bluuebunny/crossref_metadata_2025_split huggingface dataset:
Separation of nearly identical repeats in shotgun assemblies
using defined nucleotide positions, DNPs
Authors: Tammi Martti T. , Arner Erik , Britton Tom , Andersson Björn 
Published: July 2002

Abstract
An increasingly important problem in genome sequencing is the failure of the commonly used shotgun assembly programs to correctly assemble repetitive sequences. The assembly of non-repetitive regions or regions containing repeats considerably shorter than the average read length is in practice easy to solve, while longer repeats have been a difficult problem. We here present a statistical method to separate arbitrarily long, almost identical repeats, which makes it possible to correctly assemble complex repetitive sequence regions. The differencesbetween repeat units may be as low as 1% and the sequencing error may be up to ten times higher. The method is based on the realization that a comparison of only a part of all overlapping sequences at a time in a data set does not generate enough information for a conclusive analysis. Our method uses optimal multi-alignments consisting of all the overlaps of each read. This makes it possible to determine defined nucleotide positions, DNPs, which constitute the differences between the repeat units. Differences between repeats are distinguished from sequencing errors using statistical methods, where the probabilities of obtaining certain combinations of candidate DNPs are calculated using the information from the multi-alignments. The use of DNPs and combinations of DNPs will allow for optimal and rapid assemblies of repeated regions. This method can solve repeats that differ in only two positions in a read length, which is the theoretical limit for repeat separation. We predict that this method will be highly useful in shotgun sequencing in the future.
Contact: bjorn.andersson@genpat.uu.se
* To whom correspondence should be addressed.
Advanced pairwise structure alignments of proteins and analysis
of conformational changes
Authors: Ochagavia Maria Elena , Richelle Jean , Wodak Shoshana J. 
Published: July 2002

Abstract
Motivation: Comparing the 3D structures of two proteins or analyzing the structural changes undergone by a protein upon ligand binding or when it crystallizes under different conditions, can be both tricky and tedious, especially when the two proteins are distantly related, or when the structural changes are complex. Readily accessible tools for performing these tasks automatically and reliably should therefore be welcome.
Results: We describe a web interface to several automatic procedures for performing pairwise structure superposition in a flexible manner, for detailed analyses of conformational changes and for displaying the results in a pictorial fashion.
Availability: This interface can be accessed at the Brussels and Cuba Web sites, respectively: http://www.ucmb.ulb.ac.be/SCMBB/Tools.htmland http://bio.cigb.edu.cu.
Contact: shosh@ucmb.ulb.ac.be
* To whom correspondence should be addressed.
Seasonal plankton dynamics in a Mediterranean hypersaline coastal lagoon: the Mar Menor
Authors: Gilabert Javier 
Published: July 2002

Abstract
The seasonal distribution of plankton in a Mediterranean hypersaline coastal lagoon has been studied through a dataset, comprising the taxonomic composition and the size–abundance distribution of both phyto- and zooplankton, measured by image analysis techniques during a one-year time series of weekly samplings. The studied organisms ranged from small nanoplanktonic heterotrophic flagellates (2 μm diameter) to fish larvae (&gt;2 μm). The phytoplankton annual succession was characterized by a winter period dominated by Rhodomonas spp. and Cryptomonas spp. with Cyclotella spp. as the main diatom represented, a spring phase where diatoms (mainly Cyclotella) were the dominant group with some monospecific blooms of other diatoms (mainly of Chaetoceros sp.), a summer phase characterized by diatoms with blooms of Niztschia closterium, and a post-summer phase where dinoflagellates increased with peaks of Ceratium furca. High densities of the microbial food web elements, flagellates and ciliates, indicate the importance of the microbial loop in the ecosystem. Meroplankton contributed widely to the seasonal character of the zooplankton distribution. Copepods, represented by Oithona nana, Centropages ponticus and Acartia spp. (mainly latisetosa), remained relatively constant throughout the year, exhibiting a lower density in the warmer water period (July–September). At the end of the sampling period, a massive proliferation of copepods (&gt;1000 ind l –1), mainly due to O. nana, took place. The autotrophs to heterotrophs biovolume ratio (A:H) remained lower than 1 throughout the year except when, occasionally, large phytoplankton cells bloomed. Persistent very low values of A:H suggest that additional sources of energy, such as the microbial loop or detrital pathways, would be needed to sustain the high heterotrophic biovolume found in the lagoon.
Contractile response to low peroxide concentrations: myofibrillar calcium sensitivity as a likely target for redox‐modulation of skeletal muscle function
Authors: Andrade Francisco H. , Reid Michael B. , Westerblad Håkan 
Published: July 2002

