bluuebunny/crossref_metadata_2025 huggingface dataset:
Population pharmacokinetics of oral levofloxacin in healthy volunteers and dosing optimization for multidrug‐resistant tuberculosis therapy
Authors: Boonpeng Apinya , Jaruratanasirikul Sutep , Wattanavijitkul Thitima , Nawakitrangsan Monchana , Samaeng Maseetoh
Published: June 2021

Levofloxacin is considered a key component of a multidrug‐resistant tuberculosis (MDR‐TB) regimen. However, there is considerable concern regarding the subtherapeutic concentrations of the currently used doses and the development of drug resistance. Therefore, this study aimed to describe the population pharmacokinetics (PPK) of oral levofloxacin in healthy volunteers and to evaluate the probability of target attainment (PTA) in an attempt to optimize the dosing regimens for MDR‐TB therapy. Data of levofloxacin in healthy volunteers from a previous study were used to construct a PPK model. Monte Carlo simulations were performed to derive the PTAs of various regimens. A two‐compartment model with linear elimination and transit absorption compartments best described the pharmacokinetics (PK) of levofloxacin. The estimated PK parameters (interindividual variability, %) were: apparent clearance 8.32 L h−1 (22.6%), apparent central volume of distribution 35.8 L (45.2%), apparent peripheral volume of distribution 39.7 L, intercompartmental clearance 40.6 L h−1 (43.8%), absorption rate constant 7.45 h−1 (150%), mean absorption transit time 0.355 h (52.4%), and total number of transit compartments 6.01 (131.9%). Monte Carlo simulations using levofloxacin 750–1000 mg yielded a probability of achieving a target free area under the concentration–time curve/minimum inhibitory concentration (MIC) of 100 at greater than 90% for Mycobacterium tuberculosis with an MIC < 0.5 mg L−1, while a dose of 1500 mg was required for strains with an MIC of 1 mg L−1. A higher dose of levofloxacin might be needed to treat tuberculosis. However, further studies on the efficacy and safety of this dose are needed to confirm our findings.
Quantitation of six steroid hormones by ultra‐performance liquid chromatography–tandem mass spectrometry in plasma and prefrontal cortex samples from rats with chronic unpredictable mild stress‐induced depression
Authors: Zhu Ying , Han Xuemei , Li Xixuan , Qin Yanjie , Rang Ying , Zhai Xuejia , Lu Yongning
Published: June 2021

Steroid hormones such as glucocorticoids and their metabolites are closely related to mental diseases and neuroendocrine diseases. Quantitative analysis of these substances will help in understanding their roles in related research fields. In this study, an ultra‐performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method was developed to detect the concentration of corticosterone (CORT) and its metabolites, progesterone (PROG) and testosterone in rat plasma and prefrontal cortex (PFC), and was applied to investigate the changes in hormones in rats with depression induced by chronic unpredictable mild stress (CUMS). The method was shown to be linear in the quantitation range for all analytes. Intra‐ and inter‐day accuracy and precision were between 80% and 120%. Furthermore, we found that the level of CORT in plasma and PFC increased, whereas that of 11‐dehydrocorticosterone (11‐DHCORT) as well as the ratio of 11‐DHCORT and CORT declined in rats with CUMS‐induced depression. The trends of these changes in central PFC and peripheral plasma were consistent. In conclusion, this study successfully established an UPLC–MS/MS method for simultaneous measurement of CORT and its metabolites, PROG and testosterone in rat plasma and PFC, and applied it to rats with depression. The method could be further applied to the research of depression and diseases related to these steroid hormones.
Immune correlates of therapy outcomes in women with cervical cancer treated with chemoradiotherapy: A systematic review
Authors: Lakomy David S. , Wu Juliana , Lombe Dorothy , Papasavvas Emmanouil , Msadabwe Susan Citonje , Geng Yimin , Montaner Luis J. , Chiao Elizabeth , Lin Lilie L.
Published: June 2021

Background

Immune markers have been correlated with prognosis in a variety of solid tumors, including cervical cancer.

Objective

To review the literature on hematologic and immune markers and their association with recurrence and survival among patients with cervical cancer treated with chemoradiation.

Evidence review

This systematic review was conducted in accordance with PRISMA guidelines via searches of Ovid MEDLINE, Ovid Embase, and the Cochrane Library using keywords regarding cervical cancer, immune markers, and HIV. Studies involving patients treated with cisplatin‐based chemoradiotherapy were selected and reviewed by at least two independent reviewers, with disagreements resolved by a third reviewer.

Findings

A total of 737 studies were identified, of which 314 assessed immune biomarkers in immunocompetent patients (30 included in the final analysis) and 327 studies in immunosuppressed patients (5 included in the final analysis). The strongest prognostic indicators were lymphopenia and elevated neutrophil‐to‐lymphocyte ratio. Other potential markers included HPV‐specific lymphocyte response, cytokine profile, expression of immune‐blocking antigens on cell surfaces, and tumor‐associated lymphocyte, macrophage, and neutrophil infiltration. Studies of immunosuppressed patients described more severe cytopenic changes overall and concluded that viral suppression led to improved outcomes.

