Miracle-dz/UniFAR-FTUs huggingface dataset:
p.N345K mutation in TARDBP in a patient with familial amyotrophic lateral sclerosis: An autopsy case

We report the neuropathology of a patient with a family history of amyotrophic lateral sclerosis (ALS) and a p.N345K mutation in the transactivation response DNA‐binding protein 43 kDa (TDP‐43) gene (TARDBP). A 62‐year‐old man had bulbar palsy with progressive weakness in the extremities. Neurological examination revealed evident upper motor neuron signs and lower motor neuron involvement corroborated by needle electromyography. The patient was diagnosed as having probable ALS according to the revised El Escorial diagnostic criteria and was eventually diagnosed with familial ALS. At 65 years of age, respiratory failure became critical, and artificial ventilation was initiated. At 70 years of age, the patient died from a urinary tract infection. Histopathological investigation showed Bunina bodies in the remaining motor neurons and anterolateral funicular myelin pallor in the spinal cord. TDP‐43‐positive cytoplasmic inclusions were quite rare in the spinal cord motor neurons, being predominantly present in the glial cells (especially astrocytes) of the spinal cord anterior horn. Although the reason for the preferential vulnerability of spinal glial cells to TARDBP mutations remains unclear, our findings indicate that TARDBP p.N345K mutation could have an influence on the topography of TDP‐43 aggregation.
Charge sharing concept and new clocking scheme for power efficiency and electromagnetic emission improvement of boosted charge pumps

A new power saving concept for boosted charge pumps is introduced, that combines two-step adiabatic switching, charge sharing and a simplified clocking scheme to double the power efficiency. Due to the charge charging the clock driver strengths can be reduced and therefore the peak value of the charging current is reduced by a factor of three. Further, the combination of tristate drivers and a new clocking scheme eliminates parasitic charge current peaks and together with the reduced current peaks the electromagnetic emission of the charge pump circuit is reduced significantly.
Trends in biodiversity and habitat quantification tools used for market‐based conservation in the United States

Market‐based conservation mechanisms are designed to facilitate the mitigation of harm to and conservation of habitats and biodiversity. Their potential is partly hindered, however, by the quantification tools used to assess habitat quality and functionality. Of specific concern are the lack of transparency and standardization in tool development and gaps in tool availability. To address these issues, we collected information via internet and literature searchers and through conversations with tool developers and users on tools used in U.S. conservation mechanisms, such as payments for ecosystem services (PES) and ecolabel programs, conservation banking, and habitat exchanges. We summarized information about tools and explored trends among and within mechanisms based on criteria detailing geographic, ecological, and technical features of tools. We identified 69 tools that assessed at least 34 species and 39 habitat types. Where tools reported pricing, 98% were freely available. More tools were applied to states along the U.S. West Coast than elsewhere, and the level of tool transferability varied markedly among mechanisms. Tools most often incorporated conditions at numerous spatial scales, frequently addressed multiple risks to site viability, and required 1–83 data inputs. Most tools required a moderate or greater level of user skill. Average tool‐complexity estimates were similar among all mechanisms except PES programs. Our results illustrate the diversity among tools in their ecological features, data needs, and geographic application, supporting concerns about a lack of standardization. However, consistency among tools in user skill requirements, incorporation of multiple spatial scales, and complexity highlight important commonalities that could serve as a starting point for establishing more standardized tool development and feature‐incorporation processes. Greater standardization in tool design may expand market participation and facilitate a needed assessment of the effectiveness of market‐based conservation.
Celastraceae Sesquiterpenes as a New Class of Modulators That Bind Specifically to Human P-Glycoprotein and Reverse Cellular Multidrug Resistance

