Статті в журналах: "RARE TYPE MATCH"

1

Cereda, Giulia, and Richard D. Gill. "A Nonparametric Bayesian Approach to the Rare Type Match Problem." Entropy 22, no. 4 (April 13, 2020): 439. http://dx.doi.org/10.3390/e22040439.

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The “rare type match problem” is the situation in which, in a criminal case, the suspect’s DNA profile, matching the DNA profile of the crime stain, is not in the database of reference. Ideally, the evaluation of this observed match in the light of the two competing hypotheses (the crime stain has been left by the suspect or by another person) should be based on the calculation of the likelihood ratio and depends on the population proportions of the DNA profiles that are unknown. We propose a Bayesian nonparametric method that uses a two-parameter Poisson Dirichlet distribution as a prior over the ranked population proportions and discards the information about the names of the different DNA profiles. This model is validated using data coming from European Y-STR DNA profiles, and the calculation of the likelihood ratio becomes quite simple thanks to an Empirical Bayes approach for which we provided a motivation.

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2

Cereda, Giulia. "Bayesian approach to LR assessment in case of rare type match." Statistica Neerlandica 71, no. 2 (March 10, 2017): 141–64. http://dx.doi.org/10.1111/stan.12104.

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3

Van Dorp, I. N., A. J. Leegwater, I. Alberink, and G. Jongbloed. "Value of evidence in the rare type match problem: common source versus specific source." Law, Probability and Risk 19, no. 1 (March 1, 2020): 85–98. http://dx.doi.org/10.1093/lpr/mgaa002.

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Abstract In the so-called rare type match problem, the discrete characteristics of a crime stain have not been observed in the set of background material. To assess the strength of evidence, two competing statistical hypotheses need to be considered. The formulation of the hypotheses depends on which identification of source question is of interest (Ommen, 2017, Approximate statistical solutions to the forensic identification of source problem. (Phd thesis). South Dakota State University). Assuming that the evidence has been generated according to the beta-binomial model, two quantifications of the value of evidence can be found in the literature, but no clear indication is given when to use either of these. When the likelihood ratio is used to quantify the value of evidence, an estimate is needed for the frequency of the discrete characteristics. The central discussion is about whether or not one of the traces needs to be added to the background material when determining this estimate. In this article it is shown, using fully Bayesian methods, that one of the values of evidence from the literature corresponds to the so-called ‘identification of common source’ problem and the other to the ‘identification of specific source’ problem (Ommen, 2017, Approximate statistical solutions to the forensic identification of source problem. (Phd thesis). South Dakota State University). This means that the question whether or not one of the traces needs to be added to the background material reduces to the question whether a common source or specific source problem is under consideration. The distinction between the two values is especially important for the rare type match problem, since the values of evidence differ most in this situation.

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4

Cereda, G., R. D. Gill, and F. Taroni. "A solution for the rare type match problem when using the DIP-STR marker system." Forensic Science International: Genetics 34 (May 2018): 88–96. http://dx.doi.org/10.1016/j.fsigen.2017.07.010.

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5

Kazerounian, Milod, Jeffrey S. Foster, and Bonan Min. "SimTyper: sound type inference for Ruby using type equality prediction." Proceedings of the ACM on Programming Languages 5, OOPSLA (October 20, 2021): 1–27. http://dx.doi.org/10.1145/3485483.

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Many researchers have explored type inference for dynamic languages. However, traditional type inference computes most general types which, for complex type systems—which are often needed to type dynamic languages—can be verbose, complex, and difficult to understand. In this paper, we introduce SimTyper, a Ruby type inference system that aims to infer usable types—specifically, nominal and generic types—that match the types programmers write. SimTyper builds on InferDL, a recent Ruby type inference system that soundly combines standard type inference with heuristics. The key novelty of SimTyper is type equality prediction , a new, machine learning-based technique that predicts when method arguments or returns are likely to have the same type. SimTyper finds pairs of positions that are predicted to have the same type yet one has a verbose, overly general solution and the other has a usable solution. It then guesses the two types are equal, keeping the guess if it is consistent with the rest of the program, and discarding it if not. In this way, types inferred by SimTyper are guaranteed to be sound. To perform type equality prediction, we introduce the deep similarity (DeepSim) neural network. DeepSim is a novel machine learning classifier that follows the Siamese network architecture and uses CodeBERT, a pre-trained model, to embed source tokens into vectors that capture tokens and their contexts. DeepSim is trained on 100,000 pairs labeled with type similarity information extracted from 371 Ruby programs with manually documented, but not checked, types. We evaluated SimTyper on eight Ruby programs and found that, compared to standard type inference, SimTyper finds 69% more types that match programmer-written type information. Moreover, DeepSim can predict rare types that appear neither in the Ruby standard library nor in the training data. Our results show that type equality prediction can help type inference systems effectively produce more usable types.

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6

Akdogan, Leyla, Ali Kemal Oguz, Tarkan Ergun, and Ihsan Ergun. "The Rarest of the Rare: Crossed Fused Renal Ectopia of the Superior Ectopia Type." Case Reports in Nephrology 2015 (2015): 1–4. http://dx.doi.org/10.1155/2015/742419.

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Crossed fused renal ectopia is a rare congenital anomaly of the urinary system where one kidney crosses over to opposite side and the parenchyma of the two kidneys fuse. Herein, we present an atypical CFRE case whose renal anatomy does not exactly match any of the already defined CFRE types. Both of the kidneys are ectopic with the crossed ectopic right kidney lying superiorly and fused to the upper pole of the left kidney. Renal arteries were originating from the common iliac arteries. A focal 90% stenosis was observed on the right main renal artery. The patient is borderline hypertensive.

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Rai, Preeti, Geetika Sharma, Deeksha Singh, and Jyoti Garg. "Rare presentation of mixed autoimmune hemolytic anemia in children: Report of 2 cases." Journal of Laboratory Physicians 9, no. 04 (October 2017): 332–36. http://dx.doi.org/10.4103/jlp.jlp_95_17.

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AbstractImmune hemolytic anemia is characterized by clinical and laboratory features of hemolytic anemia with direct antiglobulin test (DAT) positivity. It could be autoimmune hemolytic anemia (AIHA), alloimmune, or drug-induced hemolysis based on the antigenic stimulus. Furthermore, based on thermal amplitude of autoantibody, AIHA is classified as warm (65%), cold (30%), and mixed (5%) type. Mixed AIHA is extremely rare in children and must be differentiated from warm AIHA with clinically insignificant cold agglutinins and cold hemagglutinin disease as their treatment is different. It may present as blood group discrepancy or cross-match incompatibility leading to delay in arranging suitable blood unit for transfusion. Therefore, a thorough immunohematology workup including monospecific DAT, indirect antiglobulin test at 4°C and 37°C, determination of thermal amplitude and titer is essential. We hereby present two pediatric cases of mixed AIHA presenting as ABO forward and reverse blood group discrepancy and cross-match incompatibility.

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8

Dobish, Mark A., David A. Wyler, Christopher J. Farrell, Hermandeep S. Dhami, Victor M. Romo, Daniel D. Choi, Travis Reed, and Michael E. Mahla. "Chronic Skull Base Erosion from Temporomandibular Joint Disease Causes Generalized Seizure and Profound Lactic Acidosis." Case Reports in Critical Care 2018 (September 27, 2018): 1–4. http://dx.doi.org/10.1155/2018/8795036.

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This report displays a rare presentation of lactic acidosis in the setting of status epilepticus (SE). The differential diagnosis of lactic acidosis is broad and typically originates from states of shock; however, this report highlights an alternative and rare etiology, SE, due to chronic skull base erosion from temporomandibular joint (TMJ) disease. Lactic acidosis is defined by a pH below 7.35 in the setting of lactate values greater than 5 mmol/L. Two broad classifications of lactic acidosis exist: a type A lactic acidosis which stems from global or localized tissue hypoxia or a type B lactic acidosis which occurs once mitochondrial oxidative capacity is unable to match glucose metabolism. SE is an example of a type A lactic acidosis in which oxygen delivery is unable to meet increased cellular energy requirements. This report is consistent with a prior case series that consists of five patients experiencing generalized tonic-clonic (GTC) seizures and lactic acidosis. These patients presented with a pH range of 6.8-7.41 and lactate range of 3.8-22.4 mmol/L. Although severe lactic acidosis following GTC has been described, this is the first report in the literature of chronic skull base erosion from TMJ disease causing SE.

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9

Magee, M. R., and K. Maguire. "An investigation of 56Ni shells as the source of early light curve bumps in type Ia supernovae." Astronomy & Astrophysics 642 (October 2020): A189. http://dx.doi.org/10.1051/0004-6361/202037870.

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An excess of flux (i.e. a bump) in the early light curves of type Ia supernovae has been observed in a handful of cases. Multiple scenarios have been proposed to explain this excess flux. Recently, it has been shown that for at least one object (SN 2018oh) the excess emission observed could be the result of a large amount of 56Ni in the outer ejecta (∼0.03 M⊙). We present a series of model light curves and spectra for ejecta profiles containing 56Ni shells of varying masses (0.01, 0.02, 0.03, and 0.04 M⊙) and widths. We find that even for our lowest mass 56Ni shell, an increase of >2 magnitudes is produced in the bolometric light curve at one day after explosion relative to models without a 56Ni shell. We show that the colour evolution of models with a 56Ni shell differs significantly from those without and shows a colour inversion similar to some double-detonation explosion models. Furthermore, spectra of our 56Ni shell models show that strong suppression of flux between ∼3700–4000 Å close to maximum light appears to be a generic feature for this class of model. Comparing our models to observations of SNe 2017cbv and 2018oh, we show that a 56Ni shell of 0.02–0.04 M⊙ can match shapes of the early optical light curve bumps, but the colour and spectral evolution are in disagreement. Our models also predict a strong UV bump that is not observed. This would indicate that an alternative origin for the flux excess is necessary. In addition, based on existing explosion scenarios, producing such a 56Ni shell in the outer ejecta as required to match the light curve shape, without the presence of additional short-lived radioactive material, may prove challenging. Given that only a small amount of 56Ni in the outer ejecta is required to produce a bump in the light curve, such non-monotonically decreasing 56Ni distributions in the outer ejecta must be rare, if they were to occur at all.

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10

Billeter, R., M. Messerli, E. Wey, A. Puntschart, K. Jostarndt, H. M. Eppenberger, and J. C. Perriard. "Fast myosin light chain expression in chicken muscles studied by in situ hybridization." Journal of Histochemistry & Cytochemistry 40, no. 10 (October 1992): 1547–57. http://dx.doi.org/10.1177/40.10.1382092.

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We have studied the fiber type-specific expression of the fast myosin light chain isoforms LC 1f, LC 2f, and LC 3f in adult chicken muscles using in situ hybridization and two-dimensional gel electrophoresis. Type II (fast) fibers contain all three fast myosin light chain mRNAs; Types I and III (slow) fibers lack them. The myosin light chain patterns of two-dimensional gels from microdissected single fibers match their mRNA signals in the in situ hybridizations. The results confirm and extend previous studies on the fiber type-specific distribution of myosin light chains in chicken muscles which used specific antibodies. The quantitative ratios between protein and mRNA content were not the same for all three fast myosin light chains, however. In bulk muscle samples, as well as in single fibers, there was proportionally less LC 3f accumulated for a given mRNA concentration than LC 1f or LC 2f. Moreover, the ratio between LC 3f mRNA and protein was different in samples from muscles, indicating that LC 3f is regulated somewhat differently than LC 1f and LC 2f. In contrast to other in situ hybridization studies on the fiber type-specific localization of muscle protein mRNAs, which reported the RNAs to be located preferentially at the periphery of the fibers, we found all three fast myosin light chain mRNAs quite evenly distributed within the fiber's cross-sections, and also in the few rare fibers which showed hybridization signals several-fold higher than their surrounding counterparts. This could indicate principal differences in the intracellular localization among the mRNAs coding for various myofibrillar protein families.

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11

Burd, Amy, Richard L. Schilsky, John C. Byrd, Ross L. Levine, Vassiliki A. Papadimitrakopoulou, Roy S. Herbst, Mary W. Redman, Brian J. Druker, and David R. Gandara. "Challenges and approaches to implementing master/basket trials in oncology." Blood Advances 3, no. 14 (July 23, 2019): 2237–43. http://dx.doi.org/10.1182/bloodadvances.2019031229.

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Abstract The appetite for cutting-edge cancer research, across medical institutions, scientific researchers, and health care providers, is increasing based on the promise of true breakthroughs and cures with new therapeutics available for investigation. At the same time, the barriers for advancing clinical research are impacting how quickly drug development efforts are conducted. For example, we know now that under a microscope, patients with the same type of cancer and histology might look the same; however, the reality is that most cancers are driven by genomic, transcriptional, and epigenetic changes that make each patient unique. Additionally, the immunologic reaction to different tumor types is distinct among patients. The challenge for researchers developing new therapies today is vastly different than it was in the era of cytotoxics. Today, we must identify a sufficient number of patients harboring a rare mutation or other characteristic and match this to the right therapeutic option. This summary provides a guide to help inform the scientific cancer community about the benefits and challenges of conducting umbrella or basket trials (master trials), and to create a roadmap to help make this new and evolving form of clinical trial design as effective as possible.

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12

Pousada, Thais, Jessica Garabal-Barbeira, Cristina Martínez, Betania Groba, Laura Nieto-Riveiro, and Javier Pereira. "How Loan Bank of Assistive Technology Impacts on Life of Persons with Amyotrophic Lateral Sclerosis and Neuromuscular Diseases: A Collaborative Initiative." International Journal of Environmental Research and Public Health 18, no. 2 (January 18, 2021): 763. http://dx.doi.org/10.3390/ijerph18020763.

