Miracle-dz/UniFAR-FTUs huggingface dataset:
Incidence patterns of colorectal cancers in four countries of the Middle East Cancer Consortium (Cyprus, Jordan, Israel, and İzmir, Turkey) compared with those in the United States Surveillance, Epidemiology, and End Results Program.

BACKGROUND/AIMS There are wide variations in colorectal cancer (CRC) incidence across the world. Historically, the highest incidence rates have been reported historically in more developed countries; however, increasing trends have been seen in developing countries. Here, we present the CRC incidence pattern in Cyprus, Israel, Jordan, and İzmir, Turkey, which are countries of the Middle East Cancer Consortium (MECC). MATERIALS AND METHODS We analyzed 2005-2010 CRC data from population-based registries and calculated crude and age standardized rates for CRC, colon and rectum subsites, and annual percent changes (APCs) for trends. RESULTS The age-adjusted incidence rates (AAIRs) for CRC were the highest in Israeli Jews (IJ) (46.7 for males and 35.5 for females), which exceeded those of the USA Surveillance, Epidemiology, and End Result (SEER) program registries. In both sexes, AAIRs in Cyprus and Israeli Arabs (IA) were close to those in SEER registries. For both sexes, AAIRs in İzmir and Jordan were substantially lower than those in other registries. Statistically significant decreasing trends over time were observed in AAIRs for both sexes in the SEER program (APCs: males, -3.24% and females, -2.54%), whereas the trends varied within the MECC registries. There were decreasing AAIR trends for males in IJ and IA and for females in Cyprus and IJ; APC for females in IJ (-4.29%) was significant. Conversely, increasing trends with the significant APCs were observed in males in İzmir (2.43%) and Jordan (7.57%). CONCLUSION MECC countries comprise both high- and low-risk populations for CRCs. However, increasing trends in low-risk populations have been alarming. Thus, the need for implementing tailored primary and secondary prevention programs in the region is essential.
Accelerated flooding along the U.S. East Coast: On the impact of sea‐level rise, tides, storms, the Gulf Stream, and the North Atlantic Oscillations

Recent studies identified the U.S. East Coast north of Cape Hatteras as a “hotspot” for accelerated sea‐level rise (SLR), and the analysis presented here shows that the area is also a “hotspot for accelerated flooding. ” The duration of minor tidal flooding [defined as 0.3 m above MHHW (mean higher high water)] has accelerated in recent years for most coastal locations from the Gulf of Maine to Florida. The average increase in annual minor flooding duration was ∼20 h from the period before 1970 to 1971–1990, and ∼50 h from 1971–1990 to 1991–2013; spatial variations in acceleration of flooding resemble the spatial variations of acceleration in sea level. The increase in minor flooding can be predicted from SLR and tidal range, but the frequency of extreme storm surge flooding events (0.9 m above MHHW) is less predictable, and affected by the North Atlantic Oscillations (NAO). The number of extreme storm surge events since 1960 oscillates with a period of ∼15 year and interannual variations in the number of storms are anticorrelated with the NAO index. With higher seas, there are also more flooding events that are unrelated to storm surges. For example, it is demonstrated that week‐long flooding events in Norfolk, VA, are often related to periods of decrease in the Florida Current transport. The results indicate that previously reported connections between decadal variations in the Gulf Stream (GS) and coastal sea level may also apply to short‐term variations, so flood predictions may be improved if the GS influence is considered.
Acute inhibition of diacylglycerol lipase blocks endocannabinoid‐mediated retrograde signalling: evidence for on‐demand biosynthesis of 2‐arachidonoylglycerol

• 2‐Arachidonoylglycerol (2‐AG), one of the best‐characterized retrograde messengers at central synapses, has been thought to be produced ‘on demand’ through a diacylglycerol lipase α (DGLα)‐dependent pathway upon activation of postsynaptic neurons (on‐demand synthesis hypothesis). • However, recent studies propose an alternative hypothesis that 2‐AG is pre‐synthesized by DGLα, stored in neurons, and released from such ‘pre‐formed pools’ without the participation of DGLα (pre‐formed pool hypothesis). • To test these hypotheses, we examined the effects of acute pharmacological inhibition of DGL by a novel potent DGL inhibitor, OMDM‐188, on retrograde 2‐AG signalling. • We found that 2‐AG‐mediated retrograde signalling was blocked after 1 h treatment with OMDM‐188 in acute slices from the hippocampus, striatum and cerebellum, and was blocked several minutes after OMDM‐188 application in cultured hippocampal neurons. • These results fit well with the on‐demand synthesis hypothesis, rather than the pre‐formed pool hypothesis.
Diversity is All You Need: Learning Skills without a Reward Function