Conclusions

The immunologic interplay at work in cervical cancer development, progression, and treatment is complex. Strong evidence was found in favor of lymphopenia and elevated neutrophil‐to‐lymphocyte ratio being prognostic for worse outcomes with other markers showing potential associations as well. Although the interpretation of immune status with regard to treatment approach remains unclear, future studies should aim to tailor treatment that minimizes possible detrimental immune effects.
Ein nanoporöser Goldschwamm als Katalysator
Authors: Thayssen Jan , Staubitz Anne
Published: June 2021

Unter nanoporösem Gold versteht man eine dreidimensionale, schwammartige Goldstruktur aus einer Vielzahl von Stegen und Poren, welche oft eine Größe zwischen 5–60 nm annehmen können. Das Material kann durch die gezielte Korrosion einer Legierung aus Gold und einem unedleren Metall wie Silber oder Kupfer gewonnen werden. Die anfängliche Zusammensetzung der Legierung sowie die Korrosionszeit spielen dabei eine erhebliche Rolle für die letztendliche Beschaffenheit des npAu. Das nanoporöse Material zeigt eine hohe Aktivität und Selektivität als heterogener Katalysator in der Gas‐ sowie Flüssigphase. So ist die aerobe Oxidation von CO selbst bei –30 °C möglich. Auch Alkohole wie Methanol oder größere organische Moleküle wie Silane können erfolgreich oxidiert werden. Ebenso wurde demonstriert, dass Wasserstofftransferreaktionen auf Alkine möglich sind, bei welchen eine selektive Ausbildung des Z‐Alkens erfolgt. Die Aktivität des npAu zeigt dabei eine hohe Abhängigkeit von der Größe der Stege sowie der Präsenz kleiner Mengen an Restsilber im Material. Sauerstoff wird an den niedrig koordinierten Goldatomen aktiviert, wobei angrenzende Silberatome die Energie für die Chemisorption herabsetzen. Abhängig von der Art der Reaktion sind allerdings unterschiedliche Parameter von Vorteil beziehungsweise Nachteil. Auch wenn bereits vieles über npAu als Katalysator bekannt ist, kommen stets neue Aspekte des porösen Materials ans Licht. Für die chemische Forschung ist npAu dadurch zu einem hoch interessanten und vielseitigen Kandidaten für heterogene Katalyse geworden, von dem man in Zukunft noch einiges hören wird.
Visual and instrumental assessment of interference pigments
Authors: Cramer Werner Rudolf
Published: June 2021

Discrepancies often exist between visual assessment and instrumental assessment. These are due to different geometries with which samples are viewed or measured: In visual observation at the window or in the light booth, the sample panels are usually moved up and down. This changes the angle of illumination and observation. The current measuring devices have a fixed illumination.
First‐in‐Human Study to Assess the Safety, Tolerability, and Pharmacokinetics of Pirepemat, a Cortical Enhancer, in Healthy Volunteers
Authors: Rein‐Hedin Erik , Sjöberg Folke , Waters Susanna , Sonesson Clas , Waters Nicholas , Huss Fredrik , Tedroff Joakim
Published: June 2021

Pirepemat (IRL752) is a cortical enhancer being developed for the prevention of falls in patients with Parkinson disease. This first‐in‐human, randomized, double‐blind, placebo‐controlled phase 1 study evaluated safety, tolerability, and pharmacokinetics (PK) of pirepemat administered as oral single ascending doses (10, 35, 75, 175, 350 mg) and multiple ascending doses (100 and 250 mg 3 times daily) for 7 days to healthy male volunteers. Twenty and 24 subjects were randomly assigned in the single ascending dose and multiple ascending doses parts of the study, respectively. Pirepemat was generally well tolerated, although an increased frequency of adverse events of mild intensity within nervous system disorders (headache and dizziness) was seen after administration of 350 mg as a single dose and after multiple doses of 100 and 250 mg. PK of pirepemat showed a linear relationship over the dose range studied and exhibited dose proportionality after multiple‐dose administration. Accumulation after 7 days of multiple dosing was minor. Absorption was rapid, with a median time to maximum concentration of 2.0 hours on day 1 and day 7 (100 and 250 mg) and a mean terminal half‐life between 3.7 and 5.2 hours. Food intake had no (obvious) impact on PK. The results support 3‐times‐daily dosing and further clinical development.
A feature‐based approach for guiding the selection of Internet of Things cybersecurity standards using text mining
Authors: van der Schaaf Koen , Tekinerdogan Bedir , Catal Cagatay
Published: June 2021

Cybersecurity is critical in realizing Internet of Things (IoT) applications and many different standards have been introduced specifically for this purpose. However, selecting relevant standards is not trivial and requires a broad understanding of cybersecurity and knowledge about the available standards. In this study, we present a systematic approach that guides IoT system developers in selecting relevant cybersecurity standards for their IoT projects. The systematic approach has been developed in four stages. First, the common and variant features of IoT cybersecurity have been modeled using a feature model. Second, an up‐to‐date overview of the IoT cybersecurity standards landscape has been mapped by combining existing overviews. Third, a text mining algorithm has been implemented. Fourth, the systematic approach has been modeled using business process modeling notation. Our case study demonstrated that this approach is effective and efficient for guiding the selection of IoT cybersecurity standards.
Interannual variation in food choice of white‐headed langur inhabiting limestone forests in Fusui, southwest Guangxi, China
Authors: Lu Shiyi , Chen Ting , Huang Zhonghao , Li Youbang , Lu Changhu
Published: June 2021