ABSTRACTEndogenous peroxides and related reactive oxygen species may influence various steps in the contractile process. Single mouse skeletal muscle fibers were used to study the effects of hydrogen peroxide (H2O2) andt‐butyl hydroperoxide (f‐BOOH) on force and myoplasmic Ca2+concentration ([Ca2+]i). Both peroxides (10−1to 10−5M) decreased tetanic [Ca2+]iand increased force during submaximal tetani. Catalase (1 kU/ml) blocked the effect of H2O2, but not oft‐BOOH. The decrease in tetanic [Ca2+]iwas constant, while the effect on force was biphasic: A transitory increase was followed by a steady decline to the initial level. Myofibrillar Ca2+sensitivity remained increased during incubation with either peroxide. Only the highest peroxide concentration (10 μM) increased resting [Ca2+]iand slowed the return of [Ca2+]ito its resting level after a contraction, evidence of impaired sarcoplasmic reticulum Ca2+re‐uptake. The peroxides increased maximal force production and the rate of force redevelopment, and decreased maximum shortening velocity. N‐ethylmaleimide (25 μM, thiol‐alkylating agent) prevented the response to 1 μM H2O2. These results show that myofibrillar Ca2+sensitivity and cross‐bridge kinetics are influenced by H2O2 andt‐BOOH concentrations that approach those found physiologically, and these findings indicate a role for endogenous oxidants in the regulation of skeletal muscle function.
Use of Sodium-Glucose Cotransporter 2 Inhibitors and Glucagonlike Peptide-1 Receptor Agonists in Patients With Diabetes and Cardiovascular Disease in Community Practice
Authors: Nanna Michael G. , Kolkailah Ahmed A. , Page Courtney , Peterson Eric D. , Navar Ann Marie 
Published: November 2022

ImportanceRecent national guidelines recommend sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagonlike peptide-1 receptor agonists (GLP-1 RA) in patients with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD); yet, there are limited data on the use of these agents in contemporary community practice.ObjectiveTo evaluate the use of SGLT2i and GLP-1 RA in adults with T2D and ASCVD across a diverse sample of health care systems in the US.Design, Setting, and ParticipantsThis multicenter, retrospective cohort study used electronic health record data from 88 US health care systems participating in Cerner Real World Data between January 2018 to March 2021. Adults with ASCVD and T2D taking at least 1 glucose-lowering medication, had end-stage kidney disease, or had stage 5 chronic kidney disease were excluded.Main Outcomes and MeasuresTreatment with SGLT2i or GLP-1 RA.ResultsA total of 321 304 patients were identified with T2D and ASCVD ASCVD (130 280 female [40.5%]; median [IQR] age, 70.9 [62.9-78.0] years) who were potentially eligible for SGLT2i and/or GLP-1 RA, including 37 754 Black individuals (11.8%), 51 522 Hispanic individuals (16.0%), and 256 008 White individuals (11.8%). From January 2018 to March 2021, the use of SGLT2i increased from 5.8% (11 285 of 194 264) to 12.9% (11 058 of 85 956), GLP-1 RA increased from 6.9% (13 402 of 194 264) to 13.8% (11 901 of 85 956), and use of either agent increased from 11.4% (22 069 of 194 264) to 23.2% (19 909 of 85 956). Those taking an SGLT2i or GLP-1 RA were younger, less frequently hospitalized in the year prior, and more likely to be taking additional secondary prevention medications. Treated and nontreated populations were similar in terms of race, ethnicity, and outpatient health care utilization. Sulfonylureas and dipeptidyl peptidase 4 inhibitors remained more commonly used than SGLT2i or GLP-1 RA through 2021.Conclusions and RelevanceIn this study, uptake of SGLT2i and GLP-1 RA in adults with T2D and ASCVD increased modestly after guideline recommendations, although less than a quarter of persons with ASCVD and T2D receiving medical therapy were taking either. Further efforts are necessary to maximize the potential population benefit of these therapies in this high-risk population.
Estimating Savings Opportunities From Therapeutic Substitutions of High-Cost Generic Medications
Authors: Socal Mariana P. , Cordeiro Thomas , Anderson Gerard F. , Bai Ge 
Published: November 2022