Overexpression of ABCB1 (MDR1) P-glycoprotein, a multidrug efflux pump, is one mechanism by which tumor cells may develop multidrug resistance (MDR), preventing the successful chemotherapeutic treatment of cancer. Sesquiterpenes from Celastraceae family are natural compounds shown previously to reverse MDR in several human cancer cell lines and Leishmania strains. However, their molecular mechanism of reversion has not been characterized. In the present work, we have studied the ability of 28 dihydro-β-agarofuran sesquiterpenes to reverse the P-glycoprotein-dependent MDR phenotype and elucidated their molecular mechanism of action. Cytotoxicity assays using human MDR1-transfected NIH-3T3 cells allowed us to select the most potent sesquiterpenes reversing the in vitro resistance to daunomycin and vinblastine. Flow cytometry experiments showed that the above active compounds specifically inhibited drug transport activity of P-glycoprotein in a saturable, concentration-dependent manner (Ki down to 0.24 ± 0.01 μmol/L) but not that of ABCC1 (multidrug resistance protein 1; MRP1), ABCC2 (MRP2), and ABCG2 (breast cancer resistance protein; BCRP) transporters. Moreover, sesquiterpenes inhibited at submicromolar concentrations the P-glycoprotein-mediated transport of [3H]colchicine and tetramethylrosamine in plasma membrane from CHRB30 cells and P-glycoprotein-enriched proteoliposomes, supporting that P-glycoprotein is their molecular target. Photoaffinity labeling in plasma membrane and fluorescence spectroscopy experiments with purified protein suggested that sesquiterpenes interact with transmembrane domains of P-glycoprotein. Finally, sesquiterpenes modulated P-glycoprotein ATPase-activity in a biphasic, concentration-dependent manner: they stimulated at very low concentrations but inhibited ATPase activity as noncompetitive inhibitors at higher concentrations. Sesquiterpenes from Celastraceae are promising P-glycoprotein modulators with potential applications in cancer chemotherapy because of their MDR reversal potency and specificity for P-glycoprotein.
Image Denoising Using Wavelet Transform and CUDA

The discrete wavelet transform has a huge number of applications in science, engineering, mathematics and computer science. Most notably, it is used for signal coding to represent a discrete signal in a more redundant form, often as a preconditioning for data compression. Beginning in the 1990s, wavelets have been found to be a powerful tool for removing noise from a variety of signals (denoising). In this paper the implementation of DWT (Discrete Wavelet Transform)-based denoising algorithm in parallel manner on Graphics Processing Unit is presented, using the CUDA technology.
Comparison of evidence-based interventions on outcomes of hospitalized, cognitively impaired older adults.

AIM This article reports the effects of three evidence-based interventions of varying intensity, each designed to improve outcomes of hospitalized cognitively impaired older adults. MATERIALS & METHODS In this comparative effectiveness study, 202 older adults with cognitive impairment (assessed within 24 h of index hospitalization) were enrolled at one of three hospitals within an academic health system. Each hospital was randomly assigned one of the following interventions: Augmented Standard Care (ASC; lower dose: n = 65), Resource Nurse Care (RNC; medium dose: n = 71) or the Transitional Care Model (TCM; higher dose: n = 66). Since randomization at the patient level was not feasible due to potential contamination, generalized boosted modeling that estimated multigroup propensity score weights was used to balance baseline patient characteristics between groups. Analyses compared the three groups on time with first rehospitalization or death, the number and days of all-cause rehospitalizations per patient and functional status through 6-month postindex hospitalization. RESULTS In total, 25% of the ASC group were rehospitalized or died by day 33 compared with day 58 for the RNC group versus day 83 for the TCM group. The largest differences between the three groups on time to rehospitalization or death were observed early in the Kaplan-Meier curve (at 30 days: ASC = 22% vs RNC = 19% vs TCM = 9%). The TCM group also demonstrated lower mean rehospitalization rates per patient compared with the RNC (p < 0.001) and ASC groups (p = 0.06) at 30 days. At 90-day postindex hospitalization, the TCM group continued to demonstrate lower mean rehospitalization rates per patient only when compared with the ASC group (p = 0.02). No significant group differences in functional status were observed. CONCLUSION Findings suggest that the TCM intervention, compared with interventions of lower intensity, has the potential to decrease costly resource use outcomes in the immediate postindex hospitalization period among cognitively impaired older adults.
Intraoperative Auditory Brain Stem Response Monitoring During Ultrasonic Aspiration of Posterior Fossa Tumors

