Miracle-dz/UniFAR-FTUs huggingface dataset:
Laser Ablation of Recurrent Malignant Gliomas: Current Status and Future Perspective.

Recurrent malignant glioma continues to be a clinical challenge, and repeat surgery is an option in only select patients. Stereotactic laser ablation, a new minimally invasive technique, can be used as an alternative to surgery. We review the current literature on laser ablation for recurrent malignant gliomas as well as discuss practical and theoretical advantages and disadvantages of this emerging technique in comparison with repeat surgery or radiation. We also discuss the potential for laser ablation to augment adjuvant therapies, namely, chemotherapy, radiation, and immunotherapy. ABBREVIATIONS BBB, blood-brain barrierBVZ, bevacizumabHGG, high-grade gliomaLITT, laser interstitial thermotherapyTMZ, temozolomide.
Bedaquiline in the treatment of multidrug- and extensively drug-resistant tuberculosis

Bedaquiline, a diarylquinoline, improved cure rates when added to a multidrug-resistant tuberculosis (MDR-TB) treatment regimen in a previous placebo-controlled, phase 2 trial (TMC207-C208; NCT00449644). The current phase 2, multicenter, open-label, single-arm trial (TMC207-C209; NCT00910871) reported here was conducted to confirm the safety and efficacy of bedaquiline. Newly diagnosed or previously treated patients with MDR-TB (including pre-extensively drug-resistant (pre-XDR)-TB or extensively drug-resistant (XDR)-TB) received bedaquiline for 24 weeks with a background regimen of anti-TB drugs continued according to National TB Programme treatment guidelines. Patients were assessed during and up to 120 weeks after starting bedaquiline. Of 233 enrolled patients, 63.5% had MDR-TB, 18.9% had pre-XDR-TB and 16.3% had XDR-TB, with 87.1% having taken second-line drugs prior to enrolment. 16 patients (6.9%) died. 20 patients (8.6%) discontinued before week 24, most commonly due to adverse events or MDR-TB-related events. Adverse events were generally those commonly associated with MDR-TB treatment. In the efficacy population (n=205), culture conversion (missing outcome classified as failure) was 72.2% at 120 weeks, and 73.1%, 70.5% and 62.2% in MDR-TB, pre-XDR-TB and XDR-TB patients, respectively. Addition of bedaquiline to a background regimen was well tolerated and led to good outcomes in this clinically relevant patient cohort with MDR-TB. Bedaquiline safety data in a broad patient population treated for drug-resistant TB including XDR-TB (C209 study) http://ow.ly/TcZBh
Intravitreal injection of exendin-4 analogue protects retinal cells in early diabetic rats.

PURPOSE To evaluate the protective effect of intravitreal injection of exendin-4 analogue (E4a) in early diabetic retinopathy (DR) and to explore its possible mechanism. METHODS Forty Sprague-Dawley rats were divided into three groups: normal (N), diabetic (D), and E4a-treated diabetic rats (E4a). Diabetes was induced by streptozotocin. Rats in the E4a group were treated with E4a (0.1 μg/2μL/eye), whereas the N and D groups were treated with the equivalent volume of normal saline. Electroretinography was performed at 1 month and 3 months after diabetes onset. Thicknesses and cell counts in each layer of the retina were evaluated. The concentration of glutamate was measured by high-performance liquid chromatography (HPLC). Expressions of glucagon-like peptide-1 receptor (GLP-1R) and GLAST (excitatory amino acid transporter) were detected at mRNA and protein levels and verified by immunohistochemistry in vitro and in vivo. The rMc-1 cells were cultured under high-glucose medium (25 mM), which mimicked diabetic conditions. Effects of E4a (10 μg/mL) were also tested in the rMc-1 culture system. RESULTS E4a prevented the reduction in b-wave amplitude and oscillatory potential amplitude caused by diabetes. It also prevented the cell loss of outer nuclear layer and inner nuclear layer; the thickness and cell count in the outer nuclear layer were decreased in 1-month diabetic rats. The concentration of glutamate in the retina was higher in diabetic rats and was significantly reduced in the E4a-treated group. Consistent with such changes, retinal GLP-1R and GLAST expression were reduced in the diabetic retina but upregulated in E4a-treated rats. No improvement was found in the retina in both functional and morphologic parameters 3 months after treatment. CONCLUSIONS Intravitreal administration of E4a can prevent the retina, functionally and morphologically, from the insults of diabetes in rats. GLP-1R and GLAST were proved to exist in the rat retina, and their lowered expressions in the diabetic retina might be related to retinal damage by increasing the retinal glutamate. E4a might protect the retina by reducing the glutamate level through upregulating GLP-1R and GLAST, as observed in retinal Müller cells in this study, but this protective effect was transient. Thus, this could be a potential approach for the treatment of DR.
Extracorporeal shockwave lithotripsy for solitary distal ureteral stones: does the degree of urinary obstruction affect success?

