Miracle-dz/UniFAR-FTUs huggingface dataset:
The Effects of Ponazuril on Development of Apicomplexans In Vitro

Abstract. We examined the effects of 5 μg/ml ponazuril treatment on developing tachyzoites of Neospora caninum and merozoites of Sarcocystis neurona to better determine the mode of action of this anticoccidial drug. Both parasites develop asexually by endogenesis. Neospora caninum was selected for study because it develops by endodyogeny, which results in two tachyzoites being produced internally, and S. neurona was selected because it develops by endopolygeny which results in many merozoites being produced internally. Ponazuril inhibited development of N. caninum after approximately 48 h post‐exposure. Treated tachyzoites of N. caninum developed vacuoles and underwent degeneration. Ponazuril also inhibited development of merozoites of S. neurona. Treated merozoites and maturing schizonts of S. neurona developed vacuoles and underwent degeneration. The ability of S. neurona schizonts to undergo cytokinesis was inhibited. Our results are discussed in relation to previous ultrastructural research on endogenesis of tachyzoites of Toxoplasma gondii undergoing endodyogeny which indicated that ponazuril induced multinucleate stage formation and inhibited cytokinesis. Ponazuril is believed to act on the apicoplast and our study demonstrates that this agent may express its inhibitory effects in different phenotypic manners on different apicomplexan parasites. The enzyme/enzyme systems that are the inhibitory target of ponazuril may be different in these apicomplexans, or the results of inhibition may affect different pathways downstream of its initial site of action in these parasites.
The PDZ-Binding Motif of HPV16-E6 Oncoprotein Modulates the Keratinization and Stemness Transcriptional Profile In Vivo

Objective The aim of this work was to compare the early gene expression profiles in the skin of HPV16-E6 transgenic mice regulated by the E6 PDZ-binding motif. Materials and Methods The global transcriptional profiles in dorsal skin biopsies from K14E6 and K14E6Δ146-151 transgenic mice were compared using microarrays. Relevant genes obtained from the most differentially expressed processes were further examined by RT-qPCR, in situ RT-PCR, Western blot, or immunofluorescence. Results The transcriptomic landscape of K14E6 versus K14E6Δ146-151 shows that the most affected expression profiles were those related to keratinocyte differentiation, stem cell maintenance, and keratinization. Additionally, downregulation of epidermal stemness markers such as K15 and CD34, as well as the upregulation of cytokeratin 6b, appeared to be dependent on the E6 PDZ-binding motif. Finally, wound healing, a physiological process linked to stemness, is impaired in the K14E6 mice compared to K14E6Δ146-151. Conclusion The E6 PDZ-binding motif appears to affect stemness and keratinization during early stages of skin carcinogenesis. As E6 plays a significant role in HPV-induced skin carcinogenesis, the K14E6 versus K14E6Δ146-151 transcriptional profile provides a source of valuable data to uncover novel E6 functions in the skin.
Ethanol enhancement of cocaine‐ and amphetamine‐regulated transcript mRNA and peptide expression in the nucleus accumbens

Cocaine‐ and amphetamine‐regulated transcript (CART) is a peptide neurotransmitter that has been implicated in drug reward and reinforcement. CART mRNA and peptide expression are highly concentrated in several compartments of the mesolimbic reward pathway. Several lines of evidence suggest that CART peptides may contribute to rewarding behaviors and the addiction liability of psychostimulants; however, there are no reports of basic work concerning CART in relation to alcohol and mechanisms of alcohol dependence development. Therefore, in this study we investigated the response of CART transcript and peptide to acute ethanol administration in vivo. Rats were administered ethanol (1 g/kg or 3.5 g/kg, 1 h, ip) and CART expression was measured by RT‐PCR in the nucleus accumbens (NAcc). Ethanol (3.5 g/kg) increased CART transcription markedly. The interactions of dopamine on ethanol‐induced CART expression were further evaluated pharmacologically using D1 and D2/D3 receptor antagonists. Both SCH 23390 (0.25 mg/kg) or raclopride (0.2 mg/kg) pre‐treatment significantly suppressed ethanol‐enhancement of CART mRNA transcription. Confocal immunofluorescence microscopy revealed that CART peptide immunoreactivity was also enhanced in both the core and the shell of the NAcc by ethanol administration. These findings demonstrate that CART mRNA and peptide expression are responsive to acute ethanol administrated in vivo and suggests that CART peptides may be important in regulating the rewarding and reinforcing properties of ethanol.
Primary pleomorphic xanthoastrocytoma of the spinal cord: A case report and review of literature