ImportanceUse of generics is generally understood as a cost-saving practice. However, pharmacy benefit managers have an incentive to place higher-priced generic drugs on insurers’ drug formularies to profit by creating a large difference between the price negotiated with pharmacies and the price paid by insurers (what is known as spread pricing).ObjectiveTo examine price differentials and savings potential between high-cost generics and corresponding therapeutic alternatives of same clinical value and lower cost.Design, Setting, and ParticipantsThis cross-sectional analysis examined the top 1000 generics in Colorado’s all-payer claims database (CO-APCD) in 2019. High-cost generics and lower-cost generic therapeutic alternatives of same clinical value constituted the study sample. Data were analyzed from January 2019 to December 2019.ExposuresGeneric drug prices measured by transaction prices, average wholesale price (AWP), and national drug acquisition average cost (NADAC).Main Outcomes and MeasuresPrice differentials between the high-cost generics and the corresponding therapeutic alternatives. Levels of discounts and savings that could be achieved if the high-cost generics had been substituted by their therapeutic alternatives.ResultsThis cross-sectional study of the top 1000 CO-APCD generics identified 45 high-cost products that had lower-cost therapeutic alternatives of same clinical value. Overall, high-cost generics were 15.6 times more expensive than their therapeutic alternatives (median values). If the lower-cost alternatives had been used, total spending would have been reduced from $7.5 million to $873 711, resulting in 88.3% savings. Most substitutions (28 of 45 [62.2]%) involved different dosage forms or different strengths of the same drug and provided mean (SD) discounts of 94.9% (3.8%) and 77.1% (19.9%), respectively.Conclusions and RelevanceIn this study, replacing high-cost generics with lower-cost alternatives of same clinical value would produce savings of nearly 90%. Plan sponsors should be aware that some generics are associated with higher spending and should periodically review the specific products driving their generic drug spending. Substitution of high-cost generics may provide a simple pathway to offer the same therapeutic benefit at lower cost to patients and insurers.
Clinical utility of cerebrospinal fluid biomarkers measured by LUMIPULSE® system
Authors: Nojima Hisashi , Ito Satoshi , Kushida Akira , Abe Aki , Motsuchi Wataru , Verbel David , Vandijck Manu , Jannes Geert , Vandenbroucke Ina , Aoyagi Katsumi 
Published: November 2022

AbstractObjectivesCerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) are well‐established in research settings, but their use in routine clinical practice remains a largely unexploited potential. Here, we examined the relationship between CSF biomarkers, measured by a fully automated immunoassay platform, and brain β‐amyloid (Aβ) deposition status confirmed by amyloid positron emission tomography (PET).MethodsOne hundred ninety‐nine CSF samples from clinically diagnosed AD patients enrolled in a clinical study and who underwent amyloid PET were used for the measurement of CSF biomarkers Aβ 1–40 (Aβ40), Aβ 1–42 (Aβ42), total tau (t‐Tau), and phosphorylated tau‐181 (p‐Tau181) using the LUMIPULSE system. These biomarkers and their combinations were compared to amyloid PET classification (negative or positive) using visual read assessments. Several combinations were also analyzed with a multivariable logistic regression model.ResultsAβ42, t‐Tau, and p‐Tau181, and the ratios of Aβ42 with other biomarkers had a good diagnostic agreement with amyloid PET imaging. The multivariable logistic regression analysis showed that amyloid PET status was associated with Aβ40 and Aβ42, but other factors, such as MMSE, sex, t‐Tau, and p‐Tau181, did not significantly add information to the model.ConclusionsCSF biomarkers measured with the LUMIPULSE system showed good agreement with amyloid PET imaging. The ratio of Aβ42 with the other analyzed biomarkers showed a higher correlation with amyloid PET than Aβ42 alone, suggesting that the combinations of biomarkers could be useful in the diagnostic assessment in clinical research and potentially in routine clinical practice.
A Diagnostic Prediction Model to Distinguish Multisystem Inflammatory Syndrome in Children
Authors: Clark Matthew T. , Rankin Danielle A. , Peetluk Lauren S. , Gotte Alisa , Herndon Alison , McEachern William , Smith Andrew , Clark Daniel E. , Hardison Edward , Esbenshade Adam J. , Patrick Anna , Halasa Natasha B. , Connelly James A. , Katz Sophie E. 
Published: November 2022