The use of an ultrasonic aspirator may decrease the morbidity associated with the surgical removal of Intracranial tumors by reducing the duration of surgery. In this study we monitored the auditory brain stem response (ABR) during ultrasonic surgical aspiration of 20 posterior fossa tumors. Twelve subjects had a transient decrement in the ABR during use of the ultrasonic aspirator; one had a temporary sensorineural hearing loss contralateral to the side of the surgery. Monitoring of the ABR during use of the ultrasonic aspirator in the posterior fossa helped minimize the risk of injury to normal structures. Changes in latency, amplitude, and Interpeak Interval of the ABR waves alert the surgeon to the need to adjust the aspirator settings or the conditions in the operative field before continuing to use the tool.
IT outsourcing in insurance services: risk, creative contracting and business advantage

Abstract. Risks in IT outsourcing have received little systematic academic attention, despite growing evidence of wide disappointment and difficulty as well as some successes in outsourcing IT. This paper explores the 1993–98 case history of Polaris, a software intermediary in the European insurance sector. Despite the considerable risks inherent in outsourcing business‐critical technology, Polaris was found to be achieving business advantage from such a strategy. This paper details 10 major risk areas in IT outsourcing distilled from previous research. It focuses on the sourcing, contractual and management choices made at Polaris. It assesses, against prior research findings, the degree to which these choices mitigated short‐ and long‐term risk, and whether learning points flow from the analysis for other IT outsourcing arrangements.
High Glucose Promotes Epithelial-Mesenchymal Transition, Migration and Invasion in A20 Murine Diffuse Large B-Cell Lymphoma Cells Through Increased Expression of High Mobility Group AT-Hook 2 (HMGA2)

Background Patients with type 2 diabetes mellitus have been reported to be at increased risk of developing non-Hodgkin’s lymphoma (NHL). Diffuse large B-cell lymphoma (DLBCL) is the most common type of high-grade NHL. This study aimed to investigate the effects of high glucose on cell migration, invasion and epithelial-mesenchymal transition (EMT), and the expression of high mobility group AT-hook 2 (HMGA2) in A20 murine DLBCL cells. Material/Methods Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to analyze the expression of HMGA2 at the gene and protein level and EMT markers in the A20 murine DLBCL cell line. A transwell assay evaluated cell migration and invasion of A20 cells. Short-interfering RNA (siRNA) was used to knockdown HMGA2 expression. Results High glucose levels upregulated the expression of HMGA2, induced phenotypic changes of EMT, and increased cell migration and invasion in A20 cells. Knockdown of HMGA2 by siRNA effectively inhibited EMT induced by high glucose in A20 cells by directly regulating the Wnt/β-catenin signaling pathway. Conclusions In the A20 murine DLBCL cell line, high glucose upregulated the expression of HMGA2 to induce EMT and promote cell migration and invasion through the Wnt/β-catenin signaling pathway.
School Teachers’ Awareness about National Obesity Prevention Programs in Turkey

ABSTRACT Nutritional programs are one of the most important public health policies in order to prevent obesity. School teachers are role models for students and their nutrition knowledge about these policies can affect children’s dietary habits. The aim of this observational descriptive study was to evaluate the school teachers’ awareness about nutrition programs for the prevention of obesity of the Ministry of Education in Turkey. It was conducted to 87,070 classroom teachers working at state schools from all the cities of Turkey. Data collection was obtained with a plain web-based survey, and national nutrition programs (Nutrition-Friendly School Program, White-Flag Protocol, and circular letter on foods can be sold in school canteens) were questioned. Mean age of teachers was 38.3 ± 9.30 years and 50.4% of them were male. It was determined that only 66.2% of the teachers know whether their school is nutrition-friendly. Frequency of knowing “White-Flag” Protocol was 80.1%. Present study showed that educational programs about nutrition policies are required in order to increase knowledge among school teachers and thus, prevent childhood obesity.
Estimating hand and foot reaction forces based on a generalized zero moment point for rehabilitation assist system

