Miracle-dz/UniFAR-FTUs huggingface dataset:
A Systematic Review and Meta-Analysis of Kidney and Pregnancy Outcomes in IgA Nephropathy

Background: The outcomes of pregnancy in immunoglobulin A nephropathy (IgAN) remain controversial. We sought to evaluate the effect of pregnancy on the progression of IgAN as well as the impact of IgAN on pregnancy outcomes. Methods: We systematically searched MEDLINE, Embase for cohort or case-control studies. OR reductions were calculated with a random-effects model, and kidney outcomes and adverse pregnancy events were analyzed. Results: Our literature search returned 652 relevant articles; 4 studies were included, providing data of 376 pregnancies in 273 patients with IgAN and that of 241 IgAN who did not become pregnant. Four hundred sixty seven patients with chronic kidney disease stages 1-2 were included. Pregnancy in patients with IgAN did not increase the risk of adverse renal events including doubling of serum creatinine, 50% decline in glomerular filtration rate (GFR) and end-stage kidney disease (OR 0.97, 95% CI 0.55-1.70; p = 0.90; I2 = 0.0%, p = 0.79). There was no significant difference in the change in estimated GFR at the end of follow-up in the pregnant and non-pregnant groups (weighted mean difference 0.1 ml/min/1.73 m2 (95% CI -4.85 to 5.04 ml/min/1.73 m2), p = 0.97; I2 = 0%, p = 0.95). Women with IgAN had high rates of infant loss (12.2, 7.4-19.4%), preterm delivery (8.5, 5.9-12.1%), low birth weight (9.5, 6.7-13.3%), and preeclampsia/severe preeclampsia (7.3, 4.9-10.6%). Conclusions: Pregnancy in IgAN patients with preserved kidney function did not accelerate deterioration of renal function. But pregnant women with IgAN are at higher risk of pregnancy complications.
Osteosarcomas of the mandible: multidisciplinary management of a rare tumor of the young adult a cooperative study of the GSF-GETO, Rare Cancer Network, GETTEC/REFCOR and SFCE.

BACKGROUND Mandibular osteosarcomas (MOS) mostly affect young adults. Their treatment is extrapolated from that of extragnathic osteosarcomas. MATERIAL AND METHODS A retrospective multicooperative group study was conducted to determine the impact of chemotherapy, adjuvant radiation therapy and surgery on outcomes and to identify prognostic factors. This ethical committee-approved study included a centralized review of histology slides and operative reports. RESULTS Of 111 patients, 58.6% were male, median age 35 years (13%, ≤18 years). Histology was osteoblastic, chondroblastic, fibroblastic, conventional not otherwise specified and others in 39.6%, 30.6%, 8.1%, 12.6% and 8.0%, respectively. Pathological World Health Organisation grades were low, intermediate and high grade in 6.4%, 11.8% and 81.8%, respectively. Surgery was carried out for 94.5% of patients. Neoadjuvant chemotherapy (mixed protocols) was carried out in 93.1% of patients. Postoperative chemotherapy and radiotherapy were carried out in 54.7% and 23.8%, respectively. Median follow-up was 59.6 months (range). Five-year local control, metastasis-free, disease-free and overall survival rates were 64.6%, 68.9%, 53.2% and 69.2%, respectively. Survival was significantly associated with age, tumor size and surgery. Wide surgery with clear margins and free flap reconstruction was the strongest prognostic factor. Neoadjuvant chemotherapy improved disease-free and metastatic-free survival and increased clear margins rates from 50% to 68%. Intermediate grades behaved like high grades in terms of metastatic-free and disease-free survival. CONCLUSION This homogeneous series is the largest to date and emphasizes the major impact of clear margins and multidisciplinary management. Neoadjuvant chemotherapy improves disease-free survival and should be recommended for both high and intermediate grade MOS.
β‐Site APP cleaving enzyme up‐regulation induced by 4‐hydroxynonenal is mediated by stress‐activated protein kinases pathways

