOR. To declare statistical significance, p-value less than 0.05 was used. Result A total of 825 children participated in the study with response rate of 97.6%. The overall prevalence of scabies was 16.4% [95% CI: 13.9%, 18.9%]. overcrowding index, family history of itching in the past two weeks, wealth index, knowledge of scabies, climatic zone, frequency of washing body, frequency of washing clothes, finger nails cutting practice, history of skin contact with scabies patient, washing hair more than once weekly, and sharing of clothes were significantly associated scabies disease. Conclusion In conclusion, the prevalence of scabies in Arba Minch lies at 16.4% in the global scabies range 0.2% to 71.4%. The prevalence was highest in highlands followed by midland and then lowland. This represents a significant scabies burden which we recommend warrants health service intervention. Authors summary Scabies, a common human skin disease with a prevalence range of 0.2% to 71.4% in the world. It can have considerable impact on general health leading to illness and death not only through direct effect of its infestation and as a result of secondary bacterial infection. Conducting a research on this neglected tropical disease would contribute in designing a policies and strategies on prevention and control measures in the study area. Therefore, the aim of this study was to assess the prevalence of scabies and its associated factors among school age children in Arba Minch zuria district, Gamo zone, Southern Ethiopia.
Plant origin determines seed mass, seed nutrients and germination behavior of a dominant grass species

Although number of studies exploring effects of climate change on plants is increasing, only few studies pay attention to germination. Understanding of germination behaviour is complicated by impact of climate on seed mass and possibly also seed nutrients, which play irreplaceable role in nourishing the sprout. The germination behaviour of species may also depend on trade-off between generative and vegetative reproduction. We studied Festuca rubra originating from localities situated along a natural climatic grid. Seeds of different origin were germinated in two temperature and two moisture regimes, simulating the extremes of the grid. To study relationship between generative and vegetative reproduction we used data on vegetative traits originating from the same study system. Seed mass and nutrient concentrations (nitrogen and phosphorus) were significantly affected by original climate, while carbohydrates not. Higher seed mass and warm temperature of origin caused higher and faster germination. Warm and dry condition during germination caused the lowest germination but the highest seed viability. Total germination and proportion of viable seeds negatively correlated with plant performance variables contributing to vegetative reproduction. Despite this, the patterns detected using datasets of germination and plant performance, did not provide fully comparable results. Simulated changes in climatic condition can modify seed mass and seed nutrients and these changes translate into changes in species germination behavior. After accounting for seed mass, both original and target conditions determine species germination indicating that both genetic differentiation as well as actual conditions drive the germination patterns. As the patterns detected at the level of seed germination do not fully match those detected for the vegetative traits, we urge that future studies should focus on multiple stages of plant life to understand species responses to future climates.
Learning from local to global: An efficient distributed algorithm for modeling time-to-event data

OBJECTIVE We developed and evaluated a privacy-preserving One-shot Distributed Algorithm to fit a multicenter Cox proportional hazards model (ODAC) without sharing patient-level information across sites. MATERIALS AND METHODS Using patient-level data from a single site combined with only aggregated information from other sites, we constructed a surrogate likelihood function, approximating the Cox partial likelihood function obtained using patient-level data from all sites. By maximizing the surrogate likelihood function, each site obtained a local estimate of the model parameter, and the ODAC estimator was constructed as a weighted average of all the local estimates. We evaluated the performance of ODAC with (1) a simulation study and (2) a real-world use case study using 4 datasets from the Observational Health Data Sciences and Informatics network. RESULTS On the one hand, our simulation study showed that ODAC provided estimates nearly the same as the estimator obtained by analyzing, in a single dataset, the combined patient-level data from all sites (ie, the pooled estimator). The relative bias was <0.1% across all scenarios. The accuracy of ODAC remained high across different sample sizes and event rates. On the other hand, the meta-analysis estimator, which was obtained by the inverse variance weighted average of the site-specific estimates, had substantial bias when the event rate is <5%, with the relative bias reaching 20% when the event rate is 1%. In the Observational Health Data Sciences and Informatics network application, the ODAC estimates have a relative bias <5% for 15 out of 16 log hazard ratios, whereas the meta-analysis estimates had substantially higher bias than ODAC. CONCLUSIONS ODAC is a privacy-preserving and noniterative method for implementing time-to-event analyses across multiple sites. It provides estimates on par with the pooled estimator and substantially outperforms the meta-analysis estimator when the event is uncommon, making it extremely suitable for studying rare events and diseases in a distributed manner.
Value-guided remapping of sensory circuits by lateral orbitofrontal cortex in reversal learning