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(1) Background: The study is focused on the implementation of outcome measurement tools to assess the impact of an assistive device from a loan bank in the lives of people with Amyotrophic Lateral Sclerosis and Neuromuscular Diseases. The secondary purpose is to analyse the correct matching between the person and technology, derived from the counselling of an occupational therapist. (2) Methods: Cross-sectional study. The sample was formed by 28 people with rare neurodegenerative disorders. A specific questionnaire, the Psychosocial Impact of Assistive Device Scale (PIADS), and the Matching Person and Technology (MPT) tool were applied to collect the data. (3) Results: The dimension of the PIADS with the best score was competence, and the variations according to gender were not remarkable. The three dimensions of the PIADS (competence, adaptability, and self-esteem) were correlated positively between them and with the mean score of the MPT tool (p < 0.01). The type of assistive technology (AT), diagnosis, and correct match between person–technology are the main factors that condition a positive impact. (4) Conclusions: The results noted the importance of assessing the needs, demands, and contexts of people with rare neurodegenerative diseases to prescribe the best AT. Loan banks of AT have to be considered a valid service that complements their lack in public health services.

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13

Huda, KM, and OFG Kibria. "Incompatible Crossmatch with Bombay Phenotype (Oh) - A Case Report." Pulse 9, no. 1 (March 14, 2017): 54–59. http://dx.doi.org/10.3329/pulse.v9i1.31883.

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Blood serology plays a vital role in transfusion medicine. Presence of an irregular antibody (anti H) in the plasma reacting with all the red cells exhibiting the normal red cell ABO phenotype, the h/h (Bombay) phenotype. The h/h phenotype also known as Oh or Bombay blood group is a rare blood type. It was first discovered in Bombay (Mumbai) in India by Dr.Y.G. Bhende et al in 19521 Generally present in about 4 per million of the human population, though in some places such as Mumbai (Bombay) locals can have occurrences in as much as 1 in 10,000 of inhabitants2 It is also very rare in Bangladesh. The first case was reported in 1990 where three sisters in a same family were of 'Bombay' phenotype3. A 28-year-old male of Noakhali district was admitted to Apollo Hospitals Dhaka on 21st may 2016 with road traffic accident with pelvic fracture. His ABC and Rh blood group was detected as 0 positive by usual blood grouping test procedure. But his cross match was incompatible with several 0 positive blood units. Though the patients blood group phenotype initially mimic normal group 0 type by usual test procedure but became apparent when his serum was tested against group 0 red cells and strong Mediate spin agglutination developed at a thermal range 4° to 37°C. After testing with anti H Lectin, Ulex europaeus having anti H like activity, it was detected as Bombay blood group. Therefore, proper serum grouping using A cell, B cell and 0 cell is necessary to detect this group. Bombay phenotype individual do not express H, A and B antigen on their red cells and secretions but their plasma contains potent anti H, anti A and anti B due to lack H antigen4 Normal 0 group red cells does not have A or B antigen but their membrane expresses abundant H antigen. Anti H of Bombay phenotype serum gives incompatible cross match with all red blood cells of normal ABO phenotype containing H antigen. oh phenotype person can receive only autologous blood or blood from another Bombay blood group donor.5 This patient has received blood from her own sister who was also Bombay phenotype but his other four brothers were normal 0 group. Later on he was transfused with blood from Bombay blood group donor, arranged from Think Foundation, Mumbai, India for his orthopedic surgery. Both forward and reverse grouping is important for safe transfusion. If not followed, it may lead to people with Bombay blood group, not being detected and categorized as 0 group. Therefore, proper reverse grouping is necessary to detect this group and cross matching at different thermal range also plays a vital role in transfusion safety.Pulse Vol.9 January-December 2016 p.54-59

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14

Xu, Yiqing, Jiang Yio, Amber Yang, Ashrei Bayewitz, Daniel Benasher, and Lung Fu. "Utility of tumor genomic profiling in guiding targeted therapy and referral for clinical trials in the community practice." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): e18381-e18381. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.e18381.

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e18381 Background: Next-generation sequencing (NGS), which enables tumor genomic profiling with limited tumor specimen for the guidance of targeted therapy, has been widely used in oncology practice. It also reports mutations of which no approved therapy is available, but potential therapies approved in a different tumor type may be reasonable to try, based on molecular mechanisms or limited data, either in clinical trials or off trial treatment. The utility of this information in the community practice is unclear. Methods: We performed a retrospective analysis on the usage of NGS result on patients with lung or colorectal cancers treated between November 2011 and February 2018. Patients were identified from Foundation Medicine Company database and were linked to records at Maimonides. We evaluated if NGS was used to guide FDA-approved targeted therapy, potentially-useful targeted therapy not approved for the cancer type, or referral to a clinical trial. Results: 177 patients (lung ca = 119, colon ca = 58) were included. NGS identified 34 (28.6%) lung ca patients with driver mutations, (21 EGFR, 6 RET, 3 ALK, 2 MET amplification, 1 ROS1 and 1NTRK mutation), who were all given FDA-approved therapy. 70 (58.8%) patients had at least 1 target with an FDA-approved therapy for a different cancer; 89 (74.9%) had a mutation being studied in a clinical trial, and 48 patients were eligible for the NCI-MATCH trial. None received non-FDA-approved drugs and none was referred to clinical trials. In the colon cancer cohort, NGS identified alterations in KRAS (27), BRAF (5), ERBB2 mutation (2), ERBB2 amplification (1), MLH1 (1), MSH2 (1) and BRCA 2(1). Among them, one patient received BRAF inhibitors. 45 and 24 patients were eligible for phase I/II trials and NCI-MATCH trial respectively, and none was referred. Conclusions: NGS has a high efficiency of detecting driver mutations in lung cancer; but only reveals low frequencies of alterations otherwise not tested in colon cancer. The approach of prescribing un-approved targeted treatment based on theoretical mechanism of action was very uncommon, and the referral to clinical trials was rare in this community practice, both of which decreasing the utility value of NGS.

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15

Hamilton, Jennifer R., Elizabeth C. Stahl, Connor A. Tsuchida, Enrique Lin-Shiao, C. Kimberly Tsui, Kathleen Pestal, Holly K. Gildea, et al. "Robotic RNA extraction for SARS-CoV-2 surveillance using saliva samples." PLOS ONE 16, no. 8 (August 5, 2021): e0255690. http://dx.doi.org/10.1371/journal.pone.0255690.

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Saliva is an attractive specimen type for asymptomatic surveillance of COVID-19 in large populations due to its ease of collection and its demonstrated utility for detecting RNA from SARS-CoV-2. Multiple saliva-based viral detection protocols use a direct-to-RT-qPCR approach that eliminates nucleic acid extraction but can reduce viral RNA detection sensitivity. To improve test sensitivity while maintaining speed, we developed a robotic nucleic acid extraction method for detecting SARS-CoV-2 RNA in saliva samples with high throughput. Using this assay, the Free Asymptomatic Saliva Testing (IGI FAST) research study on the UC Berkeley campus conducted 11,971 tests on supervised self-collected saliva samples and identified rare positive specimens containing SARS-CoV-2 RNA during a time of low infection prevalence. In an attempt to increase testing capacity, we further adapted our robotic extraction assay to process pooled saliva samples. We also benchmarked our assay against nasopharyngeal swab specimens and found saliva methods require further optimization to match this gold standard. Finally, we designed and validated a RT-qPCR test suitable for saliva self-collection. These results establish a robotic extraction-based procedure for rapid PCR-based saliva testing that is suitable for samples from both symptomatic and asymptomatic individuals.

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16

Lebrun, Laetitia, Martin Bizet, Barbara Melendez, Barbara Alexiou, Lara Absil, Claude Van Campenhout, Nicky D’Haene, et al. "Analyses of DNA Methylation Profiling in the Diagnosis of Intramedullary Astrocytomas." Journal of Neuropathology & Experimental Neurology 80, no. 7 (July 1, 2021): 663–73. http://dx.doi.org/10.1093/jnen/nlab052.

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Abstract Intramedullary astrocytomas (IMAs) consist of a heterogeneous group of rare central nervous system (CNS) tumors associated with variable outcomes. A DNA methylation-based classification approach has recently emerged as a powerful tool to further classify CNS tumors. However, no DNA methylation-related studies specifically addressing to IMAs have been performed yet. In the present study, we analyzed 16 IMA samples subjected to morphological and molecular analyses, including DNA methylation profiling. Among the 16 samples, only 3 cases were classified in a reference methylation class (MC) with the recommended calibrated score (≥0.9). The remaining cases were either considered “no-match” cases (calibrated score <0.3, n = 7) or were classified with low calibrated scores (ranging from 0.32 to 0.53, n = 6), including inconsistent classification. To obtain a more comprehensive tool for pathologists, we used different unsupervised analyses of DNA methylation profiles, including our data and those from the Heidelberg reference cohort. Even though our cohort included only 16 cases, hypotheses regarding IMA-specific classification were underlined; a potential specific MC of PA_SPINE was identified and high-grade IMAs, probably consisting of H3K27M wild-type IMAs, were mainly associated with ANA_PA MC. These hypotheses strongly suggest that a specific classification for IMAs has to be investigated.

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17

Bednorz, Leszek, Agnieszka Krzymińska, and Aneta Czarna. "Seed morphology and testa sculptures of some Allium L. species (Alliaceae)." Acta Agrobotanica 64, no. 2 (2012): 33–38. http://dx.doi.org/10.5586/aa.2011.015.

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The paper presents the results of the study on seed morphology of eight following Allium species: A. pyrenaicum Costa & Vayr., A. rotundum L., A. sphaerocephalon L., A. vineale L., A. moly L., A. karataviense Regel, A. fistulosum L. and A. nutans L. The study confirmed the substantial diversity in testa characters, especially curvature and relief of anticlinal walls as well as microsculpture of outer periclinal walls. The occurrence of raised anticlinal walls - an unusually rare feature in Allium seeds, previously observed only in a few species, was found in A. karataviense. It was also found that the testa type in A. pyrenaicum did not match the typical character combination, described before for subg. Allium sect. Allium.

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18

Butters, Terry D., Howard R. Mellor, Keishi Narita, Raymond A. Dwek, and Frances M. Platt. "Small–molecule therapeutics for the treatment of glycolipid lysosomal storage disorders." Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences 358, no. 1433 (May 29, 2003): 927–45. http://dx.doi.org/10.1098/rstb.2003.1278.

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Glycosphingolipid (GSL) lysosomal storage disorders are a small but challenging group of human diseases to treat. Although these disorders appear to be monogenic in origin, where the catalytic activity of enzymes in GSL catabolism is impaired, the clinical presentation and severity of disease are heterogeneous. Present attitudes to treatment demand individual therapeutics designed to match the specific disease–related gene defect; this is an acceptable approach for those diseases with high frequency, but it lacks viability for extremely rare conditions. An alternative therapeutic approach termed ‘substrate deprivation’ or ‘substrate reduction therapy’ (SRT) aims to balance cellular GSL biosynthesis with the impairment in catalytic activity seen in lysosomal storage disorders. The development of N–alkylated iminosugars that have inhibitory activity against the first enzyme in the pathway for glucosylating sphingolipid in eukaryotic cells, ceramide–specific glucosyltransferase, offers a generic therapeutic for the treatment of all glucosphingolipidoses. The successful use of N–alkylated iminosugars to establish SRT as an alternative therapeutic strategy has been demonstrated in in vitro , in vivo and in clinical trials for type 1 Gaucher disease. The implications of these studies and the prospects of improvement to the design of iminosugar compounds for treating Gaucher and other GSL lysosomal storage disorders will be discussed.

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19

Marchi, Enrica, Kensei Tobinai, Dai Maruyama, Hirokazu Nagai, and Owen A. O'Connor. "An objective based model of published treatment options for relapsed or refractory (R/R) peripheral t-cell lymphoma (PTCL): An evidence-based decision-making approach." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): e19048-e19048. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.e19048.

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e19048 Background: PTCL are rare diseases with a poor prognosis. Front line therapy achieves CR in 30% to 60% and OS of 25%. Patients with R/R disease have an even worse prognosis. There is no consensus on the management of R/R disease because evidence supporting most treatment approaches is modest. Many approaches are often not supported by literature, and categorizations regarding efficacy and toxicity without attention to details are ignored. Treatments that have achieved regulatory approval with stringent independent assessment of pathology and response are viewed as less established, or equivalent to smaller published experiences. In the effort to take a critical and comprehensive evidence-based approach to available standards in R/R PTCL we developed an objective scoring system for all types of studies published in the literature (eg randomized phase 3, case match control, phase 2, phase 1, case reports and small series) to aid decision-making based on an assessment of all the available data. Methods: An extensive review on PubMed of clinical trials published in literature for R/R PTCL was performed. A rigorous scoring system based on a survey from 100 authorities in the field to quantitate scientific impact of each study based was developed. These include: type of study (randomized phase 3, case match control analysis, phase 2 weighted based on number of PTCL patients [ > 100 vs < 100 patients], phase 1 with > 5 or < 5 PTCL patients enrolled, and retrospective); weighting for use of central pathology or response review; weighting for detailed study metrics (ORR, CR, DoR, PFS). The scoring system included a penalty for omission detail. The proposed scoring system was evaluated by a panel of experts. The scoring system was modified based on recommendations made by 2 or more panel members. Results: We identified 58 publications between 2004 and 2018. The scoring system spanned from 0 to 9. Only 12 of the 58 studies had a score above 5; 15 of 58 had a score between 1 - 5; remaining publications scored 0 - 1. Conclusions: Our analysis suggests practice patterns are based on studies with low priority scores, and underweight robust clinical experiences. This analysis aims to produce an evidenced based approach for R/R PTCL.

