bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimation of the latent therapeutic demand for immunoglobulin therapies in autoimmune neuropathies in the United States
Authors: Farrugia Albert , Bansal Megha , Marjanovic Ivan
Published: June 2021

Background and Objectives

The use of immunoglobulin (IG) solutions as an immunomodulatory therapy in certain neurological conditions has become an established modality and represents a significant proportion of total IG use. The estimation of the evidence‐based potential demand designated as the latent therapeutic demand (LTD) for IG in these diseases is required for adequate planning of the plasma supply required to manufacture the product.

Materials and Methods

The diseases studied included chronic inflammatory demyelinating polyneuropathy (CIDP), Guillain–Barré syndrome (GBS) and multifocal motor neuropathy (MMN). The LTD for IG was assessed using a decision analysis model, using Microsoft Excel. The model analysed the epidemiological and clinical factors contributing to IG usage. One‐way sensitivity analysis and probabilistic sensitivity analysis derived the LTD in grams per 1000 inhabitants. The key variables included the treatment schedule and the prevalence of the disease.

Results

The model estimates that an average annual IG demand and standard deviation for CIDP, GBS and MMN in the United States is 83.05 ± 24.5, 6.1 ± 3.2 and 36.1 ± 25.5 g/1000 inhabitants, respectively.

Conclusion

Together with previous work on the LTD for IG in immunodeficiencies, these results indicate that current IG usage reflects the estimated LTD for the main indications for IG in the United States The wide range of LTD found in all these studies emphasizes the need for more precise assessment of the underlying variables, particularly disease prevalence and dosage. Further studies on other indications such as secondary immunodeficiencies will augment these results and will assist in guiding demand planning for IG use and plasma collection in the United States and inform blood policy in other countries.
An Adaptable Computed Tomography-Derived Three-Dimensional-Printed Alignment Fixture Minimizes Errors in Radius Biomechanical Testing
Authors: Inacio Jordan V. , Cristino Danielle M. , Hast Michael W. , Dailey Hannah L.
Published: June 2021

Biomechanical testing of long bones can be susceptible to errors and uncertainty due to malalignment of specimens with respect to the mechanical axis of the test frame. To solve this problem, we designed a novel, customizable alignment and potting fixture for long bone testing. The fixture consists of three-dimensional-printed components modeled from specimen-specific computed tomography (CT) scans to achieve a predetermined specimen alignment. We demonstrated the functionality of this fixture by comparing benchtop torsional test results to specimen-matched finite element models and found a strong correlation (R2 = 0.95, p < 0.001). Additional computational models were used to estimate the impact of malalignment on mechanical behavior in both torsion and axial compression. Results confirmed that torsion testing is relatively robust to alignment artifacts, with absolute percent errors less than 8% in all malalignment scenarios. In contrast, axial testing was highly sensitive to setup errors, experiencing absolute percent errors up to 50% with off-center malalignment and up to 170% with angular malalignment. This suggests that whenever appropriate, torsion tests should be used preferentially as a summary mechanical measure. When more challenging modes of loading are required, pretest clinical-resolution CT scanning can be effectively used to create potting fixtures that allow for precise preplanned specimen alignment. This may be particularly important for more sensitive biomechanical tests (e.g., axial compressive tests) that may be needed for industrial applications, such as orthopedic implant design.
Mechanical Efficiency Investigation of an Ankle-Assisted Robot for Human Walking With a Backpack-Load
Authors: Xie Longhan , Wang Zhihou , Huang Guowei , Liu Biao , Zhou Zikang
Published: June 2021

The purpose of this work is to investigate the efficiency of wearable assistive devices under different load-carriage walking. We designed an experimental platform with a lightweight ankle-assisted robot. Eight subjects were tested in three experimental conditions: free walk with load (FWL), power-off with load (POFL), and power-on with load for different levels of force at a walking speed of 3.6 km/h. We recorded the metabolic expenditure and kinematics of the subjects under three levels of load-carried (10%, 20%, and 30% of body mass). We define the critical force, where at a certain load, the robot inputs a certain force to the human body, and with the assistance of this force, the positive effect of the robot on the human body exactly compensates for the negative effect. The critical forces from the fit of the assistive force and metabolic cost curves were 130 N, 160 N, and 215 N at three different load levels. The intrinsic weight of our device increases mechanical work at the ankle as the load weight rises with 2.08 J, 2.43 J, and 2.73 J for one leg during a gait cycle. With weight bearing increasing, the ratio of the mechanical work input by the robot to the mechanical work output by the weight of the device decreases (from 0.904 to 0.717 and 0.513), verifying that the walking assistance efficiency of such devices decreases as the weight rises.
Producing Hollow Polymer Microneedles Using Laser Ablated Molds in an Injection Molding Process
Authors: Evens Tim , Van Hileghem Lorenz , Dal Dosso Francesco , Lammertyn Jeroen , Malek Olivier , Castagne Sylvie , Seveno David , Van Bael Albert
Published: June 2021

Microneedle arrays contain needlelike microscopic structures, which facilitate drug or vaccine delivery in a minimally invasive way. However, producing hollow microneedles is currently limited by expensive, time consuming and complex microfabrication techniques. In this paper, a novel method to produce hollow polymer microneedles is presented. This method utilizes a femtosecond laser to create hollow microneedle cavities in a mold insert. This mold insert is used in an injection molding process to replicate polymethyl methacrylate microneedles. The combined effect of the mold temperature, volumetric injection rate, and melt temperature on the replication fidelity was evaluated. It was found that the combination of high injection molding parameters facilitated the replication. Furthermore, the functionality of the manufactured hollow microneedles was successfully tested by injecting a controlled flow of colored water into an agarose matrix. The developed methodology enables the production of low-cost, high-volume microneedle devices, which could be a key asset for large scale vaccination campaigns.
Evaluation of nickel self-sputtering yields by molecular-dynamics simulation
Authors: Mauchamp Nicolas A. , Isobe Michiro , Hamaguchi Satoshi
Published: June 2021

