Validated method for automated glioma diagnosis from GFAP immunohistological images: a complete pipeline

Background and objective: Glial fibrillar acid protein is a common marker for brain tumor because of its particular rearrangement during tumor development. It is commonly used in manually histological glioma detection and grading. An automatic pipeline for tumor diagnosis based on GFAP is proposed in the present manuscript for detecting and grading canine brain glioma in stages III and IV. Methods: The study was performed on canine brain tumor stages III and IV as well as healthy tissue immunohistochemically stained for gliofibrillar astroglial protein. Four stereological indexes were developed using the area of the image as reference unit: density of glioma protein, density of neuropil, density of astrocytes and the glioma nuclei number density. Images of the slides were subset for image analysis (n=1415) and indexed. The stereological indexes of each subset constituted an array of data describing the tumor phase of the subset. A 5% of these arrays were used as training set for decision tree classification with PCA. The other arrays were further classified in a supervised approach. ANOVA and PCA analysis were applied to the indexes. Results: The final pipeline is able to detect brain tumor and to grade it automatically. Added to it, the role the neuropil during tumor development has been quantified for the first time. While astroglial cells tend to disappear, glioma cells invade all the tumor area almost to a saturation in stage III before reducing the density in stage IV. The density of the neuropil is reduced during the tumour growth. Conclusions: The method validated ere allows the automated diagnosis and grading of glioma in dogs. This method opens the research of the role of the neuropil in tumor development.

Prevalence of cardiac pathology and relation to mortality in a multiethnic population hospitalised with COVID-19

ObjectiveTo determine the prevalence of cardiac abnormalities and their relationship to markers of myocardial injury and mortality in patients admitted to hospital with COVID-19.MethodsA retrospective and prospective observational study of inpatients referred for transthoracic echocardiography for suspected cardiac pathology due to COVID-19 within a London NHS Trust. Echocardiograms were performed to assess left ventricular (LV), right ventricular (RV) and pulmonary variables along with collection of patient demographics, comorbid conditions, blood biomarkers and outcomes.ResultIn the predominant non-white (72%) population, RV dysfunction was the primary cardiac abnormality noted in 50% of patients, with RV fractional area change <35% being the most common marker of this RV dysfunction. By comparison, LV systolic dysfunction occurred in 18% of patients. RV dysfunction was associated with LV systolic dysfunction and the presence of a D-shaped LV throughout the cardiac cycle (marker of significant pulmonary artery hypertension). LV systolic dysfunction (p=0.002, HR 3.82, 95% CI 1.624 to 8.982), pulmonary valve acceleration time (p=0.024, HR 0.98, 95% CI 0.964 to 0.997)—marker of increased pulmonary vascular resistance, age (p=0.047, HR 1.027, 95% CI 1.000 to 1.055) and an episode of tachycardia measured from admission to time of echo (p=0.004, HR 6.183, 95% CI 1.772 to 21.575) were independently associated with mortality.ConclusionsIn this predominantly non-white population hospitalised with COVID-19, the most common cardiac pathology was RV dysfunction which is associated with both LV systolic dysfunction and elevated pulmonary artery pressure. The latter two, not RV dysfunction, were associated with mortality.

Secondary biphenotypic leukemia following Rosai-Dorfman-Disease A coincidence?

Rosai-Dorman-Disease is one subgroup of Non-Langerhans cell histiocytosis with massive lymphadenopathy. It is a generally a benign and self-limiting disease, but an association to hemato-lymphoid malignancies or immune diseases is suspected. We present the case of a 6-year old male patient with multifocal extranodal RDD developing a secondary biphenotypic, treatment-resistant leukemia during treatment. Hypothysing that RDD and the secondary leukemia could be based on the same malign clone or on a cancer predispostion syndrome, whole-exome-sequencing of a saliva sample and leukemic cells were performed. A common marker of cell lines of histiocytosis and leukemic blasts has not been found.

