Miracle-dz/UniFAR-FTUs huggingface dataset:
Association between Outdoor Air Pollution and Childhood Leukemia: A Systematic Review and Dose–Response Meta-Analysis

Background: A causal link between outdoor air pollution and childhood leukemia has been proposed, but some older studies suffer from methodological drawbacks. To the best of our knowledge, no systematic reviews have summarized the most recently published evidence and no analyses have examined the dose–response relation. Objective: We investigated the extent to which outdoor air pollution, especially as resulting from traffic-related contaminants, affects the risk of childhood leukemia. Methods: We searched all case–control and cohort studies that have investigated the risk of childhood leukemia in relation to exposure either to motorized traffic and related contaminants, based on various traffic-related metrics (number of vehicles in the closest roads, road density, and distance from major roads), or to measured or modeled levels of air contaminants such as benzene, nitrogen dioxide, 1,3-butadiene, and particulate matter. We carried out a meta-analysis of all eligible studies, including nine studies published since the last systematic review and, when possible, we fit a dose–response curve using a restricted cubic spline regression model. Results: We found 29 studies eligible to be included in our review. In the dose–response analysis, we found little association between disease risk and traffic indicators near the child’s residence for most of the exposure range, with an indication of a possible excess risk only at the highest levels. In contrast, benzene exposure was positively and approximately linearly associated with risk of childhood leukemia, particularly for acute myeloid leukemia, among children under 6 y of age, and when exposure assessment at the time of diagnosis was used. Exposure to nitrogen dioxide showed little association with leukemia risk except at the highest levels. Discussion: Overall, the epidemiologic literature appears to support an association between benzene and childhood leukemia risk, with no indication of any threshold effect. A role for other measured and unmeasured pollutants from motorized traffic is also possible. https://doi.org/10.1289/EHP4381
PD‐L1, B7‐H3 and VISTA are highly expressed in gestational trophoblastic neoplasia

The B7 family check‐point molecules are potential therapeutic targets in cancer immunotherapy. However, their expression status in human gestational trophoblastic neoplasia (GTN) remains unknown. We investigated the expression profiles of the B7 family check‐point proteins PD‐L1, PD‐L2, B7‐H3, B7‐H4, VISTA and B7‐H6 in GTN and their clinical significance.
penner/lgl2 is required for the integrity of the photoreceptor layer in the zebrafish retina

ABSTRACT The vertebrate retina is a complex tissue built from multiple neuronal cell types, which develop from a pseudostratified neuroepithelium. These cells are arranged into a highly organized and stereotypic pattern formed by nuclear and plexiform layers. The process of lamination as well as the maturation and differentiation of photoreceptor cells rely on the establishment and maintenance of apico-basal cell polarity and formation of adhesive junctions. Defects in any of these processes can result in impaired vision and are causally related to a variety of human diseases leading to blindness. While the importance of apical polarity regulators in retinal stratification and disease is well established, little is known about the function of basal regulators in retinal development. Here, we analyzed the role of Lgl2, a basolateral polarity factor, in the zebrafish retina. Lgl2 is upregulated in photoreceptor cells and in the retinal pigment epithelium by 72 h post fertilization. In both cell types, Lgl2 is localized basolaterally. Loss of zygotic Lgl2 does not interfere with retinal lamination or photoreceptor cell polarity or maturation. However, knockdown of both maternal and zygotic Lgl2 leads to impaired cell adhesion. As a consequence, severe layering defects occur in the distal retina, manifested by a breakdown of the outer plexiform layer and the outer limiting membrane. These results define zebrafish Lgl2 as an important regulator of retinal lamination, which, given the high degree of evolutionary conservation, may be preserved in other vertebrates, including human. Summary: Knockdown of penner/lgl2 leads to a breakdown of the outer plexiform layer and the outer limiting membrane in the zebrafish retina due to impaired cell adhesion.
Snake Venom Hemotoxic Enzymes: Biochemical Comparison between Crotalus Species from Central Mexico

