Miracle-dz/UniFAR-FTUs huggingface dataset:
A study of betel quid carcinogenesis--VIII. Carcinogenicity of 3-(methylnitrosamino)propionaldehyde in F344 rats.

In assays of Areca-specific N-nitrosamines, 3-(methylnitrosamino)propionaldehyde (MNPA) exhibits higher cytotoxicity than nitrosoguvacine (NGC), nitrosoguvacoline (NG) and 3-(methylnitrosamino)propionitrile (MNPN). NGC is not mutagenic. However, NG is a weak carcinogen in F344 rats while MNPN is a potent carcinogen; MNPA had thus far not been tested. In this study MNPA was injected s.c. at a dose of 6.57 mg three times weekly for 15 weeks (total dose 2.6 mmol/rat). During the 100 weeks of the bioassay, the treated F344 rats, and especially the females, showed significantly less weight gain than the control animals, indicating high toxicity for MNPA at the tested dose. Upon termination of the bioassay, the MNPA-treated animals were found to have tumors of the lung, liver, nasal cavity, forestomach and kidneys. The control animals showed no tumors in these organs. The incidence of lung tumors in the MNPA group was statistically significant (P less than 0.025). The results of this study show that MNPA is a carcinogen in F344 rats.
Hes genes and neurogenin regulate non-neural versus neural fate specification in the dorsal telencephalic midline

The choroid plexus in the brain is unique because it is a non-neural secretory tissue. It secretes the cerebrospinal fluid and functions as a blood-brain barrier, but the precise mechanism of specification of this non-neural tissue has not yet been determined. Using mouse embryos and lineage-tracing analysis, we found that the prospective choroid plexus region initially gives rise to Cajal-Retzius cells, specialized neurons that guide neuronal migration. Inactivation of the bHLH repressor genes Hes1, Hes3 and Hes5 upregulated expression of the proneural gene neurogenin 2 (Ngn2) and prematurely depleted Bmp-expressing progenitor cells, leading to enhanced formation of Cajal-Retzius cells and complete loss of choroid plexus epithelial cells. Overexpression of Ngn2 had similar effects. These data indicate that Hes genes promote specification of the fate of choroid plexus epithelial cells rather than the fate of Cajal-Retzius cells by antagonizing Ngn2 in the dorsal telencephalic midline region, and thus this study has identified a novel role for bHLH genes in the process of deciding which cells will have a non-neural versus a neural fate.
Whole-genome nucleotide diversity, recombination, and linkage disequilibrium in the model legume Medicago truncatula

Medicago truncatula is a model for investigating legume genetics, including the genetics and evolution of legume–rhizobia symbiosis. We used whole-genome sequence data to identify and characterize sequence polymorphisms and linkage disequilibrium (LD) in a diverse collection of 26 M. truncatula accessions. Our analyses reveal that M. truncatula harbors both higher diversity and less LD than soybean (Glycine max) and exhibits patterns of LD and recombination similar to Arabidopsis thaliana. The population-scaled recombination rate is approximately one-third of the mutation rate, consistent with expectations for a species with a high selfing rate. Linkage disequilibrium, however, is not extensive, and therefore, the low recombination rate is likely not a major constraint to adaptation. Nucleotide diversity in 100-kb windows was negatively correlated with gene density, which is expected if diversity is shaped by selection acting against slightly deleterious mutations. Among putative coding regions, members of four gene families harbor significantly higher diversity than the genome-wide average. Three of these families are involved in resistance against pathogens; one of these families, the nodule-specific, cysteine-rich gene family, is specific to the galegoid legumes and is involved in control of rhizobial differentiation. The more than 3 million SNPs that we detected, approximately one-half of which are present in more than one accession, are a valuable resource for genome-wide association mapping of genes responsible for phenotypic diversity in legumes, especially traits associated with symbiosis and nodulation.
Plasmodium falciparum Infection Induces Expression of a Mosquito Salivary Protein (Agaphelin) That Targets Neutrophil Function and Inhibits Thrombosis without Impairing Hemostasis

