Miracle-dz/UniFAR-FTUs huggingface dataset:
Intracytoplasmic morphologically selected sperm injection and congenital birth defects: a retrospective cohort study

Our objective was to study the birth defect rates in intracytoplasmic morphologically selected sperm injection (IMSI) pregnancies. A cohort of couples presenting male factor infertility between January 2006 and January 2014 was retrospectively analyzed. Discharge letters and a telephone interview were performed for assessing pregnancy outcome. All clinical data were reviewed by a board certified medical geneticist. Main outcomes were fetal/birth defect and chromosomal abnormality rates. Two thousand two hundred and fifty‐eight pregnancies were available for analysis, of them, 1669 (73.9%) resulting from ICSI and 2258 (26.1%) achieved by IMSI. Pregnancy outcome distribution did not show a significant difference. For the fresh embryo transfer cohort, fetal/birth defect rate was 4.5%, chromosomal aberration rate was 1.0%, and structural malformation rate was 3.5%. IMSI vs. ICSI pregnancies were less likely to involve a fetal/birth defect: 3.5% vs. 4.8%, respectively, but did not reach a statistical significance OR 0.71 (95% CI 0.39–1.22). Split by multiplicity, this trend existed only for singleton pregnancies; 1.4% structural malformations rate vs. 3.8%, respectively, OR 0.35 (95% CI 0.11–0.9). The frozen cohort demonstrated a significantly lower birth defect rate (OR 0.25, 95% CI 0.09–0.58). We conclude that IMSI procedure does not involve an increased malformation rate and may offer a reduced anomaly incidence. Further studies are required.
3.3-Å resolution cryo-EM structure of human ribonucleotide reductase with substrate and allosteric regulators bound

Ribonucleotide reductases (RNRs) convert ribonucleotides into deoxyribonucleotides, a reaction essential for DNA replication and repair. Human RNR requires two subunits for activity, the α subunit contains the active site, and the β subunit houses the radical cofactor. Here, we present a 3.3-Å resolution structure by cryo-electron microscopy (EM) of a dATP-inhibited state of human RNR. This structure, which was determined in the presence of substrate CDP and allosteric regulators ATP and dATP, has three α2 units arranged in an α6 ring. At near-atomic resolution, these data provide insight into the molecular basis for CDP recognition by allosteric specificity effectors dATP/ATP. Additionally, we present lower-resolution EM structures of human α6 in the presence of both the anticancer drug clofarabine triphosphate and β2. Together, these structures support a model for RNR inhibition in which β2 is excluded from binding in a radical transfer competent position when α exists as a stable hexamer.
Parent-led interventions in reducing infant vaccination pain after participation in a longitudinal randomized control trial.

Caitlin McNair, BA1, Many Fung, PharmD1, Anna Taddio, BScPhm MSc PhD1, Moshe Ipp, MD2, Steven Moss, MD3, Stephen Baker, MD3, Jonathan Tolkin, MD3, Malini Dave, MD3, Sharmeen Feerasta, MD3, Preeya Govan, MD3, Rebecca Pillai Riddell, PhD4 1Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario; 2Paediatric Associates, Toronto, Ontario; 3Private Practice, Toronto, Ontario; 4Department of Psychology, Faculty of Health York University, Toronto, Ontario
Oxidative stress in Duchenne muscular dystrophy: focus on the NRF2 redox pathway

Oxidative stress is involved in the pathogenesis of Duchenne muscular dystrophy (DMD), an X-linked genetic disorder caused by mutations in the dystrophin gene and characterized by progressive, lethal muscle degeneration and chronic inflammation. In this study, we explored the expression and signaling pathway of a master player of the anti-oxidant and anti-inflammatory response, namely NF-E2-related Factor 2, in muscle biopsies of DMD patients. We classified DMD patients in two age groups (Class I, 0-2 years and Class II, 2-9 years), in order to evaluate the antioxidant pathway expression during the disease progression. We observed that altered enzymatic antioxidant responses, increased levels of oxidized glutathione and oxidative damage are differently modulated in the two age classes of patients and well correlate with the severity of pathology. Interestingly, we also observed a modulation of relevant markers of the inflammatory response, such as heme oxygenase 1 and Inteleukin-6 (IL-6), suggesting a link between oxidative stress and chronic inflammatory response. Of note, using a transgenic mouse model, we demonstrated that IL-6 overexpression parallels the antioxidant expression profile and the severity of dystrophic muscle observed in DMD patients. This study advances our understanding of the pathogenic mechanisms underlying DMD and defines the critical role of oxidative stress on muscle wasting with clear implications for disease pathogenesis and therapy in human.
Corallimorph and Montipora Reefs in Ulithi Atoll, Micronesia: documenting unusual reefs