Elderly individuals are likely to develop locomotive disorders such as osteoarthritis or osteoporosis. This increases the risk of falls and makes independent movement difficult. Elderly individuals should better understand walking function to extend their healthy life. We therefore propose a new method for estimating hand and foot reaction forces using only visual markers and a monocular camera. When humans contact the environment with their hands, their hand and feet positions define a convex hull. A proposed “ generalized zero moment point ” is projected on this convex hull, which is approximated as a line or plane, and the distance between this point and each contact point is calculated. Reaction forces are calculated based on the ratios of these distances. Evaluation experiments show high agreement between estimated and measured forces of both hands and feet, confirming the validity of the proposed algorithm.
Safety and efficacy of cetuximab-chemotherapy combination in Saudi patients with metastatic colorectal cancer.

BACKGROUND Cetuximab-based combination chemotherapy (CBCC) proved safe and effective as second-line strategy for metastatic colorectal cancer (mCRC). This prospective phase-II study was designed to assess the efficacy and safety of CBCC as first-, second- or third-line among Saudi patients with mCRC. MATERIALS AND METHODS Patients with mCRC were offered CBCC to assess time-to-disease progression (TTP), response rate and duration, overall survival (OS) and safety. RESULTS Nineteen patients were eligible and their median age was 51 years. Seven patients received CBCC as first-line and 12 as second- or third-line. Responses: 11 (58%) partial responses, 5 (26%) stable disease and 3 (16%) disease progressions. The median response duration was 4.3 months [95% confidence interval (CI): 3.4-5.2 months]. The median TTP was 6.8 months (95% CI: 2-13.9 months) for all 19 patients compared to 9.3 months (95% CI: 3.9-14.6 months) for the seven patients who received CBCC as first-line. The median OS for the entire population was 12.3 months (95% CI could not be determined). On the other hand, while the median OS for those who received CBCC as first-line have not been reached, the median OS for those who received CBCC after failure of other salvage therapies was 12.3 months (95% CI: 3.2-21.4 months). CBCC was generally tolerable. One patient had a severe hypersensitivity reaction and another fatal cardiac arrest. CONCLUSION CBCC is active with an acceptable safety profile. Until results from phase-III clinical trials are available, using CBCC as first-line is probably justified.
Tamoxifen with or without breast irradiation in women 50 years of age or older with early breast cancer.

BACKGROUND We determined the effect of breast irradiation plus tamoxifen on disease-free survival and local relapse in women 50 years of age or older who had T1 or T2 node-negative breast cancer. METHODS Between December 1992 and June 2000, 769 women with early breast cancer (tumor diameter, 5 cm or less) were randomly assigned to receive breast irradiation plus tamoxifen (386 women) or tamoxifen alone (383 women). The median follow-up was 5.6 years. RESULTS The rate of local relapse at five years was 7.7 percent in the tamoxifen group and 0.6 percent in the group given tamoxifen plus irradiation (hazard ratio, 8.3; 95 percent confidence interval, 3.3 to 21.2; P<0.001), with corresponding five-year disease-free survival rates of 84 percent and 91 percent (P=0.004). A planned subgroup analysis of 611 women with T1, receptor-positive tumors indicated a benefit from radiotherapy (five-year rates of local relapse, 0.4 percent with tamoxifen plus radiotherapy and 5.9 percent with tamoxifen alone; P<0.001). Overall, there was a significant difference in the rate of axillary relapse at five years (2.5 percent in the tamoxifen group and 0.5 percent in the group given tamoxifen plus irradiation, P=0.049), but no significant difference in the rates of distant relapse or overall survival. CONCLUSIONS As compared with tamoxifen alone, radiotherapy plus tamoxifen significantly reduces the risk of breast and axillary recurrence after lumpectomy in women with small, node-negative, hormone-receptor-positive breast cancers.
A photoactive carotenoid protein acting as light intensity sensor