4‐Hydroxynonenal (HNE), an aldehydic product of lipid peroxidation, up‐regulates expression of the β‐site APP cleaving enzyme (BACE‐1), an aspartyl protease responsible for the β‐secretase cleavage of amyloid precursor protein (AβPP), and results in increased levels of amyloid β (Aβ) peptide. The mechanisms underlying this remain unclear but are of fundamental importance because prevention of BACE‐1 up‐regulation is viewed as an important therapeutic strategy. In this study, we exposed NT2 neurons to a range of HNE concentrations (0.5–5 µm) that elicited an up‐regulation of BACE‐1 expression, a significant increase in intracellular and secreted levels of Aβ peptides as well as apoptosis involving poly‐ADP ribose polymerase cleavage and activation of caspase 3. To delineate the molecular events involved in HNE‐mediated BACE‐1 activation, we investigated the involvement of stress‐activated protein kinases (SAPK), signal transducers and activators of transcription (STAT) and serine–threonine kinase B/phosphatidylinositol phosphate 3 kinase (Akt/PtdIns3K). Using specific pharmacological inhibitors, our results show that activation of c‐Jun N‐terminal kinases and p38MAPK. , but not STAT or Akt/PtdIns3K, pathways mediate the HNE‐dependent up‐regulation of BACE‐1 expression. Therefore, HNE, an oxidative stress mediator detected in vivo in the brains of Alzheimer's disease patients, may play a pathogenetic role in Alzheimer's disease by selectively activating SAPK pathways and BACE‐1 that regulate the proteolytic processing of AβPP.
The Efe forager infant and toddler's pattern of social relationships: Multiple and simultaneous.

This study extends previous observations on the multiple caretaking system of newborns and young infants among the Efe foragers of Zaire, to Efe infants and toddlers, whose social contacts with mother, father, adults, and children at 5 and 8 months and at 1, 2, and 3 years were observed naturalistically. The Efe infant experiences a pattern of simultaneous and multiple relationships rather than a pattern that is initially focused on one person, most typically the mother, and that with development progresses to other relationships. This pattern is influenced by physical and social ecological factors and cultural practices. It is argued (a) that this pattern of social experience leads to a sense of self that incorporates other people and (b) that some of our assumptions about the nature of social development, especially that early relationships are hierarchical and sequential in nature, require reevaluation. Who are the people that make up the social world of the infant and toddler? How often are these people involved with them, and in what way? How does the infant's relationship with social partners change as the infant gets older? And what role do sociocultural, ecological, and biological factors play in shaping the infant's social network and experience? Knowledge of infants' and toddlers' social partners is central to understanding development because social partners play an important role in shaping infants' and toddlers' representations of self and the social world, their social, emotional, and cognitive capacities, and their affectionate relationships with other people. In this article we describe the social experience of Efe (Pygmy1) infants and toddlers, and we examine the social ecological factors associated with their activities. Our findings raise questions concerning popular models of early social relationships and suggest an alternative way of thinking about the social world of children. Until recently, scientific accounts (varying in theoretical orientation and relying on different empirical evidence) of the infant's early social experiences converged on the view that the infant progresses from a primary relationship with one individual (almost always the mother), or at most a very few individuals, to relationships with a growing number of people, most typically peers (Smith, 1980). This is an epigenetic, hierarchical view of social development. We have labeled this dominant
Enhanced Opioid Efficacy in Opioid Dependence Is Caused by an Altered Signal Transduction Pathway