Here we report the presence of two unusual reef types at Ulithi Atoll, Yap State, Federated States of Micronesia: 1. a corallimorph-dominated reef off the island of Mogmog is found within an otherwise coral-dominated area, and 2. a general spread of Montipora reefs that were found to dominate the reef landscapes near inhabited islands. The Montipora reefs primarily occur near villages and in disturbed areas such as near boat-launch ramps. Indigenous people in the area say these reefs are fairly recent (ca. late 1960s) and that Montipora has been spreading rapidly.
Weighting for External Validity

External validity is a fundamental challenge in treatment effect estimation. Even when researchers credibly identify average treatment effects – for example through randomized experiments – the results may not extrapolate to the population of interest for a given policy question. If the population and sample differ only in the distribution of observed variables this problem has a well-known solution: reweight the sample to match the population. In many cases, however, the population and sample differ along dimensions unobserved by the researcher. We provide a tractable framework for thinking about external validity in such cases. Our approach relies on the fact that when the sample is drawn from the same support as the population of interest there exist weights which, if known, would allow us to reweight the sample to match the population. These weights are larger in a stochastic sense when the sample is more selected, and their correlation with a given variable reflects the intensity of selection along this dimension. We suggest natural benchmarks for assessing external validity, discuss implementation, and apply our results to data from several recent experiments.
Towards Wire-speed Platform-agnostic Control of OpenFlow Switches

The possibility to offload, via a platform-agnostic specification, the execution of (some/part of the) control functions down to the switch and operate them at wire speed based on packet level events, would yield significant benefits in terms of control latency and reaction times, meanwhile retaining the SDN-type ability to program and instantiate a desired network operation from a central controller. While programmability inside the switches, at wire speed and using platform-independent abstractions, of “any possible” control function seems well beyond the OpenFlow capabilities, in this paper 1 we argue that a non trivial sub-class of stateful control functions, namely those that can be abstracted in terms of Mealy (Finite State) Machines, is already compatible with off-the-shelf OpenFlow version 1.1+ Hardware with marginal architectural modifications. With minimal additional hardware circuitry, the above sub-class can be extended to include support for bidirectional/cross-flow state handling. We demonstrate the viability of our proposed approach via two proof-of-concept implementations (hardware and software), and we show how some stateful control functionalities frequently exploited in network protocols are readily deployed using our application programming interface.
Chemical and physical behaviour of the trace elements in the silicate melts of the Earth's mantle

We explore Fe-bearing Mg-silicate melts through the pressure regime of the Earth’s mantle using First Principles Molecular Dynamics (FPMD). The equation of state results we obtained from our simulations are used to create a chemical and mineralogical model for Ultra-Low Velocity Zones (anomalous region on the mantle side of the core-mantle boundary). Furthermore we study the behaviour of Ni, Co, and Fe in these melts, and asses their spin-crossover dependencies on their concentration, pressure, temperature, and the degree of polymerization of the silicate melts. We show that a decrease in the average spin can be correlated with the previously observed kink in the partitioning coefficient of Ni and Co. We investigate the melt structure of all the compositions studied as a function of pressure. Our results provide new insight into the coordination of major and trace elements in silicate melts with different degrees of polymerization. We interpret the anomalous Ni-O coordination trend with pressure as the result of the spin state change. The effect of silicate melt polymerization on the partitioning of Co, Ni, and W between a metal and silicate melt, is investigated at isobaric and isothermic conditions using multi-anvil experiments. We have performed FPMD simulations of melts with similar degrees of polymerization as the experiments in order to explain the increasing lithophile character of W with the decrease in polymerization of the silicate melt. We propose a structural explanation for tungsten’s apparent increased affinity for depolymerized silicate melts.
Content and structure in indexing and ranking XML