Snakebite envenoming is a serious medical problem in different areas of the world. In Latin America, the major prevalence is due to snakes of the family Viperidae, where rattlesnakes (Crotalus) are included. They produce hemotoxic venom which causes bleeding, tissue degradation and necrosis. Each venom has several enzymatic activities, producing different effects in the envenoming, doing its clinical effects difficult to study. Comparison between venom molecules is also difficult when different techniques are used, and therefore, their identification/characterization using the same methodology is necessary. In this work, a general biochemical characterization in snake venom of serine proteases (SVSP), phospholipases A2 (PLA2), metalloproteases (SVMP) and hyaluronidases (SVH) of Crotalus aquilus (Ca), Crotalus polystictus (Cp) and Crotalus molossus nigrescens (Cmn) was done. Differences in protein pattern, enzyme content and enzymatic activities were observed. All the venoms showed high PLA2 activity, high molecular weight SVSP, and a wide variety of SVMP and SVH forms. Ca and Cp showed the highest enzymatic activities of SVMP and SVSP trypsin-like and chymotrypsin-like, whereas Cmn showed the highest SVH and similar PLA2 activity with Ca. All the venoms showed peptides with similar molecular weight to crotamine-like myotoxins. No previous biochemical characterization of C. aquilus has been reported and there are no previous analyses that include these four protein families in these Crotalus venoms.
Neuroimaging Studies on Disorders of Consciousness: A Meta-Analytic Evaluation

Neuroimaging tools could open a window on residual neurofunctional activity in the absence of detectable behavioural responses in patients with disorders of consciousness (DOC). Nevertheless, the literature on this topic is characterised by a large heterogeneity of paradigms and methodological approaches that can undermine the reproducibility of the results. To explicitly test whether task-related functional magnetic resonance imaging (fMRI) can be used to systematically detect neurofunctional differences between different classes of DOC, and whether these differences are related with a specific category of cognitive tasks (either active or passive), we meta-analyzed 22 neuroimaging studies published between 2005 and 2017 using the Activation Likelihood Estimate method. The results showed that: (1) active and passive tasks rely on well-segregated patterns of activations; (2) both unresponsive wakeful syndrome and patients in minimally conscious state activated a large portion of the dorsal-attentional network; (3) shared activations between patients fell mainly in the passive activation map (7492 voxels), while only 48 voxels fell in a subcortical region of the active-map. Our results suggest that DOCs can be described along a continuum—rather than as separated clinical categories—and characterised by a widespread dysfunction of brain networks rather than by the impairment of a well functionally anatomically defined one.
Marine reserves shape seascapes on scales visible from space

Marine reserves can effectively restore harvested populations, and ‘mega-reserves’ increasingly protect large tracts of ocean. However, no method exists of monitoring ecological responses at this large scale. Herbivory is a key mechanism structuring ecosystems, and this consumer–resource interaction's strength on coral reefs can indicate ecosystem health. We screened 1372, and measured features of 214, reefs throughout Australia's Great Barrier Reef using high-resolution satellite imagery, combined with remote underwater videography and assays on a subset, to quantify the prevalence, size and potential causes of ‘grazing halos’. Halos are known to be seascape-scale footprints of herbivory and other ecological interactions. Here we show that these halo-like footprints are more prevalent in reserves, particularly older ones (approx. 40 years old), resulting in predictable changes to reef habitat at scales visible from space. While the direct mechanisms for this pattern are relatively clear, the indirect mechanisms remain untested. By combining remote sensing and behavioural ecology, our findings demonstrate that reserves can shape large-scale habitat structure by altering herbivores' functional importance, suggesting that reserves may have greater value in restoring ecosystems than previously appreciated. Additionally, our results show that we can now detect macro-patterns in reef species interactions using freely available satellite imagery. Low-cost, ecosystem-level observation tools will be critical as reserves increase in number and scope; further investigation into whether halos may help seems warranted. Significance statement: Marine reserves are a widely used tool to mitigate fishing impacts on marine ecosystems. Predicting reserves' large-scale effects on habitat structure and ecosystem functioning is a major challenge, however, because these effects unfold over longer and larger scales than most ecological studies. We use a unique approach merging remote sensing and behavioural ecology to detect ecosystem change within reserves in Australia's vast Great Barrier Reef. We find evidence of changes in reefs' algal habitat structure occurring over large spatial (thousands of kilometres) and temporal (40+ years) scales, demonstrating that reserves can alter herbivory and habitat structure in predictable ways. This approach demonstrates that we can now detect aspects of reefs' ecological responses to protection even in remote and inaccessible reefs globally.
Microencapsulation of Moringa oleifera leaf extracts with vegetable protein as wall materials