Trilogy Of Southeast Sundaland Terranes: Re-Uniting Drifted Terranes of Southeast Sundaland Using Common Marker ff The Late Cretaceous Volcanics to Volcanic-Clastics of The Meratus Mountains, South Sulawesi, And Sumba - Implications For Petroleum Opportunities

Amalgamation and dispersion of terranes characterized the growth and slivering of Southeast Sundaland into the present configuration of central Indonesia. Amalgamation of the Paternoster-West Sulawesi terrane which docked, in mid-Cretaceous time, onto the Southwest Borneo terrane, thus closed the Meso-Tethys Ocean at the Meratus suture. This made Sundaland expand its area to the east and southeast. In the Late Cretaceous time, the Ceno-Tethys oceanic plate subducted beneath Southeast Sundaland, giving rise to coeval volcanism in the Meratus Mountains and the surrounding areas. Dispersion of some terranes in Southeast Sundaland occurred in the Paleogene through successive rifting and the opening of the Makassar Straits and the Flores Sea, with an eastern drift of South Sulawesi and Sumba away from Southeast Kalimantan to their present positions. Prior to the dispersion, the Meratus Mountains, South Sulawesi, and Sumba (called here the Trilogy of Southeast Sundaland) were united or adjacent to each other and underwent similar Late Cretaceous volcanism. The Late Cretaceous Volcanics and/or Volcanic-Clastics are therefore the common marker of their union. Our field studies in 2018-2019 at Sumba, South Sulawesi, and the Meratus Mountains (South Kalimantan) in the program, called the “Trilogy of Southeast Sundaland Terranes,” sampled the Late Cretaceous volcanics/ volcanic-clastics in these areas to prove that they were once united. Petrographic, petrochemical, isotopic, and geochronological data of the rock formations, based on the recent and previous analyses, show that these rocks, in the three terranes, are co-genetic spatially and temporally thus indicating their previous unity. The paired Paleogene dispersions of South Sulawesi from South Kalimantan, and successively Sumba from South Sulawesi, had resulted in rifted structures in the present Makassar Straits, the Flores Sea, and offshore Sumba. The rifted structures contain source rocks, reservoirs, seals, and structural-stratigraphic traps. Oil has been discovered therein, so further exploration is required since these objectives have not been sufficiently explored in the past and are thus still interesting.

No-go trials in task switching: effects on the task-set and task-space level

A common marker for inhibition processes in task switching are n − 2 repetition costs. The present study aimed at elucidating effects of no-go trials on n − 2 repetition costs. In contrast to the previous studies, no-go trials were associated with only one of the three tasks in the present two experiments. High n − 2 repetition costs occurred if the no-go task had to be executed in trial n − 2, irrespective of whether a response had to be withheld or not. In contrast, no n − 2 repetition costs were visible if the other two tasks were relevant in n − 2. Whereas this n − 2 effect was unaffected by whether participants could reliably exclude a no-go trial or not, effects of no-gos in trial n were determined by this knowledge. The results differ from effects of no-go trials that are not bound to a specific task. It is assumed that the present no-go variation exerted its effect not on the response level, but on the level of task sets, resulting in enhanced salience of the no-go task that leads to higher activation and, as a consequence, to stronger inhibition. The dissociation of the effects on no-gos in trials n − 2 and n as a function of foreknowledge suggests that the balance between activation and inhibition is shifted not only for single trials and tasks, but for the whole task space.

Brain Morphometry and Diminished Physical Growth in Bangladeshi Children Growing up in Extreme Poverty: a Longitudinal Study

Diminished physical growth is a common marker of malnutrition and it affects approximately 200 million children worldwide. Despite its importance and prevalence, it is not clear whether diminished growth affects brain development and neurocognitive outcomes. Further, diminished growth is more common in areas of extreme poverty, raising the possibility that it may serve as a mechanism for previously shown links between poverty and brain development. To address these questions, 79 children growing up in an extremely poor, urban area of Bangladesh underwent MRI at 6 years. Structural brain images were submitted to Mindboggle software, a Docker-compliant and highly reproducible tool for tissue segmentation and regional estimations of volume, surface area, cortical thickness, travel depth, and mean curvature. Diminished growth predicted brain morphometry and mediated the link between poverty and brain morphometry most consistently for white matter and subcortical volumes. Meanwhile, brain volume in left pallidum and right ventral diencephalon mediated the relationship between diminished growth and full-scale IQ. These findings offer malnutrition as one possible mechanism by which poverty affects brain development and neurocognitive outcomes in areas of extreme poverty.