Background Invasion of mosquito salivary glands (SGs) by Plasmodium falciparum sporozoites is an essential step in the malaria life cycle. How infection modulates gene expression, and affects hematophagy remains unclear. Principal Findings Using Affimetrix chip microarray, we found that at least 43 genes are differentially expressed in the glands of Plasmodium falciparum-infected Anopheles gambiae mosquitoes. Among the upregulated genes, one codes for Agaphelin, a 58-amino acid protein containing a single Kazal domain with a Leu in the P1 position. Agaphelin displays high homology to orthologs present in Aedes sp and Culex sp salivary glands, indicating an evolutionarily expanded family. Kinetics and surface plasmon resonance experiments determined that chemically synthesized Agaphelin behaves as a slow and tight inhibitor of neutrophil elastase (KD∼10 nM), but does not affect other enzymes, nor promotes vasodilation, or exhibit antimicrobial activity. TAXIscan chamber assay revealed that Agaphelin inhibits neutrophil chemotaxis toward fMLP, affecting several parameter associated with cell migration. In addition, Agaphelin reduces paw edema formation and accumulation of tissue myeloperoxidase triggered by injection of carrageenan in mice. Agaphelin also blocks elastase/cathepsin-mediated platelet aggregation, abrogates elastase-mediated cleavage of tissue factor pathway inhibitor, and attenuates neutrophil-induced coagulation. Notably, Agaphelin inhibits neutrophil extracellular traps (NETs) formation and prevents FeCl3-induced arterial thrombosis, without impairing hemostasis. Conclusions Blockade of neutrophil elastase emerges as a novel antihemostatic mechanism in hematophagy; it also supports the notion that neutrophils and the innate immune response are targets for antithrombotic therapy. In addition, Agaphelin is the first antihemostatic whose expression is induced by Plasmodium sp infection. These results suggest that an important interplay takes place in parasite-vector-host interactions.
Quantitative analysis of microtubule dynamics during adhesion‐mediated growth cone guidance

During adhesion‐mediated neuronal growth cone guidance microtubules undergo major rearrangements. However, it is unknown whether microtubules extend to adhesion sites because of changes in plus‐end polymerization and/or translocation dynamics, because of changes in actin–microtubule interactions, or because they follow the reorganization of the actin cytoskeleton. Here, we used fluorescent speckle microscopy to directly quantify microtubule and actin dynamics in Aplysia growth cones as they turn towards beads coated with the cell adhesion molecule apCAM. During the initial phase of adhesion formation, dynamic microtubules in the peripheral domain preferentially explore apCAM‐beads prior to changes in growth cone morphology and retrograde actin flow. Interestingly, these early microtubules have unchanged polymerization rates but spend less time in retrograde translocation due to uncoupling from actin flow. Furthermore, microtubules exploring the adhesion site spend less time in depolymerization. During the later phase of traction force generation, the central domain advances and more microtubules in the peripheral domain extend because of attenuation of actin flow and clearance of F‐actin structures. Microtubules in the transition zone and central domain, however, translocate towards the adhesion site in concert with actin arcs and bundles, respectively. We conclude that adhesion molecules guide neuronal growth cones and underlying microtubule rearrangements largely by differentially regulating microtubule–actin coupling and actin movements according to growth cone region and not by controlling plus‐end polymerization rates. © 2008 Wiley Periodicals, Inc. Develop Neurobiol, 2008
Iterative cluster‐NMA: A tool for generating conformational transitions in proteins

Computational models provide insight into the structure–function relationship in proteins. These approaches, especially those based on normal mode analysis, can identify the accessible motion space around a given equilibrium structure. The large magnitude, collective motions identified by these methods are often well aligned with the general direction of the expected conformational transitions. However, these motions cannot realistically be extrapolated beyond the local neighborhood of the starting conformation. In this article, the iterative cluster‐NMA (icNMA) method is presented for traversing the energy landscape from a starting conformation to a desired goal conformation. This is accomplished by allowing the evolving geometry of the intermediate structures to define the local accessible motion space, and thus produce an appropriate displacement. Following the derivation of the icNMA method, a set of sample simulations are performed to probe the robustness of the model. A detailed analysis of β1,4‐galactosyltransferase‐T1 is also given, to highlight many of the capabilities of icNMA. Remarkably, during the transition, a helix is seen to be extended by an additional turn, emphasizing a new unknown role for secondary structures to absorb slack during transitions. The transition pathway for adenylate kinase, which has been frequently studied in the literature, is also discussed. Proteins 2009. © 2008 Wiley‐Liss, Inc.
A cuff-shaped enzymeless glucose sensor integrated with chronically implantable peripheral nerve cuff electrode for inflammation monitoring

