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arXiv2016

Assessment of corticospinal tract dysfunction and disease severity in amyotrophic lateral sclerosis

The upper motor neuron dysfunction in amyotrophic lateral sclerosis was quantified using triple stimulation and more focal transcranial magnetic stimulation techniques that were developed to reduce recording variability. These measurements were combined with clinical and neurophysiological data to develop a novel random forest based supervised machine learning prediction model. This model was capable of predicting cross-sectional ALS disease severity as measured by the ALSFRSr scale with 97% overall accuracy and 99% precision. The machine learning model developed in this research provides a new, unique and objective diagnostic method for quantifying disease severity and identifying subtle changes in disease progression in ALS.

q-bio.NC↗

arXiv2016

When the clock strikes: Modeling the relation between circadian rhythms and cardiac arrhythmias

It has recently been observed that the occurrence of sudden cardiac death has a close statistical relationship with the time of day, viz., ventricular fibrillation is most likely to occur between 12 am-6 am, with 6 pm-12 am being the next most likely period. Consequently there has been significant interest in understanding how cardiac activity is influenced by the circadian clock, i.e., temporal oscillations in physiological activity with a period close to 24 hours and synchronized with the day-night cycle. Although studies have identified the genetic basis of circadian rhythms at the intracellular level, the mechanisms by which they influence cardiac pathologies are not yet fully understood. Evidence has suggested that diurnal variations in the conductance properties of ion channel proteins that govern the excitation dynamics of cardiac cells may provide the crucial link. In this paper, we investigate the relationship between the circadian rhythm as manifested in modulations of ion channel properties and the susceptibility to cardiac arrhythmias by using a mathematical model that describes electrical activity in ventricular tissue. We show that changes in the channel conductance that lead to extreme values for the duration of action potentials in cardiac cells can result either in abnormally high-frequency reentrant activity or spontaneous conduction block of excitation waves. Both phenomena increase the likelihood of wavebreaks that are known to initiate potentially life-threatening arrhythmias. Thus, disruptive cardiac excitation dynamics are most likely to occur in time-intervals of the day-night cycle during which the channel properties are closest to these extreme values, providing an intriguing relation between circadian rhythms and cardiac pathologies.

q-bio.TO↗

arXiv2017

A mathematical, in silico implemented, modular model for tumor growth in a spatially inhomogeneous, time-varying chemical environment (1st unrevised edition)

During the last decades, medical observations and multiscale data concerning tumor growth are mounting. At the same time, contemporary imaging techniques well established in clinical practice, provide a variety of information on real-time, in-vivo tumor growth. Mathematical and in-silico modeling has been widely recruited to provide means for further understanding of pertinent biological phenomena. However, despite the vast amounts of new evidence compiled by medical doctors, there are still many aspects of tumor growth that remain largely unknown. There is still a large variety of mechanisms to be better understood and therefore, many hypotheses to be tested. To approach this problem, starting from mathematical elaborations, we have developed a model of the early phases of tumor growth consisting of several algorithmic modules, each one corresponding to a particular biological mechanism. The modularity of the model allows keeping track of the assumptions made in each step and facilitates re-adjustment, in case new hypotheses need to be considered. Simulations showed good qualitative agreement with biological observations, and revealed a non-trivial interplay between between oxygen requirements of cancer cells and their maximum mitosis rates. The proposed model has, at least in principle, the potential to exploit data from contemporary imaging techniques and is eligible for utilizing multicore computation.

q-bio.TO↗

arXiv2016

3D hybrid modeling of vascular network formation

We develop an agent-based model of vasculogenesis, the de novo formation of blood vessels. Endothelial cells in the vessel network are viewed as linearly elastic spheres and are of two types: vessel elements are contained within the network; tip cells are located at endpoints. Tip cells move in response to forces due to interactions with neighbouring vessel elements, the local tissue environment, chemotaxis and a persistence force modeling their tendency to continue moving in the same direction. Vessel elements experience similar forces but not chemotaxis. An angular persistence force representing local tissue interactions stabilises buckling instabilities due to proliferation. Vessel elements proliferate, at rates that depend on their degree of stretch: elongated elements proliferate more rapidly than compressed elements. Following division, new cells are more likely to form new sprouts if the parent vessel is highly compressed and to be incorporated into the parent vessel if it is stretched. Model simulations reproduce key features of vasculogenesis. Parameter sensitivity analyses reveal significant changes in network size and morphology on varying the chemotactic sensitivity of tip cells, and the sensitivities of the proliferation rate and sprouting probability to mechanical stretch. Varying chemotactic sensitivity also affects network directionality. Branching and network density are influenced by the sprouting probability. Glyphs depicting multiple network properties show how network quantities change over time and as model parameters vary. We also show how glyphs constructed from in vivo data could be used to discriminate between normal and tumour vasculature and, ultimately, for model validation. We conclude that our biomechanical hybrid model generates vascular networks similar to those generated from in vitro and in vivo experiments.