Chronic morphine administration induces adaptations in neurons resulting in opioid tolerance and dependence. Functional studies have implicated a role for the periaqueductal gray area (PAG) in the expression of many signs of opioid withdrawal, but the cellular mechanisms are not fully understood. This study describes an increased efficacy, rather than tolerance, of opioid agonists at μ-receptors on GABAergic (but not glutamatergic) nerve terminals in PAG after chronic morphine treatment. Opioid withdrawal enhanced the amplitudes of electrically evoked inhibitory synaptic currents mediated by GABAA receptors and increased the frequency of spontaneous miniature GABAergic synaptic currents. These effects were not blocked by 4-aminopyridine or dendrotoxin, although both Kv channel blockers abolish acute opioid presynaptic inhibition of GABA release in PAG. Instead, the withdrawal-induced increases were blocked by protein kinase A inhibitors and occluded by metabolically stable cAMP analogs, which do not prevent acute opioid actions. These findings indicate that opioid dependence induces efficacious coupling of μ-receptors to presynaptic inhibition in GABAergic nerve terminals via adenylyl cyclase- and protein kinase A-dependent processes in PAG. The potential role of these adaptations in expression of withdrawal behavior was supported by inhibition of enhanced GABAergic synaptic transmission by the α2 adrenoceptor agonist clonidine. These findings provide a cellular mechanism that is consistent with other studies demonstrating attenuated opioid withdrawal behavior after injections of protein kinase A inhibitors into PAG and suggest a general mechanism whereby opioid withdrawal may enhance synaptic neurotransmission.
Local Inhibition of PERK Enhances Memory and Reverses Age-Related Deterioration of Cognitive and Neuronal Properties

Protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) is one of four known kinases that respond to cellular stress by deactivating the eukaryotic initiation factor 2 α (eIF2α) or other signal transduction cascades. Recently, both eIF2α and its kinases were found to play a role in normal and pathological brain function. Here, we show that reduction of either the amount or the activity of PERK, specifically in the CA1 region of the hippocampus in young adult male mice, enhances neuronal excitability and improves cognitive function. In addition, this manipulation rescues the age-dependent cellular phenotype of reduced excitability and memory decline. Specifically, the reduction of PERK expression in the CA1 region of the hippocampus of middle-aged male mice using a viral vector rejuvenates hippocampal function and improves hippocampal-dependent learning. These results delineate a mechanism for behavior and neuronal aging and position PERK as a promising therapeutic target for age-dependent brain malfunction. SIGNIFICANCE STATEMENT We found that local reduced protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) expression or activity in the hippocampus enhances neuronal excitability and cognitive function in young normal mice, that old CA1 pyramidal cells have reduced excitability and increased PERK expression that can be rescued by reducing PERK expression in the hippocampus, and that reducing PERK expression in the hippocampus of middle-aged mice enhances hippocampal-dependent learning and memory and restores it to normal performance levels of young mice. These findings uncover an entirely new biological link among PERK, neuronal intrinsic properties, aging, and cognitive function. Moreover, our findings propose a new way to fight mild cognitive impairment and aging-related cognitive deterioration.
Adverse Events in Healthy Individuals and MDR-TB Contacts Treated with Anti-Tuberculosis Drugs Potentially Effective for Preventing Development of MDR-TB: A Systematic Review

A recent systematic review concluded that there is insufficient evidence on the effectiveness to support or reject preventive therapy for treatment of contacts of patients with multidrug resistant tuberculosis (MDR-TB). Whether preventive therapy is favorable depends both on the effectiveness and the adverse events of the drugs used. We performed a systematic review to assess adverse events in healthy individuals and MDR-TB contacts treated with anti-tuberculosis drugs potentially effective for preventing development of MDR-TB. We searched MEDLINE, EMBASE, and other databases (August 2011). Record selection, data extraction, and study quality assessment were done in duplicate. The quality of evidence was assessed using the GRADE approach. Of 6,901 identified references, 20 studies were eligible. Among the 16 studies in healthy volunteers (a total of 87 persons on either levofloxacin, moxifloxacin, ofloxacin, or rifabutin, mostly for 1 week), serious adverse events and treatment discontinuation due to adverse events were rare (<1 and <5%, respectively), but mild adverse events frequently occurred. Due to small sample sizes of the levofloxacin and ofloxacin studies an increased frequency of mild adverse events compared to placebo could not be demonstrated or excluded. For moxifloxacin the comparative results were inconsistent. In four studies describing preventive therapy of MDR-TB contacts, therapy was stopped for 58–100% of the included persons because of the occurrence of adverse events ranging from mild adverse events such as nausea and dizziness to serious events requiring treatment. The quality of the evidence was very low. Although the number of publications and quality of evidence are low, the available evidence suggests that shortly after starting treatment the occurrence of serious adverse events is rare. Mild adverse events occur more frequently and may be of importance because these may provoke treatment interruption.
Morphology of high-luminosity compact radio sources.