This paper reports on a recently developed cuff-shaped enzymeless glucose sensor integrated with chronically implantable peripheral nerve cuff electrode for the reflecting nerve signal degradation, particularly in the time immediately following implantation. The cuff-shaped enzymeless glucose sensor with black Pt working electrode (WE) showed the roughness factor (RF) of 16.413 and extremely lowered impedance of 40 ohm at 1 kHz compared to the plain Pt (RF: 1, impedance 600 ohm). The enzymeless glucose sensor with black Pt WE operated without any enzyme and mediators. It exhibited dramatically increased glucose sensitivity of 38.26 μA/mMcm2 and detection limit of 25 μM in the glucose range up to 16 mM. These results indicate that the fabricated glucose sensor is promising for the inflammation monitoring application in the immediate vicinity of the implantable nerve cuff electrodes.
The Period Prevalence and Costs of Treating Nonmelanoma Skin Cancers in Patients Over 65 Years of Age Covered by Medicare

BACKGROUND Nonmelanoma skin cancer (NMSC) prevalence and treatment costs are rapidly increasing at an unknown rate. OBJECTIVE To determine actual prevalence and treatment costs for NMSC in patients over 65 years of age covered by Medicare. METHODS We used a 5% random sample of Medicare claims available for 1994 and 1995. Demographic characteristics, period prevalence, treatment types and frequencies, treating physician specialty, and allowable treatment charges associated with the diagnosis of NMSC were analyzed and described. RESULTS More than 789,000 patients over age 65 covered by Medicare had a diagnosis and treatment for NMSC in 1995. Fifty-eight percent were men and 98% were Caucasian. The majority were from the South and West regions of the United States. Dermatologists treated more than 60% of these NMSCs. Treatment costs were approximately $285 million. The largest percentage of treatment expenditures (34%) was for excisions. CONCLUSION The number of patients with NMSC is far greater than previous estimates. Dermatologists treat the majority of NMSCs. The mean treatment cost per patient is $329. Total expenditures for NMSC eradication represent 0.7% of the Medicare budget. NMSC is a major public health concern because of its increasing prevalence, costs, and the aging U.S. population.
Metabolites of Cerebellar Neurons and Hippocampal Neurons Play Opposite Roles in Pathogenesis of Alzheimer's Disease

Metabolites of neural cells, is known to have a significant effect on the normal physiology and function of neurons in brain. However, whether they play a role in pathogenesis of neurodegenerative diseases is unknown. Here, we show that metabolites of neurons play essential role in the pathogenesis of Alzheimer's disease (AD). Firstly, in vivo and in vitro metabolites of cerebellar neurons both significantly induced the expression of Aβ-degrading enzymes in the hippocampus and cerebral cortex and promoted Aβ clearance. Moreover, metabolites of cerebellar neurons significantly reduced brain Aβ levels and reversed cognitive impairments and other AD-like phenotypes of APP/PS1 transgenic mice, in both early and late stages of AD pathology. On the other hand, metabolites of hippocampal neurons reduced the expression of Aβ-degrading enzymes in the cerebellum and caused cerebellar neurodegeneration in APP/PS1 transgenic mice. Thus, we report, for the first time, that metabolites of neurons not only are required for maintaining the normal physiology of neurons but also play essential role in the pathogenesis of AD and may be responsible for the regional-specificity of Aβ deposition and AD pathology.
Improved Long-Term Health-Related Quality of Life After Islet Transplantation