q-bio.QM↗

arXiv2016

Space nutrition: the key role of nutrition in human space flight

From the basic impact of nutrient intake on health maintenance to the psychosocial benefits of mealtime, great advancements in nutritional sciences for support of human space travel have occurred over the past 60 years. Nutrition in space has many areas of impact, including provision of required nutrients and maintenance of endocrine, immune, and musculoskeletal systems. It is affected by environmental conditions such as radiation, temperature, and atmospheric pressures, and these are reviewed. Nutrition with respect to space flight is closely interconnected with other life sciences research disciplines including the study of hematology, immunology, as well as neurosensory, cardiovascular, gastrointestinal, circadian rhythms, and musculoskeletal physiology. Psychosocial aspects of nutrition are also important for more productive missions and crew morale. Research conducted to determine the impact of spaceflight on human physiology and subsequent nutritional requirements will also have direct and indirect applications in Earth-based nutrition research. Cumulative nutritional research over the past five decades has resulted in the current nutritional requirements for astronauts. Realization of the full role of nutrition during spaceflight is critical for the success of extended-duration missions. Long-duration missions will require quantitation of nutrient requirements for maintenance of health and protection against the effects of microgravity. Keywords: Space nutrition, space flight, effects of microgravity, astronauts, space food

q-bio.OT↗

arXiv2016

Histological and Histochemical Studies on the Esophagus, Stomach and Small Intestines of Vara-nus niloticus

The aim of the current study was to investigate the morphological structure of one of the most common reptilian species in Egypt, Varanus niloticus or Nile monitor. Specimens for histological examination were collected from the esophageus, stomach and small intestine of the Nile monitor and processed for paraffin embedding. Sections were stained with haematoxylin and eosin for general morphology. Periodic Acid Schiff's (PAS) and Alcian Blue (AB) staining methods were applied to detect the different types of the mucous con-tents of the gastro-intestinal tract. Some paraffin sections were stained with Grimelius silver impregnation technique for localization of the enteroendocrine cells. The folded esophageal mucosa had ciliated columnar epithelium with mucous secreting goblet cells, which stained positive with PAS and AB. The esophageal mucosa was folded and the lining epithelium was ciliated columnar epithelium with mucous secreting goblet cells, which stained positive with PAS and AB. The stomach was divided into fundic and pyloric regions. The mucosa was thrown into gastric pits, into which the gastric glands opened. The surface epithelium was mucous secreting columnar cells and stained positive with PAS but negative with AB. The fundic gland was made by oxynticopeptic cells and few mucous cells, while the entire pyloric gland was made by mucous cells stained positive for both PAS and AB. The small intestine showed many villi but occasional poorly developed intestinal crypts were. The intestinal mucosa was lined with absorptive columnar epithelium with goblet cells, which stained positive with PAS and AB. Enteroendocrine cells were of different shapes; rounded, spindle, oval or pyramidal and were localized in the surface epithelium of the esophagus and small intestine, and among the cells of the gastric glands.

q-bio.TO↗

arXiv2016

A Review of Mathematical Models for Muscular Dystrophy: A Systems Biology Approach

Muscular dystrophy (MD) describes generalized progressive muscular weakness due to the wasting of muscle fibers. The progression of the disease is affected by known immunological and mechanical factors, and possibly other unknown mechanisms. These dynamics have begun to be elucidated in the last two decades. This article reviews mathematical models of MD that characterize molecular and cellular components implicated in MD progression. A biological background for these processes is also presented. Molecular effectors that contribute to MD include mitochondrial bioenergetics and genetic factors; both drive cellular metabolism, communication and signaling. These molecular events leave cells vulnerable to mechanical stress which can activate an immunological cascade that weakens cells and surrounding tissues. This review article lays the foundation for a systems biology approach to study MD progression.

q-bio.QM↗

arXiv2016

New Insights into Initiation of Colon and Intestinal Cancer: The Significance of Central Stem Cells in the Crypt