Intelligent creatures can explore their environments and learn useful skills without supervision. In this paper, we propose DIAYN ("Diversity is All You Need"), a method for learning useful skills without a reward function. Our proposed method learns skills by maximizing an information theoretic objective using a maximum entropy policy. On a variety of simulated robotic tasks, we show that this simple objective results in the unsupervised emergence of diverse skills, such as walking and jumping. In a number of reinforcement learning benchmark environments, our method is able to learn a skill that solves the benchmark task despite never receiving the true task reward. In these environments, some of the learned skills correspond to solving the task, and each skill that solves the task does so in a distinct manner. Our results suggest that unsupervised discovery of skills can serve as an effective pretraining mechanism for overcoming challenges of exploration and data efficiency in reinforcement learning
Controlling a superconducting nanowire single-photon detector using tailored bright illumination

We experimentally demonstrate that a superconducting nanowire single-photon detector is deterministically controllable by bright illumination. We found that bright light can temporarily make a large fraction of the nanowire length normally conductive, can extend deadtime after a normal photon detection, and can cause a hotspot formation during the deadtime with a highly nonlinear sensitivity. As a result, although based on different physics, the superconducting detector turns out to be controllable by virtually the same techniques as avalanche photodiode detectors. As demonstrated earlier, when such detectors are used in a quantum key distribution system, this allows an eavesdropper to launch a detector control attack to capture the full secret key without this being revealed by too many errors in the key.
Spatially distinct and metabolically active membrane domain in mycobacteria

Significance Mycobacterium is a family of bacteria that includes a number of dangerous pathogens. Arresting the growth of mycobacteria may be possible through the disruption of control points that regulate cell envelope biosynthesis. We demonstrate that Mycobacterium smegmatis possesses a spatially distinct biosynthetic membrane domain enriched in the polar growth region of the cell. This membrane domain may act as an organizing center to spatiotemporally coordinate biosynthetic activities during growth in live cells. Thus, our findings provide an important insight into the potential regulatory mechanisms of lipid metabolism in mycobacteria. Protected from host immune attack and antibiotic penetration by their unique cell envelope, mycobacterial pathogens cause devastating human diseases such as tuberculosis. Seamless coordination of cell growth with cell envelope elongation at the pole maintains this barrier. Unraveling this spatiotemporal regulation is a potential strategy for controlling mycobacterial infections. Our biochemical analysis previously revealed two functionally distinct membrane fractions in Mycobacterium smegmatis cell lysates: plasma membrane tightly associated with the cell wall (PM-CW) and a distinct fraction of pure membrane free of cell wall components (PMf). To provide further insight into the functions of these membrane fractions, we took the approach of comparative proteomics and identified more than 300 proteins specifically associated with the PMf, including essential enzymes involved in cell envelope synthesis such as a mannosyltransferase, Ppm1, and a galactosyltransferase, GlfT2. Furthermore, comparative lipidomics revealed the distinct lipid composition of the PMf, with specific association of key cell envelope biosynthetic precursors. Live-imaging fluorescence microscopy visualized the PMf as patches of membrane spatially distinct from the PM-CW and notably enriched in the pole of the growing cells. Taken together, our study provides the basis for assigning the PMf as a spatiotemporally distinct and metabolically active membrane domain involved in cell envelope biogenesis.
Evaluation of several pre-clinical tools for identifying characteristics associated with limb bone fracture in thoroughbred racehorses