Theoretical prediction of sputtering yields of a material subject to ion bombardment requires a detailed knowledge of how atoms in the material interact with other atoms moving with high kinetic energies. In this study, molecular-dynamical (MD) simulations were performed to predict the self-sputtering yields of nickel (Ni) for an incident ion energy ranging from 100 to 4000 eV, modifying existing interatomic potential (or force-field) functions designed for bulk Ni metal in thermal equilibrium. The selection of Ni as a sample material was motivated by an interest in developing damageless etching processes for ferromagnetic materials used in semiconductor devices. The simulations were performed until the system reaches steady state, where surface roughness formed self-consistently owing to the ion bombardment. It has been found that, for high-energy impact, the short-distance atomic repulsion plays a key role in determining the sputtering yields. The Ni self-sputtering yields predicted by the MD simulations of this study were found to be in reasonable agreement with experimental yield data. However, it was also found that two interatomic potential models for Ni that gave essentially the same mechanical properties of metallic Ni gave largely different sputtering yield values. These observations indicate that, for an existing interatomic model to be used effectively to predict sputtering yields of a material by MD simulation, it, in general, requires further modification to represent atomic interactions away from the thermodynamic equilibrium positions.
High-throughput functional screening for next-generation cancer immunotherapy using droplet-based microfluidics
Authors: Wang Yuan , Jin Ruina , Shen Bingqing , Li Na , Zhou He , Wang Wei , Zhao Yingjie , Huang Mengshi , Fang Pan , Wang Shanshan , Mary Pascaline , Wang Ruikun , Ma Peixiang , Li Ruonan , Tian Yujie , Cao Youjia , Li Fubin , Schweizer Liang , Zhang Hongkai
Published: June 2021

Microfluidics system enables high-throughput functional screening of antibodies for cancer immunotherapy.
Diversification dynamics of total-, stem-, and crown-groups are compatible with molecular clock estimates of divergence times
Authors: Beavan Alan J. S. , Pisani Davide , Donoghue Philip C. J.
Published: June 2021

A wide range of divergence times is supported by birth-death models under constant rates of speciation and extinction.
Multidecadal poleward shift of the southern boundary of the Antarctic Circumpolar Current off East Antarctica
Authors: Yamazaki Kaihe , Aoki Shigeru , Katsumata Katsuro , Hirano Daisuke , Nakayama Yoshihiro
Published: June 2021

Poleward expansion of the Antarctic Circumpolar Current warms the Antarctic continental margin.
Combining generative artificial intelligence and on-chip synthesis for de novo drug design
Authors: Grisoni Francesca , Huisman Berend J. H. , Button Alexander L. , Moret Michael , Atz Kenneth , Merk Daniel , Schneider Gisbert
Published: June 2021

Generative deep learning and miniaturized bench-top synthesis were combined to automate the design of novel LXR agonists.
Engineered bridge protein with dual affinity for bone morphogenetic protein-2 and collagen enhances bone regeneration for spinal fusion
Authors: Briquez Priscilla S. , Tsai Hsiu-Ming , Watkins Elyse A. , Hubbell Jeffrey A.
Published: June 2021

The safety and efficacy of bone morphogenetic protein-2 is improved by the addition of a bridge protein in InFUSE Bone Graft.
Emergence of Resistance to Novel Cephalosporin–β-Lactamase Inhibitor Combinations through the Modification of the Pseudomonas aeruginosa MexCD-OprJ Efflux Pump
Authors: Gomis-Font María A. , Pitart Cristina , del Barrio-Tofiño Ester , Zboromyrska Yuliya , Cortes-Lara Sara , Mulet Xavier , Marco Francesc , Vila Jordi , López-Causapé Carla , Oliver Antonio
Published: June 2021

A ceftolozane-tazobactam- and ceftazime-avibactam-resistant
Pseudomonas aeruginosa
isolate was recovered after treatment (including azithromycin, meropenem, and ceftolozane-tazobactam) from a patient that had developed ventilator-associated pneumonia after COVID-19 infection. Whole-genome sequencing revealed that the strain, belonging to ST274, had acquired a nonsense mutation leading to truncated carbapenem porin OprD (W277X), a 7-bp deletion (nt213Δ7) in NfxB (negative regulator of the efflux pump MexCD-OprJ), and two missense mutations (Q178R and S133G) located within the first large periplasmic loop of MexD.
The Yeast eIF2 Kinase Gcn2 Facilitates H
2
O
2
-Mediated Feedback Inhibition of Both Protein Synthesis and Endoplasmic Reticulum Oxidative Folding during Recombinant Protein Production
Authors: Gast Veronica , Campbell Kate , Picazo Cecilia , Engqvist Martin , Siewers Verena , Molin Mikael
Published: June 2021

Recombinant protein production is a multibillion dollar industry. Optimizing the productivity of host cells is, therefore, of great interest.
Azithromycin and Ciprofloxacin Can Promote Antibiotic Resistance in Biosolids and Biosolids-Amended Soils
Authors: Sidhu Harmanpreet , Bae Hee-Sung , Ogram Andrew , O’Connor George , Yu Fahong
Published: June 2021