Primary pleomorphic xanthoastrocytoma (PXA) of the spinal cord is a rare slow growing tumor. To our knowledge, only five such cases have been reported in the literature till date. We report the clinical, radiological, and histopathological features of a spinal PXA in a 23-year-old female previously operated 5 years back for a spinal tumor, presented with weakness in lower limbs, sphincter incontinence and low back pain. Magnetic resonance imaging scan with contrast reveals an intramedullary lesion in the spinal cord from D8-D10 level. The patient was operated with reexploration of the previous incision, and gross total excision was achieved. Histopathology confirmed the diagnosis of PXA. Clinical and radiological follow-up is required to detect early recurrence. Adjunct radiotherapy or and chemotherapy should be considered only when there is postoperative residual or recurrence, however there are no definite guidelines in view of the rarity of this condition.
Adaptive human-inspired compliant contact primitives to perform surface–surface contact under uncertainty

This paper focuses on devising a control policy that is inspired by human strategy to enable robots to perform surface–surface contact between a hand-held object (e.g. a box) and the environment (e.g. table). We assume the object’s shape is partially known and consider uncertainties in both the environment and the object grasp. Our analysis on ten untrained subjects indicates that during this task: (1) the subjects start decreasing the angular velocity before the complete alignment (in contrast to existing approaches), and (2) they do not control the contact force to remain at a fixed value. Our study is also consistent with the hypothesis that the subjects determine an over-estimate of the relative angle between the object in hand and the environment. Based on these observations we propose a novel control policy, called Surface-Surface Contact Primitive (SSCP), which can perform the surface–surface alignment task with only partial information about the hand-held object and the environment. Furthermore, SSCP only requires a rough estimate of the surface normal vector and does not rely on either the estimation of contact type (i.e. point or edge contact) or locations of contact points. We evaluate the performance of the proposed controller on a set of robot experiments using two seven-degree-of-freedom robots, one for imposing uncertainty to the environment, and the other to perform the experiment. We show the applicability of the controller on four objects with different geometries, its generalization to four different surface materials, and its robustness to uncertainty in environment and grasp as well as external perturbations.
Adolescent/adult sensory profile and obsessive-compulsive disorder.

OBJECTIVE We sought to describe how the sensory processing of adults with obsessive-compulsive disorder (OCD) differs from that of the general population within the context of Dunn's (1997) model of sensory processing and to evaluate the discriminant validity of the Adolescent/Adult Sensory Profile (AASP). METHOD Using unequal variance ttests, the AASP results of 51 adults with OCD were compared with the means of the AASP standardization study's adult age group. RESULTS Adults with OCD scored higher than the means of the AASP standardization study's adult age group on sensory sensitivity and sensation avoiding, consistent with predictions based on the OCD literature. Adults with OCD also scored higher on low registration and lower on sensation seeking. CONCLUSIONS The results provide a preliminary description of how the sensory processing of adults with OCD differs from that of the general population and preliminary support for the AASP's discriminant validity.
Serum Albumin: A Promising Biomarker to Anticipate Postoperative Complications.