Food habits are important factors in the adaptation of wild nonhuman primates. White‐headed langurs (Trachypithecus leucocephalus) are endemic to heavily fragmented limestone forests and adapt to unique living environments via flexible food selection strategies. In this study, we compared the dietary data for white‐headed langurs living in Chongzuo White‐headed Langur National Nature Reserve in 2013 and 2016 to evaluate interannual variations in diet. Our results indicated that young leaves were the main food source for langurs, accounting for 52.4% (SD 25.4%) and 65.2% (SD 22.4%) of their diet in 2013 and 2016, respectively. The pattern of plant part consumption was similar between the two years. The consumption of young leaves varied with the availability of young leaves, whereas the consumption of mature leaves was negatively correlated with young leaf availability. The consumption of plant species and diet diversity were higher in 2013 than in 2016. In both 2013 and 2016, although diet diversity varied with the consumption of mature leaves, it was negatively correlated with the consumption and availability of young leaves. Dietary interannual variation is likely to either be linked to phenological variations or indicate that white‐headed langurs have a flexible ecological adaptation coping with habitat fragmentation.
Tailoring the Spatial Distribution and Content of Inorganic Nitrides in Solid–Electrolyte Interphases for the Stable Li Anode in Li–S Batteries
Authors: Jin Qi , Zhao Kaixin , Li Lu , Ma Xinzhi , Wu Lili , Zhang Xitian
Published: June 2021

Among the alternatives to lithium‐ion batteries, lithium–sulfur (Li–S) batteries are considered as an attractive option because of their high theoretical energy density of 2570 Wh kg−1. However, the application of the Li–S battery has been plagued by the rapid failure of the Li anode due to the Li dendrite growth and severe parasitic reactions between Li and lithium polysulfides. The physicochemical properties of the solid–electrolyte interphase have a profound impact on the performance of the Li anode. Herein, a lithium polyacrylic acid/lithium nitrate (LPL)‐protective layer is developed to inhibit the dendrite Li growth and parasitic reactions by tailoring the spatial distribution and content of LiNxOy and Li3N at the SEI. The modified SEI is thoroughly investigated for compositions, ion transport properties, and Li plating/stripping kinetics. Consequently, the Li–S cell with a high S loading cathode (5.0 mg cm−2), LPL layer‐protected thin Li anode (50 μm), and 40 μL electrolyte shows a long life span of 120 cycles. This work evokes the avenue for regulating the spatial distribution of inorganic nitride at the SEI to suppress the formation of Li dendrites and parasitic reactions in Li–S batteries and perhaps guiding the design of analogous battery systems.
Geochemistry and geochronology of intermediate volcanic rocks from the Compostela area, Nayarit, Mexico: Implications for petrogenesis and tectonic setting
Authors: Ruiz‐Mendoza Vivian , Verma Sanjeet K. , Torres‐Sánchez Darío , Barry Tiffany L. , Moreno Juan A. , Torres‐Hernández José Ramón
Published: June 2021

The Compostela area is located in the western Trans‐Mexican Volcanic Belt, which consists of volcanic rocks that produced during the Pliocene to Recent volcanism. In this paper, we present petrography, whole‐rock major‐ and trace‐element concentrations, Ar–Ar ages, and Sr–Nd isotopic data of volcanic rocks from the Compostela area in the south of the city of Tepic, Nayarit, Mexico. These volcanic rocks are of intermediate composition and belong to the transitional series: basaltic trachyandesites [52.72–53.94 wt% SiO2; 0.69–2.53 wt% MgO] and subalkaline series: low‐Si [55.11–60.94 wt% SiO2; 0.79–2.74 wt% MgO] and high‐Si [61.60–62.71 wt% SiO2; 0.36–0.80 wt% MgO] andesites. The 40Ar/39Ar dating of two basaltic trachyandesites yields plateau ages of 1.05 ± 0.15 Ma and 1.07 ± 0.17 Ma and the andesites yielded a plateau age of 2.42 ± 0.36 Ma. These results indicate that the studied rocks were formed during the Pleistocene in two discrete episodes. The basaltic trachyandesites show enriched light rare earth elements patterns relative to high rare earth elements [(La/Yb)N = 5.81–8.07] with negligible Eu anomalies. The andesites display enriched large‐ion lithophile elements (Ba, K) with anomalies of Nb (Th/Ce) and Ti in the three groups identified in the subalkaline series. The basaltic trachyandesites appear in a tight cluster of initial 87Sr/86Sr ratios (0.703519–0.703882) as compared to the basaltic andesite 87Sr/86Sr (0.704073) and positive ɛNd(t) values of +5.6 to +3.4, respectively, indicating that the basaltic trachyandesites were derived from intermediate magmas from a shallow mantle source. Geochemical modelling reveals that both basaltic trachyandesite and andesite rocks were derived by a process of crystal fractionation accompanied by assimilation of crustal rocks at the lower or middle level. Geochemical ratios and multidimensional discrimination diagrams, combined with the cross‐section of the subduction zone indicates that basaltic trachyandesites were generated from a rift and/or Ocean Island Basalt‐type source, whereas andesites were generated from a slab‐derived source in a subduction environment.
The effect of coverage of smoking‐cessation aids on tobacco use: Evidence from Canada
Authors: Shen Yichen , Noguchi Haruko
Published: June 2021

In clinical trials, smoking‐cessation aids (SCAs) have proven to be effective at improving the odds of smoking cessation. Because of the effectiveness of SCAs in these settings, many countries have adopted the coverage of SCAs to reduce tobacco use. However, the effect of such coverage on tobacco use is ambiguous. On one hand, the coverage may have the intended effect and reduce tobacco use. On the other hand, the coverage may cause beneficiaries to participate in tobacco use more as the drug coverage protects beneficiaries from future costs associated with tobacco use. To understand the effect of SCA coverage, we examine it using 2008–2012 Canadian Tobacco Use Monitoring Survey and a difference‐in‐differences approach. We find that SCA coverage increases cigarette and cigarillo use. Moreover, the effect of SCA coverage on tobacco use is stronger in men and in those with at least a college education. Our results point to the unintended consequences of the coverage of SCAs on tobacco use.
A snapshot of ABO, RH, and JK blood group systems in modern Ireland
Authors: Browne Anne , Kinsella Anthony , Keogh Moira , Morris Kieran , Field Stephen
Published: June 2021

Objectives

This study aimed to capture a snapshot of the Irish population to determine if there had been any changes in the ABO and RH blood group system (BGS) distribution from previous Irish studies and to establish an Irish JK BGS frequency, providing real time donor information to the Irish Blood Transfusion Service (IBTS).