BACKGROUND AND PURPOSE Extracorporeal shockwave lithotripsy (SWL) is a safe and effective way to treat stones in the distal ureter, but the impact of urinary obstruction on outcome is not clear. We investigated the relation between the degree of stone-induced urinary obstruction and the outcome of SWL treatment in patients with solitary distal ureteral stones. PATIENTS AND METHODS A series of 165 consecutive patients with solitary distal ureteral stones underwent SWL (Multimed 9200 Lithotriptor, Elmed Medical Systems, Turkey) between October 2002 and September 2003 at two separate centers. Distal ureteral stones were defined as those located below the lower border of the sacroiliac joint. Patients were divided into four groups according to the degree of stone-induced urinary obstruction: group I (N = 62) had no urinary system dilation; group II (N = 40) had mild dilation, group III (N = 35) moderate dilation, and group IV (N = 28) severe dilation. In addition to degree of obstruction, stone size, average fluoroscopy time, total number of shockwaves applied, number of sessions required to achieve stone-free status, and stone clearance time were recorded. Treatment failure was defined as persistence of fragments after three SWL sessions. RESULTS Overall, 152 (92.1%) of the patients became stone free after SWL. There were no statistically significant differences among the groups with respect to any of the factors studied. CONCLUSION In cases where there is a solitary calculus in the distal ureter, the degree of urinary obstruction caused by the stone does not affect the success of stone clearance with SWL.
Bounds for the covariance of functions of infinite variance stable random variables with applications to central limit theorems and wavelet-based estimation

We establish bounds for the covariance of a large class of functions of infinite variance stable random variables, including unbounded functions such as the power function and the logarithm. These bounds involve measures of dependence between the stable variables, some of which are new. The bounds are also used to deduce the central limit theorem for unbounded functions of stable moving average time series. This result extends the earlier results of Tailen Hsing and the authors on central limit theorems for bounded functions of stable moving averages. It can be used to show asymptotic normality of wavelet-based estimators of the self-similarity parameter in fractional stable motions.
Cochlear Implantation Assisted by Noninvasive Image Guidance

Objective We recently developed a new noninvasive registration method for image-guided otologic surgery (STAMP method). We investigated the benefit and potential drawback of our new method in clinical application and tested the feasibility of routine image-guided surgery. Study Design Retrospective case review. Setting Tertiary referral university hospital. Patients Forty-six cases (45 patients) that underwent cochlear implantation in Kyushu University Hospital during the period of 2007 and 2010 were informed of the option to use navigated surgery. Intervention Twenty-five cochlear implantations were performed using STAMP-registered image-guided surgery. Main Outcome Measure The error of image-guided surgery and time of surgery were collected and analyzed. Results STAMP method offered serviceable accuracy in 18/25 cochlear implantations. The learning curve suggested that the accuracy is at least stabilizing, if not improving, and the success rate is expected to rise. Time of cochlear implant surgery was not significantly extended by the use of image guidance. Conclusion STAMP method had comparable errors with minimal invasiveness. Our new method potentially enables routine use of image-guided surgery.
Dependence of action potential duration on extracellular calcium concentration in a model of human ventricular myocyte