To the Editor—We have read the article of Ge et al with particular interest. This study tested the predictive value of postoperative decrease of serum albumin (SA) for adverse outcomes in a retrospective cohort of colorectal surgery. Of note, the concept suggesting that ∆albumin is a predictor of complications is not exactly novel. It is, however, critical to validate the role of ∆albumin, particularly because it is an easy and inexpensive biomarker, unlike other more complex ones. The authors established that a 15% reduction in SA within 2 postoperative days was an independent predictor of complications. We address several points. First, did the authors test the predictive value of ∆albumin at postoperative day 1 because available data suggested that ∆albumin was already indicative at postoperative day 1? Second, did the authors compare the performance of absolute vs relative ∆albumin? In other words, does a reduction of 15% display a significantly better performance than, for example, 6 g/L? If not, one may assume that an absolute value may be easier to implement in clinical practice. The authors also concluded that whether the conclusion of the current study could be extrapolated to other abdominal procedures, such as gastrectomy or esophagectomy resections, is unknown. Importantly, our group recently published a prospective study including all types of major abdominal surgery that confirmed that an early postoperative decrease of SA correlated with complications and length of stay. Strikingly, the protocol of our prospective study registered in clinicaltrials.gov (NCT02356484) in February 2015 shows surprising similarities with the retrospective study published in Diseases of the Colon & Rectum Ge et al. Is this only by chance?
Moderate physical activity in relation to mammographic patterns.

High-risk mammographic patterns may be used as a surrogate end point for breast cancer in etiologic research as well as in prevention studies. Physical activity may be one of the few modifiable risk factors for breast cancer. We examined the relationship between physical activity and mammographic patterns among 2720 Norwegian women, ages 40-56 years, who participated in both the Second and Third Tromsø studies. Epidemiologic data were obtained through questionnaires. Two questions from the Second Tromsø study and five questions from the Third elicited information on physical activity. The mammograms were categorized into five groups based on anatomical-mammographic correlations. For analysis, patterns I through III were combined into a low-risk group and patterns IV and V into a high-risk group. Odds ratios that were adjusted for age, education, menopausal status, body mass index, parity, age at menarche, oral contraceptive use, and alcohol intake, with 95% confidence intervals, were estimated using logistic regression. Women who reported moderate physical activity, i.e., more than 2 h/week, were 20% less likely (odds ratio, 0.8; 95% confidence interval, 0.6-1.1) to have high-risk mammographic patterns compared with those who reported being inactive. This relationship remains consistent when stratified by menopausal status, parity, and tertiles of body mass index. However, all of the associations between various measures of physical activity and high-risk patterns found in this study are weak with confidence intervals that include 1.0. Thus, chance is a reasonable explanation for the weak associations found. The relationship between physical activity and high-risk patterns should be examined further as a means to explore the biologic mechanisms relating physical activity to breast cancer risk.
Postpartum Blood Loss in Women Treated for Intrahepatic Cholestasis of Pregnancy

OBJECTIVE: To evaluate postpartum blood loss in women with treated intrahepatic cholestasis of pregnancy. METHODS: In a retrospective case–control study, 15,083 deliveries including 348 women with intrahepatic cholestasis of pregnancy (2.3%) were analyzed from 2004 to 2014. To adjust for differences in baseline characteristics, a propensity analysis was performed and women in the control group were matched to the women in the intrahepatic cholestasis of pregnancy group in a 5:1 ratio. Blood loss was analyzed by estimated blood loss and &Dgr; hemoglobin (Hb, difference between prepartum and postpartum Hb). A subgroup analysis regarding severity of intrahepatic cholestasis of pregnancy based on maximum bile acid level (mild [less than 40 micromoles/L], moderate [40–99 micromoles/L], and severe intrahepatic cholestasis of pregnancy [100 micromoles/L or greater]) was performed. Differences in estimated blood loss, &Dgr;Hb, and meconium staining between subgroups were analyzed. A Spearman rank correlation was performed to evaluate the association of bile acid levels and blood loss within subgroups. RESULTS: Estimated blood loss (median 400 [300–600] mL compared with 400 [300–600] mL, P=.22), &Dgr;Hb (14.0 [5.0–22.0] compared with 12.0 [4.0–21.0] g/L, P=.09), meconium staining (14.5% compared with 11.4%, P=.12), and number of stillbirths after 26 weeks of gestation (0.6% compared with 1.8%, P=.10) were not significantly different in the study compared with the control group. In moderate and severe intrahepatic cholestasis of pregnancy, meconium staining was observed significantly more often compared with that in a control group (23.0% and 32.3% compared with 11.4%, P<.01). There was no correlation between estimated blood loss or &Dgr;Hb and severity of intrahepatic cholestasis of pregnancy. CONCLUSIONS: In our cohort of women with intrahepatic cholestasis of pregnancy who are treated with ursodeoxycholic acid and have planned delivery (induction of labor or planned cesarean delivery) at 38 weeks of gestation, no differences in postpartum blood loss were seen.
Cancer risk for patients using thiazolidinediones for type 2 diabetes: a meta-analysis.