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20

Mayer, Kimberly M., and James D. Forney. "A Mutation in the Flanking 5′-TA-3′ Dinucleotide Prevents Excision of an Internal Eliminated Sequence From the Paramecium tetraurelia Genome." Genetics 151, no. 2 (February 1, 1999): 597–604. http://dx.doi.org/10.1093/genetics/151.2.597.

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Abstract The germline chromosomes in Paramecium and other ciliated protozoa contain regions of DNA that are excised and eliminated during the development of a new macronuclear genome. Paramecium tetraurelia internal eliminated sequences (IESs) are invariably flanked by a 5′-TA-3′ dinucleotide sequence that is part of a larger 8-bp terminal inverted-repeat consensus sequence. Both features, the absolutely conserved 5′-TA-3′ and the remaining 6-bp terminal inverted repeat, are shared with the mariner/Tc1 class of transposons. In this article we describe a mutant cell line (AIM-2) defective in excision of a single IES from the coding region of the A51 surface antigen gene. Excision of the 370-bp IES6649 is prevented by a single A to G transition in the invariably conserved 5′-TA-3′ dinucleotide. Failure to excise IES6649 also revealed a 29-bp IES located inside IES6649. Additional experiments with the previously isolated AIM-1 mutant, which also contains an internal IES, shows that alternate excision using the wild-type end of IES2591 with an end from the internal IES is extremely rare or nonexistent. These results indicate that IESs are discrete elements whose excision depends upon nucleotides located within the consensus sequence, but also suggest that additional information is required to match one end of an IES with its excision partner.

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Agarwala, Vineeta, Anala Gossai, Gaurav Singal, Claire O'Connell, Gerald Li, Ken Kao, David Bourque, et al. "Use of cancer immunotherapies in the real-world in the setting of microsatellite instability." Journal of Clinical Oncology 36, no. 5_suppl (February 10, 2018): 30. http://dx.doi.org/10.1200/jco.2018.36.5_suppl.30.

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30 Background: In May 2017, the FDA approved for the first time a cancer therapy (pembrolizumab) for use in patients based on the presence of a genomic marker (microsatellite instability, or MSI) rather than anatomical tumor type. Real-world data on the rates and clinical impact of MSI on treatment selection and response are scant, especially outside of colorectal cancer. Methods: We performed a retrospective study of all patients treated in the Flatiron Health network (>265 oncology practices across the U.S.) between January 2011 and June 2017, and who underwent FoundationOne tumor sequencing as part of routine clinical care. Tumor type was determined by pathologist review of specimens submitted to Foundation Medicine. Data on therapy use was sourced from electronic health records (EHRs). Assessment of MSI was performed from DNA sequencing across the coding regions of >300 genes. Results: Our overall cohort included n=16,020 patients. Among patients in whom MSI status could be assessed (n=12,411), 207 patients had MSI-high tumors. The observed rate of MSI-high was 1.7% across all tumor types combined; tumor-specific rates varied significantly, from 4.9% in colorectal adenocarcinoma to 0.3% in breast and non-small cell lung cancer. The rate of MSI-high was 2.4% in patients with an unknown primary based on specimen review. A total of 1,329 patients received common checkpoint inhibitors (nivolumab, pembrolizumab, atezolizumab). Among the checkpoint-inhibitor treated patients with known MSI status (n=1,175), 14 (1.2%) had MSI-high tumors, and the majority of these patients (n=8) had colorectal cancer. Conclusions: Evidence of MSI-high is rare in real world cancer care settings. Early identification of patients with this biomarker is important in order to efficiently match them to treatment. Further evaluation of the real-world effectiveness of immune checkpoint inhibitors in the MSI-high population is still needed. Because most patients receiving these therapies today do not have high MSI, exploration of additional biomarkers for immunotherapy response is also critical.

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22

Zhang, Ershuai, and Zhiqiang Cao. "Tissue Response to Subcutaneous Infusion Catheter." Journal of Diabetes Science and Technology 14, no. 2 (March 31, 2019): 226–32. http://dx.doi.org/10.1177/1932296819837972.

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Insulin infusion pump, continuous glucose monitoring (CGM), and insulin infusion set (IIS) have been developed to be increasingly feasible for people with type 1 diabetes (T1D). Several recently approved CGMs are transitioning from 7-day to 10-day wear time without the need for fingerprick recalibration. Nevertheless, studies and improvements on IIS, a critical part of insulin pump therapy, have been limited. In particular, the recommended wear time of IIS is still 2-3 days, which can hardly match the current duration of CGM for potential closed-loop system development. It is generally believed that both the inserted catheter and the subsequent infused insulin drug could induce particular subcutaneous tissue response and skin-related complications at the infusion site. In certain cases, poor glycaemic control, increased risk of hypoglycemia, and serious cosmetic impact on people with diabetes were observed. Skin complication has also been attributed as an important factor resulting users to discontinue insulin pump therapy. This article provides the rare systematic review of IIS induced subcutaneous tissue responses and skin complications, including the impacts from the inserted catheters, the subcutaneous infused insulin, and the adhesive or tape used to immobilize the catheter. The FDA’s recommendation for the frequency of IIS change was further discussed. Future studies on this topic are required to further understand the IIS-related problems, and future strategies could be developed accordingly to significantly reduce the incidence of these problems, extend the wear time, and increase the acceptance of insulin pump based therapy.

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Allen, Richard J., and Cynthia J. Musante. "A mathematical analysis of adaptations to the metabolic fate of fructose in essential fructosuria subjects." American Journal of Physiology-Endocrinology and Metabolism 315, no. 3 (September 1, 2018): E394—E403. http://dx.doi.org/10.1152/ajpendo.00317.2017.

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Fructose is a major component of Western diets and is implicated in the pathogenesis of obesity and type 2 diabetes. In response to an oral challenge, the majority of fructose is cleared during “first-pass” liver metabolism, primarily via phosphorylation by ketohexokinase (KHK). A rare benign genetic deficiency in KHK, called essential fructosuria (EF), leads to altered fructose metabolism. The only reported symptom of EF is the appearance of fructose in the urine following either oral or intravenous fructose administration. Here we develop and use a mathematical model to investigate the adaptations to altered fructose metabolism in people with EF. First, the model is calibrated to fit available data in normal healthy subjects. Then, to mathematically represent EF subjects, we systematically implement metabolic adaptations such that model simulations match available data for this phenotype. We hypothesize that these modifications represent the major metabolic adaptations present in these subjects. This modeling approach suggests that several other aspects of fructose metabolism, beyond hepatic KHK deficiency, are altered and contribute to the etiology of this benign condition. Specifically, we predict that fructose absorption into the portal vein is altered, peripheral metabolism is slowed, renal reabsorption of fructose is mostly ablated, and alternate pathways for hepatic metabolism of fructose are upregulated. Moreover, these findings have implications for drug discovery and development, suggesting that the therapeutic targeting of fructose metabolism could lead to unexpected metabolic adaptations, potentially due to a physiological response to high-fructose conditions.

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Berman, Nikita, Melvyn Mark Jones, and Daan A. De Coster. "‘Just like a normal pain’, what do people with diabetes mellitus experience when having a myocardial infarction: a qualitative study recruited from UK hospitals." BMJ Open 7, no. 9 (September 2017): e015736. http://dx.doi.org/10.1136/bmjopen-2016-015736.

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ObjectiveThe objective of the study was to investigate the symptoms people with diabetes experience when having a myocardial infarction (MI), their illness narrative and how they present their symptoms to the health service.SettingThree London (UK) hospitals (coronary care units and medical wards).ParticipantsPatients were recruited with diabetes mellitus (DM) (types 1 and 2) with a clinical presentation of MI (ST elevated MI (STEMI), non-ST elevated MI (NSTEMI), acute MI unspecified and cardiac arrest). A total of 43 participants were recruited, and 39 interviews met the study criteria and were analysed. They were predominantly male (n=30), aged 40–90 years and white British (18/39), and just over a half were from other ethnic groups. The majority had type 2 DM (n=35), 24 had an NSTEMI, 10 had an STEMI and five had other cardiac events.Definitions of selection/exclusion criteriaA diagnosis of MI and DM and the ability to communicate enough English to complete the interview. Ward staff made a clinical judgement that the participant was post-treatment, clinically stable and well enough to participate.MethodsA qualitative study using taped and transcribed interviews analysed using a thematic analysis.ResultsWhile most participants did experience chest pain, it was often not their most striking symptom. As their chest pain did not match their expectations of what a ‘heart attack’ should be, participants developed narratives to explain these symptoms, including the symptoms being effects of their DM (‘hypos’), side effects of medication (oral hypoglycaemics) or symptoms (such as breathlessness and indigestion) related to other comorbidities, often leading to delays in seeking care.ConclusionsWhile truly absent chest pain during MI among people with DM was rare in this study, patients’ attenuated symptoms often led to delay in seeking attention, and this may result in delays in receiving treatment.

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Savran, William H., Maximilian J. Werner, Warner Marzocchi, David A. Rhoades, David D. Jackson, Kevin Milner, Edward Field, and Andrew Michael. "Pseudoprospective Evaluation of UCERF3-ETAS Forecasts during the 2019 Ridgecrest Sequence." Bulletin of the Seismological Society of America 110, no. 4 (July 21, 2020): 1799–817. http://dx.doi.org/10.1785/0120200026.

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ABSTRACT The 2019 Ridgecrest sequence provides the first opportunity to evaluate Uniform California Earthquake Rupture Forecast v.3 with epidemic-type aftershock sequences (UCERF3-ETAS) in a pseudoprospective sense. For comparison, we include a version of the model without explicit faults more closely mimicking traditional ETAS models (UCERF3-NoFaults). We evaluate the forecasts with new metrics developed within the Collaboratory for the Study of Earthquake Predictability (CSEP). The metrics consider synthetic catalogs simulated by the models rather than synoptic probability maps, thereby relaxing the Poisson assumption of previous CSEP tests. Our approach compares statistics from the synthetic catalogs directly against observations, providing a flexible approach that can account for dependencies and uncertainties encoded in the models. We find that, to the first order, both UCERF3-ETAS and UCERF3-NoFaults approximately capture the spatiotemporal evolution of the Ridgecrest sequence, adding to the growing body of evidence that ETAS models can be informative forecasting tools. However, we also find that both models mildly overpredict the seismicity rate, on average, aggregated over the evaluation period. More severe testing indicates the overpredictions occur too often for observations to be statistically indistinguishable from the model. Magnitude tests indicate that the models do not include enough variability in forecasted magnitude-number distributions to match the data. Spatial tests highlight discrepancies between the forecasts and observations, but the greatest differences between the two models appear when aftershocks occur on modeled UCERF3-ETAS faults. Therefore, any predictability associated with embedding earthquake triggering on the (modeled) fault network may only crystalize during the presumably rare sequences with aftershocks on these faults. Accounting for uncertainty in the model parameters could improve test results during future experiments.

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Shi, Jimin, Xiaojian Meng, Yi Luo, Yamin Tan, Xiaoli Zhu, Gaofeng Zheng, Jingsong He, et al. "Clinical Characteristics and Outcome of Isolated Extramedullary Relapse in Acute Leukemia Following Allogeneic Stem Cell Transplantation: A Single Institutional Analysis." Blood 120, no. 21 (November 16, 2012): 4211. http://dx.doi.org/10.1182/blood.v120.21.4211.4211.

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Abstract Abstract 4211 Isolated extramedullary relapse (EMR) of acute leukemia (AL) is a rare occurrence although it appears to be more common following allogeneic stem cell transplantation (allo-SCT). To characterize what has been observed in isolated EMR, we investigated a total of 287 consecutive AL patients (144 acute myeloid leukemia, 138 acute lymphocytic leukemia and 5 acute mixed lineage leukemia) who underwent allo-SCT. Forty-seven (16.4%) patients experienced relapse after allo-SCT. 12 cases (4.2%) experienced relapse of extramedullary sites without concomitant bone marrow involvement. Isolated EMR accounted for 25.5% of the overall initial relapse. The time to relapse after allo-SCT was longer in the extramedullary sites than in the marrow (median, 10 months vs. 5.5 months, P<0.05,). Sites of EMR varied widely including central nervous system, skin, bone, pelvis and breasts. The variables considered for univariate analysis included donor gender, age, primary disease, disease status, cytogenetics/molecular abnormalities, preconditioning regimen, donor type, HLA match, aGVHD and cGVHD. The variables that showed significant correlation with isolated EMR were the cytogenetics abnormalities at diagnosis. The prognosis for patients who develop EMR remained poor but was relatively better than that after bone marrow (BM) relapse (overall survival, 10 vs. 18 months, P<0.05). Compared with local or single therapy, patients treated with systemic in combination with local treatment could yield favorable prognosis. Three patients survived 63, 55 and 49 months after transplant respectively, of whom two received DLI with subsequent chemotherapy and (or) irradiation and one had surgery with subsequent chemotherapy. In conclusion, we observed a significant number of isolated EMR of AL after allo-SCT and intensive approaches combined of local and systemic therapy can produce favorable response which may cure a percentage of these patients. Disclosures: No relevant conflicts of interest to declare.