Although previous studies have indicated that biosolids may be important spreaders of antibiotics and antibiotic resistance genes (ARGs) in environments, the potential activities of ARGs or their responses to environmental parameters have been understudied. This study highlights that certain biosolids-borne antibiotics can induce transcriptional activities of ARGs and mobile genetic elements in biosolids and biosolids-amended soil, even when present at environmentally relevant concentrations.
Improvements to the Success of Outbreak Investigations of Legionnaires’ Disease: 40 Years of Testing and Investigation in New York State
Authors: Schoonmaker-Bopp Dianna , Nazarian Elizabeth , Dziewulski David , Clement Ernest , Baker Deborah J. , Dickinson Michelle C. , Saylors Amy , Codru Neculai , Thompson Lisa , Lapierre Pascal , Dumas Nellie , Limberger Ronald , Musser Kimberlee A.
Published: June 2021

Legionella
, the causative agent of Legionnaires’ disease (LD), can cause severe respiratory illness. In 2018, there were nearly 10,000 cases of LD reported in the United States (
https://www.cdc.gov/legionella/fastfacts.html
;
https://wonder.cdc.gov/nndss/static/2016/annual/2016-table2h.html
), with actual incidence believed to be much higher.
Extreme Acid Modulates Fitness Trade-Offs of Multidrug Efflux Pumps MdtEF-TolC and AcrAB-TolC in Escherichia coli K-12
Authors: Schaffner Samantha H. , Lee Abigail V. , Pham Minh T. N. , Kassaye Beimnet B. , Li Haofan , Tallada Sheetal , Lis Cassandra , Lang Mark , Liu Yangyang , Ahmed Nafeez , Galbraith Logan G. , Moore Jeremy P. , Bischof Katarina M. , Menke Chelsea C. , Slonczewski Joan L.
Published: June 2021

Antibiotics and other drugs that reach the gut must pass through stomach acid. However, little is known of how extreme acid modulates the effect of drugs on gut bacteria.
A Quantitative Metagenomic Sequencing Approach for High-Throughput Gene Quantification and Demonstration with Antibiotic Resistance Genes
Authors: Li Bo , Li Xu , Yan Tao
Published: June 2021

Monitoring and comprehensive assessment of microbial risks in the environment require high-throughput gene quantification. The quantitative metagenomic NGS (qmNGS) approach developed in this study incorporated numerous xenobiotic and synthetic DNA internal standard fragments into metagenomic NGS workflow, which are used to determine a new parameter called sequencing yield that relates sequence base reads to absolute concentration of target genes in the environmental samples.
Evaluation of the Fully Automated Chemiluminescence Analyzer Liaison XL for the Performance of the QuantiFERON-TB Gold Plus Assay in an Area with a Low Incidence of Tuberculosis
Authors: Fernández-Huerta Miguel , Moreto Clara , Vila-Olmo Neus , García de Cara Erika-Inés , Basaez María-Celeste , Santín Miguel , Alcaide Fernando
Published: June 2021

Diagnosis of latent tuberculosis infection (LTBI) is considered key in the control of tuberculosis. Interferon gamma (IFN-γ) release assays, such as the QuantiFERON-TB Gold Plus test (QFT-Plus), are now widely implemented for the
in vitro
diagnosis of LTBI.
Influence of NKG2C Genotypes on HIV Susceptibility and Viral Load Set Point
Authors: Alsulami Khlood , Bolastig Naomi , Dupuy Franck P. , Mabanga Tsoarello , Gilbert Louise , Kiani Zahra , Routy Jean-Pierre , Bruneau Julie , Thomas Réjean , Tremblay Cécile , Tsoukas Christos M. , Szabo Jason , Côté Pierre , Trottier Benoit , LeBlanc Roger , Rouleau Danielle , Bernard Nicole F.
Published: June 2021

We compared
NKG2C
allele and genotype distributions in subjects who remained HIV uninfected despite multiple HIV exposures (HESN subjects) with those in the group PLWH. This allowed us to determine whether
NKG2C
genotype influenced susceptibility to HIV infection.
A BMPR2/YY1 Signaling Axis Is Required for Human Cytomegalovirus Latency in Undifferentiated Myeloid Cells
Authors: Poole Emma , Carlan da Silva Maria Cristina , Huang Chris , Perera Marianne , Jackson Sarah , Groves Ian J. , Wills Mark , Rana Amer , Sinclair John
Published: June 2021

Understanding the mechanisms which regulate HCMV latency could allow therapeutic targeting of the latent virus reservoir from where virus reactivation can cause severe disease. We show that the BMPR2/TGFbeta receptor/YY1 signaling axis is crucial to maintain HCMV latency in undifferentiated cells and that pharmacological reduction of BMPR2 in latently infected cells leads to reactivation of the viral lytic transcription program, which renders the infected cell open to immune detection and clearance in infected individuals.
Challenges and Controversies Concerning Neisseria gonorrhoeae-Neutrophil Interactions in Pathogenesis
Authors: Criss Alison K. , Genco Caroline A. , Gray-Owen Scott D. , Jerse Ann E. , Seifert H Steven
Published: June 2021

The bacterium
Neisseria gonorrhoeae
(Ngo) is the main cause of the sexually transmitted infection gonorrhea. The global incidence of 87 million new Ngo infections each year, rising infection rates, and the emergence of Ngo strains that are resistant to all clinically recommended antibiotics have raised the specter of untreatable infections (M.
Host Species and Geography Differentiate Honeybee Gut Bacterial Communities by Changing the Relative Contribution of Community Assembly Processes
Authors: Ge Yuan , Jing Zhongwang , Diao Qingyun , He Ji-Zheng , Liu Yong-Jun
Published: June 2021