High-dynamic range imaging and monitoring with very-long-baseline interferometry reveal a rich morphology of luminous flat-spectrum radio sources. One-sided core-jet structures abound, and superluminal motion is frequently measured. In a few cases, both distinct moving features and diffuse underlying jet emission can be detected. Superluminal motion seen in such sources is typically complex, on curved trajectories or ridge lines, and with variable component velocities, including stationary features. The curved trajectories seen can be modeled by helical motion within the underlying jet flow. The very-long-baseline interferometry properties of the superluminal features in the jet of 3C 345 and other similar sources can be explained by models invoking the emission from shocks, at least within the vicinity of the compact core. Inverse-Compton calculations, constrained by x-ray observations, yield realistic estimates for the physical conditions in the parsec-scale jet. There is evidence for a transition region in this source beyond which other factors (e.g., plasma interactions and nonsynchrotron radiation processes) may become prominent. Multifrequency and polarization imaging (especially at high frequencies) are emerging as critical tools in testing model predictions.
Coping with Time‐Varying Demand When Setting Staffing Requirements for a Service System

We review queueing‐theory methods for setting staffing requirements in service systems where customer demand varies in a predictable pattern over the day. Analyzing these systems is not straightforward, because standard queueing theory focuses on the long‐run steady‐state behavior of stationary models. We show how to adapt stationary queueing models for use in nonstationary environments so that time‐dependent performance is captured and staffing requirements can be set. Relatively little modification of straightforward stationary analysis applies in systems where service times are short and the targeted quality of service is high. When service times are moderate and the targeted quality of service is still high, time‐lag refinements can improve traditional stationary independent period‐by‐period and peak‐hour approximations. Time‐varying infinite‐server models help develop refinements, because closed‐form expressions exist for their time‐dependent behavior. More difficult cases with very long service times and other complicated features, such as end‐of‐day effects, can often be treated by a modified‐offered‐load approximation, which is based on an associated infinite‐server model. Numerical algorithms and deterministic fluid models are useful when the system is overloaded for an extensive period of time. Our discussion focuses on telephone call centers, but applications to police patrol, banking, and hospital emergency rooms are also mentioned.
Pathophysiology of the optic neuropathy associated with Friedreich ataxia.

OBJECTIVES To describe the optic neuropathy associated with the genetic defect in Friedreich ataxia and suggest a pathophysiologic mechanism. METHODS An experimental model of retinal ganglion cell death in the presence of metal chelation was used to test a hypothetical mechanism for the optic neuropathy of Friedreich ataxia. RESULTS Study of cultured rat retinal ganglion cells suggests that abnormal regulation of intracellular iron levels could increase sensitivity to reactive oxygen species and lead to cell death in these metabolically active tissues. CONCLUSION We hypothesize that decreased expression of frataxin, the mutated gene in Friedreich ataxia, could cause an optic neuropathy by increasing the sensitivity of retinal ganglion cells to oxidative stress.
Ras and autophagy in cancer development and therapy

Autophagy, a process of self-degradation and turnover of cellular components, plays a complex role in cancer. Evidence exists to show that autophagy may support tumor growth and cell survival, whereas it can also contribute to tumor suppression and have anti-survival characteristics in different cellular systems. Numerous studies have described the effects of various oncogenes and tumor suppressors on autophagy. The small GTPase Ras is an oncogene involved in the regulation of various cell-signaling pathways, and is mutated in 33% of human cancers. In the present review, we discuss the interplay between Ras and autophagy in relation to oncogenesis. It appears that Ras can upregulate or downregulate autophagy through several signaling pathways. In turn, autophagy can affect the tumorigenicity driven by Ras, resulting in either tumor progression or repression, depending on the cellular context. Furthermore, Ras inhibitors were shown to induce autophagy in several cancer cell lines.
Adaptation Improves Neural Coding Efficiency Despite Increasing Correlations in Variability