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Popa, Irene Paula, Dragomir N. Șerban, Minela Aida Mărănducă, Ionela Lăcrămioara Șerban, Bogdan Ionel Tamba, and Ionuț Tudorancea. "Brugada Syndrome: From Molecular Mechanisms and Genetics to Risk Stratification." International Journal of Molecular Sciences 24, no. 4 (February 7, 2023): 3328. http://dx.doi.org/10.3390/ijms24043328.

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Brugada syndrome (BrS) is a rare hereditary arrhythmia disorder, with a distinctive ECG pattern, correlated with an increased risk of ventricular arrhythmias and sudden cardiac death (SCD) in young adults. BrS is a complex entity in terms of mechanisms, genetics, diagnosis, arrhythmia risk stratification, and management. The main electrophysiological mechanism of BrS requires further research, with prevailing theories centered on aberrant repolarization, depolarization, and current-load match. Computational modelling, pre-clinical, and clinical research show that BrS molecular anomalies result in excitation wavelength (k) modifications, which eventually increase the risk of arrhythmia. Although a mutation in the SCN5A (Sodium Voltage-Gated Channel Alpha Subunit 5) gene was first reported almost two decades ago, BrS is still currently regarded as a Mendelian condition inherited in an autosomal dominant manner with incomplete penetrance, despite the recent developments in the field of genetics and the latest hypothesis of additional inheritance pathways proposing a more complex mode of inheritance. In spite of the extensive use of the next-generation sequencing (NGS) technique with high coverage, genetics remains unexplained in a number of clinically confirmed cases. Except for the SCN5A which encodes the cardiac sodium channel NaV1.5, susceptibility genes remain mostly unidentified. The predominance of cardiac transcription factor loci suggests that transcriptional regulation is essential to the Brugada syndrome’s pathogenesis. It appears that BrS is a multifactorial disease, which is influenced by several loci, each of which is affected by the environment. The primary challenge in individuals with a BrS type 1 ECG is to identify those who are at risk for sudden death, researchers propose the use of a multiparametric clinical and instrumental strategy for risk stratification. The aim of this review is to summarize the latest findings addressing the genetic architecture of BrS and to provide novel perspectives into its molecular underpinnings and novel models of risk stratification.

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Hawthorne, W. D. "Holes and the sums of parts in Ghanaian forest: regeneration, scale and sustainable use." Proceedings of the Royal Society of Edinburgh. Section B. Biological Sciences 104 (1996): 75–176. http://dx.doi.org/10.1017/s0269727000006126.

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SynopsisThe current state of Ghana's forest is summarised. Considerable changes have occurred in the last decade, since Hall & Swaine's account and classification, due mainly to fire and logging. The requirements and potential for sustainable forest use are explored through a summary of patterns of regeneration, and of local and national distribution of individual species.Incisive indices of forest quality and condition are vital to good forest management. Various forest quality indices, summarising different properties of the plant community, are examined. These indices gloss over the statistically noisy behaviour of single species in small forest areas. The indices are: Forest Type – Hall & Swaine's forest ordination and classification; a Pioneer Index (PI) revealing the balance of ‘regeneration guilds’; a Genetic Heat Index (GHI), based mainly on the rarity value (Star rating) of all forest species, highlighting ‘hotspots’; and an Economic Index (EI) based on the concentration of common species (‘reddish Stars’) threatened by exploitation. Guild and Star are defined for all species and encapsulate trends of local and of global distribution and ecology. The national and local patterns and response to disturbance of the indices derived from the representation of these various guilds and stars are discussed.Scale is crucial to all discussions. A strictly hierarchical model of forest ecology/biogeography is less suitable than a continuum-of-significant-scale, and non-hierarchical model. For instance, refugia are usually perceived as discrete biogeographical units. However, major biological ‘hotspots’, which are often described as refugia and attributed to Pleistocene climatic variation, differ only in position along a continuum of scale from mini-refugia as small as individual plants. The biogeographic Dahomey gap has much in common with a canopy gap, with scale as the main distinction.There are conspicuous trends across Ghana's forests in the abundance of pioneer, rare or economic species. These differ in detail, but ‘hysteresis’ – the forest memory – and other factors related to the concept of refugia apply to all these aspects of forest quality. Major hotspot refugia are crucial to the national framework of biodiversity, but local refugia, between the size of individual plants and single forest blocks, are crucial to local regeneration and sustainable use, as they shape the probability cloud which defines the anatomy of and processes within each species' range. Short-term sustainable use depends on local refugia; longer-term sustainability requires maintenance of refugia on a wider range of scale.The implications of these phenomena to forest management are discussed in conclusion. Forest health is a multi-scale, but particularly a broad-scale, phenomenon. Local processes like the regeneration of forest under canopy gaps, are subordinate to larger-scale patterns and not determined simply by a match between species physiology and gap dynamics or patterns in the physical environment. Success of a species in a certain landscape does not automatically imply the species can be successful in similar conditions in a different landscape elsewhere: the context of the landscape in terms of the broader mosaic is also important. Managers, whether of plantations or natural forest, need to monitor, plan, and protect indigenous species on all scales. Forest managers need also to be aware of and work with the ‘forest memory’ factor. Protective measures for rare or economically threatened species should be based on current refugia and, like them, be arranged on all scales from single trees to large forest blocks.Researchers need to pay more attention to processes between the ecological and biogeographical, if they are to provide information for managers which has a useful synergy with existing types of data. Exploration is needed of the anatomy of the ‘probability clouds’ defining the statistics of dispersal and regeneration of rare or threatened species with respect to parent populations. What are the chances of a mahogany establishing at a point 500 metres from a mother tree? How is this statistic influenced by soil type? There is much to be learnt on scales between the canopy and the Dahomey Gap.

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O'Connor, Owen A., Enrica Marchi, Weining Volinn, and Won Seog Kim. "Case Match Control Analysis of Propel Reveals Survival Advantage for Patients with Relapsed/Refractory (R/R) Peripheral T-Cell Lymphoma (PTCL) Treated with Pralatrexate." Blood 128, no. 22 (December 2, 2016): 4149. http://dx.doi.org/10.1182/blood.v128.22.4149.4149.

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Abstract Overall survival (OS) remains the gold standard proof of a clinical benefit, and differences in OS can only be determined in randomized Phase 3 clinical studies. However, in rare diseases, the conduct of randomized studies is very challenging, takes protracted periods of time to conduct, can be very expensive while not offering the promise of significant commercial return, and could become clinically irrelevant as other new agents and combinations emerge over the extended time frame of the study. Many drugs approved in this setting are often approved on surrogate end-points like progression free survival (PFS) or complete response (CR) rates in single arm Phase 2 studies. A middle-ground approach could involve using case-matched control analyses (CMCA), which are statistically more robust that single arm Phase 2 studies, and can provide meaningful insights into the likelihood of success in the randomized setting. CMCA require access to large well annotated datasets with a representative patient population, and can be used to benchmark a new drug in a defined patient population. Unfortunately, these types of analyses have not been routinely used in oncology, certainly not in patients with PTCL. We established an integrated international database of patients with R/R PTCL in order to better clarify the clinical benefit and survival advantage of pralatrexate in patients with R/R PTCL, using the original raw data from the PROPEL study. Data Source. The control population is derived from a collection of four historical databases of patients with R/R PTCL, including: Memorial Sloan-Kettering Cancer Center (MSKCC), University of Nebraska Medical Center (UNMC), Groupe d'Etude des Lymphomes de l'Adulte (GELA), and Samsung Medical Center (SMC). These databases were all annotated with the criteria used to define the PROPEL study population. The cases are from the PROPEL study, an international, multicenter single arm phase II study or pralatrexate in patient with R/R PTCL. The analysis was conducted by an independent statistician in collaboration with investigators from Columbia University. Method for Matching. The propensity score match was used to match cases and controls. The following characteristics are used in the match process: histology, number of previous treatments received, age at diagnosis (with 20 years interval), and sex. With 1:1 ratio match, the process identified 83 cases and 83 controls. The analysis population includes 68.7% female from cases and 66.3% from controls. For cases and controls, the age distributions are similar: mean age is 57.2 with the range (21 - 83) for cases and 56.7 with range (24 - 89). About 60% of patients received less than three previous treatments in both cases and controls ( 58% vs 59%). More than half of the patients in both cases and controls had histology PTCL-unspecified. Other histology above 10% are AILT and ALCL, primary systemic type. Results. In total, 83 patients out of 109 treated on the PROPEL study were successfully matched with the control population. The cases were matched 1 : 1. Overall survival was plotted for each of the two study populations. The survival curves for the control population were found to be nearly identical to that reported for this population from other datasets, including the ones reported from the International T-Cell Lymphoma Project, the British Columbia experience and the T-Cell Project. The overall survival was 4.04 months (95% CI 2.83, 5.78), which is consistent with historical controls describing the natural history of R/R PTCL in this population. The PROPEL study, which reported an overall response rate of 29% in patients with multiply relapsed PTCL, reported on one of the most diverse and heavily treated populations of R/R PTCL. In PROPEL, the median number of prior therapies was three, with 19% of patient receiving more than 5 lines of prior therapy. The median OS in for the pralatrexate treated cohort in this analysis was 16.6 months (95% CI: 11.99-25.56). There was a highly significant difference in the OS between these two populations, with a hazard ratio of 0.426 (95% CI: 0.296-0/61). The OS curves are shown below. This CMCA demonstrates a highly significant difference in OS in favor of patients treated with pralatrexate. This approach can be used to better understand how new drugs in orphan diseases perform in heterogeneous patient populations. Additional statistical and sensitivity analyses will be reported. Figure. Figure. Disclosures O'Connor: Seattle Genetics: Research Funding; Mundipharma: Membership on an entity's Board of Directors or advisory committees; Spectrum: Research Funding; Seattle Genetics: Research Funding; Spectrum: Research Funding; Mundipharma: Membership on an entity's Board of Directors or advisory committees; TG Therapeutics: Research Funding; TG Therapeutics: Research Funding; Bristol Myers Squibb: Research Funding; Bristol Myers Squibb: Research Funding; Celgene: Research Funding; Celgene: Research Funding. Volinn:LLXSolutions,LLC: Employment.

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Engertsberger, Lara, Martin Benesch, Martin Mynarek, Svenja Tonn, Martina Stickan-Verfürth, Angela Funk, Kristian W. Pajtler, et al. "EPEN-19. Impact of molecular classification on prognosis in children and adolescents with spinal ependymoma: Results from the HIT-MED database." Neuro-Oncology 24, Supplement_1 (June 1, 2022): i42—i43. http://dx.doi.org/10.1093/neuonc/noac079.156.

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Abstract PURPOSE: Ependymomas of the spinal cord are rare among children, and individual risks of disease progression are difficult to predict. This study aims at evaluating the prognostic impact of DNA methylation-based classification in children with spinal ependymoma. METHODS: Eighty-two patients with spinal ependymoma <22 years registered in the HIT-MED database between 1992 and 2021 were included. Clinical, radiological, and histopathological data were collected retrospectively. DNA methylation profiles of 46 tumors were classified according to the Heidelberg Brain Tumor Classifier. RESULTS: Spinal myxopapillary ependymoma (SP-MPE, n=27) was the most common methylation group followed by spinal ependymoma (SP-EPN, n=15). Two cases belonged to MYCN-amplified subgroup, one had no match, and one was re-classified as anaplastic pilocytic astrocytoma (the latter excluded from final analysis). WHO grade I and III ependymomas (according to the WHO 2016 classification) classified predominantly as SP-MPE, whereas grade II ependymomas clustered into SP-MPE and SP-EPN. 6/15 patients with SP-EPN (40%) suffered from Neurofibromatosis type 2. Among patients with SP-MPE, 23 underwent gross-total and four a subtotal resection (GTR/STR). Relapses of SP-MPE were more common following STR (5-year progression-free survival (5y-PFS) [STR] 25.0% [95% confidence interval: 0.0-68.4], [GTR] 75.0% [53.4-96.6], p=0.003). In the SP-EPN group, 2/8 patients relapsed after STR (5y-PFS 64.3% [22,3-100]) and 0/7 after GTR (n.s.). WHO I° ependymoma had significantly inferior PFS than II° and III° ependymoma (5y-PFS [I°] 39.0% [5.8-62.2], [II°] 82.4% [67.8-97.0], [III°] 50.5% [18.9-82.1], p=0.009). However, PFS did not significantly differ between SP-MPE and SP-EPN (5y-PFS 65.9% [44.9-86.9], 76.9% [46.3-100], respectively). CONCLUSION: Spinal ependymomas of WHO grade I go along with relatively poor PFS in our cohort, while DNA methylation profiling does not segregate patients into distinct risk groups. Still, larger cohorts and further investigations of methylation class heterogeneity in pediatric spinal ependymomas are needed to complete the basis for future clinical decision-making.

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Gareton, Albane, Arnault Tauziède-Espariat, Volodia Dangouloff-Ros, Alexandre Roux, Raphaël Saffroy, David Castel, Thomas Kergrohen, et al. "The histomolecular criteria established for adult anaplastic pilocytic astrocytoma are not applicable to the pediatric population." Acta Neuropathologica 139, no. 2 (November 1, 2019): 287–303. http://dx.doi.org/10.1007/s00401-019-02088-8.