The mechanisms underlying the inverse relation between extracellular calcium concentration ([Ca<sup>2+</sup>]<sub>O</sub>) and action potential duration (APD) in ventricular myocytes are not fully clear. We computationally analysed the effects of [Ca<sup>2+</sup> ]<sub>O</sub> variations on APD of human cardiac myocyte by means of the Ten Tusscher (2004) model. The I<sub>CaL</sub> current description was then modified in order to make the simulated results coherent with experimental findings. The original model formulation produced opposite results with respect to the expected trend, i.e. an increase of APD when ([Ca<sup>2+</sup>]<sub>O</sub> was observed. By strengthening the Ca<sup>2+</sup> -dependent inactivation of I<sub>CaL</sub> it was possible to reproduce the reduction of APD when increasing [Ca<sup>2+</sup>]<sub>O</sub>. The mechanism of Ca -dependent I<sub>CaL</sub> inactivation seems to be an high sensible pathway for APD adaptation to variations in ([Ca<sup>2+</sup>]<sub>O</sub>.
Anatomy: Spotlight on Africa

Anatomy departments across Africa were surveyed regarding the type of curriculum and method of delivery of their medical courses. While the response rate was low, African anatomy departments appear to be in line with the rest of the world in that many have introduced problem based learning, have hours that are within the range of western medical schools and appear to be well resourced. Human body dissection is a constant and strong aspect of the majority of the courses surveyed. The staff to student ratio appears to be relatively high in Africa, but in many of the responding African institutions, there appears to be little difficulty in attracting suitable faculty (including those who are medically qualified) to teach anatomy. Retaining this faculty, in some cases, may be difficult because of a global demand for anatomy educators. Anat Sci Ed 1:111–118, 2008. © 2008 American Association of Anatomists.
Body Size in Five-Year-Old Twins: Heritability and Comparison to Singleton Standards

Abstract The aim of this study is to examine causes of individual differences in height, weight and body mass index (BMI) in 5-year-old children registered with the Netherlands Twin Register. In addition, we examine whether the results of twin studies can be expanded to the singleton population by comparing the data from twins to Dutch reference growth data and by looking at the twins' target height, which was derived from parental height. For 2996 5-year-old twin pairs, information on height and weight and on parental height was available. Univariate and bivariate genetic analyses of height and weight and univariate analyses of BMI were conducted. In order to compare the twins to the singleton population, standard deviation scores (SDS) for height, BMI and target height were calculated based on Dutch reference growth charts for the general population from 1997. Genetic influences were an important source of variation in height, weight and BMI and the main source of covariation between height and weight. Additive genetic factors accounted for 69% and 66% of the individual differences in height in boys and girls, respectively. For weight, heritability estimates were 59% in boys and 78% in girls and for BMI 34% and 74%. The influence of common environment on height was 25% and 27%, on weight 24% and 10% and on BMI 44% and 12% in boys and girls. The bivariate model showed a large overlap between the genes influencing height and weight. Genes explain 78% (in boys) and 76% (in girls) of the covariance between weight and height. At the age of 5 years, female twins were as tall as singleton children, while male twins were shorter than singletons. For both boys and girls, however, mean height SDS was 0.6 standard deviation scores below the mean target height. All twins had lower BMI than singletons. Twins grow fairly well compared to singletons, but they grow below their target height. This may be due to the above average height of twin parents.
Modeling and Control of Single- Link Flexible Arms With Lumped Masses