Flexible decision-making is crucial for adaptive behaviour. Such behaviour in mammals largely relies on the frontal cortex, and specifically, the orbitofrontal cortex (OFC). How OFC neurons encode decision variables and instruct sensory areas to guide adaptive behaviour is a key open question. Here we developed a reversal learning task for head-fixed mice together with two-photon calcium imaging to monitor the activity of lateral OFC neuronal populations and investigated their dynamic interaction with primary somatosensory cortex (S1). Mice trained on this task learned to discriminate go/no-go tactile stimuli and adapt their behaviour upon changes in stimulus–reward contingencies (‘rule-switch’). Longitudinal imaging at cellular resolution across weeks during all behavioural phases revealed a distinct engagement of S1 and lateral OFC neurons: S1 neural activity reflected task learning-related responses, while neurons in the lateral OFC saliently and transiently responded to the rule-switch. A subset of OFC neurons conveyed a value prediction error signal via feedback projections to S1, as direct anatomical long-range projections were revealed by retrograde tracing combined with whole-brain light-sheet microscopy. Top-down signals implemented an update of sensory representations and functionally reconfigured a small subpopulation of S1 neurons that were differentially modulated by reward-history. Functional remapping of these neurons crucially depended on top-down inputs, as chemogenetic silencing of lateral OFC neurons disrupted reversal learning and impaired plastic changes in these outcome-sensitive S1 neurons. Our results reveal the presence of long-range cortical interactions between cellular ensembles in higher and lower-order brain areas specifically recruited during context-dependent learning and task-switching. Such interactions crucially implement history-dependent reward-value computations and error heuristics, which, in turn, help guide adaptive behaviour.
Compartmentalization of the replication fork by single-stranded DNA binding protein regulates translesion synthesis

DNA replication is mediated by the coordinated actions of multiple enzymes within replisomes. Processivity clamps tether many of these enzymes to DNA, allowing access to the primer/template junction. Many clamp-interacting proteins (CLIPs) are involved in genome maintenance pathways including translesion synthesis (TLS). Despite their abundance, DNA replication in bacteria is not perturbed by these CLIPs. Here we show that while the TLS polymerase Pol IV is largely excluded from moving replisomes, the remodeling of ssDNA binding protein (SSB) upon replisome stalling enriches Pol IV at replication forks. This enrichment is indispensable for Pol IV-mediated TLS on both the leading and lagging strands as it enables Pol IV-processivity clamp binding by overcoming the gatekeeping role of the Pol III epsilon subunit. As we have demonstrated for the Pol IV-SSB interaction, we propose that the binding of CLIPs to the processivity clamp must be preceded by interactions with factors that serve as localization markers for their site of action.
The functional organization of excitation and inhibition in the dendritic arbors of retinal direction-selective ganglion cells

Recent studies indicate that the precise timing and location of excitation and inhibition (E/I) within active dendritic trees can significantly impact neuronal function. How excitatory and inhibitory inputs are functionally organized at the subcellular level in intact circuits remains unclear. To address this issue, we took advantage of the retinal direction-selective ganglion cell circuit, in which directionally tuned inhibitory GABAergic input arising from starburst amacrine cells shape direction-selective dendritic responses. We combined two-photon Ca2+ imaging with genetic, pharmacological, and single-cell ablation methods to examine local E/I. We demonstrate that when active dendritic conductances are blocked, direction selectivity emerges semi-independently within unusually small dendritic segments (<10 µm). Impressively, the direction encoded by each segment is relatively homogenous throughout the ganglion cell’s dendritic tree. Together the results demonstrate a precise subcellular functional organization of excitatory and inhibitory input, which suggests that the parallel processing scheme proposed for direction encoding could be more fine-grained than previously envisioned.
Brain-to-brain synchrony between students and teachers predicts learning outcomes

Little is known about the brain mechanisms that underpin how humans learn while interacting with one another in ecologically-valid environments (1-3). This is because cognitive neuroscientists typically measure one participant at a time in a highly constrained environment (e.g., inside a brain scanner). In the past few years, researchers have begun comparing brain responses across individuals (4-6) demonstrating that brain-to-brain synchrony can predict subsequent memory retention (7-9). Yet previous research has been constrained to non-interacting individuals. Surprisingly, the one study that was conducted in a group setting found that brain synchrony between students in a classroom predicted how engaged the students were, but not how much information they retained (10). This is unexpected because brain-to-brain synchrony is hypothesized to be driven, at least partially, by shared attention (11, 12), and shared attention has been shown to affect subsequent memory (13). Here we used EEG to simultaneously record brain activity from groups of four students and a teacher in a simulated classroom to investigate whether brain-to-brain synchrony, both between students and between the students and the teacher, can predict learning outcomes (Fig. 1A). We found that brain-to-brain synchrony in the Alpha band (8-12Hz) predicted students’ delayed memory retention. Further, moment-to-moment variation in alpha-band brain-to-brain synchrony discriminated between content that was retained or forgotten. Whereas student-to-student brain synchrony best predicted delayed memory retention at a zero time lag, student-to-teacher brain synchrony best predicted memory retention when adjusting for a ∼200 millisecond lag in the students’ brain activity relative to the teacher’s brain activity. These findings provide key new evidence for the importance of brain data collected simultaneously from groups of individuals in ecologically-valid settings. Highlights Electroencephalogram (EEG) was concurrently recorded in a simulated classroom from groups of four students and a teacher. Alpha-band (8-12Hz) brain-to-brain synchrony predicted students’ performance in a delayed post-test. Moment-to-moment variation in alpha-band brain-to-brain synchrony indicated what specific information was retained by students. Whereas student-to-student brain synchrony best predicted learning at a zero time lag, student-to-teacher brain synchrony best predicted learning when adjusting for a ∼200 millisecond lag in the students’ brain activity relative to the teacher’s brain activity.
NT-ProBNP at Admission Versus NT-ProBNP at Discharge as a Prognostic Predictor in Acute Decompensated Heart Failure