Author: Corsten, Anthony N. , M.S. BMS Institution: Purdue University. Degree Received: Master of Science in Basic Medical Sciences, Fall 2016. Title: Evaluation of Several Pre-Clinical Tools for Identifying Characteristics Associated with Limb Bone Fracture in Thoroughbred Racehorses Major Professor: Dr. Russell Main, Ph.D. Catastrophic skeletal fractures in racehorses are devastating not only to the animals, owners and trainers, but also to the perception of the sport in the public eye. The majority of these fatal accidents are unlikely to be due to chance, but are rather an end result failure from stress fractures. Stress fractures are overuse injuries resulting from an accumulation of bone tissue damage over time. Because stress fractures are pathological, it is possible that overt fractures can be predicted and prevented. In this study, third metacarpals (MC3) from 33 thoroughbred racehorse comprised of 8 non-fractured controls and 25 horses that experienced fracture of some limb bone were evaluated for correlative factors for fracture using reference point indentation (RPI; Biodent, Osteoprobe), peripheral quantitative computed tomography (pQCT) and Raman spectroscopy. As measured by RPI, fractured racehorses had reduced indentation distance of the RPI probe on the dorsal surface of the MC3, compared to controls. pQCT analysis revealed that horses that fractured long bones had lower cortical bone mineral density in the distal metaphysis than sesamoid fractured or control horses. Also in the distal metaphysis, horses that fractured their MC3s had greater trabecular and total bone mineral content, as well as greater geometric properties compared to other fracture and control groups. Raman spectroscopy showed that the lateral aspect of horses with MC3
Control of serum glucose concentration in critical illness

Purpose of review Hyperglycemia is a significant problem for children in the ICU. Use of tight glycemic control (TGC) to manage hyperglycemia remains controversial, especially given the potential risk of insulin-induced hypoglycemia. This review will address the latest evidence regarding TGC in critically ill children. Recent findings Two randomized controlled trials (RCT) involving primarily postoperative cardiac surgery patients demonstrated the feasibility and safety of TGC in pediatric patients. The trials, however, had discrepant results with regards to the benefit of TGC. There is also uncertainty about the generalizability of these results to nonpostoperative cardiac patients. There is only one published study addressing the long-term safety of TGC in children. In this study, hypoglycemia was not associated with adverse effects on neurocognitive development. In contrast, articles from adult studies demonstrate increased risk of death with hypoglycemia. Summary Although the clinical benefit of TGC in critically ill children is still unclear, TGC can be done safely in this population.
In vivo three-dimensional imaging of neovascular age-related macular degeneration using optical frequency domain imaging at 1050 nm.

PURPOSE To assess the application of optical frequency domain imaging (OFDI) at 1050 nm for the detection of choroidal neovascularization (CNV) in age-related macular degeneration (AMD) and its response to treatment. Three patients presenting with blurred vision and exudative AMD were imaged before and after anti-VEGF treatment with ranibizumab. METHODS The patients were imaged with OFDI, a swept-source-based, high-speed optical coherence tomography (OCT) system developed at the Wellman Center for Photomedicine. A center wavelength of 1050 nm was used that has been demonstrated to provide better imaging of the deeper structures of the retina below the RPE, such as the choroidal vasculature. Three-dimensional data sets were acquired in 2 to 4 seconds. RESULTS En face images were compiled from cross-sectional OFDI data and correlated with color fundus photography (CF) and fluorescein angiograms (FAs). Cross-sectional images were coregistered with CF and FA to obtain depth-resolved information about CNV, CNV volume, retinal thickness, subretinal fluid volume and height of neurosensory detachment before and after treatment with ranibizumab. A band of reduced reflectivity below the RPE was identified in all three subjects that corresponded to areas of confirmed and suspected occult CNV on FA. After treatment, this band was reduced in volume in all patients. CONCLUSIONS High-speed 3-D OFDI at 1050 nm is a promising technology for imaging the retina and choroid in neovascular AMD. The developed system at 1050 nm provides good contrast for occult (type 1) CNV and may have advantages compared with time domain and current state of the art spectral domain OCT systems (SD-OCT) at 850 nm.
Genetic polymorphisms in leptin, adiponectin and their receptors affect risk and aggressiveness of prostate cancer: evidence from a meta-analysis and pooled-review

