Summary
Globozoospermia and acephalic spermatozoa are two rare sperm head anomalies associated with male infertility. Combination of the two phenotypes in the same patient is extremely rare, so the ...underlying pathogenesis of this disorder remains unclear. Here, we report a 35‐year‐old infertile male, who presented with 30% of sperm‐lacked heads and 69% of sperm round‐headed or small‐headed with neck thickening in his ejaculate. Subsequent whole‐exome sequencing (WES) analysis identified compound heterozygous variants within the DNAH6 gene. DNAH6 is a testis‐specific‐expressed protein that was localised to the neck region in the spermatozoa of normal control; however, immunofluorescent staining failed to detect DNAH6 protein in the patient's spermatozoa. Quantitative real‐time PCR analysis also showed the complete absence of DNAH6 mRNA in the patient's spermatozoa. Moreover, two cycles of in vitro fertilisation (IVF)‐assisted reproduction were carried out, but pregnancy was not achieved after embryo transfer. Therefore, rare sequence variants in DNAH6 might be susceptibility risks for human sperm head anomaly.
The World Health Organization has recently placed new emphasis on the integration of genetic information for gliomas. While tissue sampling remains the criterion standard, noninvasive imaging ...techniques may provide complimentary insight into clinically relevant genetic mutations. Our aim was to train a convolutional neural network to independently predict underlying molecular genetic mutation status in gliomas with high accuracy and identify the most predictive imaging features for each mutation.
MR imaging data and molecular information were retrospectively obtained from The Cancer Imaging Archives for 259 patients with either low- or high-grade gliomas. A convolutional neural network was trained to classify
(
) mutation status, 1p/19q codeletion, and
(
) promotor methylation status. Principal component analysis of the final convolutional neural network layer was used to extract the key imaging features critical for successful classification.
Classification had high accuracy:
mutation status, 94%; 1p/19q codeletion, 92%; and
promotor methylation status, 83%. Each genetic category was also associated with distinctive imaging features such as definition of tumor margins, T1 and FLAIR suppression, extent of edema, extent of necrosis, and textural features.
Our results indicate that for The Cancer Imaging Archives dataset, machine-learning approaches allow classification of individual genetic mutations of both low- and high-grade gliomas. We show that relevant MR imaging features acquired from an added dimensionality-reduction technique demonstrate that neural networks are capable of learning key imaging components without prior feature selection or human-directed training.
We present Atacama Large Millimeter/submillimeter Array and Multi-Unit Spectroscopic Explorer observations of the brightest cluster galaxy in Abell 2597, a nearby (z = 0.0821) cool core cluster of ...galaxies. The data map the kinematics of a three billion solar mass filamentary nebula that spans the innermost 30 kpc of the galaxy's core. Its warm ionized and cold molecular components are both cospatial and comoving, consistent with the hypothesis that the optical nebula traces the warm envelopes of many cold molecular clouds that drift in the velocity field of the hot X-ray atmosphere. The clouds are not in dynamical equilibrium, and instead show evidence for inflow toward the central supermassive black hole, outflow along the jets it launches, and uplift by the buoyant hot bubbles those jets inflate. The entire scenario is therefore consistent with a galaxy-spanning "fountain," wherein cold gas clouds drain into the black hole accretion reservoir, powering jets and bubbles that uplift a cooling plume of low-entropy multiphase gas, which may stimulate additional cooling and accretion as part of a self-regulating feedback loop. All velocities are below the escape speed from the galaxy, and so these clouds should rain back toward the galaxy center from which they came, keeping the fountain long lived. The data are consistent with major predictions of chaotic cold accretion, precipitation, and stimulated feedback models, and may trace processes fundamental to galaxy evolution at effectively all mass scales.
Heavy alcohol drinking has been related to pancreatic cancer, but the issue is still unsolved.
To evaluate the role of alcohol consumption in relation to pancreatic cancer, we conducted a pooled ...analysis of 10 case–control studies (5585 cases and 11 827 controls) participating in the International Pancreatic Cancer Case–Control Consortium. We computed pooled odds ratios (ORs) by estimating study-specific ORs adjusted for selected covariates and pooling them using random effects models.
Compared with abstainers and occasional drinkers (<1 drink per day), we observed no association for light-to-moderate alcohol consumption (≤4 drinks per day) and pancreatic cancer risk; however, associations were above unity for higher consumption levels (OR = 1.6, 95% confidence interval 1.2–2.2 for subjects drinking ≥9 drinks per day). Results did not change substantially when we evaluated associations by tobacco smoking status, or when we excluded participants who reported a history of pancreatitis, or participants whose data were based upon proxy responses. Further, no notable differences in pooled risk estimates emerged across strata of sex, age, race, study type, and study area.
This collaborative-pooled analysis provides additional evidence for a positive association between heavy alcohol consumption and the risk of pancreatic cancer.