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Abstract Pilocytic astrocytoma (PA) is the most common pediatric glioma, arising from a single driver MAPK pathway alteration. Classified as a grade I tumor according to the 2016 WHO classification, prognosis is excellent with a 10-year survival rate > 95% after surgery. However, rare cases present with anaplastic features, including an unexpected high mitotic/proliferative index, thus posing a diagnostic and therapeutic challenge. Based on small histomolecular series and case reports, such tumors arising at the time of diagnosis or recurrence have been designated by many names including pilocytic astrocytoma with anaplastic features (PAAF). Recent DNA methylation-profiling studies performed mainly on adult cases have revealed that PAAF exhibit a specific methylation signature, thus constituting a distinct methylation class from typical PA [methylation class anaplastic astrocytoma with piloid features—(MC-AAP)]. However, the diagnostic and prognostic significance of MC-AAP remains to be determined in children. We performed an integrative work on the largest pediatric cohort of PAAF, defined according to strict criteria: morphology compatible with the diagnosis of PA, with or without necrosis, ≥ 4 mitoses for 2.3 mm2, and MAPK pathway alteration. We subjected 31 tumors to clinical, imaging, morphological and molecular analyses, including DNA methylation profiling. We identified only one tumor belonging to the MC-AAP (3%), the others exhibiting a methylation profile typical for PA (77%), IDH-wild-type glioblastoma (7%), and diffuse leptomeningeal glioneuronal tumor (3%), while three cases (10%) did not match to a known DNA methylation class. No significant outcome differences were observed between PAAF with necrosis versus no necrosis (p = 0.07), or with 4–6 mitoses versus 7 or more mitoses (p = 0.857). Our findings argue that the diagnostic histomolecular criteria established for anaplasia in adult PA are not of diagnostic or prognostic value in a pediatric setting. Further extensive and comprehensive integrative studies are necessary to accurately define this exceptional entity in children.

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Douay, Luc. "In Vitro Production of Erythrocytes." Blood 120, no. 21 (November 16, 2012): SCI—39—SCI—39. http://dx.doi.org/10.1182/blood.v120.21.sci-39.sci-39.

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Abstract Abstract SCI-39 The generation of red blood cells (RBCs) in vitro using biotechnologies could represent an interesting alternative to classical transfusion products, in that it would combine adequate supplies with the specific production of blood products of a particular phenotype and the reduction of infection risks. This presentation will review how it is now possible to obtain in vitro complete maturation of the erythroid line to the stage of enucleation, starting from hematopoietic stem cells (HSCs) from peripheral blood, bone marrow or umbilical cord blood, or embryonic stem cells or adult pluripotent stem cells (induced pluripotent stem cells, iPSCs). This presentation will discuss how the functionality of cultured human RBCs (cRBCs) is settled in terms of deformability, hemoglobin maturation, oxygen carrying capacity, enzyme content, and terminal maturation from the reticulocyte stage to mature RBC after infusion into the NOD/SCID mouse model. The clinical feasibility of this concept has recently been demonstrated by reporting that cRBCs generated in vitro from peripheral HSCs under GMP conditions encounter in vivo the conditions required for their maturation and that they persist in the circulation for several weeks in humans. These data have established the proof of principle for transfusion of in vitro-generated RBCs and the pathway toward new developments in transfusion medicine. The most proliferative source of stem cells for generating cRBCs is cord blood, but it is limited in terms of HSCs and is dependent on donations. Pluripotent stem cell technology represents a potentially unlimited source of RBCs and opens the door to the development of a new generation of allogeneic transfusion products. Because iPSCs can be selected for a phenotype of interest, they are obviously the best candidate for organizing complementary sources of RBCs for transfusion. It is established that only three human iPSC clones would have been sufficient to match more than 99 percent of the patients in need of RBC transfusions. As a whole, a very limited number of RBC clones would provide for the needs of most alloimmunized patients and those with a rare blood group. Generating cRBCs from iPSCs has been done but needs to be optimized to lead to a clinical application in blood transfusion. Several crucial points remain to be resolved, notably, the choice of the initial cell type, the method of reprogramming (i.e., to ensure the safety of the iPSCs and to ensure their clinical grade), the optimization of the erythrocyte differentiation, and the definition of GMP conditions for industrial production. Assuming that in vitro large-scale cultured RBC production efficiently operates in the near future, this presentation will highlight the potential applications for alloimmunized patients and those with a rare blood group. Disclosures: No relevant conflicts of interest to declare.

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Kazlauskaite, Rasa, Yuanqing Liu, Pankaja Desai, Angela M. Jackson-Morris, Carrie Ngongo, and Rachel Nugent. "ODP182 Diabetes types and risk of severe COVID-19." Journal of the Endocrine Society 6, Supplement_1 (November 1, 2022): A306—A307. http://dx.doi.org/10.1210/jendso/bvac150.634.

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Abstract Background Associations of diabetes (DM) types with severe COVID have not adequately been investigated in clinical databases. Methods Analytical cohort of n=5713 patients with diabetes was selected from the electronic medical record-based COVID Registry in the urban academic health care system from March 2020 to March 2021. All cases in the registry tested positive for SARS-CoV-2 infection on the clinical assessments. Severe COVID was defined in cases requiring hospitalization or if fatal outcome. Demographics variables, clinic visits, vaccination status, multi-morbidity, ambulatory medication data, biochemical markers, and other diabetes characteristics were collected on or before the date of COVID diagnosis. After excluding pregnancy-related diabetes, cases were classified into type 1 (DM1), type 2 (DM2) and other/hybrid DM based on disease coding and clinical variables. Univariable and multivariable logistic regression models were used to assess the association of the three diabetes types with severe COVID after adjustment for age, sex, race/ethnicity. FindingsDiverse cohort included 37.6% Latino, 37.5% Black, 19.5% White, and 5.3% other; 53.7% were women. DM1 was identified in n=141 cases, Type 2 diabetes in n=2749, and other/hybrid diabetes in n=2823. The diabetes subtypes could not be reliably explored due to limitations of the clinical database. Compared to DM2, the odds of severe COVID were similar in DM1 (1.11, 95%CI 0.65, 1.81, p=0.700), but higher in other/hybrid DM (1.53, 95%CI 1.34, 1.76), after adjustment for sex, age, and race/ethnicity. Summary Other and hybrid diabetes types are not rare and are associated with a higher risk of severe COVID-19. The diabetes subtypes could not be reliably explored due to limitations of the clinical database. Presentation: No date and time listed

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Gruhn, Bernd, Ilona Wolff, James F. Beck, and Clemens Arndt. "A Prognostic Score For Children Undergoing Allogeneic Hematopoietic Stem Cell Transplantation." Blood 122, no. 21 (November 15, 2013): 3389. http://dx.doi.org/10.1182/blood.v122.21.3389.3389.

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Abstract Background The effects of certain risk factors on the survival of adults undergoing allogeneic hematopoietic stem cell transplantation (HSCT) have been the subject of research for many years. The impact of graft source and donor type, for instance, has already been examined closely. Lately iron parameters like ferritin became point of interest. Several prognostic scores utilizing those risk factors have been proposed. However, observations of pediatric populations considering those factors remain rare and no score in this regard for children with HSCT is available yet. Methods We retrospectively analyzed the effects of patient sex, recipient-donor sex match status, patient age, donor age, disease risk, graft source, donor HLA match as well as ferritin, albumin, total bilirubin, aspartate transaminase (AST), alanine transaminase (ALT), cholinesterase (CHE), gamma glutamyl transpeptidase (GGT), C-reactive protein (CRP) and lactate dehydrogenase (LDH) taken at the time of transplantation on the 5-year-overall survival of 132 children with malignant or non-malignant diseases undergoing allogeneic HSCT between 2001 and 2011 in a single center. The graft source was either bone marrow (n=82) or peripheral blood stem cells (n=50). The patients had the following underlying diseases: acute lymphoblastic leukemia (n=44), acute myeloid leukemia (n=29), chronic myeloid leukemia (n=5), myelodysplastic syndrome (n=16), non-Hodgkin lymphoma (n=7), solid tumor (n=4), severe aplastic anemia (n=7), myelofibrosis (n=2) and genetic disease (n=18). Conditioning regimen was myeloablative in all cases. The disease risk was formed by dividing the patients into two groups according to their clinical risk. Patients with genetic diseases, severe aplastic anemia, refractory cytopenia, myelofibrosis, leukemia and lymphoma in first or second remission as well as chronic myeloid leukemia in chronic phase were low risk, while patients with solid tumors, leukemia and lymphoma in relapse or in more than second remission and refractory anemia with excess blast in or not in transformation were high risk. For statistics we used Kaplan-Meier-method for univariate analysis and Cox regression for multivariate analysis. Results On univariate analysis 5-year-overall survival decreased significantly in patients with ferritin >1500 µg/L (40.8% versus 78.8%, p<0.001), GGT >1 µmol/L∙s (43.2% versus 67.9%, p=0.032), CRP >10 mg/L (54.6% versus 69.4%, p=0.017), LDH >6 µmol/L∙s (22.2% versus 66.8%, p=0.001), CHE <60 µmol/L∙s (35.7% versus 70%, p=0.002) as well as in patients with high disease risk (38.3% versus 74.7%, p<0.001), peripheral blood stem cells as graft source (47.1% versus 72.2% for bone marrow, p=0.001). For HLA donor match there was a 5-year-overall survival of 82.0% for matched related, 58.4% for matched unrelated, 56.3% for mismatched unrelated and 50.0% for haploidentical related donors (p=0.020). Other factors did not show a significant correlation. We subsequently developed a score of those parameters that were significant in multivariate analysis, i.e. disease risk (HR=3.744, p=0.035), ferritin (HR=6.860, p=0.002) and cholinesterase (HR=4.556, p=0.043), dividing the patient population into three groups: low with no risk factor, intermediate with one risk factor and high with two or three risk factors. For this score we found a 5-year-overall survival of 92.3% for low risk group, 66.2% for intermediate risk and 17.4% for high risk (p<0.001). Conclusion Our data show that ferritin, cholinesterase and disease risk are factors that decisively influence the prognosis after allogeneic HSCT in children. They should be evaluated in further trials as well as our proposed score. The characteristics that showed up significant in univariate but not in multivariate analysis appear to have an influence as well and might show a stronger correlation in larger trials. Disclosures: No relevant conflicts of interest to declare.

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Snyder, Rose, Christopher Leyton, Richard Elkind, Sireesha Vutukuri, Rosmi Mathew, Ioannis Mantzaris, Mendel Goldfinger, et al. "Utilization & Barriers to Curative Therapies Among Adult Aplastic Anemia Patients in a Multiethnic Urban Underserved Cohort." Blood 136, Supplement 1 (November 5, 2020): 11–12. http://dx.doi.org/10.1182/blood-2020-142704.

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Introduction Acquired Aplastic Anemia (AA) is a rare life-threatening immune-mediated bone marrow disorder. AlloHSCT is the only available curative therapy for SAA with a 3 year survival probability for adults between 72-80% in the United States. (D'Souza et all, Biol BMT 2020). The management of AA is complex and requires complicated regimens, recruitment of a BM donor, supportive care and close monitoring of hematopoietic response to therapy. Patients unable to follow closely with their physician or who lack sufficient social support are often deemed inappropriate candidates for BMT. The Bronx is one of the poorest urban counties in the US. 27.4% of Bronx residents live below the poverty line and 59% speak a language other than English at home. The socioeconomic circumstances for many Bronx residents present a multitude of health challenges that lead to poor health outcomes. Delivering the complex diagnosis and treatment strategies required for AA, a rare disease, can be particularly challenging for this population. Through this retrospective cohort study, we sought to find out the rate of utilization of curative therapies among patients with severe aplastic anemia in the Bronx, NY and to identify barriers to their care. We hypothesized that despite several social & financial barriers, SAA patients that can avail of IST +/- AlloHSCT at a tertiary care center will have similar survival trends as the national standard. Methods Our study used a data search tool called Clinical Looking Glass to identify adult patients diagnosed with AA at Montefiore Medical Center (MMC) between 2000 and 2018. Under an IRB approved protocol, we extracted all patients with a bone marrow biopsy performed between 2000 and 2018 and an ICD-9 diagnosis code of AA. Only patients aged 17 and above at the time of the index date (BM biopsy) were included. We also reviewed each chart to ensure the diagnosis of AA was confirmed by the BM biopsy. We performed a retrospective chart review of each patient in our cohort using our electronic medical records. Clinical data collected included patient demographic information, AA classification, date of diagnosis, date of last follow up or date of death, type of therapy received, and identification of socioeconomic barriers to receiving appropriate care. Results Thirty three adult patients (aged 17 and above at time of BM biopsy-confirmed diagnosis) were diagnosed with AA at Montefiore Medical Center between 2000 and 2018. Age at diagnosis ranged from 17-79, with a mean age of 36 and median age 28. Fifty five percent of patients were younger than 30 at the time of diagnosis. Forty two percent of patients were female and 57.6% were male. Fifty two percent of patients were African American or Black, 27.3% were Hispanic, 12.1% were White, and 9.1% were Asian or Asian Indian. Forty two percent of cases were non-severe, 18.2% were severe, and 36.4% were very severe. Additionally, approximately 70% of our cohort was unmarried. Thirty (90%) of the patients were treated with IST (CSA + ATG), and ten (30.3%) were also treated with eltrombopag. Of the 18 patients with severe and very severe disease, seven patients (38.9%) underwent AlloHSCT. Twenty five patients (76%) were noted to be alive at the time of data-cut off for analysis (March 2020), 4 of which were post-AlloHSCT. 45% of patients in our cohort noted significant social & financial barriers to their care. Discussion: Our study demonstrates that despite significant socio-economic barriers to care, adult patients with SAA that are treated with IST +/- AlloHSCT when indicated, have overall survival that equals the national standard. Notably, our patient cohort was more than 75% Black and Hispanic.Race in the US is strongly correlated to socioeconomic status, education, and health insurance status. Some specific social barriers were identified in provider notes. These included difficulty finding a donor match, recent immigration, housing & financial insecurity, difficulty keeping follow up appointments due to transportation issues, lack of adequate health insurance. We believe the first step toward addressing the inequities in AA treatment is the continued acknowledgement of social barriers to care and addressing them in a timely manner. Socio-demographic research should inform health policy and guide interventions to ultimately reduce inequities in access and treatment for rare diseases in some of the most vulnerable in our population. Figure Disclosures No relevant conflicts of interest to declare.