Leptin and adiponectin signaling was associated with development and progression of various cancers. The present study aimed to clarify the role of genetic variants in leptin, adiponectin and their receptors in prostate cancer. After comprehensive search and manuscript scanning, a total of 49 genetic variants were enrolled and examined for their relations to cancer risk and aggressiveness. In the meta-analysis, LEP rs7799039 (allele contrast: OR 1.133, 95%CI 1.024-1.254), ADIPOQ rs2241766 (allele contrast: OR 1.201, 95%CI 1.015-1.422) and ADIPOR1 rs10920531 (allele contrast: OR 1.184, 95%CI 1.075-1.305) variants were identified to be correlated with increased risk of prostate cancer. On the contrary, LEPR rs1137101 (allele contrast: OR 0.843, 95%CI 0.730-0.973) and ADIPOR1 rs2232853 (allele contrast: OR 0.638, 95%CI 0.535-0.760) variants were associated with decreased risk of prostate cancer. From the pooled-review, we additionally recognized eight variants associated with cancer risk and another eight variants associated with cancer aggressiveness, respectively. These observations indicated important roles of leptin, adiponectin and their receptors in the development and progression of prostate cancer. The identified polymorphisms might assist in developing better risk-assessment tools, as well as generating novel targeted therapies, especially for obese cancer patients with impaired leptin and adiponectin signaling.
A Randomized Controlled Phase Ib Trial of the Malaria Vaccine Candidate GMZ2 in African Children

Background GMZ2 is a fusion protein of Plasmodium falciparum merozoite surface protein 3 (MSP3) and glutamate rich protein (GLURP) that mediates an immune response against the blood stage of the parasite. Two previous phase I clinical trials, one in naïve European adults and one in malaria-exposed Gabonese adults showed that GMZ2 was well tolerated and immunogenic. Here, we present data on safety and immunogenicity of GMZ2 in one to five year old Gabonese children, a target population for future malaria vaccine efficacy trials. Methodology/Principal Findings Thirty children one to five years of age were randomized to receive three doses of either 30 µg or 100 µg of GMZ2, or rabies vaccine. GMZ2, adjuvanted in aluminum hydroxide, was administered on Days 0, 28 and 56. All participants received a full course of their respective vaccination and were followed up for one year. Both 30 µg and 100 µg GMZ2 vaccine doses were well tolerated and induced antibodies and memory B-cells against GMZ2 as well as its antigenic constituents MSP3 and GLURP. After three doses of vaccine, the geometric mean concentration of antibodies to GMZ2 was 19-fold (95%CI: 11,34) higher in the 30 µg GMZ2 group than in the rabies vaccine controls, and 16-fold (7,36) higher in the 100 µg GMZ2 group than the rabies group. Geometric mean concentration of antibodies to MSP3 was 2.7-fold (1.6,4.6) higher in the 30 µg group than in the rabies group and 3.8-fold (1.5,9.6) higher in the 100 µg group. Memory B-cells against GMZ2 developed in both GMZ2 vaccinated groups. Conclusions/Significance Both 30 µg as well as 100 µg intramuscular GMZ2 are immunogenic, well tolerated, and safe in young, malaria-exposed Gabonese children. This result confirms previous findings in naïve and malaria-exposed adults and supports further clinical development of GMZ2. Trial Registration ClinicalTrials.gov NCT00703066
LncRNA profile study reveals four-lncRNA signature associated with the prognosis of patients with anaplastic gliomas

Anaplastic glioma is Grade III and the median overall survival is about 37.6 months. However, there are still other factors that affect the prognosis for anaplastic glioma patients due to variable overall survival. So we screened four-lncRNA signature (AGAP2-AS1, TPT1-AS1, LINC01198 and MIR155HG) from the lncRNA expression profile from the GSE16011, CGGA and REMBRANDT datasets. The patients in low risk group had longer overall survival than high risk group (median OS 2208.25 vs. 591.30 days; P < 0.0001). Moreover, patients in the low risk group showed similar overall survival to Grade II patients (P = 0.1669), while the high risk group showed significant different to Grade IV (P = 0.0005) with similar trend. So based on the four-lncRNA, the anaplastic gliomas could be divided into grade II-like and grade IV-like groups. On the multivariate analysis, it showed the signature was an independent prognostic factor (P = 0.000). The expression of four lncRNAs in different grades showed that AGAP2-AS1, LINC01198 and MIR155HG were increased with tumor grade, while TPT1-AS1 was decreased. Knockdown of AGAP2-AS1 can inhibit the cell proliferation, migration and invasion, while increase the apoptosis cell rates in vitro. In conclusion, our results showed that the four-lncRNA signature has prognostic value for anaplastic glioma. Moreover, clinicians should conduct corresponding therapies to achieve best treatment with less side effects for two groups patients.
A flow cytometer for the measurement of Raman spectra