Moringa oleifera, often referred to as ‘miracle tree’ contains high amount of bioactive nutrients and dietary antioxidants, which help in ameliorating oxidative stress and degenerating diseases. However, the bioactive compounds are highly susceptible to degradation, and this may decrease the antioxidants activity present in M. oleifera. To prevent these limitations, the utilisation of microencapsulation technique is of necessity. This study investigated the effect of two vegetable proteins: soy protein isolate and pea protein isolate as wall materials for M. oleifera leaf extracts encapsulation by spray drying technique. Three inlet air temperatures (140, 160, and 180 ℃) and two different formulations of core:wall material ratios (1:4 and 1:9, w/w) were studied. The total phenolic contents, antioxidant activity, microencapsulation yield, morphology, colour, tapped and bulk densities, particle size, and storage stability of M. oleifera microcapsules were analysed. Moringa microencapsulates with pea protein isolate had better powder quality than Moringa microencapsulates with soy protein isolate considering its significant higher particle size, bulk and tapped densities. Moringa microencapsulates with soy protein isolate proved to be a better carrier of bioactive compounds of both total phenolic content and 2,2-diphenyl-1-picrylhydrazyl activity at inlet air temperature in the range of 140–180 ℃. The total phenolic content and 2,2-diphenyl-1-picrylhydrazyl activity tend to be the most stable compound. The storage stability of bioactive compounds of both Moringa microencapsulates with pea protein isolate and Moringa microencapsulates with soy protein isolate was better preserved at 4 ℃ compared to that of 25 ℃.
Bumetanide-Derived Aquaporin 1 Inhibitors, AqB013 and AqB050 Inhibit Tube Formation of Endothelial Cells through Induction of Apoptosis and Impaired Migration In Vitro

AqB013 and AqB050 compounds inhibit aquaporin 1 (AQP1), a dual water and ion channel implicated in tumour angiogenesis. We tested AqB013 and AqB050 either as monotherapy or in combination on tube formation of murine endothelial cells (2H-11 and 3B-11) and human umbilical vascular endothelial cells (HUVECs). The mechanism underlying their anti-tubulogenic effect was explored by examining cell viability, induction of apoptosis and migration using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay, Annexin V/propidium iodide apoptosis assay and scratch wound assay. Tube formation of all the cell lines was inhibited by AqB013, AqB050 and the combination of the two compounds. The inhibition of 2H-11 and 3B-11 was frequently accompanied by impaired migration, whereas that of HUVEC treated with AqB050 and the combination was associated with reduced cell viability due to apoptosis. AqB013 and AqB050 exhibited an anti-tubulogenic effect through inhibition of AQP1-mediated cell migration and induction of apoptosis. Together with previously reported anti-tumour cell effect of AqB013 and AqB050, our findings support further evaluation of these compounds as potential cancer therapeutics.
Kinetics of Mimivirus Infection Stages Quantified Using Image Flow Cytometry