The radiation belts and plasma in the Earth’s magnetosphere pose hazards to satellite systems which restrict design and orbit options with a resultant impact on mission performance and cost. For ...decades the standard space environment specification used for spacecraft design has been provided by the NASA AE8 and AP8 trapped radiation belt models. There are well-known limitations on their performance, however, and the need for a new trapped radiation and plasma model has been recognized by the engineering community for some time. To address this challenge a new set of models, denoted AE9/AP9/SPM, for energetic electrons, energetic protons and space plasma has been developed. The new models offer significant improvements including more detailed spatial resolution and the quantification of uncertainty due to both space weather and instrument errors. Fundamental to the model design, construction and operation are a number of new data sets and a novel statistical approach which captures first order temporal and spatial correlations allowing for the Monte-Carlo estimation of flux thresholds for user-specified percentile levels (e.g., 50th and 95th) over the course of the mission. An overview of the model architecture, data reduction methods, statistics algorithms, user application and initial validation is presented in this paper.
Coronavirus disease 2019 (COVID-19) is a highly heterogeneous disease regarding severity, vulnerability to infection due to comorbidities, and treatment approaches. The hypothalamic–pituitary–adrenal ...(HPA) axis has been identified as one of the most critical endocrine targets of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that might significantly impact outcomes after infection. Herein we review the rationale for glucocorticoid use in the setting of COVID-19 and emphasize the need to have a low index of suspicion for glucocorticoid-induced adrenal insufficiency, adjusting for the glucocorticoid formulation used, dose, treatment duration, and underlying health problems. We also address several additional mechanisms that may cause HPA axis dysfunction, including critical illness-related corticosteroid insufficiency, the direct cytopathic impacts of SARS-CoV-2 infection on the adrenals, pituitary, and hypothalamus, immune-mediated inflammations, small vessel vasculitis, microthrombotic events, the resistance of cortisol receptors, and impaired post-receptor signaling, as well as the dissociation of ACTH and cortisol regulation. We also discuss the increased risk of infection and more severe illness in COVID-19 patients with pre-existing disorders of the HPA axis, from insufficiency to excess. These insights into the complex regulation of the HPA axis reveal how well the body performs in its adaptive survival mechanism during a severe infection, such as SARS-CoV-2, and how many parameters might disbalance the outcomes of this adaptation.
Manipulating the surface energy, and thereby the wetting properties of solids, has promise for various physical, chemical, biological and industrial processes. Typically, this is achieved by either ...chemical modification or by controlling the hierarchical structures of surfaces. Here we report a phenomenon whereby the wetting properties of vermiculite laminates are controlled by the hydrated cations on the surface and in the interlamellar space. We find that vermiculite laminates can be tuned from superhydrophilic to hydrophobic simply by exchanging the cations; hydrophilicity decreases with increasing cation hydration free energy, except for lithium. The lithium-exchanged vermiculite laminate is found to provide a superhydrophilic surface due to its anomalous hydrated structure at the vermiculite surface. Building on these findings, we demonstrate the potential application of superhydrophilic lithium exchanged vermiculite as a thin coating layer on microfiltration membranes to resist fouling, and thus, we address a major challenge for oil-water separation technology.
We recently used in situ Hi-C to create kilobase-resolution 3D maps of mammalian genomes. Here, we combine these maps with new Hi-C, microscopy, and genome-editing experiments to study the physical ...structure of chromatin fibers, domains, and loops. We find that the observed contact domains are inconsistent with the equilibrium state for an ordinary condensed polymer. Combining Hi-C data and novel mathematical theorems, we show that contact domains are also not consistent with a fractal globule. Instead, we use physical simulations to study two models of genome folding. In one, intermonomer attraction during polymer condensation leads to formation of an anisotropic “tension globule.” In the other, CCCTC-binding factor (CTCF) and cohesin act together to extrude unknotted loops during interphase. Bothmodels are consistent with the observed contact domains and with the observation that contact domains tend to form inside loops. However, the extrusion model explains a far wider array of observations, such as why loops tend not to overlap and why the CTCF-binding motifs at pairs of loop anchors lie in the convergent orientation. Finally, we perform 13 genome-editing experiments examining the effect of altering CTCF-binding sites on chromatin folding. The convergent rule correctly predicts the affected loops in every case. Moreover, the extrusion model accurately predicts in silico the 3D maps resulting from each experiment using only the location of CTCF-binding sites in the WT. Thus, we show that it is possible to disrupt, restore, and move loops and domains using targeted mutations as small as a single base pair.
To evaluate the dose–response relationship between cigarette smoking and pancreatic cancer and to examine the effects of temporal variables.
We analyzed data from 12 case–control studies within the ...International Pancreatic Cancer Case–Control Consortium (PanC4), including 6507 pancreatic cases and 12 890 controls. We estimated summary odds ratios (ORs) by pooling study-specific ORs using random-effects models.
Compared with never smokers, the OR was 1.2 (95% confidence interval CI 1.0–1.3) for former smokers and 2.2 (95% CI 1.7–2.8) for current cigarette smokers, with a significant increasing trend in risk with increasing number of cigarettes among current smokers (OR = 3.4 for ≥35 cigarettes per day, P for trend <0.0001). Risk increased in relation to duration of cigarette smoking up to 40 years of smoking (OR = 2.4). No trend in risk was observed for age at starting cigarette smoking, whereas risk decreased with increasing time since cigarette cessation, the OR being 0.98 after 20 years.
This uniquely large pooled analysis confirms that current cigarette smoking is associated with a twofold increased risk of pancreatic cancer and that the risk increases with the number of cigarettes smoked and duration of smoking. Risk of pancreatic cancer reaches the level of never smokers ∼20 years after quitting.
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