Honeybees provide crucial pollination services and valuable apiarian products. The symbiotic intestinal communities facilitate honeybee health and fitness by promoting nutrient assimilation, detoxifying toxins, and resisting pathogens.
Cellulosome Localization Patterns Vary across Life Stages of Anaerobic Fungi
Authors: Lillington Stephen P. , Chrisler William , Haitjema Charles H. , Gilmore Sean P. , Smallwood Chuck R. , Shutthanandan Vaithiyalingam , Evans James E. , O’Malley Michelle A.
Published: June 2021

Anaerobic fungi (
Neocallimastigomycota
) isolated from the guts of herbivores excel at degrading ingested plant matter, making them attractive potential platform organisms for converting waste biomass into valuable products, such as chemicals and fuels. Major contributors to their biomass-hydrolyzing power are the multienzyme cellulosome complexes that anaerobic fungi produce, but knowledge gaps in how cellulosome production is controlled by the cellular life cycle and how cells spatially deploy cellulosomes complicate the use of anaerobic fungi and their cellulosomes in industrial bioprocesses.
Genetic and biochemical distinction among Chinese hamster cell emtA, emtB, and emtC mutants
Authors: Chang S , Wasmuth J J
Published: June 2021

Genetic and biochemical experiments have enabled us to more clearly distinguish three genetic loci, emtA, emtB, and emtC, all of which can be altered to give rise to resistance to the protein synthesis inhibitor, emetine, in cultured Chinese hamster cells. Genetic experiments have demonstrated that, unlike the emtB locus, neither the emtA locus nor the emtC locus is linked to chromosome 2 in Chinese hamster cells, clearly distinguishing the latter two genes from emtB. emtA mutants can also be distinguished, biochemically, from emtB and emtC mutants based upon different degrees of cross-resistance to another inhibitor of protein synthesis, cryptopleurine. Two-dimensional gel electrophoretic analysis of ribosomal proteins failed to detect any electrophoretic alterations in ribosomal proteins from emtA or emtC mutants that could be correlated with emetine resistance. However, a distinct electrophoretic alteration in ribosomal protein S14 was observed in an emtB mutant. In addition, the parental Chinese hamster peritoneal cell line of an emtC mutant, and the emtC mutant itself, are apparently heterozygous for an electrophoretic alteration in ribosomal protein L9.
Deletion and amplification of the HGPRT locus in Chinese hamster cells
Authors: Fuscoe J C , Fenwick R G , Ledbetter D H , Caskey C T
Published: June 2021

Somatic cell selective techniques and hybridization analyses with a cloned cDNA probe were used to isolate and identify Chinese hamster cell lines in which the X-linked gene for hypoxanthine-guanine phosphoribosyltransferase (HGPRT) has been altered. Two of 19 HGPRT-deficient mutants selected were found to have major DNA deletions affecting the HGPRT locus. Cytogenetic studies revealed that the X chromosome of each deletion mutant had undergone a translocation event, whereas those from the remaining 17 mutants were normal. Phenotypic revertants of the thermosensitive HGPRT mutant RJK526 were isolated, and amplification of the mutant allele was shown to be the predominant mechanism of reversion. Comparisons of restriction enzyme fragments of DNA from deletion versus amplification strains identified two regions of the Chinese hamster genome that contained homology to the cDNA probe. One was shown to be much larger than the 1,600-nucleotide mRNA for HGPRT and to be comprised of linked fragments that contained the functional HGPRT gene. The second was neither transcribed nor tightly linked to the functional gene. These initial studies of HGPRT alterations at the level of DNA thus identified molecular mechanisms of phenotypic variation.
Metagenomes, Metatranscriptomes, and Metagenome-Assembled Genomes from Chesapeake and Delaware Bay (USA) Water Samples
Authors: Ahmed Mir Alvee , Lim Shen Jean , Campbell Barbara J.
Published: June 2021

Here, we present 36 metagenomes, 59 metatranscriptomes, and 373 metagenome-assembled genomes (MAGs) from Chesapeake and Delaware Bay water samples. This data set will be useful for studying microbial biogeochemical cycling in estuaries.
Complete Genome Sequence of
Streptomyces
sp. Strain CA-256286
Authors: Beck Charlotte , Gren Tetiana , Jørgensen Tue S. , González Ignacio , Román-Hurtado Fernando , Oves-Costales Daniel , Genilloud Olga , Weber Tilmann
Published: June 2021

Here, we report the sequencing, assembly, and annotation of the genome of
Streptomyces
sp. strain CA-256286. The genome consists of a linear 7,726,360-nucleotide chromosome and a linear 466,817-nucleotide putative plasmid. This strain is predicted to produce a range of novel secondary metabolites.
High-Quality Reference Genome Sequence for the Oomycete Vegetable Pathogen Phytophthora capsici Strain LT1534
Authors: Stajich Jason E. , Vu Andrea L. , Judelson Howard S. , Vogel Gregory M. , Gore Michael A. , Carlson Maryn O. , Devitt Nicholas , Jacobi Jennifer , Mudge Joann , Lamour Kurt H. , Smart Christine D.
Published: June 2021

The oomycete
Phytophthora capsici
is a destructive pathogen of a wide range of vegetable hosts, especially peppers and cucurbits. A 94.17-Mb genome assembly was constructed using PacBio and Illumina data and annotated with support from transcriptome sequencing (RNA-Seq) reads.
Identification of a Novel Regulator of Clostridioides difficile Cortex Formation
Authors: Touchette Megan H. , Benito de la Puebla Hector , Alves Feliciano Carolina , Tanenbaum Benjamin , Schenone Monica , Carr Steven A. , Shen Aimee
Published: June 2021