Background

Ireland's population is constantly increasing and becoming more diverse, this has potential implications for the IBTS to provide blood with extended phenotypes for certain cohorts of patients.

Materials and methods

All first time blood donors had relevant testing performed in the Automated Donor Grouping (ADG) laboratory using the Beckman Coulter PK7300 analyzer with appropriate antisera by validated methods. All pertinent information and test results were categorized and analyzed.

Results

The number of donors tested was 3427. ABO phenotype: A: 29.82%, B: 12.02%, O: 54.95% and A,B: 3.21%. RHD: 82.26%. RHCE: R1R1: 17.62%, R2R2: 2.89%, R1R2: 13.95%, R1r: 33.35%, R2r: 13.07%, Ror: 1.25%, R1RZ: 0.06%, R2RZ: 0.06%, r′r: 0.55%, r″r: 0.53%, rr: 16.66%. Kidd phenotype: Jk(a + b+): 49.63%, Jk(a‐b+): 23.34%, Jk(a + b‐): 27.02%.

Conclusion

The observed frequencies for the relevant BGSs remained relatively unchanged to the prevalence values expected; however, statistically significant differences between the 2015 study and some of the previous studies were found for ABO distribution. 14.24% of the first time donors were born outside Ireland and statistically significant differences (P‐value < 0.001) were noted for aspects of the ABO and Rh phenotype distribution for the Irish born donors (BiI) vs those born outside Ireland (BoI).
Occupational exposure to crystalline silica and peripheral biomarkers: An update
Authors: Peruzzi Caroline Portela , Brucker Natália , Bubols Guilherme , Cestonaro Larissa , Moreira Rafael , Domingues Daiane , Arbo Marcelo , Olivo Neto Pedro , Knorst Marli Maria , Garcia Solange Cristina
Published: June 2021

Peripheral biomarkers are important tools for detecting occupational exposures to prevent the onset and/or progression of diseases. Studies that reveal early peripheral biomarkers are highly important to preserve the health of workers and can potentially contribute to diagnosing and/or prognosing occupational pathologies. Exposure to crystalline silica is a problem in several workplaces because it increases the risk of chronic obstructive pulmonary disease (COPD), tuberculosis, cancer, and pulmonary fibrosis, clinically defined as silicosis. Silicosis is diagnosed by chest radiography and/or lung tomography in advanced stages when there is a severe loss of lung function. Peripheral biomarkers can help in diagnosing early changes prior to silicosis and represent a highly important technical‐scientific advance that is minimally invasive. This review aimed to investigate the biomarkers studied for evaluating occupational exposure to crystalline silica and to understand the recent advances in this area. Potential oxidative, inflammatory, and immunological biomarkers were reviewed, as well as routine biomarkers such as biochemical parameters. It was found that biomarkers of effect such as serum CC16 and l‐selectin levels could represent promising alternatives. Additionally, studies have shown that neopterin levels in urine and serum can be used to monitor worker exposure. However, further studies are needed that include a greater number of participants, different times of exposure to crystalline silica, and a combination of silicosis patients and healthy volunteers. Evaluating the concentration of crystalline silica in occupational environments, its impact on biomarkers of effect, and alterations in lung function could contribute to revealing early health alterations in workers in a more robust manner.
A mutant fibrinogen that is unable to form fibrin can improve renal phenotype in mice with sickle cell anemia
Authors: Narciso Marilou G. , Hoeting Blair , James Jeanne M. , VandenHeuvel Katherine , Nasimuzzaman Md.
Published: June 2021

Sickle cell anemia (SCA) causes nephropathy which may progress to kidney failure. To determine if soluble fibrinogen (FibAEK) can prevent kidney damage in mice with SCA, we performed bone marrow transplantation (BMT) of Berkeley sickle mice into wild‐type fibrinogen (FibWT), and FibAEK mice that bear a germ‐line mutation in fibrinogen Aα chain at thrombin cleavage site which prevents fibrin formation. We found improved albuminuria in SS FibAEK mice compared with SS FibWT mice at 12 months post‐BMT due to the reduced kidney fibrosis, ischemic lesions, and increased survival of podocytes in the glomeruli, but did not improve urine concentrating defect. Therefore, our study clarifies the distinct role of fibrinogen and fibrin in the renal pathology of SCA.
Managing seasonality in West African informal urban vegetable markets: The role of household relations
Authors: Bellwood‐Howard Imogen , Ansah Isaac Gershon Kodwo , Donkoh Samuel Arkoh , Korbéogo Gabin
Published: June 2021

Seasonality influences African informal agricultural markets, but existing literature inadequately explores its interactions with market actors' social relations and livelihood outcomes. Thus, agricultural commercialisation policy ineffectively supports such actors to manage seasonality. Across Bamako, Ouagadougou and Tamale, we conducted interviews, focus group discussions, and a survey of farmer and marketer profits across seasons. Hot, dry season lettuce transactions performed by marketers are more likely to make profit. Farmers and marketers rely on household and community relations and reproduce gendered skills to optimise profit and secure future income streams. Policies supporting household reproduction, and infrastructure, may best support their marketing activity.
An efficient CHA‐WMA control strategy for a non‐isolated quasi‐Z‐source novel multilevel inverter‐based grid connected PV system
Authors: Santhi R. , Srinivasan A.
Published: June 2021