This paper deals with the modeling and control of a special class of single-link flexible arms. These arms consist of flexible massless structures having some masses concentrated at certain points of the beam. In this paper, the dynamic model of such flexible arms is dewloped and some of the control properties are deduced. A robust control scheme to remove the effects of friction in the joins is proposed. The control scheme consists of two nested feedback loops, an inner loop to control the position of the motor and an outer loop to control the tip position. The inner loop is described in other publications. A simple fedforward-feedback controller is designed for the outer loop to driw the beam accurately along a desired trajectoty. Effects of the changes in the tip’s mass are studied. This modeling and control method is then generalized to the distributed-mass flexible beam case. Finally, experimentaf results are presented. This paper deals with the modeling and control of a special class of single-link, lumped-mass, flexible arms. These arms consist of massless flexible structures that have masses concentrated at certain points of the beam (see Fig. 1). Although the translations of these masses produce stresses in the flexible structure, their rotations do not generate any torque in the beam. Therefore, the number of vibrational modes in the structure coincides with the number of lumped masses. Book (1979) studied the case of two rigid masses connected by a chain of massless beams having an arbitrary number of rotation joints. Our problem differs from this in the sense that our structure has only one rotation joint and an arbitrary number of lumped masses. These two particular structures are studied because: Some lightweight robots and other applications can be reasonably approximated by these models. Their dynamics may be easily modeled as compared to distributed-mass flexible arms. Interesting properties for the control of flexible arms are deduced from their dynamic models. A method to control these arms is inferred from the structure of the model. The influence of changes in the tip’s mass are easily characterized. Given a distributed-mass flexible arm, there always exits a truncated dynamic model which is of the same form as the lumped-mass flexible arm model and which reproduces the dynamics of the measured variables. This allows us to generate the above mentioned control method to the case of distributed-mass flexible arms. - Contributed by the Dynamic Systems and Control Division for publication
THE INTEGRATION OF VISION AND HAPTIC SENSING: A COMPUTATIONAL & NEURAL PERSPECTIVE

When looking at an object while exploring and manipulating it with the hands, visual and haptic senses provide information about the properties of the object. How these two streams of sensory information are integrated by the brain to form a single percept is still not fully understood. Recent advances in computational neuroscience and brain imaging research have added new insights into the underlying mechanisms and identified possible brain regions involved in visuo-haptic integration. This review examines the following main findings of previous research: First, the notion that the nervous sys-tem combines visual and haptic inputs in a fashion that minimizes the variance of the final percept and performs operations commen-surable to a maximum-likelihood integrator. Second, similar to vision, haptic information may be mediated by two separate neural pathways devoted to perception and action. This claim is based on a set of psychophysical studies investigating how humans judge the size and orientation of objects. Third, a cortical neural system described as the lateral occipital complex (LOC) has been identified as a possible locus of visuo-haptic integration. This claim rests on functional imaging studies revealing an activation of LOC to both visual and haptic stimulation. We conclude that much progress has been made to provide a computational framework that can formalize and explain the results of behavioral and psychophysical studies on visuo-haptic integration. Yet, there still exists a gap between the computationally driven studies and the results derived from brain imaging studies. One reason why the closing of this gap has proven to be difficult is that visuo-haptic integration processes seem to be highly influenced by the task and context.
Hunting for superheavy dark matter with the highest-energy cosmic rays

In 15 years of data taking the Pierre Auger Observatory has observed no events beyond $10^{11.3}$ GeV. This null result translates into an upper bound on the flux of ultrahigh-energy cosmic rays implying $J (> 10^{11.3}$ GeV) $< 3.6 \times 10^{-5}$ km$^{-2}$ sr$^{-1}$ yr$^{-1}$, at the 90\%C.L. We interpret this bound as a constraint on extreme-energy photons originating in the decay super-heavy dark matter (SHDM) particles clustered in the Galactic halo. Armed with this constraint we derive the strongest lower limit on the lifetime of hadronically decaying SHDM particles with masses in the range, $10^{14} < M_X/ $ GeV $< 10^{15}$. We also explore the capability of future NASA's POEMMA mission to search for SHDM signals.
Canine distemper virus persistence in the nervous system is associated with noncytolytic selective virus spread

Canine distemper virus (CDV), a negative-strand RNA morbillivirus, causes a progressive demyelinating disease in which virus persistence plays an essential role. The antiviral immune response leads to virus clearance in the inflammatory lesions. However, CDV can replicate and persist outside these inflammatory lesions within the brain. How CDV is capable of persisting in the presence of an effective antiviral immune response is poorly understood. In the present investigation, we studied several aspects of virus replication in primary dog brain cell cultures (DBCC), comparing an attenuated CDV strain and a virulent CDV strain. Confluent DBCC were infected with either virulent A75/17-CDV or attenuated Onderstepoort-CDV and monitored for 60 days. Persistence was not associated with defective virus production, because all mRNAs and corresponding proteins were continuously expressed in the noncytolytic infection. Quantitative measurements did not detect a difference between the two types of infection in the rate of virus transcription and protein synthesis at the level of the single cell. However, electron microscopy and virus titration experiments showed that in the persistent CDV infection virus budding is strongly limited compared with that of the attenuated virus. Morphometry and immunocytochemistry showed profound differences in the way the two viruses spread in the culture. The attenuated CDV spread randomly to immediately adjacent cells, whereas persistent CDV spread selectively to more-distant cells by way of cell processes. In conclusion, the present study supports a mechanism of CDV persistence through selective spread by way of cell processes, enabling virulent CDV to invade the central nervous system without the need of releasing much virus into the extracellular space.
MicroRNAs' role in brain development and disease