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Burba, Domininkas. "TILTAI IR KELTAI KAIP XVIII AMŽIAUS VILNIAUS PAVIETO BAJORŲ TEISINIŲ GINČŲ OBJEKTAI IR NUSIKALTIMŲ ERDVĖS." Lietuvos Didžioji Kunigaikštystė Visuomenė. Kasdienybės istorija, T. 4 (October 8, 2018): 299–318. http://dx.doi.org/10.33918/xviiiastudijos/t.4/a14.

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Bridges and ferries, as objects of dispute and crime locations among the eighteenth century nobles of Vilnius district, is the main topic of research in this article. Case materials and auxiliary documents from the records of Vilnius district castle and land courts reveal how often bridges are mentioned in the court processes in both violent and non-violent crimes. Research explores what types of violent crimes took place on bridges or ferries most often. It also works on questions of geographic localisation and statistics, discussing general situation of bridges in Vilnius and its neighbouring areas in the eighteenth century. Bridges are regularly mentioned in the books of the eighteenth century Vilnius castle and land courts, albeit most references are not related to conflicts and bridges are mentioned as orientation marks or in reference to location of a real estate object. Both non-violent legal disputes, involving bridges as objects, and violent crimes on the bridges were not in multitude, however non-violent crimes were in smaller numbers. There were seven dispute cases about lands, properties and plots of land where bridges and ferries are mentioned. Non-violent conflicts mostly took place in rural areas of the district, four of them, and three such disputes happened in Vilnius (one on the Green Bridge and two on the bridges over the River Vilnia). Most commonly recorded violent crime on a bridge was beating and, since this was the most common type of crime perpetrated by nobles in the eighteenth century Vilnius district, this trend is logical. A bridge is once mentioned in the record about a raid. In terms of location, more crimes on the bridges took place in the rural space, although this particular space wasn’t dominant, since six crimes were reported in the province and five in the city – two in Vilnius on the Green (Stone) Bridge, two on the bridges over the River Vilnia and one on a ferry near Šnipiškės. Trends in crime locations match general crime tendencies in Vilnius district, where more crimes took place in the rural space than in the urban one. One may guess, that the rare mention of bridges partially testifies to the fact that in the eighteenth century Vilnius district level of communication was not high and there were not too many bridges. On the other hand, when assessing trends in violent crimes in Vilnius district it was revealed that bridge based crimes comprised only one percent of all crimes. Having in mind that bridge is a relatively small object, compared to several different or other urban and rural spaces, this number isn’t that small. Keywords: Vilnius district, castle court, land court, crimes, nobles, peasants, bridges, ferries, passings.

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Yoneta, Akihiro, Kohei Horimoto, Keiko Nakahashi, Satoru Mori, Kazuo Maeda, and Toshiharu Yamashita. "A Case of Cystic Basal Cell Carcinoma Which Shows a Homogenous Blue/Black Area under Dermatoscopy." Journal of Skin Cancer 2011 (2011): 1–4. http://dx.doi.org/10.1155/2011/450472.

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Basal cell carcinoma (BCC) is the most common skin tumor and contains several different histopathological types. Here, we report a case of cystic basal cell carcinoma, which is relatively rare and might be clinically misdiagnosed. A dermatoscopic examination of the case revealed a homogenous blue/black area usually not seen in BCC. We reviewed 102 BCC cases resected and diagnosed at Sapporo Medical University Hospital between April 2005 and March 2010. Among them, only three were the cystic type.

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Uttley, Lesley, Anne Hillairet de Boisferon, Eve Dupierrix, Kang Lee, Paul C. Quinn, Alan M. Slater, and Olivier Pascalis. "Six-month-old infants match other-race faces with a non-native language." International Journal of Behavioral Development 37, no. 2 (January 23, 2013): 84–89. http://dx.doi.org/10.1177/0165025412467583.

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Early in life, infants possess an effective face-processing system which becomes specialized according to the faces present in the environment. Infants are also exposed to the voices and sounds of caregivers. Previous studies have found that face–voice associations become progressively more tuned to the types of association most prevalent in the environment. The present study investigated whether 6-month-old infants associate own-race faces with their native language and faces from a different race with a non-native language. Infants were presented with pictures of own- and other-race faces simultaneously, with a native or non-native language in a habituation paradigm. Results indicate that 6-month-olds are able to match other-race faces to a non-native language.

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Tan, Wanxia, Yuelin He, Xiaoqin Feng, Xuedong Wu, Chunfu Li, Jianyun Liao, Xuan Liu та ін. "Evolving Selection of Unrelated Donor for Hematopoietic Stem Cell Transplantation for Patients with β Thalassemia". Blood 134, Supplement_1 (13 листопада 2019): 3330. http://dx.doi.org/10.1182/blood-2019-129934.

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Background: Many Chinese patients with hematologic disease, who need allogeneic hematopoietic stem cell transplantation(HSCT) commonly lack an HLA matched sibling since a Chinese family often has a single child due to Chinese one-child policy in the past 10years. As an alternative option, unrelated HSCT is the feasible option for the patients without matched related donors (MRD). Many study have found that thalassemia-free survival (TFS) was approximately 90% in unrelated donor HSCT (UDT) for TM patients. Donor selection is one of key factors for better outcomes after hematopoietic stem cell transplantation (HSCT). Choosing the most suitable donors for TM patients can be challenging to physicians and search coordinators. It is shown that increased donor age is associated with high mortality. However, outcomes of donor factors such as age, sex, CMV status, ABO type, matching of HLA loci and female donor pregnancy history for TM patients have rare been taken into account and evaluated. Aims: The aim of this study was to develop and validate the principal of donor selection and to evaluate the impact of donor characteristics on survival outcomes especially in case of mismatch unrelated donor. Patients and Methods: Between December 2008 to December 2018,274 TM patients with a median age of 6 years (2-23) had no suitable matched related donor performed an unrelated HSCT. 189 patients have been typed by high resolution (HR) HLA typing for HLA-A/B/C/DRB1 loci, at the start of the donor's search process and 85 typed by high resolution (HR) HLA typing for HLA-A/B/C/DRB1/DQB1 loci. Patients, donors and transplant characteristics are summarized in Table 1 Result: 217 (79.2%) recipient were HLA full matched (FM) with donors, 51 (18.6%) of recipient-donor pairs were HLA one locus mismatched (mm) and 6 (2.2%) two loci mm . Statistically significant differences were observed in overall survival (OS) and thalassemia-free survival (TFS) among full matched group, one loci mm matched group and two loci mm group, the corresponding OS, TFS were 95.4%,88.2%,66.7% (P=0.010,shown in Figure one) and 93%,88%,66.7% (P=0.089) respectively. Risks for cGVHD were higher in recipient-donor HLA-mm transplantation, particularly significant in two loci mm transplant,P=0.000(Figure2). ABO compatibility did not affect OS and TFS (94.8 vs. 93%,P=0.572 and 94.8% vs. 90.2, P=0.190 respectively in ABO matched group and ABO mismatched group), whereas ABO mismatched was associated with higher rate of graft rejection (GR) although not statistically significant ( 0% vs. 4.3%, P=0.069). Notably, donor age was significantly associated with worse survival. Both OS and TFS for donor older than 40 years old was significantly worse than those <40 years old(94.6%vs.85% P=0,051)and (93% vs.82%, P=0.042) respectively( Figue3). Interestingly, previous pregnancy of female donors prior to donation had an impact on acute GVHD, parous female donors resulted in a significantly increased risk of aGVHD (31.8 vs. 13.1%,P=0.024) . However, donor other characteristics such as sex, parity, and cytomegalovirus serostatus were not associated with survival . For CMV- recipients, a CMV+ donor was not significantly associated with an increase in OS or TFS (92.7 vs. 93.3%, P=0.998, P=0.998 and 90.5% vs. 93.3%;P=0.601 respectively). Conclusion:Donor age and donor-recipient HLA match are important when selecting unrelated donors. Transplants from donors older than 40 years old should probably be avoided. Younger donors associates with better overall survival and lower rates of acute and cGVHD. When selecting unrelated donors, avoidance of parous female donors if possible as to avoid high incidence of aGVHD. Other donor characteristics such as sex, parity, and cytomegalovirus serostatus were not associated with survival. ABO mismatching (any type: major, minor or bidirectional) was not associated with OS, TFS or GVHD but related to graft rejection. In the future we will observe ABO mismatch among donors and recipients on engraftment time. Disclosures No relevant conflicts of interest to declare.

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Buck, Kelly, Jason Dehn, Michelle Setterholm, Martin Maiers, Dennis L. Confer, Robert J. Hartzman, Kim Wadsworth, Soo Young Yang, and Alexander H. Schmidt. "7/8 High-Resolution Unrelated Donor HLA Match Rate: Caucasian, African American, Hispanic, and Asian-Pacific Islander." Blood 122, no. 21 (November 15, 2013): 1998. http://dx.doi.org/10.1182/blood.v122.21.1998.1998.

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Abstract Aim Estimation of the National Marrow Donor Program's Be The Match Registry (BTMR) 8/8 (HLA-A, B, C, DRB1) high resolution (HR) unrelated donor (URD) match rate was determined in a 2009 study for each of the four most frequent patient race/ethnic groups in the United States- Caucasian (CAU), African American (AFA), Hispanic (HIS), and Asian Pacific Islander (API) (Dehn et al, ASBMT/CIBMTR abstract 2011). For patients without an 8/8 matched URD, a 7/8 match is often the minimum acceptable mismatch used by many transplant centers. A follow up to the 8/8 study was designed to determine the 7/8 or better match rate among the 4 major race/ethnic groups, using the same study cohort. Methods 1344 previously high resolution tested URD in the BTMR were randomly selected and treated as pseudopatients (PP) where HR testing was performed to identify an 8/8 matched URD. Following 8/8 potential URD testing, a search was performed on each PP to determine the 7/8 match rate, regardless of whether an 8/8 match was previously identified. The searches used a fixed BTMR file from January of 2012, composed of over 8.6 million URD. The BTMR race/ethnic diversity breakdown for 2012 was 65% CAU, 7% AFA, 10% HIS, 7% API, and 11% miscellaneous categories such as Multiple, Unknown, American Indian- Alaska Native, and Declined to answer. Search results from CAU (N=377), AFA (N=390), HIS (N=307), and API (N=270) PP were evaluated and classified as follow: 1) 7/8 HR matched donor exists on BTMR 2) Potential 7/8 HR donors exist on BTMR 3) No 7/8 potential donors exist on BTMR PP searches falling into category 2 had an HLA search strategy expert rank potential URD within BTMR in order of their matching likelihood. URD samples were HR HLA tested in order of ranking and evaluated to determine match status. Consecutive rounds of URD sample testing were performed until either a 7/8 matched URD was identified, no potential URD with stored samples remained, or a patient maximum number of URD testing was reached. Since many PP searches had greater than 100 potential 7/8 matched URD, it was not possible to type every URD. In these cases, up to 35 URD with sample were tested per patient. For analysis of the 7/8 match rate, PP with no 7/8 match identified after URD testing were considered as having no HR match. Results 98% of CAU and over 80% of the non-CAU race/ethnic groups- AFA, HIS, and API- had at least a 7/8 match identified (Table 1). For cases where an 8/8 matched donor had been previously identified, all but 8 PP also had a 7/8 match (CAU= 1, AFA= 3, API= 3, HIS= 1). Only three PP cases had no 7/8 potential donors on the search prior to URD testing. The range of donors tested for the cases resulting in a match was larger for the non-CAU race groups. The maximum number of URD tested before a 7/8 match was identified was 24 for AFA, 6 for HIS, and 10 for API, while for CAU the maximum number of URD tested was 2 (Table 2). A median of 1 URD was typed for cases resulting in a 7/8 match for each of the four race/ethnic groups. HLA expert review of cases where no 7/8 match was identified but additional 7/8 potential URD remained suggests that few additional cases would likely yield HR matches. Conclusions This study estimates a 7/8 or better HR match rate for the BTMR of over 80% for all four broad race/ethnic group categories. These results show that in the majority of cases, after first testing to identify an 8/8 matched URD, a 7/8 matched URD was identified after typing just one URD. However, particularly with non-CAU patients, testing additional URD may be needed to identify a 7/8 match. This study provides a baseline match rate that can be further supplemented using the additional worldwide URD inventory. Disclosures: No relevant conflicts of interest to declare.

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Di Luca, Javier, Pablo E. Penchaszadeh, and Guido Pastorino. "A Subantarctic rare gastropod reveals a new type of spawn among heterobranchs." Zoological Journal of the Linnean Society 190, no. 2 (January 10, 2020): 508–17. http://dx.doi.org/10.1093/zoolinnean/zlz173.