OBJECTIVE To clarify and quantify the effect of thiazolidinediones (TZDs; e.g., pioglitazone, rosiglitazone) on the risk of bladder cancer, other selected cancers, and overall cancer in patients with type 2 diabetes, we performed a systematic review and meta-analysis of observational studies. METHODS A PubMed/MEDLINE search was conducted for studies published in English up to June 30, 2012. Random-effect models were fitted to estimate summary relative risks (RR). RESULTS Seventeen studies satisfying inclusion criteria (3 case-control studies and 14 cohort studies) were considered. Use of TZDs was not associated to the risk of cancer overall (summary RR: 0.96; 95% confidence interval [CI]: 0.91-1.01). A modest excess risk of bladder cancer was reported in pioglitazone (RR: 1.20; 95% CI: 1.07-1.34 from six studies) but not in rosiglitazone (RR: 1.08; 95% CI: 0.95-1.23 from three studies) users. The RRs of bladder cancer were higher for longer duration (RR: 1.42 for >2 years) and higher cumulative dose of pioglitazone (RR: 1.64 for >28,000 mg). Inverse relations were observed with colorectal cancer (RR: 0.93; 95% CI: 0.90-0.97 from six cohort studies) and liver cancer (RR: 0.65; 95% CI: 0.48-0.89 from four studies), whereas there was no association with pancreatic, lung, breast, and prostate cancers. CONCLUSIONS Adequate evidence excludes an overall excess cancer risk in TZD users within a few years after starting treatment. However, there is a modest excess risk of bladder cancer, particularly with reference to pioglitazone. Assuming that this association is real, the potential implications on the risk-benefit analysis of TZD use should be evaluated.
Finite Element Method for Epitaxial Growth with Thermodynamic Boundary Conditions

We develop an adaptive finite element method for island dynamics in epitaxial growth. We study a step-flow model, which consists of an adatom (adsorbed atom) diffusion equation on terraces of different height; thermodynamic boundary conditions on terrace boundaries including anisotropic line tension; and the normal velocity law for the motion of such boundaries determined by a two-sided flux, together with the one-dimensional anisotropic ``surface'' diffusion (edge diffusion) of edge adatoms along the step edges. The problem is solved using independent meshes: a two-dimensional mesh for the adatom diffusion and one-dimensional meshes for the boundary evolution. A penalty method is used to incorporate the boundary conditions. The evolution of the terrace boundaries includes both the weighted/anisotropic mean curvature flow and the weighted/anisotropic edge diffusion. Its governing equation is solved by a semi-implicit front-tracking method using parametric finite elements.
Acridine orange used for photodynamic therapy accumulates in malignant musculoskeletal tumors depending on pH gradient.

BACKGROUND Intra-operative photodynamic therapy has been applied with acridine orange (AO-PDT) to human musculoskeletal sarcomas for the past 4 years, resulting in a low local recurrence rate, within 10%, after intra-marginal tumor resection and excellent limb function. However, it is still unclear why acridine orange (AO) specifically accumulates in tumor cells, especially in malignant tumor cells. The purpose of this study was to clarify the mechanism of AO accumulation in malignant musculoskeletal tumors. MATERIALS AND METHODS Sixty-two musculoskeletal tumors, including 35 malignant and 27 benign tumors, were studied. Using freshly resected tumor material, the extracellular pH (pHe) was measured and the fluorescence intensity of AO accumulated in the tumors was measured by an image analyzer after ex vivo exposure to 1.0 microg/ml AO, followed by blue excitation. In the in vitro study, bafilomycin A1 was exposed to LM 8 mouse osteosarcoma cells, in order to inhibit V-ATPase, subsequently causing a decrease in the pHgradient (deltapH) between the intracellular pH (pHi) and extracellular pH (pHe) or between the pHi and the pHe. AO accumulation and the cytocidal effect of AO were evaluated. RESULTS The results of the in vivo study, using human materials freshly resected at surgery, revealed that the pHe of the malignant musculoskeletal tumors was significantly lower than that of the benign tumors and normal muscles or adipose tissues and also showed that the AO fluorescence intensity of the malignant musculoskeletal tumors was significantly stronger than that of the benign tumors and normal muscles or adipose tissues. The results also revealed that the AO fluorescence intensity negatively correlated with the pHe in tumors and normal tissues. The in vitro study showed that bafilomycin A1 inhibited the accumulation of AO in acidic organelles, such as lysosomes, and that the cytocidal effect of AO-PDT was also remarkably inhibited. DISCUSSION Based on results of the in vivo and in vitro studies, it is suggested that malignant musculoskeletal tumors have a large deltapH between the pHi and the pHe or between the pHi and the vaculolar pH and also that a large ApH increases AO accumulation in tumors. We, therefore, believe that AO-PDT may be more effective in highly malignant musculoskeletal tumors than low grade ones, because of their acidity. CONCLUSION AO accumulation in musculoskeletal tumors was dependent on the ApH between the pHi and the pHe, or between the pHi and the vacuolar pH.
The complex LMS algorithm