This manuscript proposes a hybrid approach for non‐isolated quasi Z‐source (QZS)‐novel cascaded multilevel inverter (NIQZS‐NMLI)‐based grid‐connected photovoltaic (PV) system. The proposed hybrid approach is the combined execution of both the color harmony algorithm (CHA) and woodpecker‐mating algorithm (WMA), and hence it is called CHA‐WMA method. Initially, the NIQZS‐NMLI design is developed to gain the optimal control signal using the proposed controller. The NIQZS‐NMLI is developed with the reduced count of switches, diodes, and sources. The major objective of the proposed method is “to satisfy the load power requirement and to maintain the power regulation or maximum energy conversion of the wind and solar subsystems.” The proposed method strictly prohibits the variations present in the output voltage of the NIQZS‐NMLI. Here, the CHA is employed to evaluate the optimal gain parameters in light of the source currents variety from the normal value, also it is useful for generating the optimum control signals dataset in the offline way. In the online way, the WMA predicts the most optimal control signals of the NIQZS‐NMLI in light of the satisfied dataset. The resultant control signals have been utilized for controlling the insulated gate bi‐polar switches (IGBT) of NIQZS‐NMLI. The proposed method is implemented in MATLAB/Simulink site and the performance is analyzed with existing methods. Moreover, the PV performance is analyzed under three test cases. The PV efficiency of the proposed method for all cases is 89.3975%, 90.2653%, and 97.8095%. Overall, the comparison outcomes demonstrate that the proposed method is more efficient than the other existing methods.
Evaluation of liver tissue extraction protocol for untargeted metabolomics analysis by ultra‐high‐performance liquid chromatography/tandem mass spectrometry
Authors: Liu Zhipeng , Wang Peng , Liu Zengjiao , Wei Chunbo , Li Ying , Liu Liyan
Published: June 2021

The aim of the untargeted metabolomics study is to obtain a global metabolome coverage from biological samples. Therefore, a comprehensive and systematic protocol for tissue metabolite extraction is highly desirable. In this study, we evaluated a comprehensive liver pretreatment strategy based on ultra‐high‐performance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry to obtain more metabolites using four different protocols. These protocols included (A) methanol protein precipitation, (B) two‐step extraction of dichloromethane‐methanol followed by methanol–water, (C) two‐step extraction of methyl tert‐butyl ether‐methanol followed by methanol–water, and (D) two‐step extraction of isopropanol‐methanol followed by methanol–water. Our results showed that protocol D was superior to the others due to more extracted features, annotated metabolites, and better reproducibility. And then, the stability and extraction sequence of protocol D were evaluated. The results showed that extraction with isopropanol‐methanol followed by methanol–water was the optimum preparation sequence, which offered higher extraction efficiency, satisfactory repeatability, and acceptable stability. Furthermore, the optimal protocol was successfully applied by liver samples of rats after high‐fat intervention. In summary, our protocol enabled a comprehensive and systematic evaluation of liver pretreatment to obtain more medium‐polar and nonpolar metabolites and was suitable for high‐throughput metabolomics analysis.
Long‐term efficacy and safety of dichlorphenamide for treatment of primary periodic paralysis
Authors: Sansone Valeria A. , Johnson Nicholas E. , Hanna Michael G. , Ciafaloni Emma , Statland Jeffrey M. , Shieh Perry B. , Cohen Fredric , Griggs Robert C.
Published: June 2021

Introduction/Aim

Long‐term efficacy and safety of dichlorphenamide (DCP) were characterized in patients with primary periodic paralysis (PPP).

Methods

Patients with PPP in a double‐blind, placebo‐controlled study were randomly assigned to receive DCP 50 mg twice daily or placebo for 9 weeks, followed by a 52‐week open‐label DCP treatment phase (DCP/DCP and placebo/DCP populations). Efficacy (attack rate, severity‐weighted attack rate) and safety were assessed in patients completing the study (61 weeks). In this post hoc analysis, efficacy and safety data were pooled from hyperkalemic and hypokalemic substudies.

Results

Sixty‐three adults (age, 19‐76 years) completed the double‐blind phase; 47 (74.6%) of these patients completed 61 weeks. There were median decreases in weekly attack and severity‐weighted attack rates from baseline to week 61 (DCP/DCP [n = 25], −1.00 [P < .0001]; placebo/DCP [n = 20], −0.63 [P = .01] and DCP/DCP, −2.25 [P < .0001]; placebo/DCP, −1.69 [P = .01]). Relatively smaller median decreases in weekly attack and severity‐weighted attack rates occurred from weeks 9 to 61 among patients receiving DCP continuously (n = 26; −0.14 [P = .1] and −0.24 [P = .09]) than among those switching from placebo to DCP after 9 weeks (n = 16; −1.04 [P = .049] and −2.72 [P = .08]). Common adverse events (AEs) were paresthesia and cognition‐related events, which typically first occurred within 1 month of blinded treatment initiation and in rare cases led to treatment discontinuation. Dose reductions were frequently associated with common AE resolution.