The Centers for Disease Control has designated
Clostridioides difficile
as an urgent threat because of its intrinsic antibiotic resistance.
C. difficile
persists in the presence of antibiotics in part because it makes metabolically dormant spores. While recent work has shown that preventing the formation of infectious spores can reduce
C. difficile
disease recurrence, more selective antisporulation therapies are needed.
Temporal Kinetics of RNAemia and Associated Systemic Cytokines in Hospitalized COVID-19 Patients
Authors: van Riel Debby , Embregts Carmen W. E. , Sips Gregorius J. , van den Akker Johannes P. C. , Endeman Henrik , van Nood Els , Raadsen Mathijs , Bauer Lisa , van Kampen Jeroen , Molenkamp Richard , Koopmans Marion , van de Vijver David , GeurtsvanKessel Corine H.
Published: June 2021

Severe COVID-19 can be considered a systemic disease as many extrarespiratory complications occur. However, the systemic pathogenesis is poorly understood.
VB
12
Path for Accurate Metagenomic Profiling of Microbially Driven Cobalamin Synthesis Pathways
Authors: Zhou Jiayin , Yu Xiaoli , Liu Jihua , Qin Wei , He Zhili , Stahl David , Jiao Nianzhi , Zhou Jizhong , Tu Qichao
Published: June 2021

Vitamin B12 (VB
12
) is an indispensable nutrient for all living entities in the world but can only be synthesized by a small subset of prokaryotes. Therefore, this small subset of prokaryotes controls ecosystem stability and host health to some extent.
Thermotectonic events recorded by U-Pb geochronology and Zr-in-rutile thermometry of Ti oxides in basement rocks along the P2 fault, eastern Athabasca Basin, Saskatchewan, Canada
Authors: Adlakha E. , Hattori K.
Published: June 2021

Basement rocks below the Athabasca Basin, Saskatchewan, have been intensely altered through paleoweathering and multiple hydrothermal events, including the formation of world-class unconformity-type uranium deposits. Here, we demonstrate the utility of Ti-oxide thermochronology for identifying thermotectonic events in these altered rocks leading to uranium mineralization along basement structures. Rutile grains along the P2 fault, a major fault in the eastern Athabasca Basin, exhibit 207Pb/206Pb ages of ca. 1850–1700 Ma, with a weighted mean of 1757 ± 6 Ma (mean square of weighted deviation [MSWD] = 1.4, n = 116). The older ages (>1770 Ma) record regional metamorphism reaching a temperature of 875 °C during the Trans-Hudson orogeny. Pb diffusion modeling indicates that metamorphic rutile should exhibit cooling ages of 1760–1750 Ma. Rutile grains showing young ages, <1750 Ma, reflect isotopic resetting during regional asthenospheric upwelling between 1770 and 1730 Ma related to the emplacement of the Kivalliq igneous suite to the north. This thermotectonic event (temperature > 550 °C) promoted hydrothermal activity to produce silicified rocks, i.e., “quartzite,” along the P2 fault, which later focused mineralizing fluids for unconformity-type uranium deposits. The young rutile ages also indicate that the basement rocks remained hot until 1700 Ma, providing the maximum age for the deposition of the Athabasca sediments. Anatase yields a concordia age of 1569 ± 31 Ma (MSWD = 0.30, n = 5), which is within uncertainty of the oldest ages for uraninite of the McArthur River deposit. This age corresponds to the incursion of basinal fluids in the basement along the P2 fault during uranium mineralization.
Supplemental Material: Alpine relief limited by glacial occupation time
Authors: Salcher Bernhard , al. et
Published: June 2021

Mean elevation, relief, and glacial occupation time (GOT) for delineated basins and 10 km2 squares.
Synthetic Antimicrobial Peptides: III—Effect of Cationic Groups of Lysine, Arginine, and Histidine on Antimicrobial Activity of Peptides with a Linear Type of Amphipathicity
Authors: Amirkhanov N. V. , Bardasheva A. V. , Tikunova N. V. , Pyshnyi D. V.
Published: June 2021

We have studied the antimicrobial and hemolytic activity of synthetic antimicrobial peptides (SAMPs), i.e., Arg9Phe2 (P1-Arg), Lys9Phe2 (P2-Lys), and His9Phe2 (P3-His), which have a “linear” type of amphipathicity and contain the cationic amino acid residues of arginine, lysine, or histidine. In this study, we have used various pathogenic microorganism strains of gram-negative bacteria (Pseudomonas aeruginosa, Escherichia coli, and Salmonella enterica), gram-positive bacteria (Staphylococcus aureus), and the conditionally pathogenic yeast fungus (Candida albicans). It has been shown that the replacement of the arginine residues by lysine or histidine residues in the tested SAMPs significantly degrades their antibacterial properties in the series: P1-Arg > P2-Lys $$ \gg $$P3-His. The cationic analog of SAMP, P1-Arg, has the highest antibacterial activity (MIC50 = 43–76 μM), while peptide P3-His does not exhibit this activity (MIC50 > 100 μM). The P1-Arg and P2-Lys peptides were 6–10 times more active against the opportunistic fungus C. albicans (MIC50 6.7 and 10.9 μM, respectively) and the P3-His peptide has 100-times increased antimycotic activity (MIC50 0.6 μM) compared with their effect on bacterial cells. All of the tested peptides with the linear type of amphipathicity and low hydrophobicity, i.e., P1-Arg, P2-Lys, and P3-His, that contain only two Phe residues regardless of the presence of cationic amino acids (Arg, Lys, or His) exhibit a relatively low hemolytic activity (not more than 4% hemolysis at 1000 μM peptide concentration). Thus, considering the same synthesis efficiency (56–63%) and approximately the same low toxicity of the tested SAMPs with a linear type of amphipathicity, it is recommended to use those that contain the cationic arginine or histidine residues to create antibacterial or antifungal peptide agents, respectively.
Future of biomarker evaluation in the realm of artificial intelligence algorithms: application in improved therapeutic stratification of patients with breast and prostate cancer
Authors: Fitzgerald Jenny , Higgins Debra , Mazo Vargas Claudia , Watson William , Mooney Catherine , Rahman Arman , Aspell Niamh , Connolly Amy , Aura Gonzalez Claudia , Gallagher William
Published: June 2021