microRNA (miRNA) function is required for normal animal development, in particular in stem cell and precursor populations. I hypothesize that miRNAs are similarly required for stem cell maintenance and appropriate fate commitment in the brain. To test the requirement for global microRNA production, I depleted the microRNA biosynthetic enzyme DICER in the developing mouse brain. I found that DICER loss in embryonic neural progenitor cells leads to embryonic lethality with microcephaly. By histological analysis, I found defects in both neural progenitor cell maintenance and cell differentiation. I also identified new candidate microRNAs for this phenotype by profiling miRNAs in DICER-depleted and control cells. Three microRNAs which are good candidates to modulate nervous differentiation are miR-23b, -182, and 34a. I describe the expression pattern and functional characterization of these candidates. In particular, miR-34a depletes neuron production after progenitor cell differentiation in culture, likely by modulating cell cycling and Notch pathway genes. Abstract Approved: ______________________________________________________ Thesis SupervisorApproved: ______________________________________________________ Thesis Supervisor Title and Department ______________________________________________________ Date MICRORNAS' ROLE IN BRAIN DEVELOPMENT AND DISEASE By Sarah Kathryn Fineberg A thesis submitted in partial fulfillment of the requirements for the Doctor of Philosophy degree in Molecular Physiology and Biophysics in the Graduate College of The University of Iowa
Subclinical Macular Edema Detected by Spectral-domain Optical Coherence Tomography (SD-OCT) in HLA-B27 Positive Anterior Uveitis

Purpose: To assess foveal thickness by spectral-domain optical coherence tomography (SD-OCT) during acute anterior uveitis (AAU) in HLA–B27 patients. Methods: Foveal thickness was measured at baseline and after clinical resolution of the uveitis. Data of the affected eyes of 11 patients were compared to those of a fellow, healthy eyes and to those of counterpart volunteers. Results: At baseline mean foveal thickness was 190 ± 28 µm in affected eyes, 166 ± 20 µm in fellow eyes (p < 0.001), and 162±14 µm in control group (p = 0.01). On the second OCT evaluation, no significant change was observed in affected eyes while the difference versus fellow eyes and control group remained statistically significant. Conclusions: A significant increase in foveal thickness was observed in eyes with HLA –B27 AAU when compared with healthy eyes. The difference persisted for at least one month, despite full clinical and functional recovery.
Characteristics of Hemodynamic Disorders in Patients with Severe Traumatic Brain Injury

Purpose. To define specific features of central hemodynamic parameter changes in patients with isolated severe traumatic brain injury (STBI) and in patients with clinically established brain death and to determine the required course of treatment for their correction. Data and Research Methods. A close study of central hemodynamic parameters was undertaken. The study involved 13 patients with isolated STBI (group STBI) and 15 patients with isolated STBI and clinically established brain death (group STBI-BD). The parameters of central hemodynamics were researched applying transpulmonary thermodilution. Results. In the present study, various types of hemodynamic reaction (normodynamic, hyperdynamic, and hypodynamic) were identified in patients with isolated STBI in an acute period of traumatic disease. Hyperdynamic type of blood circulation was not observed in patients with isolated STBI and clinically established brain death. Detected hemodynamic disorders led to the correction of the ongoing therapy under the control of central hemodynamic parameters. Conclusions. Monitoring of parameters of central hemodynamics allows to detect the cause of disorders, to timely carry out the required correction, and to coordinate infusion, inotropic, and vasopressor therapy.