Genitourinary syndrome of menopause: a modern approach to treatment

Life expectancy over the past half century has increased significantly and by 2025 approximately one in six people on Earth will be over 60 years old, thus, age-related diseases become even more relevant, this also applies to menopausal syndrome in postmenopausal women. The average age of menopause is 5052 years. In the world 25 million women annually experience menopause and only 10% of them have no pathological manifestations. Genitourinar menopausal syndrome is the second most common marker of menopause. Urogenital disorders are a fairly common nosology, which is confirmed by numerous studies, but not every woman considers it necessary to report a problem to a doctor, considering this a natural course of aging. The increase in life expectancy and rejuvenation of the population is undoubtedly associated with socio-social development and the achievement of medicine, the purpose of which is also to increase the extension of the term of a healthy and quality life. Studies conducted in recent decades to study atrophic hypoestrogenic changes in the urogenital tract will allow us to reconsider our attitude to genitourinar menopausal syndrome and to select appropriate treatment for various groups of patients. But the inability of women, at times, to declare their symptoms associated with vulvovaginal atrophy, and the lack of active interest in this issue by doctors, especially gynecologists, leaves this problem unresolved.

Concurrent assessment of gait kinematics using marker-based and markerless motion capture

Kinematic analysis is a useful and widespread tool used in research and clinical biomechanics for the estimation of human pose and the quantification of human movement. Common marker-based optical motion capture systems are expensive, time intensive, and require highly trained operators to obtain kinematic data. Markerless motion capture systems offer an alternative method for the measurement of kinematic data with several practical benefits. This work compared the kinematics of human gait measured using a deep learning algorithm-based markerless motion capture system to those of a common marker-based motion capture system. Thirty healthy adult participants walked on a treadmill while data were simultaneously recorded using eight video cameras (markerless) and seven infrared optical motion capture cameras (marker-based). Video data were processed using markerless motion capture software, marker-based data were processed using marker-based capture software, and both sets of data were compared. The average root mean square distance (RMSD) between corresponding joints was less than 3 cm for all joints except the hip, which was 4.1 cm. Lower limb segment angles indicated pose estimates from both systems were very similar, with RMSD of less than 6° for all segment angles except those that represent rotations about the long axis of the segment. Lower limb joint angles captured similar patterns for flexion/extension at all joints, ab/adduction at the knee and hip, and toe-in/toe-out at the ankle. These findings demonstrate markerless motion capture can measure similar 3D kinematics to those from marker-based systems.

Neuronal NOX4 knockdown alleviates pathological tau-related alterations in a humanized mouse model of tauopathy

Approximately 44 million people worldwide live with Alzheimer’s disease (AD) or a related form of dementia. Aggregates of the microtubule-associated protein tau are a common marker of these neurodegenerative diseases collectively termed as tauopathies. However, all therapeutic attempts based on tau have failed, suggesting that tau may only indicate a higher-level causal mechanism. For example, increasing levels of reactive oxygen species (ROS) may trigger protein aggregation or modulate protein degradation. Here we show that type 4 NADPH oxidase (NOX), the most abundant isoform of the only dedicated reactive oxygen producing enzyme family, is upregulated in dementia and AD patients and in a humanized mouse model of tauopathy. Both global knockout and neuronal knockdown of the Nox4 gene in mice, diminished the accumulation of pathological tau and positively modified established tauopathy by a mechanism that implicates modulation of the autophagy-lysosomal pathway (ALP). Moreover, neuronal-targeted NOX4 knockdown was sufficient to reduce neurotoxicity and prevented cognitive decline, suggesting a direct and causal role for neuronal NOX4. Thus, NOX4 is a previously unrecognized causal, mechanism-based target in tauopathies and blood-brain barrier permeable specific NOX4 inhibitors could have therapeutic potential even in established disease.Graphical abstract