Due to the heterogeneity of viruses and their hosts, a comprehensive view of viral infection is best achieved by analyzing large populations of infected cells. However, information regarding variation in infected cell populations is lost in bulk measurements. Motivated by an interest in the temporal progression of events in virally infected cells, we used image flow cytometry (IFC) to monitor changes in Acanthamoeba polyphaga cells infected with Mimivirus. This first use of IFC to study viral infection required the development of methods to preserve morphological features of adherent amoeba cells prior to detachment and analysis in suspension. It also required the identification of IFC parameters that best report on key events in the Mimivirus infection cycle. The optimized IFC protocol enabled the simultaneous monitoring of diverse processes including generation of viral factories, transport, and fusion of replication centers within the cell, accumulation of viral progeny, and changes in cell morphology for tens of thousands of cells. After obtaining the time windows for these processes, we used IFC to evaluate the effects of perturbations such as oxidative stress and cytoskeletal disruptors on viral infection. Accurate dose‐response curves could be generated, and we found that mild oxidative stress delayed multiple stages of virus production, but eventually infection processes occurred with approximately the same amplitudes. We also found that functional actin cytoskeleton is required for fusion of viral replication centers and later for the production of viral progeny. Through this report, we demonstrate that IFC offers a quantitative, high‐throughput, and highly robust approach to study viral infection cycles and virus–host interactions. © The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of International Society for Advancement of Cytometry.
Genotoxicity Evaluation of the Soybean Isoflavone Genistein in Human Papillary Thyroid Cancer Cells. Study of Its Potential Use in Thyroid Cancer Therapy

Abstract Genistein is one of the several known isoflavonic phytoestrogens found in a number of plants, with soybeans and soy products being the primary food source. The aim of the study is to evaluate if genistein is able to exert antineoplastic action in primary human papillary thyroid cancer (PTC) cells. Thyroid tissues were treated with genistein (1–10–50–100 µM). Cell viability, proliferation, DNA primary damage and chromosomal damage were evaluated. An antiproliferative effect was induced by the highest doses of genistein, and such an effect was synergistically enhanced by the cotreatment with the antineoplastic drug sorafenib. Comet assay did not show any genotoxic effect in terms of primary DNA damage at all the times (4 and 24 h) and tested doses. A reduction of hydrogen peroxide-induced DNA primary damage in primary thyrocytes from PTC cells pretreated with genistein was observed. Data suggest that genistein exerts antineoplastic action, does not induce genotoxic effects while reduces oxidative-induced DNA damage in primary thyrocytes from PTC cells, supporting its possible use in therapeutic intervention.
HEALTH-RELATED QUALITY OF LIFE IN CHILDREN AND ADOLESCENTS WITH NON-CLASSIC CONGENITAL ADRENAL HYPERPLASIA.

Objective: Non-classic congenital adrenal hyperplasia (NCCAH) is a late-onset milder form of congenital adrenal hyperplasia (CAH) which differs dramatically from the classic form. Health-related quality of life (HRQOL) in pediatric patients with the sole diagnosis of NCCAH has not been determined, in this study we aimed to determine whether HRQOL is compromised in comparison to the general population. Methods: Single-center, cross-sectional, case-control study. Twenty-three hydrocortisone-treated children and adolescents (seven males) diagnosed with NCCAH by cosyntropin stimulation test and CYP21A2 gene mutation analysis were recruited to this study, six healthy siblings were also recruited. HRQOL was assessed by the child and parent-proxy PedsQL Inventory and compared between NCCAH subjects and healthy siblings. HRQOL scores of NCCAH subjects were compared with known standards from the USA and Israeli general healthy population. Anthropometric measurements of children and parents were performed and compared between NCCAH subjects and healthy siblings. Pearson correlation coefficients were calculated. Results: HRQOL scores of the participants and parents did not differ between NCCAH subjects and healthy siblings. The HRQOL emotional domain scores of the NCCAH patients and parent were significantly lower than the healthy USA pediatric population (P = .046), but not different from established standards of the healthy Israeli population (P = .583). Anthropometric measurements were within the normal range and did not differ between NCCAH subjects and their siblings. Total, school functioning and psychosocial HRQOL domain scores were positively correlated with BMI-SDS in NCCAH subjects. Conclusion: HRQOLwas not adversely affected by NCCAH among adequately treated children and adolescents.
Nurses' perceptions of pain management adequacy in mechanically ventilated patients.