Clinical workflows in oncology depend on predictive and prognostic biomarkers. However, the growing number of complex biomarkers contributes to costly and delayed decision-making in routine oncology care and treatment. As cancer is expected to rank as the leading cause of death and the single most important barrier to increasing life expectancy in the 21st century, there is a major emphasis on precision medicine, particularly individualisation of treatment through better prediction of patient outcome. Over the past few years, both surgical and pathology specialties have suffered cutbacks and a low uptake of pathology specialists means a solution is required to enable high-throughput screening and personalised treatment in this area to alleviate bottlenecks. Digital imaging in pathology has undergone an exponential period of growth. Deep-learning (DL) platforms for hematoxylin and eosin (H&E) image analysis, with preliminary artificial intelligence (AI)-based grading capabilities of specimens, can evaluate image characteristics which may not be visually apparent to a pathologist and offer new possibilities for better modelling of disease appearance and possibly improve the prediction of disease stage and patient outcome. Although digital pathology and AI are still emerging areas, they are the critical components for advancing personalised medicine. Integration of transcriptomic analysis, clinical information and AI-based image analysis is yet an uncultivated field by which healthcare professionals can make improved treatment decisions in cancer. This short review describes the potential application of integrative AI in offering better detection, quantification, classification, prognosis and prediction of breast and prostate cancer and also highlights the utilisation of machine learning systems in biomarker evaluation.
Applications of machine learning in the chemical pathology laboratory
Authors: Punchoo Rivak , Bhoora Sachin , Pillay Nelishia
Published: June 2021

Machine learning (ML) is an area of artificial intelligence that provides computer programmes with the capacity to autodidact and learn new skills from experience, without continued human programming. ML algorithms can analyse large data sets quickly and accurately, by supervised and unsupervised learning techniques, to provide classification and prediction value outputs. The application of ML to chemical pathology can potentially enhance efficiency at all phases of the laboratory’s total testing process. Our review will broadly discuss the theoretical foundation of ML in laboratory medicine. Furthermore, we will explore the current applications of ML to diverse chemical pathology laboratory processes, for example, clinical decision support, error detection in the preanalytical phase, and ML applications in gel-based image analysis and biomarker discovery. ML currently demonstrates exploratory applications in chemical pathology with promising advancements, which have the potential to improve all phases of the chemical pathology total testing pathway.
Novel selection paradigms for endovascular stroke treatment in the extended time window
Authors: Bouslama Mehdi , Haussen Diogo C , Rodrigues Gabriel , Barreira Clara , Frankel Michael , Nogueira Raul G
Published: June 2021

Background and purpose

The optimal selection methodology for stroke thrombectomy beyond 6 hours remains to be established.

Methods

Review of a prospectively collected database of thrombectomy patients with anterior circulation strokes, adequate CT perfusion (CTP) maps, National Institute of Health Stroke Scale (NIHSS)≥10 and presenting beyond 6 hours from January 2014 to October 2018. Patients were categorised according to five selection paradigms: DAWN clinical-core mismatch (DAWN-CCM): between age-adjusted NIHSS and CTP core, DEFUSE 3 perfusion imaging mismatch (DEFUSE-3-PIM): between CTP-derived perfusion defect (Tmax >6 s lesion) and ischaemic core volumes and three non-contrast CT Alberta Stroke Program Early CT Score (ASPECTS)-based criteria: age-adjusted clinical-ASPECTS mismatch (aCAM): between age-adjusted NIHSS and ASPECTS, eloquence-adjusted clinical ASPECTS mismatch (eCAM): ASPECTS 6–10 and non-involvement of the right M6 and left M4 areas and standard clinical ASPECTS mismatch (sCAM): ASPECTS 6–10.

Results

310 patients underwent analysis. DEFUSE-3-PIM had the highest proportion of qualifying patients followed by sCAM, eCAM, aCAM and DAWN-CCM (93.5%, 92.6%, 90.6%, 90% and 84.5%, respectively). Patients meeting aCAM, eCAM, sCAM and DAWN-CCM criteria had higher rates of 90-day good outcome compared with their non-qualifying counterparts(43.2% vs 12%,p=0.002; 42.4% vs 17.4%, p=0.02; 42.4% vs 11.2%, p=0.009; and 43.7% vs 20.5%, p=0.007, respectively). There was no difference between patients meeting DEFUSE-3-PIM criteria versus not(40.8% vs 31.3%,p=0.45). In multivariate analysis, all selection modalities except for DEFUSE-3-PIM were independently associated with 90-day good outcome.