Rooted in electronic publishing, XML is now widely used for modelling and storing structured text documents. Especially in the WWW, retrieval of XML documents is most useful in combination with a relevance-based ranking of the query result. Index structures with ranking support are therefore needed for fast access to relevant parts of large document collections. This paper proposes a classification scheme for both XML ranking models and index structures, allowing to determine which index suits which ranking model. An analysis reveals that ranking parameters related to both the content and structure of the data are poorly supported by most known XML indices. The IR-CADG index, owing to its tight integration of content and structure, supports various XML ranking models in a very efficient retrieval process. Experiments show that it outperforms separate content/structure indexing by more than two orders of magnitude for large corpora of several hundred MB.
IMU-based smart fitness devices for weight training

The automated tracking and analysis of sport activities has become increasingly important in the recent years. While it is already very common in endurance sports, in weight training the tracking is still done mainly manually, which is a tedious task. This work aims at exploring the problem of automated tracking and analysing of weight training exercises by the use of low-power smart fitness devices based on inertial measurement units (IMUs), sensors containing accelerometers and gyroscopes. Therefore, basic state-of-the-art signal and data processing approaches, including various filtering techniques, sensor fusion, time series segmentation and classification methods like hidden Markov models (HMMs), support vector machines (SVMs) and nearest neighbours classifiers, are studied and applied to the specific problem domain. A proof-of-concept approach of the proposed methods is implemented on a purpose-built constrained embedded system. Finally, a comprehensive evaluation based on dumbbell exercises is done. The developed prototype achieves a segmentation misdetection rate of 1.5 %, a classification accuracy of 99.7 % and an average response time of about 300 ms. In conclusion, the results show that the initially specified requirements are met and that an accurate and fast tracking of selected weight training exercises is possible.
Dysregulated expression of microRNAs and mRNAs in pulmonary artery remodeling in ascites syndrome in broiler chickens

Ascites syndrome (AS), also known as pulmonary artery hypertension, remains a challenging disease that severely affects both humans and broiler chickens. Pulmonary artery remodeling presents a key step in the development of AS. In this study, we obtained pulmonary artery tissues from broilers with and without AS to perform miRNA sequencing analysis, miRNA-mRNA association analysis and pathological examinations. 29 significantly differentially expressed miRNAs were found both in known and novel miRNAs with 18 up-regulated and 11 down-regulated miRNAs. Their predicted potential targets were involved in a wide range of functional clusters as indicated via GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analyses. The upregulation of miR-155, miR-23b-3p, miR-146b-5p and miR-146b-3p were found closely associated with the pathogenesis of pulmonary artery remodeling in AS progression. The association analysis for the miRNAs-mRNAs showed that these 29 significantly differentially expressed miRNAs regulate 162 differentially expressed target genes. Among them, 20 miRNAs correlated with 18 predicted target genes that appear to be involved in pulmonary artery remodeling, mainly in three broad physiological processes: the hypoxia sensing response (HIF1a, NHE1, STAT5 and STAT3), endothelial permeability dysfunction (CD44, TRAF2, CDK2AP1, LZTFL1, JAZF1, PEBP1, LRP1B, RPS14 and THBS2) and inflammation (MEOX2, STAT5, STAT3, IRF8, MAP3K8, IL-1BETA and TNFRSF1B). Pathological pulmonary artery remodeling in the AS broilers was consistently observed in the present study. Taken together, the current analysis further illuminates the molecular mechanism of pulmonary artery remodeling underlying AS progression.
Advances in understanding river‐groundwater interactions