Background. Health related quality of life (HRQoL) is one of the most important outcomes to measure effectiveness of an intervention, especially for islet transplantation in which benefits should outweigh risks of long-term immunosuppression. This study aimed to evaluate long-term effects of islet transplantation and to outline possible influential factors. Methods. Forty islet transplant recipients who completed 344 Health Status Questionnaires (HSQ 2.0) and 384 Diabetes Quality of Life Questionnaires (DQoL) between 2000 and 2007 were retrospectively reviewed. Assessments were analyzed in pretransplantation period, then every 3 months after the first infusion for 18 months and every 6 months thereafter. The mean follow-up posttransplantation was 40.8±21.9 months (9–72 months). Results. Sustained improvement in DQoL-impact score was observed at all time-points posttransplantation. Similarly, worry and satisfaction scales were significantly better than pretransplant evaluation for most time-points. Four of eight HSQ 2.0 scales demonstrated a significant improvement at some time-points. Longitudinal analysis, after adjustments for potential confounding factors, showed significantly sustained improvement in impact scale up to 72 months. Longer diabetes duration, higher insulin dosage, and occurrence of adverse events had negative effects on HRQoL. Single islet infusion or islet after kidney transplant recipients showed the lowest values in HSQ 2.0. In contrast, subjects on exenatide therapy had significantly higher HSQ 2.0 scores. Conclusions. Islet transplantation is associated with long-term improvement in HRQoL. Exenatide usage had a positive effect whereas single islet infusion, islet after kidney transplantation, longer diabetes duration, higher insulin dosage, and adverse events had a negative impact on HRQoL scores.
Palonosetron plus dexamethasone in highly emetogenic chemotherapy: pooled data from two Phase III trials.

AIM Data from two randomized trials were pooled to further characterize the effectiveness of palonosetron combined with dexamethasone in the setting of highly emetogenic chemotherapy. PATIENTS & METHODS The analysis included 1411 patients who were randomized to receive palonosetron or ondansetron/granisetron intravenously on day 1 plus either 1-day or 3-day dexamethasone dosing. The primary end point was complete response (no vomiting and no rescue antiemetics over days 1-5) in cycle one. Data across the studies were analyzed by the Mantel-Haenszel method. RESULTS The vast majority of patients received either cisplatin (62%) or anthracycline plus cyclophosphamide (34%). The palonosetron regimen provided a 12 percentage-point improvement in the rate of overall complete response compared with the control regimen (49.2 vs 37.3%; odds ratio: 1.65; 95% CI: 1.33-2.04; p < 0.0001). The frequency of no delayed nausea at all daily periods was consistently higher in the palonosetron group. CONCLUSION The current analysis confirmed that palonosetron plus dexamethasone improved control of highly emetogenic chemotherapy-induced nausea and vomiting throughout 5 days postchemotherapy to a significantly greater extent than the combination including older 5-HT3 antagonists.
Rural-to-Urban Migrants' Experiences with Primary Care under Different Types of Medical Institutions in Guangzhou, China

Objectives China is facing the unprecedented challenge of rapidly increasing rural-to-urban migration. Migrants are in a vulnerable state when they attempt to access to primary care services. This study was designed to explore rural-to-urban migrants’ experiences in primary care, comparing their quality of primary care experiences under different types of medical institutions in Guangzhou, China. Methods The study employed a cross-sectional survey of 736 rural-to-urban migrants in Guangzhou, China in 2014. A validated Chinese version of Primary Care Assessment Tool—Adult Short Version (PCAT-AS), representing 10 primary care domains was used to collect information on migrants’ quality of primary care experiences. These domains include first contact (utilization), first contact (accessibility), ongoing care, coordination (referrals), coordination (information systems), comprehensiveness (services available), comprehensiveness (services provided), family-centeredness, community orientation and culturally competent. These measures were used to assess the quality of primary care performance as reported from patients’ perspective. Analysis of covariance was conducted for comparison on PCAT scores among migrants accessing primary care in tertiary hospitals, municipal hospitals, community health centers/community health stations, and township health centers/rural health stations. Multiple linear regression models were used to explore factors associated with PCAT total scores. Results After adjustments were made, migrants accessing primary care in tertiary hospitals (25.49) reported the highest PCAT total scores, followed by municipal hospitals (25.02), community health centers/community health stations (24.24), and township health centers/rural health stations (24.18). Tertiary hospital users reported significantly better performance in first contact (utilization), first contact (accessibility), coordination (information system), comprehensiveness (service available), and cultural competence. Community health center/community health station users reported significantly better experience in the community orientation domain. Township health center/rural health station users expressed significantly better experience in the ongoing care domain. There were no statistically significant differences across settings in the ongoing care, comprehensiveness (services provided), and family-centeredness domains. Multiple linear regression models showed that factors positively associated with higher PCAT total scores also included insurance covering parts of healthcare payment (P<0.001). Conclusions This study highlights the need for improvement in primary care provided by primary care institutions for rural-to-urban migrants. Relevant policies related to medical insurance should be implemented for providing affordable healthcare services for migrants accessing primary care.
Strategies in Evaluation and Management of Bam Earthquake Victims