Discussion

One‐year open‐label DCP treatment after a 9‐week randomized, controlled study confirmed long‐term DCP remains safe and effective for chronic use. Tolerability issues (paresthesia, cognition‐related AEs) were manageable in most patients.
Spectroscopic cyclic voltammetry, and molecular docking study on the molecular interaction between synthesized blue emitting nitrogen‐doped carbon dots and human serum albumin
Authors: Liu Yufeng , Zhang Lizhi , Liang YuanHao , Yang Hongtian , Guo Xingjia , Dong Wei
Published: June 2021

Fluorescent carbon dots are a promising drug carrier and bio‐sensor material. The study between human serum albumin and carbon dots could explore the possible interaction mechanism. In this paper, melamine was adopted as passivating agent and citric acid as carbon source, high fluorescence nitrogen doped carbon dots (N‐CDs) were synthetized by one‐pot solid phase pyrolysis successfully. The obtained blue emissive N‐CDs with an average particle size of 2.8 ± 0.7 nm displayed an excitation‐dependent photoluminescence behavior, and the fluorescence quantum yield was estimated to be 12.8%. Moreover, the N‐CDs contained abundant hydroxyl, carboxyl, and amine groups. The molecular interaction between as‐prepared N‐CDs and HSA was systematically investigated in vitro through several spectroscopic methods associated with cyclic voltammetry (CV) and molecular docking. The quenching mechanism of HSA by N‐CDs was static through forming the HSA‐N‐CDs complex, and both hydrogen bonding and van der Waals forces were the fundamental driving forces in the spontaneous binding process. The distance between N‐CDs and HSA was 2.2 nm on the basis of Förster's theory. The competitive binding experiment showed that the binding of N‐CDs was primarily in site I of HSA. Through the analysis of circular dichroism (CD), synchronous fluorescence, and three‐dimensional fluorescence spectra, the secondary structure of HSA was altered in the presence of N‐CDs and the polarity around the amino acid residues of HSA was not changed. Besides, molecular simulation was applied to determine the possible binding situation. Our study explored the interaction mechanism of N‐CDs with HSA, which provided some valuable information for understanding the structure and function of proteins as well as the transport and metabolism of N‐CDs.
Prediction the structure, mechanical properties and melting point ofD8m‐Mo5SiB2andCmcm‐Mo5SiB2
Authors: Pu Delin , Pan Yong
Published: June 2021

Mo5SiB2is an ideal candidate for high temperature material. Although the D8l‐Mo5SiB2has been published, the other phases and the related properties of Mo5SiB2are still unclear. Here, two possible Mo5SiB2phases (D8m‐Mo5SiB2andCmcm‐Mo5SiB2) are predicted by using the first principles method. The structural stability, mechanical properties, melting point and electronic structure of Mo5SiB2are studied. The results show that the D8m‐Mo5SiB2andCmcm‐Mo5SiB2are thermodynamically and dynamically stables. The calculated bulk elastic modulus, shear modulus and Young's modulus of theCmcm‐Mo5SiB2are close to D8l‐Mo5SiB2. In addition, the predictedCmcm‐Mo5SiB2has high melting point (2518.5°C) compared to the D8l‐Mo5SiB2and D8m‐Mo5SiB2. In particular, the predicted D8m‐Mo5SiB2exhibits better plasticity than the D8l‐Mo5SiB2. The calculated density of states and Mulliken overlap population shows that the D8m‐Mo5SiB2andCmcm‐Mo5SiB2all exhibit metallic behavior. The metallic behavior mainly depends on the electronic interaction between Mo atom and B atom near Fermi level. Furthermore, the bond length of Mo‐B bond in the D8m‐Mo5SiB2is longer than the other two structures, which may be the reason why the ductility of the former is better than the latter.
Carbon‐ZnO Composite Synthesized from ZIF‐8 Depositing Vegetable Biomass for Efficient Removal of Phosphate from Aqueous Solution
Authors: Zhu Rixin , Zhang Zhaoran , Li Jing , Yan Liangguo
Published: June 2021

In order to combine the advantage of biochar and zeolitic imidazolate frameworks (ZIF‐8), the carbon‐ZnO composite were prepared by calcination the hybrid of two vegetable biomasses (rape, Ra, Brassia campestris L. and Chinese cabbage, Cc, Brassica rapa pekinensis) and ZIF‐8. The characterization results showed Cc‐ZnO and Ra‐ZnO had the random, irregular and hollow structure. The adsorptive removal of carbon‐ZnO composite for aqueous phosphate was performed using batch equilibrium method. Both Cc‐ZnO and Ra‐ZnO showed higher adsorption capacities than the pristine biochars and ZIF‐8, and Ra‐ZnO can remove phosphate quickly within 60 min. The adsorption kinetic data were consistent to the pseudo‐second‐order equation and the isothermal data followed the Langmuir and Freundlich models. The main interactions of phosphate adsorption by Cc‐ZnO and Ra‐ZnO were electrostatic attraction and surface complexation. The above results indicated the carbon‐ZnO composite could be used as a promising adsorbent to treat wastewater containing phosphate.
High‐Level Electron Correlation of the Indirect Nuclear Spin‐Spin Coupling Constants in Some Small Diboranes and Lithium‐Doped Diboranes
Authors: Santos Neto Antonio P. , Rivelino Roberto , Pagola Gabriel I. , Provasi Patricio F.
Published: June 2021

We have investigated the spin‐spin coupling constants (SSCC's) of diborane(4) and diborane(6), their Li‐doped counterparts, and the dimerization of diborane(6), using the second order polarization propagator approximation with coupled cluster singled and double [SOPPA(CCSD)] substitutions. We employed an adapted basis set to perform the calculations of their SSCC's. Energetically, from optimized structures at second‐order Møller‐Plesset perturbation theory, our results indicate that the stable isomers of diborane(4) may exist as independent molecular entities, separate by
20 kJ/mol, obtained in our best level of calculation. Distinct geometric configurations and energetic stability are well related to the nuclear coupling mechanism in these diborane compounds. We found that dimerization of diborane(6) is possible with different symmetries, although it does not significantly change the geometric parameters of the monomers. This is also confirmed by the SSCC's calculations with SOPPA(CCSD).
The Effects of Multiple‐Exposure Textual Enhancement on Child L2 Learners’ Development in Derivational Morphology: A Multi‐Site Study
Authors: Révész Andrea , Bunting Leona , Florea Adrian , Gilabert Roger , Hård af Segerstad Ylva , Mihu Ioan P. , Parry Cliff , Benton Laura , Vasalou Asimina
Published: June 2021