Rapidly dividing tissues, like intestinal crypts, are frequently chosen to investigate the process of tumor initiation, because of their high rate of mutations. To study the interplay between normal and mutant as well as immortal cells in the human colon or intestinal crypt, we developed a 4-compartmental stochastic model for cell dynamics based on current discoveries. Recent studies of the intestinal crypt have revealed the existence of two stem cell groups. Therefore, our model incorporates two stem cell groups (central stem cells (CeSCs) and border stem cells (BSCs)), plus one compartment for transit amplifying (TA) cells and one compartment of fully differentiated (FD) cells. However, it can be easily modified to have only one stem cell group. We find that the worst-case scenario occurs when CeSCs are mutated, or an immortal cell arises in the TA or FD compartments. The probability that the progeny of a single advantageous CeSC mutant will take over the entire crypt is more than $0.2$, and one immortal cell always causes all FD cells to become immortals.Moreover, when CeSCs are either mutants or wild-type (w.t.) individuals, their progeny will take over the entire crypt in less than 100 days if there is no immortal cell. Unexpectedly, if the CeSCs are wild-type, then non-immortal mutants with higher fitness are washed out faster than those with lower fitness. Therefore, we suggest one potential treatment for colon cancer might be replacing or altering the CeSCs with the normal stem cells.

q-bio.TO↗

arXiv2016

Three-dimensional contact of TITH cartilage layers, a closed-form solution

Inhomogeneity and anisotropy play a crucial role in attributing articular cartilage its properties. The frictionless contact model constructed here consists in two thin biphasic transversely isotropic transversely homogeneous (TITH) cartilage layers firmly attached onto rigid substrates and shaped as elliptic paraboloids of different radii. Using asymptotic techniques, a solution to the deformation problem of such material has been recently obtained extending previous ones referred to homogeneous materials. The layer itself is thin in comparison with the size of the contact area and the observed time is shorter than the hydrogel characteristic time. The emerging three-dimensional contact problem is solved in closed-form and numerical benchmarks for constant and oscillating loads are given. The results are shown in terms of contact pressure and approach of the bones. The latter is derived to be directly proportional to the contact area. Existing experimental data are reinterpreted in view of the current model formulation. Comparisons are made with existing solutions for homogeneous biphasic materials in order to underline the functional importance of inhomogeneity in spreading the contact pressure distribution across the contact area. Particular attention is paid to the applicability of the retrieved formulas for interpreting measurements of in vivo experiments. Future directions are also prospected.

q-bio.TO↗

arXiv2018

Collective cell migration without proliferation: density determines cell velocity and wave velocity

Collective cell migration contributes to embryogenesis, wound healing and tumor metastasis. Cell monolayer migration experiments help understanding what determines the movement of cells far from the leading edge. Inhibiting cell proliferation limits cell density increase and prevents jamming; we observe long-duration migration and quantify space-time characteristics of the velocity profile over large length- and time-scales. Velocity waves propagate backwards and their frequency depends only on cell density at the moving front. Both cell average velocity and wave velocity increase linearly with the cell effective radius regardless of the distance to the front. Inhibiting lamellipodia decreases cell velocity while waves either disappear or have a lower frequency. Our model combines conservation laws, monolayer mechanical properties and a phenomenological coupling between strain and polarity: advancing cells pull on their followers which then become polarized. With reasonable values of parameters, this model agrees with several of our experimental observations. Together, our experiments and model disantangle the respective contributions of active velocity and of proliferation in monolayer migration, explain how cells maintain their polarity far from the moving front, and highlight the importance of strain-polarity coupling and density in long-range information propagation.

physics.bio-ph↗

arXiv2016

Lumbar degenerative spondylolisthesis epidemiology: a systemic review with a focus on gender-specific and age-specific prevalence

The epidemiology of lumbar degenerative spondylolisthesis (DS) remains controversial. We performed a systemic review with the aim to have a better understanding of DS's prevalence in general population. The results showed the prevalence of DS is very gender specific and age specific. Both women and men have few DS before 50 years old, after 50 years old both women and men start to develop DS, with women having a faster developing rate than men. For elderly Chinese (>=65 yrs, mean age: 72.5 yrs), large population based studies (MsOS(Hong Kong) and MrOS (Hong Kong), females n=2000 and males n=2000) showed DS prevalence was for 25.0% for women and 19.1% for men, and the prevalence F:M (women:men) ratio was 1.3:1. The published data (MsOS(USA) and MrOS(USA) studies) seem to show elderly Caucasian American has a higher DS prevalence, being approximately 60-70% higher than elderly Chinese; however the prevalence F:M ratio was similar to elderly Chinese population. Patient data showed female patients more often received treatment than men; and preliminary data show the ratio of numbers of female patients received treatment compared with men did not differ between Northeast Asians (Chinese, Japanese, and Korean) and European and American Caucasians, being around 2:1 in elderly population. The existing data also suggest that menopause may be a contributing factor for the accelerated DS development in post-menopausal

q-bio.TO↗

arXiv2016

Decreased aneurysmal subarachnoid hemorrhage incidence rate in elderly population than in middle aged population: a retrospective analysis of 8,144 cases in Mainland China