Abstract Background: On 26 December 2003, an earthquake measuring 6.5 on the Richter scale occurred in the city of Bam in southeastern Iran. Bam was destroyed completely, >43,000 people were killed, and 30,000 were injured. The national and international responses were quick and considerable. Many field hospitals werecreated and large numbers of patients were evacuated from their homes and transported to hospitals throughoutIran. Nearly 700 patients were transferred to Chamran hospital in Shiraz within the first 48 hours after the earthquake. Methods: This is a retrospective study based on the medical records of earthquake casualties dispatched to Chamran Hospital. A screening tunnel composed of multiple stations was prepared before patients entered to facilitate the large influx of patients. Each of the victims was passed through this screening tunnel and assigned into one of three groups: (1) those needing emergency surgical intervention; (2) those needing less urgent surgery; and (3) those needing elective operations, supportive care, observation, and/or rehabilitation. Results: Among the 708 patients, 392 were male (male/female ratio: 1.24) with a mean value of their ages of 30.5 years. (range: 1.5 months–70 years). Extremity fractures (136, 19%) were more common than were axial skeleton fractures (28, 4%). Out of the total 708 patients, 152 (21.5%) patients needed emergency operations, 26 (4%) needed less urgent surgery, and 530 (74.5%) required wound care or antibiotic therapy and other forms of supportive care. Some complications occurred, such as two patients with compartment syndromes of theleg, three required below-the-knee amputation, eight suffered acute renal failure, two developed fat emboli syndrome, and one had a brain injury that resulted in death. Conclusion: A comprehensive disaster plan is required to ensure a prompt disaster response and coordinated management of a multi-casualty incident. This can influence the outcomes of patients directly. A patient screening tunnel has advantages in rapid and effective evaluation and management of victims in any multi-casualty incident.
Multidimensional Waveform Encoding: A New Digital Beamforming Technique for Synthetic Aperture Radar Remote Sensing

This paper introduces the innovative concept of multidimensional waveform encoding for spaceborne synthetic aperture radar (SAR). The combination of this technique with digital beamforming on receive enables a new generation of SAR systems with improved performance and flexible imaging capabilities. Examples are high-resolution wide-swath radar imaging with compact antennas, enhanced sensitivity for applications like alongtrack interferometry and moving object indication, and the implementation of hybrid SAR imaging modes that are well suited to satisfy hitherto incompatible user requirements. Implementation-specific issues are discussed and performance examples demonstrate the potential of the new technique for different remote sensing applications.
Estimating the Fundamental Component of Harmonically Distorted Signals From Noncoherently Sampled Data

This paper describes an algorithm for estimating the frequency, amplitude, and phase of the fundamental component in harmonically distorted waveforms. The algorithm minimizes the phase difference between the sine model and the sampled waveform by effectively minimizing the influence of the harmonic components. It uses a three-parameter sine-fitting algorithm for all phase calculations. The resulting estimates show up to two orders of magnitude smaller sensitivity to harmonic distortions than the results of the four-parameter sine fitting algorithm.