River‐groundwater interactions are at the core of a wide range of major contemporary challenges, including the provision of high‐quality drinking water in sufficient quantities, the loss of biodiversity in river ecosystems, or the management of environmental flow regimes. This paper reviews state of the art approaches in characterizing and modeling river and groundwater interactions. Our review covers a wide range of approaches, including remote sensing to characterize the streambed, emerging methods to measure exchange fluxes between rivers and groundwater, and developments in several disciplines relevant to the river‐groundwater interface. We discuss approaches for automated calibration, and real‐time modeling, which improve the simulation and understanding of river‐groundwater interactions. Although the integration of these various approaches and disciplines is advancing, major research gaps remain to be filled to allow more complete and quantitative integration across disciplines. New possibilities for generating realistic distributions of streambed properties, in combination with more data and novel data types, have great potential to improve our understanding and predictive capabilities for river‐groundwater systems, especially in combination with the integrated simulation of the river and groundwater flow as well as calibration methods. Understanding the implications of different data types and resolution, the development of highly instrumented field sites, ongoing model development, and the ultimate integration of models and data are important future research areas. These developments are required to expand our current understanding to do justice to the complexity of natural systems.
T-Type Calcium Channels Are Required to Maintain Viability of Neural Progenitor Cells

T-type calcium channels are low voltage-activated calcium channels that evoke small and transient calcium currents. Recently, T-type calcium channels have been implicated in neurodevelopmental disorders such as autism spectrum disorder and neural tube defects. However, their function during embryonic development is largely unknown. Here, we investigated the function and expression of T-type calcium channels in embryonic neural progenitor cells (NPCs). First, we compared the expression of T-type calcium channel subtypes (CaV3.1, 3.2, and 3.3) in NPCs and differentiated neural cells (neurons and astrocytes). We detected all subtypes in neurons but not in astrocytes. In NPCs, CaV3.1 was the dominant subtype, whereas CaV3.2 was weakly expressed, and CaV3.3 was not detected. Next, we determined CaV3.1 expression levels in the cortex during early brain development. Expression levels of CaV3.1 in the embryonic period were transiently decreased during the perinatal period and increased at postnatal day 11. We then pharmacologically blocked T-type calcium channels to determine the effects in neuronal cells. The blockade of T-type calcium channels reduced cell viability, and induced apoptotic cell death in NPCs but not in differentiated astrocytes. Furthermore, blocking T-type calcium channels rapidly reduced AKT-phosphorylation (Ser473) and GSK3β-phosphorylation (Ser9). Our results suggest that T-type calcium channels play essential roles in maintaining NPC viability, and T-type calcium channel blockers are toxic to embryonic neural cells, and may potentially be responsible for neurodevelopmental disorders.
Comparing the efficiency of Fib‐4, Egy‐score, APRI, and GUCI in liver fibrosis staging in Egyptians with chronic hepatitis C

Assessment of hepatic fibrosis in chronic hepatitis C virus patients by liver biopsy is not widely accepted despite its accuracy, being invasive, carrying complications, and adding cost. This paved the way to development and use of non‐invasive markers of fibrosis in diagnosis of hepatic fibrosis. We aimed at evaluating the efficiency of Fib‐4, Egy‐score, Aspartate‐to‐platelet ratio index (APRI), and Göteborg University Cirrhosis Index (GUCI) in comparison to liver biopsy, in the assessment of hepatic fibrosis in chronic hepatitis C patients. This was a cross sectional study including 200 chronic HCV patients were divided into two groups according to stage of fibrosis (Metavir score) into non‐significant fibrosis (1.27, APRI >0.48, Egy‐score >0.73, and GUCI >0.57 significantly predict significant fibrosis (P < 0.01). Fib‐4 carries the best performance and significant reliability with AUROC 0.783, sensitivity 74%, specificity 69%, PPV 0.55, and NPV 0.86. The addition of BMI to Fib‐4 improved the significant fibrosis AUROC curve performance but did not reach statistical significant improvement. We concluded that age and BMI are good predictors of hepatic fibrosis. Fib‐4 (>1.27) is the best method of prediction of significant fibrosis compared to Egy‐score, APRI, and GUCI. Addition of BMI to Fib‐4 did not improve diagnostic value of Fib‐4.
Genetic predisposition and induced pro-inflammatory/pro-oxidative status may play a role in increased atherothrombotic events in nilotinib treated chronic myeloid leukemia patients