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Abstract Spawn and specimens of Toledonia biplicata comb. nov. were collected from Burdwood Bank during March 2013. Species-level identification was derived from radular, shell and spawn characters. A low number of eggs laid per spawn (one to three), absence of an external gelatinous mass and a considerably thickened capsule wall (~50 µm) constitute a unique combination of spawn characters among heterobranchs. Egg capsules are ovoid in shape and measure 600–763 × 450–656 µm. They are filled with albuminous liquid, allowing complete intracapsular development of a single embryo. The developmental stages recognized are uncleaved eggs (153 µm in average diameter), veliger stages (279–378 µm in maximal length) and prehatchling juveniles (442–609 µm). Toledonia biplicata increases its volume 40-fold during its intracapsular development, whereas other comparable cephalaspids increase ≤ 4-fold. The role of the capsule wall as protection and an additional source of food is discussed. The adaptive value of these characters in relationship to the environmental conditions of the Magellanic region is discussed. A comparison with the spawn of other cephalaspids, nudibranchs and pleurobranchids is conducted, and the taxonomic implications are discussed. This is the first description of the spawn and developmental stages of a representative of the genus Toledonia.

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Agnisya Putri, Chintya, and Gunarto Gunarto. "Efektivitas Pengecekan Sertifikat Terhadap Pencegahan Sengketa Tanah Dalam Proses Peralihan Hak Atas Tanah." Jurnal Akta 5, no. 1 (March 18, 2018): 267. http://dx.doi.org/10.30659/akta.v5i1.2611.

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ABSTRAKTujuan Penelitian ini 1.) Untuk mengkaji prosedur pengecekan sertipikat terhadap pencegahan sengketa tanah dalam peralihan hak atas tanah 2.) Untuk mengkaji efektivitas pengecekan sertipikat terhadap pencegahan sengketa tanah dalam peralihan hak atas tanah. Penelitian ini menggunakan metode pendekatan yuridis empiris dengan menggunakan jenis sumber data seperti data sekunder,data primer,dan data tersier. Berdasarkan hasil analisis data disimpulkan bahwa: 1.) Prosedur pengecekan sertipikat hak atas tanah yaitu dengan menyerahkan sertipikat asli disertai data pendukung berupa identitas pemegang hak atas tanah, dan apabila dikuasakan kepada pihak lain, harus dilengkapi dengan surat kuasa yang dilegalisir oleh pejabat berwenang (Lurah / Camat / Notaris / PPAT). 2.) Pengecekan dilakukan untuk mencocokkan data fisik dan data yuridis yang tersimpan dalam peta pendaftaran, daftar tanah, surat ukur dan buku tanah dan mutlak dilakukan dalam mencegah sengketa pertanahan. Secara umum pengecekan sertipikat telah efektif dalam mencegah sengketa pertanahan pada Kantor Pertanahan Kota Makassar dan menjadi suatu hal yang mutlak sebelum dilakukan peralihan hak atas tanah. Adapun masih terdapat celah dimana pengecekan tidak sempurna memberikan jaminan kepastian hukum terhadap data yuridis maupun data fisik sertipikat,akan tetapi melihat rasio perbandingan kasus yang ditimbulkan karena kesalahan administrasi pada pencatatan sita jaminan pada buku tanah yang sangat jarang terjadi dibandingkan keseluruhan proses peralihan hak yang diproses di Kantor Pertanahan Kota Makassar.KATA KUNCI : Pengecekan Sertipikat , Sertipikat , Peralihan Hak Atas Tanah. ABSTRACTObjectives of this study 1.) To examine the procedure of checking the certificate on the prevention of land disputes in the transfer of land rights 2.) To examine the effectiveness of certification checks on the prevention of land disputes in the transfer of land rights. This research uses empirical juridical approach method by using data source type such as secondary data, primary data, and tertiary data. Based on the result of data analysis, it is concluded that: 1.) Procedure of checking of certificate of land right that is by submitting original certificate accompanied by supporting data in the form of identity of holder of land rights and, if authorized to other party, must be completed with power of attorney legalized by authorized officer / Sub-district / Notary / PPAT). 2.) Checks are made to match physical data and juridical data stored in registration maps, land lists, measuring letters and land books and are absolutely essential in preventing land disputes. In general, certification checks have been effective in preventing land disputes at the Makassar Land Affairs Office and becoming an absolute matter prior to the transfer of land rights. There is still a gap where imperfect checks provide legal certainty for juridical data and physical data of the certificate, but see the ratio of cases caused by administrative error in the confiscation of confiscation records on the land book that is very rare compared to the whole process of transfer of rights processed in Land Office of Makassar City.KEYWORDS: Checking the Certificate, Certificate, Transfer of Land Rights.

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Alexandrova, Ksenia S. "The change of approach to English translations of Alexander Pushkin's A Journey to Arzrum." Vestnik Tomskogo gosudarstvennogo universiteta, no. 480 (2023): 5–12. http://dx.doi.org/10.17223/15617793/480/1.

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The author compares five English translations of Alexander Pushkin's A Journey to Arzrum that we know now. These are works made by Birgitta Ingemanson (1974), Ronald Wilks (1998), David and Ludmila Matthews (2003), Nicholas Pasternak Slater (2013), and Richard Pevear and Larissa Volokhonsky (2016). Four of these translations (the latter ones) have not been included into the latest bibliography of English translations and studies of Pushkin's works (1999). The growing number of translations may indicate an increasing interest to A Journey to Arzrum. This study aims to detect the translators' strategies (the level of domestication or foreignization) and their approach to Pushkin's work; to mark the mistakes and inaccuracies, stylistic features, lexical and syntactic peculiarities of translations and differences between them and between them and the original text. The study also shows how the translators' approach to A Journey to Arzrum changed over time. By pointing out all these we can conclude which type of audience suits each translation most and what the general tendency is. In the article the author gives basic information about these translations and their authors and analyze the examples according to the following sections: formal distinctions and main difference in the approaches; toponyms and ethnonyms; exoticisms and direct speech; stylistic peculiarities of the translations (where the author analyzes bigger, complicated, most stylistically expressive fragments of the text and variations in translating names and titles, along with noting syntactic peculiarities). The majority of inaccuracies the author has found come from David and Ludmila Matthews' translation. At the same time this work is the easiest to perceive for broad (especially non-academic) audience or readers that are not well familiar with Russian and Caucasian culture of that period (foreign-language quotes are translated as well as many exoti-cisms etc.). The other translators tend to save accurately the specificities of Pushkin's text and local peculiarities. The author states that, in general, earlier translators chose domestication as a strategy while the later ones preferred foreignization. The highest degree of foreignization in addition to tendency towards maximal figurativeness of the text is observed in Richard Pevear and Larissa Volokhonsky's version. The latter characteristic sometimes does not clearly match the lucidity of Pushkin's style. Birgitta Ingemanson with rare exceptions shows quite a good balance at this point in her translation. It is also interesting to mention that Nicholas Pasternak Slater tries to correct Pushkin's own inaccuracies. The author concludes that all the translations are done properly. Ingemanson's, Wilks', Pasternak Slater's and Pevear and Volokhonsky's versions are distinguished by a very accurate and thorough approach. However, Matthews' translation is good and unique in terms of accomplishing a specific purpose - being understandable by common readers. This way it serves to the popularization of A Journey to Arzrum among the English-speaking audience.

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Cyaniuk, Anissa, David L. Cooper, Desiree Hall, David Ungar, Chioma Smith, and Tami Wisniewski. "Methodological Considerations In The Assessment Of Comorbidities Among Patients With Hemophilia Using Retrospective Claims Data." Blood 122, no. 21 (November 15, 2013): 2947. http://dx.doi.org/10.1182/blood.v122.21.2947.2947.

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Abstract Introduction The availability of recombinant products for the treatment of hemophilia has substantially reduced the risk of viral transmission previously associated with plasma-derived products. This may be a contributing factor to the increased life expectancy of people with hemophilia (PWH). However, this increased life expectancy may result in increasing prevalence of chronic comorbidities at a different rate from the general population either as a result of disease or its treatment. Retrospective claims databases are one source for investigation of comparative point prevalence estimates. However, because hemophilia is rare, it is unknown to what extent claims databases can be leveraged to answer these questions. The purpose of this study is to describe differences in point prevalence estimates of chronic comorbidities in PWH compared to the general population using a large commercial database. Methods Using Clinformatics Data Mart, a product of OptumInsight Life Sciences, four hemophilia cohorts were developed based on data available January 2009 - September 2011. Cohort 1 included male patients with 2+ claims for hemophilia A/B diagnosis (ICD-9 286.0 or 286.1), 1 year of continuous eligibility and at least two diagnosis claims for each comorbidity of interest. Cohort 2 included patients from Cohort 1 who also had at least one prescription for a comorbidity related product of interest. Cohort 3 included patients who were male, had a hemophilia A/B diagnosis (ICD-9 286.0 or 286.1), at least 1 order for a factor product, 1 year of continuous eligibility, and at least two diagnosis claims for each comorbidity of interest. Cohort 4 consisted of patients from Cohort 3 who also had at least one prescription for a comorbidity related product of interest. Propensity scores for age, geography, ethnicity, insurance type, and a primary care office visit were employed to match each hemophilia cohort with a general population (GenP) cohort using a 1:50 ratio at 0.00001 caliper. GenP patients were also male with continuous enrollment January-December, 2009, and fulfilled the same inclusion criteria as PWH except for hemophilia specific requirements. Comorbidities were defined via ICD-9 codes. After matching, chi-square or Fisher’s exact tests determined directional differences. Fifteen common comorbidities were assessed. Results The table below summarizes results of the comorbidities with the greatest differences between PWH and GenP. For Cohort 1, twelve of fifteen comorbidities were significantly higher in PWH. For Cohort 2, one of fifteen were significantly higher. In Cohort 3, eight comorbidities were significantly different while in Cohort 4, no significant differences were noted. Conclusions Claims databases offer the potential to explore comorbidities in the aging hemophilia population though such analyses should be undertaken with appreciation for potential differences that may arise due to study definitions and inclusion/exclusion criteria. We hypothesize that Cohorts 1 and 2 include mild PWH while Cohorts 3 and 4 may reflect moderate and severe PWH with a requirement for factor prescription. The differences in results observed highlight the need for inclusion of disease severity within ICD-9 codes to facilitate assessment of hemophilia specific versus disease specific impact on comorbidities. Small sample sizes continue to challenge our abilities to make statistical inferences. One option for consideration in rare diseases would be to pool claims databases, where metadata are consistent, across payers to maximize potential sample sizes beyond that which are currently available. Disclosures: Cyaniuk: Optum Insight Life Sciences: Ms. Cyaniuk works for Optum Life Sciences, which recieved funding from Novo Nordisk Inc. to conduct the analyses for this research study. Other. Cooper:Novo Nordisk Inc.: Employment. Hall:Optum Insight Life Sciences: Ms. Hall is an employee of Optum insight Life Sciences, which received funding from Novo Nordisk to conduct the analyses for this research study. Other. Ungar:Novo Nordisk Inc.: Employment. Smith:Novo Nordisk Inc.: Employment. Wisniewski:Novo Nordisk Inc.: Employment.

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Tenover, Fred C., Isabella A. Tickler, Richard V. Goering, Barry N. Kreiswirth, José R. Mediavilla, and David H. Persing. "Characterization of Nasal and Blood Culture Isolates of Methicillin-Resistant Staphylococcus aureus from Patients in United States Hospitals." Antimicrobial Agents and Chemotherapy 56, no. 3 (December 12, 2011): 1324–30. http://dx.doi.org/10.1128/aac.05804-11.

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ABSTRACTA total of 299 nares and 194 blood isolates of methicillin-resistantStaphylococcus aureus(MRSA), each recovered from a unique patient, were collected from 23 U.S. hospitals from May 2009 to March 2010. All isolates underwentspaand staphylococcal cassette chromosomemecelement (SCCmec) typing and antimicrobial susceptibility testing; a subset of 84 isolates was typed by pulsed-field gel electrophoresis (PFGE) using SmaI. Seventy-sixspatypes were observed among the isolates. Overall, for nasal isolates,spatype t002-SCCmectype II (USA100) was the most common strain type (37% of isolates), while among blood isolates,spatype t008-SCCmectype IV (USA300) was the most common (39%). However, the proportion of all USA100 and USA300 isolates varied by United States census region. Nasal isolates were more resistant to tobramycin and clindamycin than blood isolates (55.9% and 48.8% of isolates versus 36.6% and 39.7%, respectively; for both,P< 0.05). The USA300 isolates were largely resistant to fluoroquinolones. High-level mupirocin resistance was low among allspatypes (<5%). SCCmectypes III and VIII, which are rare in the United States, were observed along with several unusual PFGE types, including CMRSA9, EMRSA15, and the PFGE profile associated with sequence type 239 (ST239) isolates. Typing data from this convenience sample suggest that in U.S. hospitalized patients, USA100 isolates of multiplespatypes, while still common in the nares, have been replaced by USA300 isolates as the predominant MRSA strain type in positive blood cultures.

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Guo, Yaojie, Jens C. Frisvad, and Thomas O. Larsen. "Review of Oxepine-Pyrimidinone-Ketopiperazine Type Nonribosomal Peptides." Metabolites 10, no. 6 (June 15, 2020): 246. http://dx.doi.org/10.3390/metabo10060246.