A least-mean-square (LMS) adaptive algorithm for complex signals is derived. The original Widrow-Hoff LMS algorithm is W<inf>j+l</inf>= W<inf>j</inf>+ 2µεjX<inf>j</inf>. The complex form is shown to be W<inf>j+1</inf>= W<inf>j</inf>+ 2µεjX<sup>-</sup><inf>j</inf>, where the boldfaced terms represent complex (phasor) signals and the bar above X<inf>j</inf>designates complex conjugate.
Computer assisted electromagnetic navigation improves accuracy in computed tomography guided interventions: A prospective randomized clinical trial

Purpose To assess the accuracy and usability of an electromagnetic navigation system designed to assist Computed Tomography (CT) guided interventions. Materials and methods 120 patients requiring a percutaneous CT intervention (drainage, biopsy, tumor ablation, infiltration, sympathicolysis) were included in this prospective randomized trial. Nineteen radiologists participated. Conventional procedures (CT group) were compared with procedures assisted by a navigation system prototype using an electromagnetic localizer to track the position and orientation of a needle holder (NAV group). The navigation system displays the needle path in real-time on 2D reconstructed CT images extracted from the 3D CT volume. The regional ethics committee approved this study and all patients gave written informed consent. The main outcome was the distance between the planned trajectory and the achieved needle trajectory calculated from the initial needle placement. Results 120 patients were analyzable in intention-to-treat (NAV: 60; CT: 60). Accuracy improved when the navigation system was used: distance error (in millimeters: median[P25%; P75%]) with NAV = 4.1[2.7; 9.1], vs. with CT = 8.9[4.9; 15.1] (p<0.001). After the initial needle placement and first control CT, fewer subsequent CT acquisitions were necessary to reach the target using the navigation system: NAV = 2[2; 3]; CT = 3[2; 4] (p = 0.01). Conclusion The tested system was usable in a standard clinical setting and provided significant improvement in accuracy; furthermore, with the help of navigation, targets could be reached with fewer CT control acquisitions.
Comparing bioelectrical impedance values in assessing early upper limb lymphedema after breast cancer surgery.

AIM The purpose of this prospective study was to evaluate resistance (R) and phase angle (Pa) determined by single-frequency whole-body bioelectrical impedance analysis (BIA), as predictors for the early onset of edema of the upper limb in patients undergoing surgical treatment for breast cancer. MATERIALS AND METHODS Whole-body BIA was performed before surgery, as well as at two days, at one and three months after surgery. RESULTS A total of 33 women undergoing breast cancer surgery were examined. Four patients developed an edema of the upper limb within the first three months after surgery. Both analyzed parameters showed a fairly good performance in terms of sensitivity (R=75%, Pa=75%) and specificity (R=86%, Pa=83%). The positive predictive values of 43% (R) and 38% (Pa) were unsatisfactory, whereas the negative predictive values were 96% for both parameters. CONCLUSION Pa, as well as R, in whole-body BIA can be used to rule out a developing edema of the upper limb.