Fundamento: Pacientes internados por insuficiencia cardiaca (IC) descompensada recebem intensa terapia diuretica e vasodilatadora nos primeiros dias, conduta normalmente bem-sucedida na compensacao do quadro, permitindo alta hospitalar. No entanto, e comum a recorrencia de agravamento nas primeiras semanas apos a alta. Objetivo: Avaliar se o principal preditor de recorrencia de desfechos em pacientes com IC e o grau de descompensacao na admissao ou o estado volemico obtido apos controle clinico. Metodos: coorte prospectiva de pacientes admitidos entre janeiro de 2013 e outubro de 2014, com diagnostico de IC agudamente descompensada, acompanhados ate 60 dias apos a alta hospitalar. O criterio de inclusao foi aumento da dosagem plasmatica do NT-proBNP (> 450 pg/mL para pacientes abaixo de 50 anos ou NT-proBNP > 900 pg/mL para pacientes acima de 50 anos). O desfecho primario foi a combinacao de obito cardiovascular apos compensacao e reinternacao por IC descompensada em 60 dias. Resultados: Foram estudados 90 pacientes, com mediana do NT-proBNP da admissao 3947 pg/mL (IIQ = 2370 pg/mL a 7000 pg/mL), mediana da variacao absoluta do NT-proBNP de -1533 pg/mL (IIQ = -3569 pg/mL a 747 pg/mL), e mediana do NT-proBNP da alta de 1946 pg/mL (IIQ = 1000 pg/mL a 3781 pg/mL). A incidencia do desfecho combinado foi de 30%, sendo 12,2% de obitos e 20% de readmissao. A curva ROC do NT-proBNP da admissao e eventos cardiovasculares em 60 dias apresentou uma area sob a curva de 0,49 (p = 0,89; IC 95% = 0,36 - 0,62). A variacao absoluta do NT-proBNP apresentou area sob a curva de 0,65 (p = 0,04; IC 95% = 0,51 - 0,79) para eventos em 60 dias, e o NT-proBNP da alta apresentou area sob a curva de 0,69 (p = 0,03; IC 95% = 0,58 - 0,80). Em analise multivariada, NT-proBNP que precedeu a alta foi preditor do desfecho primario, independente do valor mensurado na admissao e de outros fatores de risco. Conclusao: Diferente do grau de descompensacao que motivou a internacao, o estado volemico obtido apos compensacao da IC se associa a eventos recorrentes. Este achado sugere que, independentemente da gravidade inicial, e a resposta ao tratamento durante o internamento que determina a vulnerabilidade do paciente para nova descompensacao.
Plasmodium oocysts respond with dormancy to crowding and nutritional stress

Malaria parasites develop as oocysts in the mosquito for several days before they are able to infect a human host. During this time, mosquitoes take bloodmeals to replenish their nutrient and energy reserves needed for flight and reproduction. We hypothesized that these bloodmeals are critical for oocyst growth and that experimental infection protocols, typically involving a single bloodmeal at the time of infection, cause nutritional stress to the developing oocysts. Therefore, enumerating oocysts disregarding their growth and differentiation state may lead to erroneous conclusions about the efficacy of transmission blocking interventions. Here, we examine this hypothesis in Anopheles coluzzii mosquitoes infected with the human and rodent parasites Plasmodium falciparum and Plasmodium berghei , respectively. We show that oocyst growth and maturation rates decrease at late developmental stages as infection intensities increase; an effect exacerbated at very high infection intensities but fully restored with post infection bloodmeals. High infection intensities and starvation conditions reduce RNA Polymerase III activity in oocysts unless supplemental bloodmeals are provided. Our results suggest that oocysts respond to crowding and nutritional stress with a dormancy-like strategy, which urges the development of alternative methods to assess the efficacy of transmission blocking interventions.