Several reports described an increased risk of cardiovascular (CV) events, mainly atherothrombotic, in Chronic Myeloid Leukemia (CML) patients receiving nilotinib. However, the underlying mechanism remains elusive. The objective of the current cross-sectional retrospective study is to address a potential correlation between Tyrosine Kinase Inhibitors (TKIs) treatment and CV events. One hundred and 10 chronic phase CML patients in complete cytogenetic response during nilotinib or imatinib, were screened for CV events and evaluated for: traditional CV risk factors, pro/anti-inflammatory biochemical parameters and detrimental ORL1 gene polymorphisms (encoding for altered oxidized LDL receptor-1). Multivariate analysis of the whole cohort showed that the cluster of co-existing nilotinib treatment, dyslipidaemia and G allele of LOX-1 polymorphism was the only significant finding associated with CV events. Furthermore, multivariate analysis according to TKI treatment confirmed IVS4-14 G/G LOX-1 polymorphism as the strongest predictive factor for a higher incidence of CV events in nilotinib patients. Biochemical assessment showed an unbalanced pro-inflammatory cytokines network in nilotinib vs imatinib patients. Surprisingly, pre-existing traditional CV risk factors were not always predictive of CV events. We believe that in nilotinib patients an induced “inflammatory/oxidative status”, together with a genetic pro-atherothrombotic predisposition, may favour the increased incidence of CV events. Prospective studies focused on this issue are ongoing.
Isotopic characterization of aerosol organic carbon components over the eastern United States

[1] Carbon isotopic signatures (δ13C, Δ14C) of aerosol particulate matter total organic carbon (TOC) and operationally defined organic carbon (OC) components were measured in samples from two background sites in the eastern U.S. TOC and water-soluble OC (WSOC)δ13C values (−27 to −24‰) indicated predominantly terrestrial C3 plant and fossil derived sources. Total solvent extracts (TSE) and their aliphatic, aromatic, and polar OC components were depleted in δ13C (−30 to −26‰) relative to TOC and WSOC. Δ14C signatures of aerosol TOC and TSE (−476 to +25‰) suggest variable fossil contributions (∼5–50%) to these components. Aliphatic OC while comprising a small portion of the TOC (<1%), was dominated by fossil-derived carbon (86 ± 3%), indicating its potential utility as a tracer for fossil aerosol OC inputs. In contrast, aromatic OC contributions (<1.5%) contained approximately equal portions contemporary (52 ± 8%) and fossil (48 ± 8%) OC. The quantitatively significant polar OC fraction (6–25% of TOC) had fossil contributions (30 ± 12%) similar to TOC (26 ± 7%) and TSE (28 ± 9%). Thus, much of both of the fossil and contemporary OC is deduced to be oxidized, polar material. Aerosol WSOC consistently showed low fossil content (<8%) relative to the TOC (5–50%) indicating that the majority of fossil OC in aerosol particulates is insoluble. Therefore, on the basis of solubility and polarity, aerosols are predicted to partition differently once deposited to watersheds, and these chemically distinct components are predicted to contribute in quantitatively and qualitatively different ways to watershed carbon biogeochemistry and cycling.
Development and evaluation of an ultrasonic personal aerosol sampler

Abstract Assessing personal exposure to air pollution has long proven challenging due to technological limitations posed by the samplers themselves. Historically, wearable aerosol monitors have proven to be expensive, noisy, and burdensome. The objective of this work was to develop a new type of wearable monitor, an ultrasonic personal aerosol sampler (UPAS), to overcome many of the technological limitations in personal exposure assessment. The UPAS is a time‐integrated monitor that features a novel micropump that is virtually silent during operation. A suite of onboard environmental sensors integrated with this pump measure and record mass airflow (0.5–3.0 L/min, accurate within 5%), temperature, pressure, relative humidity, light intensity, and acceleration. Rapid development of the UPAS was made possible through recent advances in low‐cost electronics, open‐source programming platforms, and additive manufacturing for rapid prototyping. Interchangeable cyclone inlets provided a close match to the EPA PM2.5 mass criterion (within 5%) for device flows at either 1.0 or 2.0 L/min. Battery life varied from 23 to 45 hours depending on sample flow rate and selected filter media. Laboratory tests of the UPAS prototype demonstrate excellent agreement with equivalent federal reference method samplers for gravimetric analysis of PM2.5 across a broad range of concentrations.