Purpose: Rupture of an intracranial aneurysm is the most common cause of subarachnoid haemorrhage (SAH), which is a life-threatening acute cerebrovascular event that typically affects working-age people. This study aims to investigate the aneurysmal SAH incidence rate in elderly population than in middle aged population in China. Materials and methods: Aneurysmal SAH cases were collected retrospectively from the archives of 21 hospitals in Mainland China. All the cases collected were from September 2016 and backward consecutively for a period of time up to 8 years. SAH was initially diagnosed by brain computed tomography, and CT angiography (CTA) or digital subtraction angiography (DSA) was followed and SAH was confirmed to be due to cerebral aneurysm. When for cases multiple bleeding occurred, the age of the first SAH was used in this study. The toltal incidence from all hospital at each age were summed together for females and males; then adjusted by the total population number at each age for females and males. The total population data was from the 2010 population census of the People's Republic of China. Results: In total there were 8,144 cases, with 4,861 females and 3,283 males. Our analysis shows for both females and males the relative aneurysmal SAH rate started to decrease after around 65 years old. The males the relative aneurysmal SAH rate might have started to decrease after around 55 years old. Conclusion: In contrast to previous reports, our data demonstrated a decreased aneurysmal subarachnoid hemorrhage incidence rate in elderly population than in middle aged population. Our data therefore support the hypothesis that aneurysms do not grow progressively once they form but probably either rupture or stabilize and that very elderly patients are at a reduced risk of rupture compared with atients who are younger with the same-sized aneurysms.

q-bio.TO↗

arXiv2016

Improved liver T1rho measurement precision with a breathhold black blood single shot fast spin echo acquisition: a validation study in healthy volunteers

Purpose: To explore the usability and normal T1rho value of liver parenchyma with a novel single breathhold black blood single shot fast spin echo acquisition based liver imaging sequence. Materials and Methods: In total 19 health subjects (10 males, 9 females; mean age: 37.4 yrs; range: 23-54 yrs) participated in the study. 11 subjects had liver scanned twice in the same session to access scan-rescan repeatability. 12 subjects had liver scanned twice in two sessions with 7-10 days' interval to access scan-rescan reproducibility. MR was performed with a 3.0 T scanner with dual transmitter. The MR sequence allows simultaneous acquisition of 4 spin lock times (TSLs: 0ms, 10 ms, 30 ms, 50ms) in 10 second. Inherent black blood effect of fast spin echo and double inversion recovery were utilized to achieve blood signal suppression. Results: The technique demonstrated good image quality and minimal artifacts. For liver parenchyma, Bland-Altman plot showed the scan-rescan repeatability mean difference was 0.025 ms (95% limits of agreement: -1.163 to 1.213 ms), and intraclass correlation coefficient (ICC) was 0.977. The scan-rescan reproducibility mean difference was -0.075 ms (95% limits of agreement: -3.280 to 3.310 ms), and ICC was 0.820 which is better than the ICC of 0.764 of a previous bright blood multi-breath hold gradient echo acquisition technique. The liver T1rho value was 39.9 +/- 2.4 ms (range: 36.1 - 44.2 ms), which is lower than the value of 42.8=/-2.1 ms acquired with the previous bright blood technique. Conclusion: This study validated the application of a single breathhold black blood single shot fast spin echo acquisition based for human liver T1rho imaging. The lower liver parenchyma T1rho value and higher scan rescan reproducibility may improve of the sensitivity of this technique.

q-bio.TO↗

arXiv2016

South Korean degenerative spondylolisthesis patients had surgical treatment at earlier age than Japanese, American, and European patients: a published literature observation

Physical therapy is the first line of treatment for adults with symptoms from degenerative spondylolisthesis. Surgical management is offered when nonoperative options have not adequately relieved symptoms. We performed PubMed literature search with the word 'spondylolisthesis', and updated till September 18, 2016. We selected original research data involving surgical treatment of degenerative spondylolisthesis, and in total there were n articles, including data reported from Japan (n=37 series), South Korea (n=11 series), mainland China (n=5 series), and ROC (Taiwan, n=3 series), America (n=20 series), Europe (n=23 series). The mean age of each study were extracted and used a single entry. We tried our best to filter out double/multiple reported data. Our results showed the median age of degenerative spondylolisthesis patients underwent surgical treatment was 66 years in Japan, 60 years in South Korea, 59 years in mainland China, 59 years in ROC (Taiwan), 65 years in USA, and 66 years in Europe. This study indicates Japan and South Korea may have different surgical practice pattern. It will be of interested to investigate whether more proportion of degenerative spondylolisthesis patients have been treated surgically in South Korea than in Japan. The cost-effectiveness of different approaches may warrant further analysis by professional spine surgeons.