Intense sunlight is dangerous for photosynthetic organisms. Cyanobacteria, like plants, protect themselves from light-induced stress by dissipating excess absorbed energy as heat. Recently, it was discovered that a soluble orange carotenoid protein, the OCP, is essential for this photoprotective mechanism. Here we show that the OCP is also a member of the family of photoactive proteins; it is a unique example of a photoactive protein containing a carotenoid as the photoresponsive chromophore. Upon illumination with blue-green light, the OCP undergoes a reversible transformation from its dark stable orange form to a red “active” form. The red form is essential for the induction of the photoprotective mechanism. The illumination induces structural changes affecting both the carotenoid and the protein. Thus, the OCP is a photoactive protein that senses light intensity and triggers photoprotection.
Using Markets to Inform Policy : The Case of the Iraq War

Market prices incorporate large amounts of information, and our aim in this paper is to demonstrate that prediction markets can help extract this information, prospectively allowing this aggregated expertise to inform policy decisions in real-time. We provide a case study, exploiting data from a market trading in contracts which paid off if Saddam Hussein was removed as leader of Iraq, to learn about financial market participants’ expectations of the consequences of the 2003 Iraq war. We conducted an ex-ante analysis, which we disseminated before the war, finding that a 10 percent increase in the probability of war was accompanied by a $1 increase in spot oil prices that futures markets suggested was expected to dissipate quickly. Equity prices movements implied that the same shock led to a 11⁄2 percent decline in the S&P 500. Further, the existence of widely-traded options allows us to back out the entire distribution of market expectations of the war’s near-term effects, finding that these large effects reflected a negatively skewed distribution, with a substantial probability of an extremely adverse outcome. The flow of war-related news through our sample explains a large proportion of daily oil and equity price movements. Subsequent analysis suggests that these relationships continued to hold out-of-sample. Our analysis also allows us to characterize which industries and countries were most sensitive to war news, and when the war turned out somewhat better than ex-ante expectations, these sectors recovered, confirming these cross-sectional implications. We highlight the particular features of this case study that make it particularly amenable to this style of policy analysis, and discuss some of the issues in applying this method to other policy contexts.
Health care resource utilization associated with a diabetes center and a general medicine clinic

AbstractOBJECTIVE: Studies have proposed that the features of diabetes clinics may decrease hospital utilization and costs by reducing complications and providing more efficient outpatient care. We compared the health care utilization associated with a diabetes center (DC) and a general medicine clinic (GMC). DESIGN: Retrospective cohort study. SETTING: An urban academic medical center. PATIENTS/PARTICIPANTS: Type 2 diabetes patients (N=601) under care in a DC and GMC before March 1996. MEASUREMENTS AND MAIN RESULTS: We compared baseline patient characteristics and outpatient care for the period of March 1996 to August 1997. Using administrative data from March 1996 to October 2000, we compared the probability of a hospitalization, length of stay, costs of hospitalizations, the probability of an emergency room visit, and costs of emergency room visits. Diabetes center patients had a longer mean duration of diabetes (12 years vs 6 years, P<.01), more baseline microvascular disease (65% vs 44%, P<.01), and higher baseline glucose levels (hemoglobin A1c 8.6% vs 7.9%, P<.01) than GMC patients. Diabetes center patients received more intensive outpatient care directed toward glucose monitoring and control. In all crude and adjusted analyses of hospitalizations and emergency room visits, we found no statistically significant differences for inpatient utilization or cost outcomes comparing clinic populations. CONCLUSIONS: Diabetes center attendance did not have a definitive positive or negative impact on inpatient resource utilization over a 4-year period. However, DC patients had more severe diabetes but no greater hospital utilization compared with GMC patients. Clear demonstration of the clinical and financial benefits of features of diabetes centers will require long-term controlled trials of interventions that promote comprehensive diabetes care, including cardiovascular prevention.