Conclusions

ASPECTS-based selection paradigms for late presenting and wake-up strokes ET have comparable proportions of qualifying patients and similar 90-day functional outcomes as DAWN-CCM and DEFUSE-3-PIM. They also might lead to better outcome discrimination. These could represent a potential alternative for centres where access to advanced imaging is limited.
The Judgment of the German Federal Constitutional Court regarding assisted suicide: a template for pluralistic states?
Authors: Wiesing Urban
Published: June 2021

The article presents the judgment of the German Federal Constitutional Court from 26 February 2020 on assisted suicide. The statements regarding human dignity, human rights and the relationship between citizens and the state are examined. Furthermore, the consequences resulting from this interpretation of human dignity for states that are pluralistic and based on human rights will be laid out. The court’s judgment limits the power of parliaments and poses a challenge to many laws in states that see themselves as pluralistic, human rights-based states.
Novel drug candidates targeting Alzheimer’s disease: ethical challenges with identifying the relevant patient population
Authors: Gustavsson Erik , Raaschou Pauline , Lärfars Gerd , Sandman Lars , Juth Niklas
Published: June 2021

Intensive research is carried out to develop a disease-modifying drug for Alzheimer’s disease (AD). The development of drug candidates that reduce Aß or tau in the brain seems particularly promising. However, these drugs target people at risk for AD, who must be identified before they have any, or only moderate, symptoms associated with the disease. There are different strategies that may be used to identify these individuals (eg, population screening, cascade screening, etc). Each of these strategies raises different ethical challenges. In this paper, we analyse these challenges in relation to the risk stratification for AD necessary for using these drugs. We conclude that the new drugs must generate large health benefits for people at risk of developing AD to justify the ethical costs associated with current risk stratification methods, benefits much larger than current drug candidates have. This conclusion raises a new set of ethical questions that should be further discussed.
Voluntary COVID-19 vaccination of children: a social responsibility
Authors: Brusa Margherita , Barilan Yechiel Michael
Published: June 2021

Nearly 400 million adults have been vaccinated against COVID-19. Children have been excluded from the vaccination programmes owing to their lower vulnerability to COVID-19 and to the special protections that apply to children’s exposure to new biological products. WHO guidelines and national laws focus on medical safety in the process of vaccine approval, and on national security in the process of emergency authorisation. Because children suffer much from social distancing, it is argued that the harms from containment measures should be factored in a broader perspective on the good of the child. Considering the available knowledge on the disease, vaccine, and coping strategies, the decision about vaccine access to children is a public responsibility. The ultimate choice is a matter of paediatric informed consent. Moreover, jurisdictions that permit non-participation in established childhood vaccination programmes should also permit choice of vaccines outside of the approved programmes. Even if vaccine supply is too short to cover the paediatric population, the a priori exclusion of children is unjust. It may also exacerbate local and global inequalities. The second part of the paper delineates a prudent and ethical scheme for gradual incorporation of minors in vaccination programmes that includes a rigorous postvaccination monitoring. This is a theoretical paper in ethics that uses the Pfizer vaccine as a stock example, without discussing possible differences among existing vaccines. The key purpose is reflection on the good of the child in emergencies and vaccine policymaking.
Making smoking history: temporal changes in support for a future smoking ban and increasing taxes in the general population of Denmark
Authors: Toxværd Cecilie Goltermann , Pisinger Charlotta , Lykke Maja Bülow , Lau Cathrine Juel
Published: June 2021

Background

An end date for smoking has been adopted in several countries and is now being discussed by governments all over the world. However, little is known about temporal changes in citizens’ support for a future smoking ban.

Aim

To examine temporal changes in support for a future smoking ban and for increasing taxes on tobacco in Denmark, and to explore whether these changes differ across sex, age, educational attainment, smoking status and between smokers with/without intention to quit.

Method

The study was based on two waves of ‘The Danish Capital Region Health Survey’ conducted in 2013 and 2017. The pooled study sample included 96 521 citizens aged ≥16 years old.

Results

Public support for a future smoking ban increased from 30.6% in 2013 to 50.3% in 2017, whereas support for increasing tobacco taxes remained unchanged at 59%. Support for a future smoking ban increased significantly in almost all subgroups from 2013 to 2017: Support among daily smokers increased by 27% between 2013 and 2017. Support among never smokers was almost 2.63 times higher than among smokers in 2013 and increased further in 2017 (OR: 2013=2.63; 2017=5.13).

Conclusion

This study indicates a readiness to support a future smoking ban and increasing tobacco taxes. Support for a future smoking ban has increased from 2013 to 2017 among both young people and adults. By 2017, about half of the population supported a future smoking ban and increasing tobacco taxes. Findings may help inform policy-making related to endgame strategies.
Optimal quantum tomography with constrained measurements arising from unitary bases
Authors: Chaturvedi S. , Ghosh S. , Parthasarathy K. R. , Singh Ajit Iqbal
Published: June 2021

The purpose of this paper is to introduce techniques of obtaining optimal ways to determine a [Formula: see text]-level quantum state or distinguish such states. It entails designing constrained elementary measurements extracted from maximal abelian subsets of a unitary basis [Formula: see text] for the operator algebra [Formula: see text] of a Hilbert space [Formula: see text] of finite dimension [Formula: see text] or, after choosing an orthonormal basis for [Formula: see text], for the ⋆-algebra [Formula: see text] of complex matrices of order [Formula: see text]. Illustrations are given for the techniques. It is shown that the Schwinger basis [Formula: see text] of unitary operators can give for [Formula: see text], a product of primes [Formula: see text] and [Formula: see text], the ideal number [Formula: see text] of rank one projectors that have a few quantum mechanical overlaps (or, for that matter, a few angles between the corresponding unit vectors). Finally, we give a combination of the tensor product and constrained elementary measurement techniques to deal with all [Formula: see text], though with more overlaps or angles depending on the factorization of [Formula: see text] as a product of primes or their powers like [Formula: see text] with [Formula: see text], all primes, [Formula: see text] for [Formula: see text], or other types. A comparison is drawn for different forms of unitary bases for the Hilbert space factors of the tensor product like [Formula: see text] or [Formula: see text], where [Formula: see text] is the Galois field of size [Formula: see text] and [Formula: see text] is the ring of integers modulo [Formula: see text]. Even though as Hilbert spaces they are isomorphic, but quantum mechanical system-wise, these tensor products are different.