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Recently, a rare class of nonribosomal peptides (NRPs) bearing a unique Oxepine-Pyrimidinone-Ketopiperazine (OPK) scaffold has been exclusively isolated from fungal sources. Based on the number of rings and conjugation systems on the backbone, it can be further categorized into three types A, B, and C. These compounds have been applied to various bioassays, and some have exhibited promising bioactivities like antifungal activity against phytopathogenic fungi and transcriptional activation on liver X receptor α. This review summarizes all the research related to natural OPK NRPs, including their biological sources, chemical structures, bioassays, as well as proposed biosynthetic mechanisms from 1988 to March 2020. The taxonomy of the fungal sources and chirality-related issues of these products are also discussed.

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Roy, Mukut, Pranab Kumar Sahana, Chanchal Das, Nilanjan Sengupta, Prashant Somani, and Ranen Dasgupta. "An Unusual Presentation of Type 2 Diabetes Mellitus." Bangladesh Critical Care Journal 2, no. 1 (August 11, 2014): 46–47. http://dx.doi.org/10.3329/bccj.v2i1.19971.

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In this part of world, the mode of presentation of type 2 diabetes is enormously varied and infections may be the first presenting feature of previously unknown diabetes. In this case, we report an initial way of presentation of type 2 diabetes mellitus as emphysematous pyelonephritis. He was treated successfully by antibiotics and percutaneous drainage. Emphysematous pyelonephritis is a rare life-threatening gas-producing, necrotizing infection of the renal parenchyma and surrounding areas which can be focal or diffuse and may spread to the collecting system or perinephric tissues. It is rapidly progressive and fatal if untreated. Prompt recognition and aggressive treatment helps in complete recovery of patients. DOI: http://dx.doi.org/10.3329/bccj.v2i1.19971 Bangladesh Crit Care J March 2014; 2 (1): 46-47

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Sakhalkar, Vishwas S., Diana M. Veillon, James D. Cotelingam, Linda M. Hawthorne, Gloria C. Caldito, and Deborah M. McCaskill. "Transfusion Reactions in Sickle Cell Disease (SCD) Patients Receiving Multiple Blood Transfusions." Blood 106, no. 11 (November 16, 2005): 946. http://dx.doi.org/10.1182/blood.v106.11.946.946.

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Abstract Aim: To study transfusion reactions in our SCD patients before and after instituting the practice of transfusing C, E, K blood type negative (CEKneg) packed red blood cell (pRBC) units. Material and Methods: We retrospectively reviewed blood bank records of all SCD patients transfused pRBCs since 1990. Statistical analysis was performed using the Chi square test and Fischer’s exact test. Results: During 1990–2004, 500 SCD patients received pRBCs in our medical center. Of these, 387 received pRBC units crossmatched only for ABO and Rh blood types and suffered 37 transfusion reactions. Table I: General data of various patient groups Major patient groups Number of patients Median age in yrs # of pRBCs Tx Total (%) Sex (m/f) (range) Total units Median (range) Grand total of all patients 500 240/260 22 (0.7–79) 16617 14 (1–524) CEK (&ABO) matched transfusion patients 113 62/51 8 (0.5–35) 2354 10 (1–143) Regular (only ABORh) matched Tx patients 387 (100) 178/209 26 (0.7–79) 14263 18 (1–524) AlloAB forming patients 121 (31.3) 56/65 29 (5–70) 7338 26 (1–500) Non-alloAB forming pts 266 (68.7) 122/144 25 (0.7–79) 6925 12 (1–524) Table 2: Transfusion reactions in various patient groups Major patient groups Total # of pts Total # of pRBCs Transfusion reactions (% of pts) [Incidence/1000 Tx] Total Febrile Allergic dHTR CEK matched pts 113 2354 0 0 0 0 Regular (ABORh) Tx pts 387 14263 37 (10%)[2.594] 10 23 (6%)[1.61] 4 (1%)[0.28] AlloAB forming pts 121 7338 23 (19%)[3.134] 4 (3%)[0.55] 15 (12%)[2.04] 4 (3%)[0.55] Non-alloAB forming pts 266 6925 14 (5%)[2.0] 6(2%)[0.87] 8 (3%)[1.16] 0 P value (alloAB vs non-alloAB) # of pts 0.25 0.684 0.266 - P value (alloAB vs non-alloAB) # of Tx <0.001 0.809 0.002 - 121 developed alloantibodies (alloABs). 113 patients always received CEKneg pRBCs (from 1997). The technologist required 30 more minutes and $153 extra in reagent costs for this extended CEK match. Most Rh negative pRBC units were also CEKneg. 90% of our donors are Caucasian. Discussion: ’Non-alloAB forming’ patients who received ABORh matched transfusions were 4 times less likely (and twice less likely when number of transfusions was considered) to develop allergic transfusion reaction (p=0.002), compared with ’alloAB forming’ counterparts. Similar finding is seen in patients receiving CEK matched pRBCs. It would be interesting to know if ’slow/rapid/non alloAB producer patients had any genetic predisposition accounting for early/slow/non-development of ABs and transfusion reactions or if alloAB formation transforms the immune system to a hyper-reactive state leading to autoAB formation/allergic reaction. Conclusions: This study showed that utilizing extended antigen (C, E, K) matching for pRBC transfusion ↓↓ alloAB(p<0.01) and autoAB(p=0.005) formation in our SCD patients and eliminated transfusion reactions. Universal availability of leukopoor pRBCs may have eliminated febrile reactions. AlloAB forming patients were more prone to develop allergic transfusion reaction (p=0.002). AutoAB formation was more common in patients with alloABs and did not cause complications. dHTRs were rare and mild. CEK matching made it easier to find and transfuse blood due to less formation of ABs and reactions. However, it resulted in marked overuse of Rh negative pRBCs, extra cost and additional effort to find CEKneg pRBCs for every transfusion.

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Tahir, T., Hamzah Upu, and S. Suradi. "Komparasi Prestasi Belajar Matematika antara Siswa yang diajar menggunakan Model Pembelajaran Kooperatif tipe Snowball Throwing dan Tipe Make a Match di Kelas VII SMP." Issues in Mathematics Education (IMED) 3, no. 2 (January 29, 2020): 101. http://dx.doi.org/10.35580/imed11043.

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Penelitian ini dilakukan untuk mengetahui perbandingan prestasi belajar siswa melalui penerapan model kooperatif tipe Snowball Throwing dan Make a Match dalam pembelajaran matematika. Penelitian ini adalah penelitian eksperimen yang melibatkan dua kelompok yang diberi perlakuan dengan sampel penelitian sebanyak 47 siswa dari kelas VII SMP di Sinjai yang dipilih dengan menggunakan teknik double cluster random sampling. Teknik pengumpulan data menggunakan instrumen: (1) lembar observasi keterlaksanaan model pembelajaran dan (2) tes hasil belajar matematika. Data dianalisis dengan statistik deskriptif dan statistik inferensial dengan analisis uji-t. Hasil penelitian menunjukkan bahwa : (1) Skor rara-rata prestasi belajar matematika dari 25 siswa setelah pembelajaran menggunakan model pembelajaran kooperatif tipe Snowball Throwing yaitu 4% berada pada kategori sangat rendah, 40% pada kategori sedang, 36% pada kategori tinggi dan 20% pada kategori sangat tinggi. (2) Skor rara-rata prestasi belajar matematika dari 22 siswa setelah pembelajaran menggunakan model pembelajaran kooperatif tipe Make a Match yaitu 9,09% berada pada kategori sangat rendah, 4,54% pada kategori rendah, 50% pada kategori sedang serta 18,18 % masing-masing pada kategori tinggi dan sangat tinggi. (3) Tidak terdapat perbedaan yang signifikan antara prestasi siswa setelah menerapkan model pembelajaran kooperatif tipe snowball throwing dan tipe make a match di Kelas VII SMP dengan materi Bangun Datar Segiempat.Kata Kunci: Prestasi belajar, pembelajaran matematika, model pembelajaran kooperatif, snowball throwing, make a matchAbstract. This research was conducted to determine the comparison of student learning achievement through the application of the cooperative model type Snowball Throwing and Make a Match in mathematics learning. This research was an experimental research involving two groups treated with research sample of 47 students from class VII SMP Sinjai selected by using the double cluster random sampling technique. Techniques of collecting data using instruments: (1) observation sheet of learning model implementation and (2) tests of mathematics learning result.Data were analyzed with descriptive statistics and inferential statistics with t-test analysis. The results showed that : (1) Average score of mathematics learning achievement of 25 students after learning using the Snowball Throwing type of cooperative learning model which is 4% in the very low category, 40% in the medium category, 36% in the high category and 20% in the very high category. (2) The average score of mathematics learning achievement from 22 students after learning using the Make a Match type of learning model is 9.09% in the very low category, 4.54% in the low category, 50% in the medium category and 18, 18% in the high and very high categories. (3) There is no significant difference between student achievement after applying the snowball throwing type cooperative learning model and the type of make a match in Class VII Junior High School with the Rectangular Build Up material.Keywords: Learning achievement, mathematics learning, cooperative learning model, snowball throwing, make a match.

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Dai, Yanpei, Yudi Zhu, Lianchang Zhang, and Mingtian Zhu. "Meso- and Neoarchean Banded Iron Formations and Genesis of High-Grade Magnetite Ores in the Anshan-Benxi Area, North China Craton." Economic Geology 112, no. 7 (November 1, 2017): 1629–51. http://dx.doi.org/10.5382/econgeo.2017.4524.

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Abstract The Anshan-Benxi area in the North China craton has numerous occurrences of Algoma-type banded iron formations (BIFs) with subordinate high-grade magnetite ores. These ores provide insight into iron metallogenesis and early evolution of the North China craton. In this paper, we present Sm-Nd-Fe-O isotope, mineralogical, and structural data for four BIF-type iron deposits to place constraints on their depositional ages and formation mechanism. Previous SIMS and LA-ICP-MS zircon U-Pb dating results indicated a Mesoarchean age (ca. 3.10 Ga) for the Dagushan BIF and a Neoarchean age (ca. 2.55 Ga) for other regional BIFs (Dai et al., 2012, 2013, 2014). This is confirmed by Sm-Nd isochron ages of these BIFs, high-grade magnetite ores, and host metavolcanics, which yield two regression lines and match apparent ages of 3149 ± 85 Ma (MSWD = 1.2) for Dagushan, and 2671 ± 120 Ma (MSWD = 3.0) for the other three deposits. Our new chronological data thus suggest Meso- and Neoarchean BIF deposition and potentially significant BIF-type iron deposits at depth. The regional high-grade magnetite ores are all hosted in the BIFs that occur in the same orientation and have transitional boundaries between them. They also show similar Sm-Nd isotope compositions and magnetite rare earth elements + yttrium (REY) profiles, indicating that the Anshan-Benxi BIFs were most likely the source beds. The high-grade magnetite ores contain abundant pyrite and actinolite, with systematically lower δ56Fe values (0.67–0.40‰) when compared to the BIFs (1.88–0.64‰), suggesting a hydrothermal origin. In the field, some high-grade orebodies with schistose textures are adjacent to undeformed granitic plutons. This geologic relationship implies that the high-grade magnetite ores were formed earlier and probably did not result from magmatic hydrothermal fluids. Therefore we suggest that the Anshan-Benxi high-grade magnetite ores were most likely produced by infiltration of metamorphic fluids into primary BIFs, based on the following: (1) magnetite δ18O values within the high-grade magnetite ores (+2.5 to −0.6‰) are significantly lower than those in the BIFs (9.2–2.6‰); (2) magnetite (avg 0.39 ppm) and pyrite (avg 0.098 ppm) in the high-grade magnetite ores have much lower REY abundances than magnetite in the BIFs (avg 14.6 ppm); (3) skeletal quartz in the high-grade magnetite ores shows systematically higher FeOtolal contents (1.36–0.56 wt %) than those in laminated chert bands (0.06–0.00 wt %); and (4) hydrothermal zircons within the Nanfen BIF yield a U-Pb age of 2480 Ma, which is comparable to ca. 2.48 Ga regional metamorphism (Zhu et al., 2015). Furthermore, microstructural textures indicate a maximum regional deformation temperature of up to 500°C, which is lower than the plastic flow temperature (>600°C) of magnetite. Finite strain measurements and electron backscatter diffraction analyses suggest a general flattening deformation and similar crystallographic preferred orientation for all magnetite crystals. These structural features reveal that magnetite in the high-grade magnetite ores never experienced a separate tectonic event. Our microscopic studies also show that microfractures at the interfaces of BIF bands contain fragmented quartz crystals and are filled with abundant metamorphic minerals (e.g., actinolite and chlorite). Considering that the Anshan-Benxi high-grade magnetite ores are commonly adjacent to weak structural planes (e.g., faults), we propose that macro- and microscopic fractures probably provided channels for metamorphic fluids. Recent zircon U-Pb geochronology has indicated widespread BIF formation at ca. 2.55 Ga in the North China craton, corresponding to a pronounced peak in BIF deposition of other Precambrian cratons. It is thus implied that a global geologic event triggered the extensive occurrence of BIFs. We correlate the Neoarchean tectonic evolution of the North China craton with the 2.7 to 2.5 Ga Kenorland supercontinent. Significantly, planar distribution signatures of the North China craton BIFs indicate ca. 2.5 Ga cratonization through the amalgamation of at least seven microblocks that were welded by several Neoarchean greenstone belts. Hf-Nd isotope studies have highlighted the Archean episodic crustal evolution of the North China craton, and the Meso- and Neoarchean BIF deposition could have benefitted from these geologic processes. The Anshan-Benxi high-grade magnetite ores that formed at ca. 2.48 Ga were closely related to important metamorphic events during the North China cratonization process.

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