ObjectiveFeatures of multisystem inflammatory syndrome in children (MIS‐C) overlap with other syndromes, making the diagnosis difficult for clinicians. We aimed to compare clinical differences between patients with and without clinical MIS‐C diagnosis and develop a diagnostic prediction model to assist clinicians in identification of patients with MIS‐C within the first 24 hours of hospital presentation.MethodsA cohort of 127 patients (<21 years) were admitted to an academic children's hospital and evaluated for MIS‐C. The primary outcome measure was MIS‐C diagnosis at Vanderbilt University Medical Center. Clinical, laboratory, and cardiac features were extracted from the medical record, compared among groups, and selected a priori to identify candidate predictors. Final predictors were identified through a logistic regression model with bootstrapped backward selection in which only variables selected in more than 80% of 500 bootstraps were included in the final model.ResultsOf 127 children admitted to our hospital with concern for MIS‐C, 45 were clinically diagnosed with MIS‐C and 82 were diagnosed with alternative diagnoses. We found a model with four variables—the presence of hypotension and/or fluid resuscitation, abdominal pain, new rash, and the value of serum sodium—showed excellent discrimination (concordance index 0.91; 95% confidence interval: 0.85‐0.96) and good calibration in identifying patients with MIS‐C.ConclusionA diagnostic prediction model with early clinical and laboratory features shows excellent discrimination and may assist clinicians in distinguishing patients with MIS‐C. This model will require external and prospective validation prior to widespread use.
Vis–NIR Electrochromism and NIR–Green Electroluminochromism in Dual Functional Benzothiadiazole‐Arylamine Mixed‐Valence Compounds
Authors: Corrente Giuseppina Anna , González Dora A. , Aktas Ece , Capodilupo Agostina Lina , Mazzone Gloria , Ruighi Francesco , Accorsi Gianluca , Imbardelli Daniela , Rodriguez‐Seco Cristina , Martinez‐Ferrero Eugenia , Palomares Emilio , Beneduci Amerigo 
Published: November 2022

AbstractElectrochromism/electrofluorochromism is the reversible tuning of the absorption/photoluminescence by redox processes. Dual functional electrochromic/electrofluorochromic materials can be exploited in, for example, smart windows, encryption/anticounterfeiting technologies, displays, and biomedical sensors. While electrofluorochromic materials showing tunable fluorescence intensity are relatively widespread, those with tunable color emission are not. Moreover, electrofluorochromic materials with tunable emission in the near‐infrared (NIR) range are seldom encountered. Here, this work shows a new molecular approach to afford both the above functionalities, in addition to red–NIR electrochromism, by combining the properties of highly stable arylamine radical cation mixed valence species, with those of donor–acceptor systems exhibiting the photoinduced twisted intramolecular charge transfer mechanism.
Improving the Operational Stability of Near‐Infrared Quasi‐2D Perovskite Light‐Emitting Diodes by Cation Engineering
Authors: Wang Qiangqiang , Ding Shuo , He Siliang , Zhang Ting , Qian Lei , Xiao Peng , Chen Tao , Xiang Chaoyu 
Published: November 2022

AbstractAlthough organic metal halide perovskite light‐emitting diodes (PeLEDs) have been developed rapidly in recent years, their commercialization and further applications are still hindered by ion migration‐induced inferior operational stability. Although the formation of a quasi‐2D structure is a well‐known solution that can efficiently suppress ion migration, the operation lifetime improvement is still limited. In this study, long‐chain phenylbutanammonium is used to replace the commonly used phenethylammonium as the L‐site cations. With large steric hindrance, ion migration inside the PeLEDs is effectively suppressed. Consequently, the PeLED with near‐infrared emission at 763 nm exhibited an operational lifetime (T90) of up to 5.3 h, which is 53‐fold higher than that of the control device. This study demonstrates the feasibility of significant stability improvement using a simple cation engineering strategy for PeLEDs.
Enabling Extreme Fast‐Charging: Challenges at the Cathode and Mitigation Strategies
Authors: Tanim Tanvir R. , Weddle Peter J. , Yang Zhenzhen , Colclasure Andrew M. , Charalambous Harry , Finegan Donal P. , Lu Yanying , Preefer Molleigh , Kim Sangwook , Allen Jeffery M. , Usseglio‐Viretta Francois L. E. , Chinnam Parameswara R. , Bloom Ira , Dufek Eric J. , Smith Kandler , Chen Guoying , Wiaderek Kamila M. , Weker Johanna Nelson , Ren Yang 
Published: November 2022