Multiparameter measurements in flow cytometry are limited by the broad emission spectra of fluorescent labels. By contrast, Raman spectra are notable for their narrow spectral features. To increase the multiparameter analysis capabilities of flow cytometry, we investigated the possibility of measuring Raman signals in a flow cytometry‐based system. We constructed a Raman Spectral Flow Cytometer, substituting a spectrograph and CCD detector for the traditional mirrors, optical filters, and photomultiplier tubes. Excitation at 633 nm was provided by a HeNe laser, and forward‐angle light scatter is used to trigger acquisition of complete spectra from individual particles. Microspheres were labeled with nanoparticle surface enhanced Raman scattering (SERS) tags and measured using the RSFC. Fluorescence and Raman spectra from labeled microspheres were acquired using the Raman Spectral Flow Cytometer. SERS spectral intensities were dependent on integration time, laser power, and detector pixel binning. Spectra from particles labeled with one each of four different SERS tags could be distinguished by either a virtual bandpass approach using commercial flow cytometry data analysis software or by principal component analysis. Raman flow cytometry opens up new possibilities for highly multiparameter and multiplexed measurements of cells and other particles using a simple optical design and a single detector and light source. © 2008 International Society for Analytical Cytology
Cross‐sectional association between physical activity and serum testosterone levels in US men: results from NHANES 1999–2004

Testosterone levels and physical activity each play important roles in men's health, but the relationship between the two remains unclear. We evaluated the cross‐sectional association between self‐reported total physical activity and serum testosterone levels in 738 men (mean age 42.4 years, range 20–≥85 years) who participated in National Health and Nutrition Examination Survey 1999–2004. We compared geometric mean testosterone concentrations measured by radioimmunoassay (RIA) and calculated the odds ratio (OR) of having low or low normal testosterone (≤3.46 ng/mL) across tertiles of total physical activity in all men, and men stratified by age (20–49, ≥50 years), and obesity status (BMI < 30, ≥30 kg/m2). The geometric mean testosterone concentration was 5.31 ng/mL; 18.6% of the men had low or low normal serum testosterone levels. Physical activity tertiles were not associated with testosterone levels overall, or when stratified by age or obesity status. Similarly, there was no association between physical activity tertiles and the odds of low or low normal testosterone, overall or by age. However, among non‐obese men, those in the highest physical activity tertile were significantly less likely to have low or low normal testosterone than those in the lowest tertile (OR 0.50; 95% CI = 0.26–0.95); there was no association among obese men. Greater physical activity was not associated with testosterone levels, but may be associated with a reduced odds of low or low normal testosterone in non‐obese men, but not in obese men.
Colony-forming unit cell (CFU-C) assays at diagnosis: CFU-G/M cluster predicts overall survival in myelodysplastic syndrome patients independently of IPSS-R

Background In vitro colony-forming unit cell (CFU-C) assays are usually-used to detect the quantitative and qualitative features of haematopoietic stem cells (HSCs). We studies CFU-C assays in bone marrow samples from 365 consecutive subjects with newly-diagnosed myelodysplastic syndrome (MDS). Data were interrogated for associations with prognosis. Methods CFU-C assays were performed according to the protocol of MethoCultTM H4435 Enriched. 365 consecutive newly-diagnosed, untreated subjects with MDS diagnosed from July, 2007 to April, 2014 were studied. All subjects were reclassified according to the 2008 WHO criteria. Subjects were observed for survival until July 31, 2015. Follow-up data were available for 289 (80%) subjects. Median follow-up of survivors was 22 months (range, 1-85) months. Erythroid and myeloid colonies were isolated from each subject with one cytogenetic abnormality such as del(5/5q), +8, del(7/7q) or del(20q). Cytogenetic abnormalities of each colony were analyzed by fluorescence in situ hybridization (FISH). SPSS 17.0 software was used to make statistical analysis. Results The numbers of burst-forming units-erythroid (BFU-E), colony forming unit-erythroid (CFU-E) and colony forming unit-granulocytes/macrophages (CFU-G/M) were significantly lower than normals. A high ratio of cluster- to CFU-G/M was associated with poor-risk cytogenetics. In multivariable analyses a cluster- to CFU-G/M ratio >0.6 was an independent risk-factor for OS after adjusting for IPSS-R (HR 3.339, [95%CI 1.434-7.778]; P = 0.005) in very high-risk cohort. Conclusion These data suggest abnormalities of proliferation and differentiation of erythroid and myeloid precursor cells in vitro parallel the ineffective hematopoiesis typical of MDS and may be useful in predicting outcomes of persons with higher-risk MDS.