Exposure of cortical cells to sustained sensory stimuli results in changes in the neuronal response function. This phenomenon, known as adaptation, is a common feature across sensory modalities. Here, we quantified the functional effect of adaptation on the ensemble activity of cortical neurons in the rat whisker-barrel system. A multishank array of electrodes was used to allow simultaneous sampling of neuronal activity. We characterized the response of neurons to sinusoidal whisker vibrations of varying amplitude in three states of adaptation. The adaptors produced a systematic rightward shift in the neuronal response function. Consistently, mutual information revealed that peak discrimination performance was not aligned to the adaptor but to test amplitudes 3–9 μm higher. Stimulus presentation reduced single neuron trial-to-trial response variability (captured by Fano factor) and correlations in the population response variability (noise correlation). We found that these two types of variability were inversely proportional to the average firing rate regardless of the adaptation state. Adaptation transferred the neuronal operating regime to lower rates with higher Fano factor and noise correlations. Noise correlations were positive and in the direction of signal, and thus detrimental to coding efficiency. Interestingly, across all population sizes, the net effect of adaptation was to increase the total information despite increasing the noise correlation between neurons.
A novel SEM cross-section analysis of paper coating for separation of latex from void volume

Mesoporous silica crystals have a large variety of structures mainly due to the versatility of their structure template. The configuration and the chemical state of the templating micellar surfactants, together with the kinetic process of silica will determine the final outcome of the synthesis. Increasing the understanding of the complex formation processes involved will enable a possibilityto fine tune the material for specific uses, today focused into the fields of photoniccrystals, drug delivery, catalysis and separation technology.In this thesis emphasis is put on (1) increasing the understanding the formation mechanism yielding the different species of mesoporous silica crystals through an in depth study of quasicrystallinity (2) Characterization and description of the structural complexity through various characterization techniquesand also by studying the kinetic structural transformation phenomenon related to the minimal G- and D-surfaces. (3) The structural studies of the versatile surfactant liquid crystals for establishing a thermodynamically stable basis to evaluate the kinetic mesoporous silica growth processes. Furthermorethe thesis both enlightens the possibilities of and contributes to the developmentof electron microscopy characterization techniques.In these studies, electron microscopy is largely employed in the characterization to give a thorough picture of the mesoporous structures. This is combined with the sample preparation techniques cross-section polishing and ionslicing. Low voltage scanning electron microscopy is utilized for studying the surfaces and cross-sections of various materials at the limit of the resolution. Here, a deep understanding of the electron beam-material interaction is used for a better interpretation of the detected signals. Transmission electron microscopyis combined with electron crystallographic reconstruction to yield a three dimensional structural model. For determination of the quasicrystallinity level for a structure of dodecagonal tiling, revealed in the scope of this study,a phason strain analysis was made.
Surfels: surface elements as rendering primitives

Surface elements (surfels) are a powerful paradigm to efficiently render complex geometric objects at interactive frame rates. Unlike classical surface discretizations, i.e., triangles or quadrilateral meshes, surfels are point primitives without explicit connectivity. Surfel attributes comprise depth, texture color, normal, and others. As a pre-process, an octree-based surfel representation of a geometric object is computed. During sampling, surfel positions and normals are optionally perturbed, and different levels of texture colors are prefiltered and stored per surfel. During rendering, a hierarchical forward warping algorithm projects surfels to a z-buffer. A novel method called visibility splatting determines visible surfels and holes in the z-buffer. Visible surfels are shaded using texture filtering, Phong illumination, and environment mapping using per-surfel normals. Several methods of image reconstruction, including supersampling, offer flexible speed-quality tradeoffs. Due to the simplicity of the operations, the surfel rendering pipeline is amenable for hardware implementation. Surfel objects offer complex shape, low rendering cost and high image quality, which makes them specifically suited for low-cost, real-time graphics, such as games.