AIMS AND OBJECTIVES To examine how nurses' knowledge of behaviours indicating pain in mechanically ventilated patients and self-perceived collaboration between nurses and physicians affects the adequacy of departmental pain management. BACKGROUND Pain management is a vital factor of medical treatment in a hospital setting. Inadequate pain management requires attention both from a patient-focused perspective and from a departmental one. It would be particularly troubling in the case of inadequate pain management of mechanically ventilated patients. DESIGN The study utilised a cross-sectional design. The instruments developed were validated by a focus group of 25 pain management nurses, who reviewed the questionnaire for face validity, feasibility and comprehensibility, and who did not participate in the study. The questionnaire was revised, readjusted and formulated based on their responses and comments. METHODS A self-administered questionnaire administered in Israel with a convenience sample of 187 registered nurses (RN) from internal medicine and surgical departments and ICUs. Data were collected during February-May 2015. The "STROBE" EQUATOR checklist was used. RESULTS Nurses working in the ICU scored significantly higher on knowledge of behaviours indicating pain in mechanically ventilated patients and on self-perceived collaboration between nurses and physicians. Self-perceived collaboration between physicians and nurses was positively correlated with perceived departmental pain treatment adequacy. Self-perceived collaboration between nurses and physicians, knowledge of behaviours indicating pain in mechanically ventilated patients and seniority (with a borderline significance) explained 27% of the variance of perceived departmental pain management. CONCLUSION Nurses' knowledge of behaviours indicating pain in mechanically ventilated patients, as well as self-perceived collaboration between nurses and physicians, promotes reported adequate pain management. RELEVANCE TO CLINICAL PRACTICE Pain management would benefit from being conducted as a well-performed interprofessional self-perceived collaborative practice. Knowledgeable nurses tend to critically assess the level of departmental pain management.
Correlates of Future Violence in People Being Treated for Schizophrenia.

OBJECTIVE Violent behavior is infrequent among individuals with schizophrenia but is clinically important. The purpose of this study was to provide data on the correlates of violence, which may allow better risk assessment and care. METHODS A total of 1,435 individuals with schizophrenia who participated in the National Institute of Mental Health's Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study and were followed for 18 months were examined. The dependent variables were self-reported injurious and noninjurious violence during follow-up. The independent variables, assessed at study entry, comprised participants' recent injurious and noninjurious violence, demographic and background variables, childhood risk factors, clinical condition, current circumstances, and recent contact with hospitals and prisons. Proportional hazards models of time to first injurious violence were used to generate bivariable and multivariable hazard ratios for all participants and, separately, for participants with no injurious violence at study entry. RESULTS Seventy-seven participants (5.4%) reported engaging in injurious violence during follow-up, and 119 (8.3%) reported engaging in exclusively noninjurious violence. In the multivariable analysis, baseline injurious violence (hazard ratio=4.02), recent violent victimization (hazard ratio=3.52), severity of drug use (hazard ratio=2.93), baseline noninjurious violence (hazard ratio=2.72), childhood sexual abuse (hazard ratio=1.85), and medication nonadherence (hazard ratio=1.39) were associated with future injurious violence. For participants with no history of injurious violence at study entry, baseline noninjurious violence was the strongest predictor (hazard ratio=3.02). Recent violent victimization was no longer a significant correlate. The remaining correlates and the strength of their association with future injurious violence were similar to those for all participants. CONCLUSIONS This is the first longitudinal multivariable analysis of predictors of injurious violence in a large cohort of patients with schizophrenia followed over 18 months. The results revealed simultaneous strong effects of baseline injurious violence and recent violent victimization on future injurious violent behavior. Among clinical variables, poor medication adherence, but not baseline symptoms of psychosis or depression, significantly predicted injurious violence. Treatment strategies to reduce risk should emphasize medication adherence.