Much research exists on the role of textual enhancement in instructed second language (L2) development, yet little is known about how its effectiveness is influenced by multiple exposures, whether it can facilitate the acquisition of L2 derivational morphology, and how it may affect child language learning. To fill these gaps, this study employed a six‐week multiple‐exposure design to investigate the extent which to textual enhancement can benefit children’s knowledge of L2 derivational morphemes. The study employed a pretest‐posttest design, with six treatment sessions. Participants were 91 L2 learners of English in two primary school EFL contexts (Romania, Sweden). In each context, participants were randomly assigned to two groups: the +highlight group received textually enhanced texts, whereas the –highlight group read unenhanced texts during the treatment. The children read the texts through a digital reader application during their English lessons. The target constructions were the –ion and –ment morphemes. The pretest and posttest included a non‐word derivational suffix choice and a nonword derivational suffix decomposition task. Results of linear mixed effects models found a small advantage of textual enhancement for the acquisition of the –ion morpheme by Swedish learners on the suffix choice task, but Romanian learners showed no benefits from highlighting.
Bending the Bruhat-Tits tree. Part I. Tensor network and emergent Einstein equations
Authors: Chen Lin , Liu Xirong , Hung Ling-Yan
Published: June 2021

Abstract

As an extended companion paper to [1], we elaborate in detail how the tensor network construction of a p-adic CFT encodes geometric information of a dual geometry even as we deform the CFT away from the fixed point by finding a way to assign distances to the tensor network. In fact we demonstrate that a unique (up to normalizations) emergent graph Einstein equation is satisfied by the geometric data encoded in the tensor network, and the graph Einstein tensor automatically recovers the known proposal in the mathematics literature, at least perturbatively order by order in the deformation away from the pure Bruhat-Tits Tree geometry dual to pure CFTs. Once the dust settles, it becomes apparent that the assigned distance indeed corresponds to some Fisher metric between quantum states encoding expectation values of bulk fields in one higher dimension. This is perhaps a first quantitative demonstration that a concrete Einstein equation can be extracted directly from the tensor network, albeit in the simplified setting of the p-adic AdS/CFT.
Neuropathologie der Demenzen
Authors: Klotz Sigrid , Gelpi Ellen
Published: June 2021

Demenz ist die klinische Folge verschiedener neurologischer Erkrankungen mit einer Vielzahl von Ätiologien. Dabei ist die genaue Kenntnis der zugrunde liegenden pathologischen Veränderungen entscheidend für die passgenaue Versorgung der Patienten und für die Entwicklung geeigneter Krankheitsbiomarker. Eine definitive Diagnose vieler dieser Erkrankungen, insbesondere der neurodegenerativen Formen, kann nur nach gründlicher postmortaler neuropathologischer Untersuchung gestellt werden. Dies unterstreicht die Wichtigkeit der Durchführung einer Gehirnautopsie und die Relevanz einer engen Zusammenarbeit zwischen Klinikern, Neuroradiologen und Neuropathologen sowie mit Grundlagenforschern. Ziel der vorliegenden Arbeit ist es, einen kurzen Überblick über die Neuropathologie der Demenz mit Schwerpunkt auf neurodegenerative Erkrankungen zu geben, um die interdisziplinäre Zusammenarbeit weiter zu fördern.
The Norm of a Skew Polynomial
Authors: Pumplün S. , Thompson D.
Published: June 2021

Let D be a finite-dimensional division algebra over its center and R = D[t;σ,δ] a skew polynomial ring. Under certain assumptions on δ and σ, the ring of central quotients D(t;σ,δ) = {f/g|f ∈ D[t;σ,δ],g ∈ C(D[t;σ,δ])} of D[t;σ,δ] is a central simple algebra with reduced norm N. We calculate the norm N(f) for some skew polynomials f ∈ R and investigate when and how the reducibility of N(f) reflects the reducibility of f.
Curved-ribbon-based track modelling for minimum lap-time optimisation
Authors: Lovato S. , Massaro M. , Limebeer D. J. N.
Published: June 2021

Three-dimensional road models for vehicular minimum-lap-time manoeuvring are typically based on curvilinear coordinates and generalizations of the Frenet–Serret formulae. These models describe the road as a parametrized ‘ribbon’, which can be described in terms of three curvature variables. In this abstraction the road is assumed laterally flat. While this class of road models is appropriate in many situations, this is not always the case. In this research we extend the laterally-flat ribbon-type road model to include lateral curvature. This accommodates the case in which the road camber can change laterally across the track. Lateral-position-dependent camber is introduced as a generalisation that is required for some race tracks. A race track model with lateral curvature is constructed using high-resolution LiDAR measurement data. These ideas are demonstrated on a NASCAR raceway, which is characterized by large changes in lateral camber angle ($$\approx 10^\circ$$

≈

10
∘

) on some parts of the track. A free-trajectory optimization is employed to solve a minimum-lap-time optimal control problem. The calculations highlight the practically observed importance of lateral camber variations.
Serum fatty acid binding protein 5 (FABP5) as a potential biomarker of inflammation in psoriasis
Authors: Kozłowska Dorota , Myśliwiec Hanna , Harasim-Symbor Ewa , Milewska Anna Justyna , Chabowski Adrian , Flisiak Iwona
Published: June 2021