q-bio.TO↗

arXiv2018

On a Cahn--Hilliard--Darcy system for tumour growth with solution dependent source terms

We study the existence of weak solutions to a mixture model for tumour growth that consists of a Cahn--Hilliard--Darcy system coupled with an elliptic reaction-diffusion equation. The Darcy law gives rise to an elliptic equation for the pressure that is coupled to the convective Cahn--Hilliard equation through convective and source terms. Both Dirichlet and Robin boundary conditions are considered for the pressure variable, which allows for the source terms to be dependent on the solution variables.

math.AP↗

arXiv2016

Multiple Sclerosis and Geomagnetic Disturbances: Investigating a Potentially Important Environmental Risk Factor

Multiple sclerosis (MS) is the most common disabling neurological disorders in the young adults. In spite of many researches, the cause of the disease has remained mainly not understood. All evidences indicate that environmental risk factors play key roles in this disease etiology. Various hypotheses have been posited up to now on the presumed disease risk factors, however, they were not successful in explaining all MS features. The aim of this article is to introduce the concept of the newly proposed "geomagnetic disturbance hypothesis of MS" and its abilities in explaining the special features of the disease to encourage medical geologist and other biomedical researchers to contribute to this area of research.

q-bio.TO↗

arXiv2016

Renal Parenchymal Area and Kidney Collagen Content

The extent of renal scarring in chronic kidney disease (CKD) can only be ascertained by highly invasive, painful and sometimes risky tissue biopsy. Interestingly, CKD-related abnormalities in kidney size can often be visualized using ultrasound. Nevertheless, not only does the ellipsoid formula used today underestimate true renal size but also the relation governing renal size and collagen content remains unclear. We used coronal kidney sections from healthy mice and mice with renal disease to develop a new technique for estimating the renal parenchymal area. While treating the kidney as an ellipse with the major axis the polar distance, this technique involves extending the minor axis into the renal pelvis. The calculated renal parenchymal area is remarkably similar to the measured area. Biochemically determined kidney collagen content revealed a strong and positive correlation with the calculated renal parenchymal area. The extent of renal scarring, i.e. kidney collagen content, can now be computed by making just two renal axial measurements which can easily be accomplished via noninvasive imaging of this organ.

q-bio.TO↗

arXiv2016

Prevalence of algorithm-based qualitative (ABQ) method osteoporotic vertebral fracture in elderly Chinese men and women with reference to semi-quantitative (SQ) method: Mr. Os and Ms Os. (Hong Kong) studies

Introduction: This study evaluated algorithm-based qualitative (ABQ) method for vertebral fracture (VF) evaluation with reference to semi-quantitative (SQ) method and bone mineral density (BMD) measurement. Methods: Mr. OS (Hong Kong) and Ms. OS (Hong Kong) represent the first large-scale cohort studies on bone health in elderly Chinese men and women. The current study compared Genant's SQ method and ABQ method in these two cohorts. Based on quantitative measurement, the severity of ABQ method detected fractures was additionally classified into grade-1, grad-2, and grade-3 according to SQ's deformity criteria. The radiographs of 1,954 elderly Chinese men (mean: 72.3 years) and 1,953 elderly Chinese women (mean: 72.5 years) were evaluated. Results: according to ABQ, grade-1,-2,-3 VFs accounted for 1.89%, 1.74%, 2.25% in men, and 3.33%, 3.07%, and 5.53% in women. In men and women, 15.7% (35/223) and 34.5% (48/139) of vertebrae with SQ grade-1 deformity were ABQ(+, with fracture) respectively. In men and women, 89.7% (35/39) and 66.7% (48/72) of vertebrae with ABQ grade-1 fracture had SQ grade-1 deformity. For grade-1 change, SQ (-, negative without fracture) & ABQ (+, positive with vertebral cortex line fracture) subjects tend to have a lower BMD than the SQ(+)& ABQ(-) subjects. In subjects with SQ grade-2 deformity, those were also ABQ(+) tended to have a lower BMD than those were ABQ(-). In all grades, SQ(-)&ABQ(-) subjects tended to have highest BMD, while SQ(+)&ABQ(+)subjects tended to have lowest BMD. Conclusion: ABQ method may be more sensitive to VF associated mild lower BMD than SQ method.

q-bio.TO↗