AbstractCharging lithium‐ion batteries (LiBs) in 10 to 15 min via extreme fast‐charging (XFC) is important for the widespread adoption of electric vehicles (EVs). Lately, the battery research community has focused on identifying XFC bottlenecks and determining novel design solutions. Like other LiB components, cathodes can present XFC bottlenecks, especially when considering long‐term battery life. Therefore, it is necessary to develop a comprehensive understanding of how XFC conditions degrade LiB cathodes. The present article reviews relevant cathode‐focused studies and summarizes the current understanding regarding cathode performance and aging issues under XFC conditions. Dominant aging modes and mechanisms are identified at different length‐scales with electrochemical correlations for LiNixMnyCozO2 (NMC)‐based cathodes. A range of electrochemical techniques and models provide key insights into cathode performance and life issues. A suite of multimodal and multiscale microscopy and X‐ray techniques is surveyed to quantify chemical, structural, and crystallographic NMC‐cathode degradation. Cathode cycle‐life is scaled to equivalent EV miles to illustrate how cathode degradation translates to real‐world scenarios and quantifies cathode‐related bottlenecks that hinder XFC adoption. Finally, the article discusses several cathode cycle‐life aging mitigation strategies with example case studies and identifies remaining challenges.
Estimating phenological sensitivity in contemporary vs. historical data sets: Effects of climate resolution and spatial scale
Authors: Zettlemoyer Meredith A. , Wilson Jill E. , DeMarche Megan L. 
Published: November 2022

AbstractPremisePhenological sensitivity, or the degree to which a species' phenology shifts in response to warming, is an important parameter for comparing and predicting species' responses to climate change. Phenological sensitivity is often measured using herbarium specimens or local studies in natural populations. These approaches differ widely in spatiotemporal scales, yet few studies explicitly consider effects of the geographic extent and resolution of climate data when comparing phenological sensitivities quantified from different data sets for a given species.MethodsWe compared sensitivity of flowering phenology to growing degree days of the alpine plant Silene acaulis using two data sets: herbarium specimens and a 6 yr observational study in four populations at Niwot Ridge, Colorado, USA. We investigated differences in phenological sensitivity obtained using variable spatial scales and climate data sources.ResultsHerbarium specimens underestimated phenological sensitivity compared to observational data, even when herbarium samples were limited geographically or to nearby weather station data. However, when observational data were paired with broader‐scale climate data, as is typically used in herbarium data sets, estimates of phenological sensitivity were more similar.ConclusionsThis study highlights the potential for variation in data source, geographic scale, and accuracy of macroclimate data to produce very different estimates of phenological responses to climate change. Accurately predicting phenological shifts would benefit from comparisons between methods that estimate climate variables and phenological sensitivity over a variety of spatial scales.
5p13 microduplication in a malformed fetus and his unaffected father
Authors: Kariminejad Ariana , Ghaderi‐Sohi Siavash , Gholami Soheila , Najafi Kimia , Kariminejad Roxana , Hennekam Raoul C. M. 
Published: November 2022

AbstractThe 5p13 microduplication syndrome is a contiguous gene syndrome characterized by developmental delay intellectual disability, hypotonia, unusual facies with marked variability, mild limb anomalies, and in some cases brain malformations. The duplication ranges in size from 0.25 to 1.08 Mb and encompasses five genes (NIPBL, SLC1A3, CPLANE1, NUP155, and WDR70), of which NIPBL has been suggested to be the main dose sensitive gene. All patients with duplication of the complete NIPBL gene reported thus far have been de novo. Here, we report a 25‐week‐old male fetus with hypertelorism, wide and depressed nasal bridge, depressed nasal tip, low‐set ears, clenched hands, flexion contracture of elbows, knees, and left wrist, and bilateral clubfeet, bowing and shortening of long bones and brain malformation of dorsal part of callosal body. The fetus had a 667 kb gain at 5p13.2 encompassing SLC1A3, NIPBL and exons 22–52 of CPLANE1. The microduplication was inherited from the healthy father, in whom no indication for mosaicism was detected. The family demonstrates that incomplete penetrance of 5p13 microduplication syndrome may occur which is important in genetic counseling of families with this entity.