Fatty acid binding protein 5 (FABP5) is elevated in psoriatic keratinocytes and could be involved in systemic metabolic disturbances in psoriasis. The aim of the study was to evaluate serum FABP5 in obese and non-obese psoriatic patients, to assess the relationship between FABP5 and the duration, severity of the disease, inflammatory and metabolic markers and influence of treatment with narrowband—ultraviolet B (NB-UVB). Seventy-four patients (30 treated with NB-UVB) with psoriasis were enrolled in the study. The serum concentrations of FABP5 were measured using Human FABP5 Enzyme-Linked Immunosorbent Assay kit. Serum fatty acids were measured by gas–liquid chromatography. Serum FABP5 levels in psoriatic patients were higher versus control group (P < 0.001). FABP5 in patients with PASI > 20 was higher compared to the mild group (PASI < 10) (P < 0.001) and serum FABP5 correlated positively with PASI score (r = 0.41, P < 0.001). There was also positive correlation between FABP5 and basic inflammation indices. Decrease of PASI after NB-UVB treatment (P < 0.001) was observed and accompanied by decrease of the serum FABP5 (P = 0.007). FABP5 is a potential marker of psoriasis, its severity and clinical outcome after therapy with NB-UVB. FABP5 may reflect metabolic disturbances in psoriatic patients.
Landscape/mindscape/langscape: The ephemerality of the digital and of the real in Marlene Creates’s video-poems for ice and snow
Authors: Concilio Carmen
Published: June 2021

The present essay aims at illustrating Marlene Creates’s web project Brickle, nish, and knobbly (2015), as a key example of Eco-Digital Humanities. First of all, it is a digital work of art made of ice images. Besides, it is also a digital archive meant to salvage a linguistic treasury of local idioms that both name and describe all types of snow and ice formations in Newfoundland, Canada. Therefore, the present analysis proves the special quality and inevitable ephemeral status of this project, for it constitutes a multimodal and multimedia web-archive, subject to possible erasure, or obsolescence in the face of new computer programmes and platforms developments. The archive is also an open instrument for everybody’s use: a digital audio-visual (poetic) dictionary, that ultimately functions as a challenge to climate change effects, that might dissolve both the ice formations and the language that accompanies them. Since the real world is no less ephemeral than the world of the web, this contribution also proves how Marlene Creates’s artwork envisions and embraces an ecological salvaging of our present and future landscape, mindscape, and langscape.
Towards a reliable implementation of least-squares collocation for higher index differential-algebraic equations—Part 2: the discrete least-squares problem
Authors: Hanke Michael , März Roswitha
Published: June 2021

In the two parts of the present note we discuss questions concerning the implementation of overdetermined least-squares collocation methods for higher index differential-algebraic equations (DAEs). Since higher index DAEs lead to ill-posed problems in natural settings, the discrete counterparts are expected to be very sensitive, which attaches particular importance to their implementation. We provide in Part 1 a robust selection of basis functions and collocation points to design the discrete problem whereas we analyze the discrete least-squares problem and substantiate a procedure for its numerical solution in Part 2.
Using Item Response Theory to Identify Responders to Treatment: Examples with the Patient-Reported Outcomes Measurement Information System (PROMIS®) Physical Function Scale and Emotional Distress Composite
Authors: Hays Ron D. , Spritzer Karen L. , Reise Steven P.
Published: June 2021

The reliable change index has been used to evaluate the significance of individual change in health-related quality of life. We estimate reliable change for two measures (physical function and emotional distress) in the Patient-Reported Outcomes Measurement Information System (PROMIS®) 29-item health-related quality of life measure (PROMIS-29 v2.1). Using two waves of data collected 3 months apart in a longitudinal observational study of chronic low back pain and chronic neck pain patients receiving chiropractic care, and simulations, we compare estimates of reliable change from classical test theory fixed standard errors with item response theory standard errors from the graded response model. We find that unless true change in the PROMIS physical function and emotional distress scales is substantial, classical test theory estimates of significant individual change are much more optimistic than estimates of change based on item response theory.
Identification of Elite Potato Clones with Resistance to Late Blight Through Participatory Varietal Selection in Peru
Authors: Gastelo Manuel , Burgos Gabriela , Bastos Carolina , Perez Juan Miguel , Otiniano Ronal , Cabrera Hector , Ccanto Raul , de Scurrah Maria Mayer , Felde Thomas zum
Published: June 2021

Potato is the most important crop in Peru and late blight is the main disease affecting the crop. However, new varieties that are resistant to late blight often lack other traits that farmers and consumers prefer. Using participatory varietal selection, this study seeks to identify clones with high potential to become varieties with resistance to late blight but also feature a high marketable tuber yield and other preferred agronomic traits. During 2016–2017, 36 clones previously selected for high levels of resistance to late blight from population B developed by the International Potato Center, and three varieties used as controls (INIA 302 Amarilis moderately resistant, INIA303 Canchan and Yungay susceptible to late blight), were evaluated in five Peruvian locations. At harvest, five clones were selected based on (i) evaluations made by farmers through Participatory Varietal Selection, (ii) analysis of mixed models and Best Linear Unbiased Predictors for tuber yield, (iii) low glycoalkaloid content in tubers, and (iv) good organoleptic quality. These clones were evaluated again during 2017–2018 in four locations. Resistance to late blight and good marketable tuber yields were identified as the most important criteria for the selection of a new potato variety. The clones CIP308488.92, CIP308495.227 and CIP308478.59 were selected as promising clones having resistance to late blight and tuber yield superior to the local varieties, INIA-303 Canchan, Yungay, as well as good organoleptic quality and low glycoalkaloid content. These clones can be suggested for variety release in similar agroecological environments.