In the process, we also study the equivalence relation on unitary bases defined by R. F. Werner [J. Phys. A: Math. Gen. 34 (2001) 7081–7094], connect it to local operations on maximally entangled vectors bases, find an invariant for equivalence classes in terms of certain commuting systems, called fan representations, and, relate it to mutually unbiased bases and Hadamard matrices. Illustrations are given in the context of Latin squares and projective representations as well.
Tracing method based on heterodyne interferometer for scanning electron microscopes
Authors: Li Shi , Li Wei , Gao Sitian , Hu Xiaodong
Published: June 2021

In this study, a tracing method for a scanning electron microscope was developed based on a heterodyne interferometer, which can directly trace the measured values to the laser wavelength and then to the internationally defined meter length reference. In this method, a sample scanning motion is introduced, and the measuring mirror of the interferometer is fixed on the sample stage. The movement and displacement of the sample stage is recorded by the laser interferometer displacement measurement system, which synchronously collects the secondary electrons or backscattered electron signals excited on the sample surface. The feature size of the sample is measured, and the value can be traced directly to the international unit of length using the frequency-stabilized laser reference, which proves that the proposed method is an absolute measurement method. This study analyzed the specific technology implementation methods and experimental results, including positioning control of the displacement system and its measurement and control during the measurement process. Measurement uncertainty budgets are also discussed. Experimental measurements were carried out and their accuracy was verified. Results showed that this method could effectively obtain the performance parameters of the feature size intuitively and significantly improve the measurement accuracy.
Linear time algorithm for the conjugacy problem in the first Grigorchuk group
Authors: Modi Mitra , Seedhom Mathew , Ushakov Alexander
Published: June 2021

We prove that the conjugacy problem in the first Grigorchuk group [Formula: see text] can be solved in linear time. Furthermore, the problem to decide if a list of elements [Formula: see text] contains a pair of conjugate elements can be solved in linear time. We also show that a conjugator for a pair of conjugate element [Formula: see text] can be found in polynomial time.
EFFECT OF CARBON CONTENT ON MICROSTRUCTURE EVOLUTION AND PROPERTIES OF HYPEREUTECTIC HIGH CHROMIUM CAST IRON
Authors: GUO QIANG , FU HANGUANG , GUO XINGYE , XING ZHENGUO , LIN JIAN
Published: June 2021

This study is to reveal the influence of the amount of carbon content on the microstructure evolution, mechanical properties, and wear properties of Hypereutectic High Chromium Cast Iron (HHCCI). The results indicated that the carbon content plays a key role in the regulation of carbides in the cast iron microstructure. As the amount of carbon content rises, the primary carbides in the cast iron microstructure become apparently coarser, and the volume fraction of carbides gradually increases. The carbide volume fraction reaches 62% when the carbon content is 5[Formula: see text]wt.%. When the value of the carbon content increases, the accumulation and growth of eutectic carbides in the heat-treated cast iron become more and more obvious. After heat treatment, a large number of secondary carbides will be precipitated from the austenite matrix, in the form of fine particles or short rods, with a dispersed distribution. The macroscopic hardness of HHCCI has increased. When the carbon content is 3.5[Formula: see text]wt.%, the macroscopic hardness is 61.2 HRC, and when the carbon content becomes 5[Formula: see text]wt.%, it reaches 64.3 HRC. The wear resistance of HHCCI increases with the value of the carbon content increases. When the carbon content was increased from 3.5[Formula: see text]wt.% to 5.0[Formula: see text]wt.%, the wear resistance of the material increased by 85.7%. The wear of HHCCI is mainly adhesive wear and fatigue wear, and the wear morphology is mainly spalling pits and wear debris.
Creep Effect on the Dynamic Response of Train-Track-Continuous Bridge System
Authors: Xiang Ping , Wei Minglong , Sun Mengmeng , Li Qiusheng , Jiang Lizhong , Liu Xiang , Ren Jianying
Published: June 2021

The influence of track irregularity and deck deformation on the running safety of high-speed railway (HSR) trains is investigated, with emphasis placed on those caused by the creep of continuous prestressed bridges. A bridge model is established with CRTS II ballastless track to account for a train-track-bridge (TTB) system. The creep effect is calculated by the finite element software MIDAS/Civil. The accuracy of the numerical simulation is confirmed by comparing the numerical predictions with field measurements. Considering the stability index of the moving train, the deformation threshold for safe operation of the train is determined. The results show that the initial prestressing stress has a great impact on the residual deformation of the bridge, but the deformation of the rail is less affected by the stiffness of the fastener. Creep irregularity has a great influence on the comfort of the moving train, but does not affect its running safety. When the creep amplitude is greater than 4[Formula: see text]mm, the increase in the amplitude of the creep irregularity has a greater effect on the acceleration of the car body.